Orthodontically induced osteocyte apoptosis under different force magnitudes in rats: an immunohistochemical study

We investigated the effect of different force magnitudes on osteocyte apoptosis in a model of orthodontic tooth movement. Forty-nine male Sprague Dawley rats (7–9 wk of age) were divided into light- and heavy-force groups (n = 21 each group) and a control group (n = 7). A coil spring delivered pressure (either 10–15 g or 20–25 g) to the left maxillary first molar. The rats were sacrificed 1, 3, or 5 d after placement of the appliance. Sections of the maxillary first molars were immunostained for caspase-3. Upon force application, the number of apoptotic osteocytes significantly increased in the pressure side at 1 d and remained the same at 3 d and 5 d. However, there was no significant difference in the number of apoptotic osteocytes between the two force groups. We conclude that osteocyte apoptosis appears to increase under orthodontic loading, reaching a plateau after 1 d. However, osteocyte apoptosis seems to be independent of the magnitude of orthodontic forces tested.

from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2vgSRjZ
via IFTTT

Oral sex linked to increase in throat cancers | Stuff.co.nz - Stuff.co.nz

Stuff.co.nz

Oral sex linked to increase in throat cancers | Stuff.co.nz Stuff.co.nz Actor Michael Douglas started a public conversation about the link between oral sex and HPV-related throat cancers in 2013. Oral sex is being blamed for ... and more »

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hEKzPO
via IFTTT

Endoscopic DCR using bipedicled interlacing mucosal flaps

Objective

Obstruction of the nasolacrimal duct is a relatively common condition that affects patients of all ages, races, and sexes. The surgical gold standard for complete nasolacrimal duct obstruction and dacryocystitis is dacryocystorhinostomy (DCR). The purpose of this study was to describe a novel, bipedicled interlacing mucosal sparing flap technique for endoscopic DCR (eDCR).

Methods

A posteriorly based mucosal flap over the fundus is combined with a novel, anteriorly based mucosal flap over the intraosseus portion of the nasolacrimal duct (NLD). This exposes a wide area of the maxillary bone, allowing for exposure and identification of the NLD/sac complex in a safer, more inferior position. The interlacing mucosal flaps may be replaced at the conclusion of the procedure, thereby minimizing bone exposure and maintaining excellent long-term patency.

Results

The authors have utilized this technique in 55 procedures with 100% positive identification of the NLD and lacrimal sac, 0% complication rate, 100% anatomical patency rate, and 96.4% success rate after a minimal follow-up of 6 months.

Discussion

The bipedicled interlacing flap technique for eDCR provides for safe and reproducible identification of the NLD and lacrimal sac while minimizing bone exposure and restenosis rate.

Conclusion

The bipedicled interlacing flap technique for eDCR provides for safe and reproducible identification of the NLD and lacrimal sac while minimizing bone exposure and restenosis rate.

Level of Evidence

N/A Laryngoscope, 2017

from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2vA0Pre
via IFTTT

Adjuvant photodynamic therapy in head and neck cancer after tumor-positive resection margins

Objective

In case of close or positive resection margins after oncological resection in head and neck surgery, additional treatment is necessary. When conventional options are exhausted, photodynamic therapy (PDT) can play a role in achieving clear margins. The purpose of the current study was to evaluate the clinical benefit of PDT as adjuvant therapy next to surgery with positive resection margins. The role of the time interval between surgery and PDT on survival outcomes also was investigated.

Study Design

Retrospective cohort analysis.

Methods

Adjuvant PDT was performed in patients with a malignancy in the head and neck region with close or positive resection margins who were not eligible for conventional treatment options. The primary endpoint was progression-free survival. Secondary endpoints were disease-free survival, overall survival, and optimal time interval between surgery and PDT.

Results

Fifty-four patients were treated with surgery followed by meta-tetrahydroxyphenylchlorin-mediated PDT. There was a large diversity in tumor location and histopathology, as well as in time interval between surgery and PDT. The 2-year progression-free survival rate was 30%; 2-year disease-free survival rate was 28%; and 2-year overall survival was 51%. Disease-free survival was significantly better when the time interval between surgery and PDT was ≥ 6 weeks (P = 0.02).

Conclusion

PDT can be applied as adjuvant therapy after surgery in cases of a malignancy with close or positive tumor resection margins. However, the clinical benefits are yet to be determined. There is a significantly better disease-free survival with a time interval between surgery and PDT of minimal 6 weeks.

Level of Evidence

4. Laryngoscope, 2017

from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2vzljjV
via IFTTT

FtseMib future: spunti operativi per martedì 8 agosto - Milano Finanza

Milano Finanza

FtseMib future: spunti operativi per martedì 8 agosto Milano Finanza E' stata una giornata positiva sul mercato azionario italiano che ha compiuto un nuovo balzo in avanti e si è spinto sui massimi delle ultime settimane. Il Ftse Mib future (scadenza settembre 2017), dopo un'apertura a 21.970, è sceso fino ad un minimo ... and more »

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wCDx0v
via IFTTT

The fate of the vitelline and umbilical veins during the development of the human liver

Abstract

Differentiation of endodermal cells into hepatoblasts is well studied, but the remodeling of the vitelline and umbilical veins during liver development is less well understood. We compared human embryos between 3 and 10 weeks of development with pig and mouse embryos at comparable stages, and used Amira 3D reconstruction and Cinema 4D remodeling software for visualization. The vitelline and umbilical veins enter the systemic venous sinus on each side via a common entrance, the hepatocardiac channel. During expansion into the transverse septum at Carnegie Stage (CS)12 the liver bud develops as two dorsolateral lobes or 'wings' and a single ventromedial lobe, with the liver hilum at the intersection of these lobes. The dorsolateral lobes each engulf a vitelline vein during CS13 and the ventromedial lobe both umbilical veins during CS14, but both venous systems remain temporarily identifiable inside the liver. The dominance of the left-sided umbilical vein and the rightward repositioning of the sinuatrial junction cause de novo development of left-to-right shunts between the left umbilical vein in the liver hilum and the right hepatocardiac channel (venous duct) and the right vitelline vein (portal sinus), respectively. Once these shunts have formed, portal branches develop from the intrahepatic portions of the portal vein on the right side and the umbilical vein on the left side. The gall bladder is a reliable marker for this hepatic vascular midline. We found no evidence for large-scale fragmentation of embryonic veins as claimed by the 'vestigial' theory. Instead and in agreement with the 'lineage' theory, the vitelline and umbilical veins remained temporally identifiable inside the liver after being engulfed by hepatoblasts. In agreement with the 'hemodynamic' theory, the left–right shunts develop de novo.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vIglAN
via IFTTT

Frailty and Risk of Cardiovascular Diseases in Older Persons: The Age, Gene/Environment Susceptibility-Reykjavik Study

Rejuvenation Research , Vol. 0, No. 0.


from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wpqznU
via IFTTT

Response to: "Maternal infection can cause spontaneous abortion" [Letters]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujvNA3
via IFTTT

Canada needs a holistic First Nations health strategy [Commentary]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vI3w9V
via IFTTT

Alcoholic versus aqueous chlorhexidine for skin antisepsis: the AVALANCHE trial [Research]

BACKGROUND:

Preoperative skin antisepsis is routine practice. We compared alcoholic chlorhexidine with aqueous chlorhexidine for skin antisepsis to prevent surgical site infection after minor skin excisions in general practice.

METHODS:

We conducted this prospective, multicentre, randomized controlled trial in 4 private general practices in North Queensland, Australia, from October 2015 to August 2016. Consecutive adult patients presenting for minor skin excisions were randomly assigned to undergo preoperative skin antisepsis with 0.5% chlorhexidine in 70% ethanol (intervention) or 0.5% chlorhexidine aqueous solution (control). Our primary outcome was surgical site infection within 30 days of excision. We also measured the incidence of adverse reactions.

RESULTS:

A total of 916 patients were included in the study: 454 underwent antisepsis with alcoholic chlorhexidine and 462 with aqueous chlorhexidine. Of these, 909 completed follow-up. In the intention-to-treat analysis of cases available at follow-up, there was no significant difference in the incidence of surgical site infection between the alcoholic chlorhexidine arm (5.8%, 95% confidence interval [CI] 3.6% to 7.9%) and the aqueous chlorhexidine arm (6.8%, 95% CI 4.5% to 9.1%). The attributable risk reduction was 0.010 (95% CI –0.021 to 0.042), the relative risk was 0.85 (95% CI 0.51 to 1.41), and the number needed to treat to benefit was 100. Per protocol and sensitivity analyses produced similar results. The incidence of adverse reactions was low, with no difference between groups (p = 0.6).

INTERPRETATION:

There was no significant difference in efficacy between alcoholic and aqueous chlorhexidine for the prevention of surgical site infection after minor skin excisions in general practice. Trial registration: http://ift.tt/1F0tq3G, no. ACTRN12615001045505

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujBLB0
via IFTTT

New evidence of contaminants from fracking [News]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujFgHC
via IFTTT

Bariatric surgery [Practice]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uji500
via IFTTT

Maternal infection can cause spontaneous abortion [Letters]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vI64Ve
via IFTTT

Severe allergic contact dermatitis due to Polysporin [Practice]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vI1xCq
via IFTTT

The expert [Humanities]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujiPlX
via IFTTT

Reactions to international health care rankings [News]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vIaDz1
via IFTTT

Laser and Light Treatments for Hair Reduction in Fitzpatrick Skin Types IV–VI: A Comprehensive Review of the Literature

Abstract

Unwanted facial and body hair presents as a common finding in many patients, such as females with hirsutism. With advances in laser and light technology, a clinically significant reduction in hair can be achieved in patients with light skin. However, in patients with darker skin, Fitzpatrick skin types (FST) IV–VI, the higher melanin content of the skin interferes with the proposed mechanism of laser-induced selective photothermolysis, which is to target the melanin in the hair follicle to cause permanent destruction of hair bulge stem cells. Many prospective and retrospective studies have been conducted with laser and light hair-removal devices, but most exclude patients with darkly pigmented skin, considering them a high-risk group for unwanted side effects, including pigmentation changes, blisters, and crust formation. We reviewed the published literature to obtain studies that focused on hair reduction for darker skin types. The existing literature for this patient population identifies longer wavelengths as a key element of the treatment protocol and indicates neodymium-doped yttrium aluminum garnet (Nd:YAG), diode, alexandrite, and ruby lasers as well as certain intense pulsed light sources for safe hair reduction with minimal side effects in patients with FST IV–VI, so long as energy settings and wavelengths are appropriate. Based on the findings in this review, safe and effective hair reduction for patients with FST IV–VI is achievable under proper treatment protocols and energy settings.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ukPFXG
via IFTTT

ParticiPAte CP: a protocol of a randomised waitlist controlled trial of a motivational and behaviour change therapy intervention to increase physical activity through meaningful participation in children with cerebral palsy

Introduction

Children with cerebral palsy (CP) participate in leisure-time physical activities (PA) less often, with less intensity and reduced diversity than their typically developing peers. Participation in leisure-time physical activities may be an important source of habitual physical activity (HPA) for children with CP, who as a group have lower levels of HPA and increased sedentary time compared with their typically developing peers. The proposed study aims to compare the efficacy of a participation focused therapy (ParticiPAte CP) to usual care in a pragmatic, randomised waitlist controlled trial.

Methods and analysis

Thirty-six children with CP (18 in each group), classified as Gross Motor Function Classification System levels I to III, aged between 8 and 12 years will be recruited across South East Queensland, Australia. Children will be randomised to receive either ParticiPAte CP or waitlist usual care using concealed allocation. ParticiPAte CP is an individually tailored, goal-directed intervention model of pragmatic participation-focused therapy using a toolbox of evidence-based strategies in the treatment of children with CP. This will include goal-setting; identification of barriers and facilitators to participation goals, strategy formation and planning and communication guided by principles of Self-Determination Theory using strategies of Motivational Interviewing. The intervention comprises 8 weekly sessions of 1 hour duration conducted by a physiotherapist in the child's home or community.

Trial registration number

ACTRN12615001064594.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vI9Jm5
via IFTTT

Answering medical questions at the point of care: a cross-sectional study comparing rapid decisions based on PubMed and Epistemonikos searches with evidence-based recommendations developed with the GRADE approach

Introduction

Using the best current evidence to inform clinical decisions remains a challenge for clinicians. Given the scarcity of trustworthy clinical practice guidelines providing recommendations to answer clinicians' daily questions, clinical decision support systems (ie, assistance in question identification and answering) emerge as an attractive alternative. The trustworthiness of the recommendations achieved by such systems is unknown.

Objective

To evaluate the trustworthiness of a question identification and answering system that delivers timely recommendations.

Design

Cross-sectional study.

Methods

We compared the responses to 100 clinical questions related to inpatient management provided by two rapid response methods with 'Gold Standard' recommendations. One of the rapid methods was based on PubMed and the other on Epistemonikos database. We defined our 'Gold Standard' as trustworthy published evidence-based recommendations or, when unavailable, recommendations developed locally by a panel of six clinicians following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Recommendations provided by the rapid strategies were classified as potentially misleading or reasonable. We also determined if the potentially misleading recommendations could have been avoided with the appropriate implementation of searching and evidence summary tools.

Results

We were able to answer all of the 100 questions with both rapid methods. Of the 200 recommendations obtained, 6.5% (95% CI 3% to 9.9%) were classified as potentially misleading and 93.5% (95% CI 90% to 96.9%) as reasonable. 6 of the 13 potentially misleading recommendations could have been avoided by the appropriate usage of the Epistemonikos matrix tool or by constructing summary of findings tables. No significant differences were observed between the evaluated rapid response methods.

Conclusion

A question answering service based on the GRADE approach proved feasible to implement and provided appropriate guidance for most identified questions. Our approach could help stakeholders in charge of managing resources and defining policies for patient care to improve evidence-based decision-making in an efficient and feasible manner.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujqNez
via IFTTT

Associations between hyponatraemia, volume depletion and the risk of falls in US hospitalised patients: a case-control study

Objective

We aimed to determine if abnormal laboratory values which may indicate volume depletion are associated with increased odds of experiencing a hospital-acquired fall.

Design

Matched case–control study.

Setting

Four hospitals located in the Southeast USA.

Participants

Data from 699 adult fallers and 1189 matched controls (non-fallers) were collected via chart review from 2005 to 2010. Controls were matched to cases by nursing unit, time of fall and length of stay.

Outcome measures

The primary exposures included serum sodium, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio and haematocrit. Conditional logistic regression with m:n matching was used to determine adjusted and unadjusted ORs.

Results

Serum sodium levels were strongly associated with falls. In models controlling for demographic and other fall risk factors, patients with serum sodium levels of 125 mEq/L or less were associated with increased odds of experiencing a fall as compared with those with serum sodium levels of greater than 134 mEq/L (adjusted OR (aOR)=5.08, 95% CI 1.43 to 18.08). Conversely, elevated BUN, creatinine and elevated BUN/creatinine ratios were not associated with increased odds of experiencing a fall (aOR=0.64, 95% CI 0.49 to 0.84; aOR=0.70, 95% CI 0.54 to 0.92 and aOR=0.77, 95% CI 0.58 to 1.04, respectively.)

Conclusions

Laboratory indices that may indicate volume depletion appear to be unrelated to falls. However, hyponatraemia does appear to be a risk factor for falls, and those with serum sodium levels below 126 mEq/L are at especially high risk. It may be that other deficits associated with hyponatraemia, like altered mental status, are associated with risk of experiencing a hospital-acquired fall. These results indicate that abnormal laboratory values, like low sodium, can be useful for identifying hospitalised patients at risk of falling. Therefore, further investigation into abnormal laboratory values as predictors of hospital-acquired falls is warranted.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vIwOVG
via IFTTT

Two tales of cardiovascular risks--middle-aged women living in Sweden and Scotland: a cross-sectional comparative study

Objectives

To compare cardiovascular risk factors as well as rates of cardiovascular diseases in middle-aged women from urban areas in Scotland and Sweden.

Design

Comparative cross-sectional study.

Setting

Data from the general population in urban areas of Scotland and the general population in two major Swedish cities in southeast Sweden, south of Stockholm.

Participants

Comparable data of middle-aged women (40–65 years) from the Scottish Health Survey (n=6250) and the Swedish QWIN study (n=741) were merged together into a new dataset (n=6991 participants).

Main outcome measure

We compared middle-aged women in urban areas in Sweden and Scotland regarding risk factors for cardiovascular disease (CVD), CVD diagnosis, anthropometrics, psychological distress and lifestyle.

Results

In almost all measurements, there were significant differences between the countries, favouring the Swedish women. Scottish women demonstrated a higher frequency of alcohol consumption, smoking, obesity, low vegetable consumption, a sedentary lifestyle and also more psychological distress. For doctor-diagnosed coronary heart disease, there were also significant differences, with a higher prevalence among the Scottish women.

Conclusions

This is one of the first studies that clearly shows that Scottish middle-aged women are particularly affected by a worse profile of CVD risks. The profound differences in CVD risk and outcome frequency in the two populations are likely to have arisen from differences in the two groups of women's social, cultural, political and economic environments.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujLzdZ
via IFTTT

Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol

Introduction

Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients.

Methods and analysis

This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay.

Ethics and dissemination

This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals.

Trial registration

Clinical Trials NCT02534974

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vIhHvp
via IFTTT

Impact of nutritional index on the association between phosphorus concentrations and mortality in haemodialysis patients: a cohort study from dialysis outcomes and practice pattern study in Japan

Objectives

While maintenance of both phosphorus concentration and nutritional status is a major concern in managing haemodialysis patients, the interaction between these parameters is not well understood. The aim of this study was to assess whether or not nutritional index influences the association between phosphorus concentration and all-cause mortality.

Design

A cohort study.

Setting

The Dialysis Outcomes and Practice Pattern Study, which included 99 representative dialysis facilities in Japan between 1997 and 2010.

Participants

A total of 6230 adult haemodialysis patients who had spent at least 6 months on haemodialysis.

Main predictors

Six categories based on time-averaged factors of the geriatric nutritional risk index (GNRI; the lowest two and highest tertiles) and phosphorus concentration (<3.5, 3.5 to <6 and ≥6 mg/dL).

Primary outcome measure

All-cause mortality rate.

Analysis

Time-dependent Cox regression adjusting for potential confounders.

Results

During the follow-up period (12 294 person-years), we noted 561 deaths (4.6 per 100 person-years), and both high phosphorus concentrations and low-middle GNRI were separately associated with all-cause mortality. The harmful effect of high phosphorus concentrations on all-cause mortality was stronger in patients with high GNRI than in those with low-middle GNRI. On the other hand, the harmful effect of low phosphorus concentrations was stronger in those with low-middle GNRI than in those with high GNRI. Relative excess risk due to interaction (RERI) between high phosphorus concentrations and low-middle GNRI was –0.57, indicating an antagonistic interaction. We also observed a significant statistical multiplicative interaction between phosphorus concentrations and GNRI (p=0.05 by likelihood ratio test).

Conclusions

The association between time-averaged serum phosphorus concentration and all-cause mortality differs across the nutritional index. Accordingly, nutritional index should be considered when the impact of phosphorus concentration on mortality in haemodialysis patients is evaluated.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujKuCZ
via IFTTT

Access 3 project protocol: young people and health system navigation in the digital age: a multifaceted, mixed methods study

Background

The integration of digital technology into everyday lives of young people has become widespread. It is not known whether and how technology influences barriers and facilitators to healthcare, and whether and how young people navigate between face-to-face and virtual healthcare. To provide new knowledge essential to policy and practice, we designed a study that would explore health system access and navigation in the digital age. The study objectives are to: (1) describe experiences of young people accessing and navigating the health system in New South Wales (NSW), Australia; (2) identify barriers and facilitators to healthcare for young people and how these vary between groups; (3) describe health system inefficiencies, particularly for young people who are marginalised; (4) provide policy-relevant knowledge translation of the research data.

Methods and analysis

This mixed methods study has four parts, including: (1) a cross-sectional survey of young people (12–24 years) residing in NSW, Australia; (2) a longitudinal, qualitative study of a subsample of marginalised young people (defined as young people who: identify as Aboriginal and/or Torres Strait Islander; are experiencing homelessness; identify as sexuality and/or gender diverse; are of refugee or vulnerable migrant background; and/or live in rural or remote NSW); (3) interviews with professionals; (4) a knowledge translation forum.

Ethics and dissemination

Ethics approvals were sought and granted. Data collection commenced in March 2016 and will continue until June 2017. This study will gather practice and policy-relevant intelligence about contemporary experiences of young people and health services, with a unique focus on five different groups of marginalised young people, documenting their experiences over time. Access 3 will explore navigation around all levels of the health system, determine whether digital technology is integrated into this, and if so how, and will translate findings into policy-relevant recommendations.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vI9K9D
via IFTTT

Role of Ultrasound in Predicting Tumor Invasiveness in Follicular Variant of Papillary Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.


from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2uB5Xa7
via IFTTT

Age-Related Differences in Non-Persistence with Statin Treatment in Patients after a Transient Ischaemic Attack

Abstract

Background and Objective

Non-persistence with secondary preventive measures, including medications such as statins, adversely affects the prospects of successful outcomes. This study was aimed at evaluating non-persistence with statin therapy in cohorts of young and elderly patients after a transient ischaemic attack (TIA) and identifying patient-associated characteristics that influence the risk for non-persistence.

Methods

The study cohorts included 797 adult patients who were initiated on statin therapy following a TIA diagnosis between 1 January 2010 and 31 December 2010. Patients were followed up for 3 years and those with a treatment gap of at least a 6-month period were considered 'non-persistent'. In order to identify any age-related differences, all analyses were conducted in the entire study cohort (n = 797) as well as separately in the 'younger' (aged <65 years, n = 267) and the 'older' (aged ≥65 years, n = 530) patients.

Results

Non-persistence was significantly more common in younger patients compared to older patients (67.8% vs. 49.1%; p < 0.001). Factors that decreased the probability of non-persistence in younger and older patients included diabetes mellitus (hazard ratio [HR] = 0.72 and HR = 0.64, respectively) and hypercholesterolaemia (HR = 0.43 and HR = 0.62, respectively). Female gender (HR = 1.42) was associated with a higher and increasing number of medications taken (HR = 0.93), with lower probability for non-persistence in younger patients but not in the older patients.

Conclusions

Our results indicate that certain patients with TIA require special counselling to improve persistence with statin therapy. These include younger patients, especially females and those not on polypharmacy, and both younger and older patients without diabetes mellitus or hypercholesterolaemia.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vJTqG6
via IFTTT

The merits of decision modelling in the earliest stages of the IDEAL framework – an innovative case in DIEP flap breast reconstructions

IDEAL framework aims at improving the evidence base of available surgical innovations. However, the development of such innovations and collection of evidence is costly. Surgical innovation can provide more value for money if innovations are evaluated in an early stage, where evaluations can inform the decision whether to stop or further develop an innovation. We illustrate how decision modelling can be readily adopted at the earliest stages (0-1) of the IDEAL framework, using an innovation in bilateral DIEP flap breast reconstruction as an example.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wp5Dx6
via IFTTT

GSK2586184, a JAK1 selective inhibitor, in two patients with ulcerative colitis

Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC). Tofacitinib inhibits cytokine signalling through blockade of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Adverse events including neutropenia and anaemia resulting from JAK2 inhibition have been observed in actively treated patients. By selectively targeting JAK1, such adverse events could be expected to be avoided. This open label study was designed to enrol 15 patients with UC, however the trial was discontinued after two inclusions due to safety concerns with the agent in a parallel trial for systemic lupus erythematosus. GSK2586184 was administered in two patients with moderate-to-severe UC. The JAK1 selective inhibitor GSK2586184 was well tolerated and induced clinical and endoscopic response in two patients with moderate-to-severe UC. In addition, treatment with GSK2586184 decreased histology scores and faecal calprotectin levels at early withdrawal.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ukeHpK
via IFTTT

Aggressive large-cell neuroendocrine carcinoma of the sigmoid colon in a patient with ulcerative colitis

Colonic inflammation seen in inflammatory bowel disease (IBD) predisposes to the development of colorectal adenocarcinoma. In contrast, colorectal neuroendocrine carcinomas (NECs) have rarely been reported in the setting of IBD, and no definitive relationship between these tumours and IBD has been established. Dysplasia from chronic inflammation leading to neuroendocrine cell differentiation may be responsible for NEC development, though this finding has not been seen consistently. We present a case of large-cell neuroendocrine carcinoma of the sigmoid colon in a 65-year-old woman with long-standing ulcerative colitis. Although she underwent regular endoscopic follow-ups and was receiving the tumour necrosis factor alpha inhibitor infliximab, her tumour was large and aggressive, with metastases to the liver discovered at time of diagnosis. This case highlights the aggressive nature and poor prognosis of NECs and stresses the need to identify patients at high risk of developing NECs and develop improved surveillance guidelines for detecting them.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uBiRVk
via IFTTT

Rare combination of left-sided congenital diaphragmatic hernia and omphalocele

We reported a rare case of left-sided posterolateral congenital diaphragmatic hernia (CDH) and omphalocele, which is not associated with chromosomal abnormalities or other syndromes. Omphalocele was detected antenatally (CDH was not detected in antenatal ultrasound). The patient suffered from respiratory failure secondary to severe pulmonary hypertension. As the combination of CDH and omphalocele is rare and with the abdominal content herniating into the omphalocele instead of the thorax, antenatal diagnosis of such condition can be difficult. Unlike other reported cases in the literature, our patient's respiratory condition has been improving with time and is surviving beyond the infancy period. We believe this to be the first such survival case reported in the literature.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ukFpyk
via IFTTT

Gallstone ileus of the duodenum: an unexpected presentation of Bouveret's syndrome

This report describes a patient who presented with a large gallstone obstructing the duodenal bulb, with the chief complaint of acute on chronic abdominal pain. Classically, this is known as Bouveret's syndrome or a gallstone ileus of the duodenum. Our patient's current health status presented a challenge, with the presence of several comorbidities, particularly a large abdominal aortic aneurism. We chose an open procedure for this reason. The stone was removed through a laparotomy, and the cholecystoduodenal fistula that the stone used to pass into the small bowel was repaired. With our patient's future medical needs in mind, only the necessary interventions were performed to regain functionality of the bowel. This came in the form of a diverting gastrojejunostomy, with a distal jejunostomy and feeding tube inserted. The patient tolerated the procedure well, only remaining intubated postoperative due to her chronic obstructive pulmonary disease (COPD). She achieved a complete recovery and transitioned home.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uBkUJi
via IFTTT

Splenic rupture following synchronised direct current cardioversion

Atraumatic rupture of the normal spleen is a rare entity. Often, a triggering factor or minor physical event can be ascribed as the aetiology for rupture, including coughing, vomiting or minor medical procedures not involving the spleen. A 65-year-old man who was hospitalised for eosinophilic pneumonia developed haemodynamically unstable atrial flutter that necessitated urgent synchronised direct current cardioversion (DCCV). Two hours after successful cardioversion, he developed signs of an acute abdomen with free intraperitoneal fluid identified on bedside ultrasonography. Exploratory laparotomy revealed gross haemoperitoneum and splenic rupture requiring splenectomy. With exception of capsular defects and haemorrhage suggestive of organ rupture, the gross and histological examination of the spleen was otherwise unremarkable. The patient denied recent trauma. The cause of his spleen rupture was attributed to cardioversion and subsequent abdominal muscle contraction. This represents the first known case of splenic rupture associated with DCCV.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ukJnXR
via IFTTT

Orbital multiple myeloma: a diagnostic challenge

Orbital involvement in multiple myeloma is unusual. We describe the case of an 85-year-old woman who presented with right eye proptosis, reduced visual acuity and diplopia. Computed tomography showed a lobulated, enhancing soft tissue mass arising from the right greater wing of the sphenoid with intraconal, lacrimal gland and ocular muscle involvement. Histopathology revealed predominantly atypical plasma cells in a background of reactive lymphocytes, with monoclonality towards kappa light chain protein, suggestive of multiple myeloma. This case illustrates the diagnostic imaging challenge of orbital multiple myeloma.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ukCWnG
via IFTTT

Paraneoplastic cerebellar degeneration secondary to ovarian carcinosarcoma: a cerebellar conundrum

We present a case of an elderly female patient who presented with a 6-month history of progressive slurred speech, vertigo, unsteadiness and falls. She underwent an extensive battery of neurological and cardiovascular investigations, none of which demonstrated a diagnostic cause for her symptoms. She was referred to the stroke and neurology teams and was started on treatment for presumed anxiety. As her symptoms continued to progress, she was referred to the falls service. Following a multidisciplinary team discussion, she was reviewed by the consultant geriatrician who felt this may be due to a malignancy so the consultant geriatrician arranged blood testsand CT scan of her chest, abdomen and pelvis. These demonstrated a large left adnexal mass and a raised Ca-125 level. The patient was diagnosed with an ovarian tumour, which was treated surgically. A provisional diagnosis of paraneoplastic cerebellar degeneration, secondary to ovarian carcinosarcoma, was made.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uBBsk2
via IFTTT

Abdominal aortic aneurysm in the setting of Clostridium perfringens pancreatitis

We report a case of a 56-year-old woman who presented with worsening abdominal pain located in the left upper quadrant together with abdominal distention, nausea and anorexia. One month prior to this admission, she had presented and had been diagnosed with concurrent acute pancreatitis and rapidly expanding abdominal aortic aneurysm. The aneurysm was prioritised over the pancreatitis and she underwent uncomplicated endovascular repair. Cross-sectional imaging was consistent with infected pancreatic necrosis and also revealed a large collection located in the anterior pararenal space with extensive gas formation. An image-guided fluid aspiration revealed Clostridium perfringens as the causative organism. She was treated by placement of large bore drains along with irrigation and targeted intravenous antibiotic for 6 weeks. The collections resolved completely and at 6 months follow-up she was well and symptom free.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ukJrqz
via IFTTT

Scabies

Scabies: Infestation of the skin by the human itch mite, Sarcoptes scabiei. The initial symptom of scabies are red, raised bumps that are intensely itchy. A magnifying glass will reveal short, wavy lines of red skin, which are the burrows made by the mites. Treatment is with any of several scabicide medications.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vgxKhI
via IFTTT

Histomorphometric and osteocytic characteristics of cortical bone in male subtrochanteric femoral shaft

Abstract

The histomorphometric properties of the subtrochanteric femoral region have rarely been investigated. The aim of this study was to investigate the age-associated variations and regional differences of histomorphometric and osteocytic properties in the cortical bone of the subtrochanteric femoral shaft, and the association between osteocytic and histological cortical bone parameters. Undecalcified histological sections of the subtrochanteric femoral shaft were obtained from cadavers (n = 20, aged 18–82 years, males). They were cut and stained using modified Masson-Goldner stain. Histomorphometric parameters of cortical bone were analysed with ×50 and ×100 magnification after identifying cortical bone boundaries using our previously validated method. Within cortical bone areas, only complete osteons with typical concentric lamellae and cement line were selected and measured. Osteocytic parameters of cortical bone were analyzed under phase contrast microscopy and epifluorescence within microscopic fields (0.55 mm² for each). The cortical widths of the medial and lateral quadrants were significantly higher than other quadrants (P < 0.01). Osteonal area per cortical bone area was lower and cortical porosities were higher in the posterior quadrant than in the other quadrants (P < 0.05). Osteocyte lacunar number per cortical bone area was found higher in the young subjects (≤ 50 years) than in the older ones (> 50 years) both before and after adjustments for body height and weight (P < 0.05). Moreover, significant but low correlations were found between the cortical bone and osteocytic parameters (0.20 ≤ R² ≤ 0.35, P < 0.05). It can be concluded that in healthy males, the cortical histomorphometric parameters differ between the anatomical regions of the subtrochanteric femoral shaft, and are correlated with the osteocytic parameters from the same site. These findings may be of use when discussing mechanisms that predispose patients to decreasing bone strength.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2veDx9o
via IFTTT

A Literature Review on Current and Proposed Technologies of Noninvasive Blood Pressure Measurement

Telemedicine and e-Health , Vol. 0, No. 0.


from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujVlBc
via IFTTT

Tele-ophthalmology for Age-Related Macular Degeneration and Diabetic Retinopathy Screening: A Systematic Review and Meta-analysis

Telemedicine and e-Health , Vol. 0, No. 0.


from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uAZ7Bt
via IFTTT

Identity Theft, a Reprise

Telemedicine and e-Health Aug 2017, Vol. 23, No. 8: 619-620.


from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ukyBkc
via IFTTT

FPIES: not so rare after all!

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ukSpUV
via IFTTT

Anaphylaxis associated with omalizumab administration: Risk factors and patient characteristics

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uBkzq1
via IFTTT

MicroRNA-150 controls differentiation of intraepithelial lymphocytes via TGF-β receptor II regulation

miR-150 deficiency reduces IEL population in the small intestine, resulting in increased susceptibility to anti-cancer drug-induced damage in the intestinal epithelial cells.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ukIuyr
via IFTTT

Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures

Using reconstituted airway epithelia, we highlight marked differences in in vitro pathogenesis of respiratory viruses. In the absence of immune cells, we observe viral persistence linked to a contained tissue-response rather than to viral mutations.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ukv4m8
via IFTTT

Development of Human Salivary Gland-Like Tissue In Vitro

Tissue Engineering Part A , Vol. 0, No. 0.


from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vHPyox
via IFTTT

Extracellular Vesicles and Their Versatile Roles in Tissue Engineering

Tissue Engineering Part A , Vol. 0, No. 0.


from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujwJo6
via IFTTT

Blockade of Stearoyl-CoA-Desaturase 1 activity reverts resistance to Cisplatin in lung cancer stem cells

Poor prognosis in lung cancer has been attributed to the presence of lung cancer stem cells (CSCs) which resist chemotherapy and cause disease recurrence. Hence, the strong need to identify mechanisms of chemoresistance and to develop new combination therapies. We have previously shown that Stearoyl-CoA-desaturase 1 (SCD1), the enzyme responsible for the conversion of saturated to monounsaturated fatty acids is upregulated in 3D lung cancer spheroids and is an upstream activator of key proliferation pathways β-catenin and YAP/TAZ.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vHNFIi
via IFTTT

PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer

Program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling plays an important role in tumor adaptive immune resistance. The streptavidin-granulocyte-macrophage colony stimulating factor (SA-GM-CSF) surface-modified tumor cells vaccine developed through our novel protein-anchor technology could significantly promote the activation of dendritic cells. Although GM-CSF vaccine could significantly increase the number of tumor-specific CD8+T-cells, the majority of these CD8+T-cells expressed PD-1.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujrkgw
via IFTTT

The HSP90 inhibitor, NVP-AUY922, attenuates intrinsic PI3K inhibitor resistance in KRAS-mutant non-small cell lung cancer

More than 25% of non-small cell lung cancers (NSCLCs) carry mutations in KRAS, one of the most common oncogenic drivers in this disease. KRAS-mutant NSCLC responds poorly to currently available therapies; therefore, novel treatment strategies are needed. Here, we describe a particularly promising targeted therapeutic strategy against KRAS mutation-harboring NSCLC intrinsically resistant to treatment by PI3K inhibition. We found that intrinsic resistance to PI3K inhibition derived from RAF/MEK/ERK and RSK activation, bypassing blockage of the PI3K/AKT/mTOR pathway.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujvK7o
via IFTTT

The HSP90 inhibitor, NVP-AUY922, attenuates intrinsic PI3K inhibitor resistance in KRAS-mutant non-small cell lung cancer

More than 25% of non-small cell lung cancers (NSCLCs) carry mutations in KRAS, one of the most common oncogenic drivers in this disease. KRAS-mutant NSCLC responds poorly to currently available therapies; therefore, novel treatment strategies are needed. Here, we describe a particularly promising targeted therapeutic strategy against KRAS mutation-harboring NSCLC intrinsically resistant to treatment by PI3K inhibition. We found that intrinsic resistance to PI3K inhibition derived from RAF/MEK/ERK and RSK activation, bypassing blockage of the PI3K/AKT/mTOR pathway.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujvK7o
via IFTTT

Blockade of Stearoyl-CoA-Desaturase 1 activity reverts resistance to Cisplatin in lung cancer stem cells

Poor prognosis in lung cancer has been attributed to the presence of lung cancer stem cells (CSCs) which resist chemotherapy and cause disease recurrence. Hence, the strong need to identify mechanisms of chemoresistance and to develop new combination therapies. We have previously shown that Stearoyl-CoA-desaturase 1 (SCD1), the enzyme responsible for the conversion of saturated to monounsaturated fatty acids is upregulated in 3D lung cancer spheroids and is an upstream activator of key proliferation pathways β-catenin and YAP/TAZ.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vHNFIi
via IFTTT

PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer

Program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling plays an important role in tumor adaptive immune resistance. The streptavidin-granulocyte-macrophage colony stimulating factor (SA-GM-CSF) surface-modified tumor cells vaccine developed through our novel protein-anchor technology could significantly promote the activation of dendritic cells. Although GM-CSF vaccine could significantly increase the number of tumor-specific CD8+T-cells, the majority of these CD8+T-cells expressed PD-1.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujrkgw
via IFTTT

Dr. Burtness on Challenges Facing Immunotherapy in Head and Neck - OncLive

OncLive

Dr. Burtness on Challenges Facing Immunotherapy in Head and Neck OncLive Barbara Burtness, MD, professor of medicine, Yale Cancer Center, discusses challenges regarding immunotherapy for patients with head and neck cancer. Although immunotherapy can lead to durable responses, there are still a population of patients who do ...

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujx6yY
via IFTTT

Three-year cytohistological correlation of salivary gland FNA cytology at a tertiary center with the application of the Milan system for risk stratification

BACKGROUND

Fine-needle aspiration (FNA) cytology of salivary glands is a well-established technique that plays a critical role in the preoperative diagnosis of lesions. A risk stratification of FNA diagnostic categories has been recently proposed to be useful in reporting. The aims of this study were to evaluate the diagnostic accuracy of salivary gland FNA and to apply the proposed Milan system for reporting salivary gland lesions.

METHODS

A retrospective audit of FNA specimens of salivary gland lesions reported from 2014 to 2016 was performed. A correlation with the follow-up histopathology, wherever it was available, was performed. The aspirates were then categorized according to the Milan system as follows: nondiagnostic, nonneoplastic, atypical, benign neoplasm, neoplasm of uncertain malignant potential (NUMP), suspicious for malignancy, or positive for malignancy. Furthermore, the risk of malignancy and the risk of high-grade malignancy were calculated for all diagnostic categories.

RESULTS

A total of 631 salivary gland aspirates were evaluated: 2.2% were nondiagnostic, 55.8% indicated nonneoplastic lesions, and 40.4% indicated neoplastic lesions. Histopathology was available for 94 cases (14.9%). FNA had a sensitivity of 79.4% and a specificity of 98.3% with an overall diagnostic accuracy of 91.4% for differentiating malignant tumors from benign tumors. The overall risk of malignancy was 17.4% for the nonneoplastic category, 100% for the atypical category, 7.3% for the benign neoplasm category, 50% for the NUMP category, and 96% for the positive-for-malignancy category.

CONCLUSIONS

Salivary gland FNA continues to have high diagnostic accuracy and is thus helpful for guiding management. Neoplasms with classic cytomorphology are easily diagnosed; however, in difficult cases showing overlapping features, the use of the Milan system could be beneficial. Cancer Cytopathol 2017. © 2017 American Cancer Society.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vg2a3H
via IFTTT

Extracellular vesicles: Novel promising delivery systems for therapy of brain diseases

Publication date: 28 September 2017
Source:Journal of Controlled Release, Volume 262
Author(s): David Rufino-Ramos, Patrícia R. Albuquerque, Vitor Carmona, Rita Perfeito, Rui Jorge Nobre, Luis Pereira de Almeida
Extracellular vesicles (EVs) are cell-derived membrane vesicles virtually secreted by all cells, including brain cells. EVs are a major term that includes apoptotic bodies, microvesicles and exosomes. The release of EVs has been recognized as an important modulator in cross-talking between neurons, astrocytes, microglia and oligodendrocytes, not only in central nervous system (CNS) physiology but also in neurodegenerative and neuroinflammatory disease states as well as in brain tumors, such as glioma. EVs are able to cross the blood brain barrier (BBB), spread to body fluids and reach distant tissues. This prominent spreading ability has suggested that EVs can be exploited into several different clinical applications ranging from biomarkers to therapeutic carriers.Exosomes, the well-studied group of EVs, have been emerging as a promising tool for therapeutic delivery strategies due to their intrinsic features, such as the stability, biocompatibility and stealth capacity when circulating in bloodstream, the ability to overcome natural barriers and inherent targeting properties. Over the last years, it became apparent that EVs can be loaded with specific cargoes directly in isolated EVs or by modulation of producer cells. In addition, the engineering of its membrane for targeting purposes is expected to allow generating carriers with unprecedented abilities for delivery in specific organs or tissues. Nevertheless, some challenges remain regarding the loading and targeting of EVs for which more research is necessary, and will be discussed in this review. Recently-emerged promising derivations are also discussed, such as exosome associated with adeno-associated virus (AAV) vectors (vexosomes), enveloped protein nanocages (EPNs) and exosome-mimetic nanovesicles.This article provides an updated review of this fast-progressing field of EVs and their role in brain diseases, particularly focusing in their therapeutic applications.

Graphical abstract

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2woFIpc
via IFTTT

Identification of cyclic peptides for facilitation of transcellular transport of phages across intestinal epithelium in vitro and in vivo

Publication date: 28 September 2017
Source:Journal of Controlled Release, Volume 262
Author(s): Shunsuke Yamaguchi, Shingo Ito, Mio Kurogi-Hirayama, Sumio Ohtsuki
Methodology to enhance intestinal absorption of macromolecular drugs is an important challenge for developing next-generation biomedicines. So far, various cationic cell-penetrating peptides have been reported to facilitate uptake of certain bioactive proteins. However, cyclic peptides might be better candidates, as they are more metabolically stable than linear peptides. Accordingly, we hypothesized that suitable cyclic peptides would promote the absorption of macromolecules across intestinal epithelium. To test this idea, we adopted Caco-2 cell permeability assay as an in vitro human intestinal absorption model, and M13 phage as a model of macromolecules. Successive screenings of a phage library displaying cyclic heptapeptides via a short GGGS linker yielded 3 hits. Among them, phage displaying cyclic heptapeptide DNPGNET (DNP-phage) showed the greatest permeability across a Caco-2 cell monolayer and mouse intestinal epithelium. Interestingly, DNPGNET (DNP) does not contain any basic amino acids. Its isoelectric point (pI) was estimated to be 2.72. It did not reduce the viability or tight-junction integrity of Caco-2 cells at concentrations up to 100μM for 24h. Uptake of either DNP-phage or a fluorescence-labeled DNP derivative (AC-DNPGNET-CGGGS modified with 5/6-FAM at the C-terminal; the cysteines serve to generate the cyclic peptide via disulfide bond formation, and GGGS is the phage linker) by Caco-2 cells was inhibited by low temperature, unlabeled AC-DNPGNET-CGGGS and EIPA, a macropinocytosis inhibitor. Thus, DNP appears to facilitate transcellular permeability of phages via macropinocytosis, but not paracellular diffusion. These findings indicate that DNP is a promising candidate as a carrier to promote intestinal absorption of macromolecular drugs.

Graphical abstract

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2woEaf6
via IFTTT

pH-labile PEGylation of siRNA-loaded lipid nanoparticle improves active targeting and gene silencing activity in hepatocytes

Publication date: 28 September 2017
Source:Journal of Controlled Release, Volume 262
Author(s): Kazuki Hashiba, Yusuke Sato, Hideyoshi Harashima
Lipid nanoparticles (LNPs) are one of the promising technologies for the in vivo delivery of short interfering RNA (siRNA). Modifying LNPs with polyethyleneglycol (PEG) is widely used to inhibit non-specific interactions with serum components in the blood stream, and is a useful strategy for maximizing the efficiency of active targeting. However, it is a widely accepted fact that PEGylation of the LNP surface strongly inhibits fusion between LNPs and endosomal membranes, resulting in poor cytosolic siRNA delivery, a process that is referred to as the 'PEG-dilemma'. In the present study, in an attempt to overcome this problem, siRNA-loaded LNPs were modified with PEG through maleic anhydride, a pH-labile linkage. The in vitro, suppression of cationic charge, stealth function at physiological pH up to 1h and the rapid desorption of PEG and restoration of fusogenic activity under slightly acidic conditions (within only 2min) were achieved by PEG modification of the LNPs through maleic anhydride. In vivo, PEG modification through maleic anhydride resulted in a dramatic improvement in the targeting capability of the active targeting of ligand (N-acetyl-d-galactosamine)-modified LNPs to hepatocytes, with an approximately 14-fold increase in gene silencing activity in factor 7 model mice. Taken together, the maleic anhydride-mediated pH-labile PEGylation of the active targeting LNPs is a useful strategy for achieving the specific and efficient delivery of siRNAs in vivo.

Graphical abstract

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2woTusa
via IFTTT

Chains of magnetosomes with controlled endotoxin release and partial tumor occupation induce full destruction of intracranial U87-Luc glioma in mice under the application of an alternating magnetic field

Publication date: 28 September 2017
Source:Journal of Controlled Release, Volume 262
Author(s): Edouard Alphandéry, Ahmed Idbaih, Clovis Adam, Jean-Yves Delattre, Charlotte Schmitt, François Guyot, Imène Chebbi
Previous studies showed that magnetic hyperthermia could efficiently destroy tumors both preclinically and clinically, especially glioma. However, antitumor efficacy remained suboptimal and therefore required further improvements. Here, we introduce a new type of nanoparticles synthesized by magnetotactic bacteria, called magnetosomes, with improved properties compared with commonly used chemically synthesized nanoparticles. Indeed, mice bearing intracranial U87-Luc glioma tumors injected with 13μg of nanoparticles per mm³ of tumor followed by 12 to 15 of 30min alternating magnetic field applications displayed either full tumor disappearance in 40% of mice or no tumor regression using magnetosomes or chemically synthesized nanoparticles, respectively. Magnetosome superior antitumor activity could be explained both by a larger production of heat and by endotoxins release under alternating magnetic field application. Most interestingly, this behavior was observed when magnetosomes occupied only 10% of the whole tumor volume, which suggests that an indirect mechanism, such as an immune reaction, takes part in tumor regression. This is desired for the treatment of infiltrating tumors, such as glioma, for which whole tumor coverage by nanoparticles can hardly be achieved.

Graphical abstract

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wod4Vt
via IFTTT

Double-blind, randomized phase 3 trial of low-dose 13-cis retinoic acid in the prevention of second primaries in head and neck cancer: Long-term follow-up of a trial of the Eastern Cooperative Oncology Group-ACRIN Cancer Research Group (C0590)

BACKGROUND

13-Cis retinoic acid (13-CRA) is a synthetic vitamin A derivative. High-dose 13-CRA in patients with squamous cell cancers of the head and neck (SCCHNs) reduces the incidence of second primary tumors (SPTs). The authors report long-term results from a phase 3 randomized trial that compared treatment with low-dose 13-CRA versus placebo for patients who had early stage SCCHN, with a focus on the development of SPTs and overall survival (OS).

METHODS

In total, 176 patients who received treatment for stage I/II SCCHN were randomized to receive either low-dose 13-CRA (weight-based dose of 7.5 mg or 10 mg) or placebo for 2 years. A competing-risk approach and the log-rank test were used to compare the time to SPT and OS, respectively, between groups.

RESULTS

13-CRA neither significantly reduced the cumulative incidence of SPT (P = .61) nor improved the time to SPT (hazard ratio [HR] for 13-CRA/placebo; 0.86; P = .61). Despite limited power, there was a trend toward improved OS for the 13-CRA arm (HR, 0.75; P = .14), particularly among patients whose index tumor was surgically excised (N = 26; HR, 0.50; P = .057) and among women (N = 39; HR, 0.44; P = .065) and never/former smokers (N = 129; HR, 0.61; P = .055), with a median follow-up of 16 years. The main 13-CRA related toxicities were dry skin and cheilitis.

CONCLUSIONS

Treatment with low-dose 13-CRA for 2 years did not decrease the incidence of SPT; subset analysis indicates a potential survival advantage among patients who are women and never/former smokers. More targeted interventions based on clinical risk factors and molecular characterization of tumors may yield greater success in future prevention trials. Cancer 2017. © 2017 American Cancer Society.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ukr59a
via IFTTT

Hyoscine butylbromide for colorectal polyp detection: prospective, randomized, placebo-controlled trial

OBJECTIVES: The removal of pre-malignant colorectal lesions prevents cancer. Hyoscine has been proposed as a means of improving diagnosis by reducing colonic movements. The aim of this study was to analyze whether this anti-spasmodic enhances the detection of pre-malignant colorectal lesions. METHODS: In a randomized, double-blinded fashion patients received hyoscine or a saline solution in all consecutive colonoscopies in which the cecum was reached. Lesions were analysed with respect to number, size, location, histology and capillary pattern. RESULTS: A total of 440 colonoscopies were randomized. The overall polyp detection rate (PDR) and the adenoma detection rate (ADR) were 65.2% and 49.3%, respectively. In the hyoscine group, non-polypoid lesions were detected significantly more often (p=0.01). In the placebo group 281 lesions were diagnosed (202 adenomas) and in the hyoscine group 282 lesions were detected (189 adenomas) (p=0.23). The PDR and ADR were similar between the placebo and hyoscine groups (64% vs 66% and 50% vs 47%, respectively). No differences were observed between the two groups in the advanced-ADR or advanced neoplasia detection rate, as well the mean numbers of polyps, adenomas, advanced adenomas and advanced neoplasias detected per patient. The administration of hyoscine also did not improve the diagnostic accuracy of digital chromoendoscopy. The presence of adenomatous polyps in the right colon was detected significantly more frequently in the hyoscine group (OR 5.41 95% CI 2.7 - 11; p<0.01 vs OR 2.3 95% CI 1.1 - 4.6; p=0.02). CONCLUSION: The use of hyoscine before beginning the withdrawal of the colonoscope does not seem to enhance the PDR and the ADR.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vJpb1Z
via IFTTT

Validation of QF-PCR for prenatal diagnoses in a Brazilian population

OBJECTIVES: Quantitative fluorescence polymerase chain reaction (QF-PCR) is a rapid and reliable method for screening aneuploidies, but in Brazil, it is not used in public services. We investigated the accuracy of QF-PCR for the prenatal recognition of common aneuploidies and compared these results with cytogenetic results in our laboratory. METHOD: A ChromoQuant QF-PCR kit containing 24 primer pairs targeting loci on chromosomes 21, 13, 18, X and Y was employed to identify aneuploidies of the referred chromosomes. RESULTS: A total of 162 amniotic fluid samples analyzed using multiplex QF-PCR were compared with karyotyping analysis. The QF-PCR results were consistent with the results of cytogenetic analysis in 95.4% of all samples. CONCLUSION: QF-PCR was demonstrated to be efficient and reliable for prenatal aneuploidy screening. This study suggests that QF-PCR can be used as a rapid diagnostic method. However, rearrangements and some mosaic samples cannot be detected with this test; thus, those exceptions must undergo cytogenetic analysis.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wCoEvs
via IFTTT

Clinical Features of Refractory Ascites in Outpatients

OBJECTIVES: To present the clinical features and outcomes of outpatients who suffer from refractory ascites. METHODS: This prospective observational study consecutively enrolled patients with cirrhotic ascites who submitted to a clinical evaluation, a sodium restriction diet, biochemical blood tests, 24 hour urine tests and an ascitic fluid analysis. All patients received a multidisciplinary evaluation and diuretic treatment. Patients who did not respond to the diuretic treatment were controlled by therapeutic serial paracentesis, and a transjugular intrahepatic portosystemic shunt was indicated for patients who required therapeutic serial paracentesis up to twice a month. RESULTS: The most common etiology of cirrhosis in both groups was alcoholism [49 refractory (R) and 11 non-refractory ascites (NR)]. The majority of patients in the refractory group had Child-Pugh class B cirrhosis (p=0.034). The nutritional assessment showed protein-energy malnutrition in 81.6% of the patients in the R group and 35.5% of the patients in the NR group, while hepatic encephalopathy, hernia, spontaneous bacterial peritonitis, upper digestive hemorrhage and type 2 hepatorenal syndrome were present in 51%, 44.9%, 38.8%, 38.8% and 26.5% of the patients in the R group and 9.1%, 18.2%, 0%, 0% and 0% of the patients in the NR group, respectively (p=0.016, p=0.173, p=0.012, p=0.012, and p=0.100, respectively). Mortality occurred in 28.6% of the patients in the R group and in 9.1% of the patients in the NR group (p=0.262). CONCLUSION: Patients with refractory ascites were malnourished, suffered from hernias, had a high prevalence of complications and had a high postoperative death frequency, which was mostly due to infectious processes.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vJftgb
via IFTTT

Intermittent claudication and severe renal artery stenosis are independently associated in hypertensive patients referred for renal arteriography

OBJECTIVE: The purpose of this study was to evaluate the association between the presence of clinical symptoms of peripheral artery disease and severe renal artery stenosis in patients referred for renal angiography. METHOD: We included 82 patients with clinical suspicion of renovascular hypertension and performed an imaging investigation (renal Doppler ultrasound and/or renal scintigraphy) for possible renal artery stenosis. All patients underwent renal arteriography and were examined for peripheral artery disease based on the presence of intermittent claudication and ankle-brachial index test results. Severe renal artery stenosis was defined as a lesion causing 70% obstruction. RESULTS: Severe renal artery stenosis was present in 32 of 82 (39%) patients. Patients with severe renal artery stenosis were older (63±12 vs 56±12 years, p=0.006), had more intermittent claudication (55 vs 45%, p=0.027), and had a greater prevalence of an ankle-brachial index <0.9 (44% vs 20%, p=0.021) than patients without severe renal artery stenosis. Multivariate logistic regression analysis showed that the presence of intermittent claudication was independently associated with renal artery stenosis ≥70% (OR: 3.33; 95% CI 1.03-10.82, p=0.04), unlike the ankle-brachial index, which showed no association (OR: 1.44; 95% CI 0.37-5.66, p=0.60). CONCLUSION: Intermittent claudication is independently associated with severe renal artery stenosis (≥70%) in patients clinically suspected of having renovascular hypertension.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wC3mhd
via IFTTT

Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure

OBJECTIVES: Recent studies have shown a high prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D level less than 30 ng/ml, in both healthy populations and patients with chronic kidney disease. Patients undergoing kidney transplant are at an increased risk of skin cancer and are advised to avoid sunlight exposure. Therefore, these patients might share two major risk factors for hypovitaminosis D: chronic kidney disease and low sunlight exposure. This paper describes the prevalence and clinical characteristics of hypovitaminosis D among patients undergoing kidney transplant. METHODS: We evaluated 25-hydroxyvitamin D serum levels in a representative sample of patients undergoing kidney transplant. We sought to determine the prevalence of hypovitaminosis D, compare these patients with a control group, and identify factors associated with hypovitaminosis D (e.g., sunlight exposure and dietary habits). RESULTS: Hypovitaminosis D was found in 79% of patients undergoing kidney transplant, and the major associated factor was low sunlight exposure. These patients had higher creatinine and intact parathyroid hormone serum levels, with 25-hydroxyvitamin D being inversely correlated with intact parathyroid hormone serum levels. Compared with the control group, patients undergoing kidney transplant presented a higher prevalence of 25-hydroxyvitamin D deficiency and lower serum calcium, phosphate and albumin but higher creatinine and intact parathyroid hormone levels. CONCLUSIONS: Our results confirmed the high prevalence of hypovitaminosis D in patients undergoing kidney transplant. Therapeutic strategies such as moderate sunlight exposure and vitamin D supplementation should be seriously considered for this population.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vJkgyc
via IFTTT

Laryngeal tube suction for airway management during in-hospital emergencies

OBJECTIVE: The role of supraglottic airway devices in emergency airway management is highlighted in international airway management guidelines. We evaluated the application of the new generation laryngeal tube suction (LTS-II/LTS-D) in the management of in-hospital unexpected difficult airway and cardiopulmonary resuscitation. METHODS: During a seven-year period, patients treated with a laryngeal tube who received routine anesthesia and had an unexpected difficult airway (Cormack Lehane Grade 3-4), who underwent cardiopulmonary resuscitation, or who underwent cardiopulmonary resuscitation outside the operating room and had a difficult airway were evaluated. Successful placement of the LTS II/LTS-D, sufficient ventilation, time to placement, number of placement attempts, stomach content, peripheral oxygen saturation/end-tidal carbon dioxide development (SpO2/etCO2) over 5 minutes, subjective overall assessment and complications were recorded. RESULTS: In total, 106 adult patients were treated using an LTS-II/LTS-D. The main indication for placement was a difficult airway (75%, n=80), followed by cardiopulmonary resuscitation (25%, n=26) or an overlap between both (18%, n=19). In 94% of patients (n=100), users placed the laryngeal tube during the first attempt. In 93% of patients (n=98), the tube was placed within 30 seconds. A significant increase in SpO2 from 97% (0-100) to 99% (5-100) was observed in the whole population and in cardiopulmonary resuscitation patients. The average initial etCO2 of 39.5 mmHg (0-100 mmHg) decreased significantly to an average of 38.4 mmHg (10-62 mmHg) after 5 minutes. A comparison of cardiopulmonary resuscitation patients with non-cardiopulmonary resuscitation patients regarding gastric contents showed no significant difference. CONCLUSIONS: LTS-D/LTS-II use for in-hospital unexpected difficult airway management provides a secure method for primary airway management until other options such as video laryngoscopy or fiber optic intubation become available.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wBIozg
via IFTTT

Complete axillary dissection without drainage for the surgical treatment of breast cancer: a randomized clinical trial

OBJECTIVE: This randomized clinical trial evaluated the possibility of not draining the axilla following axillary dissection. METHODS: The study included 240 breast cancer patients who underwent axillary dissection as part of conservative treatment. The patients were divided into two groups depending on whether or not they were subjected to axillary drainage. ClinicalTrials.gov: NCT01267552. RESULTS: The median volume of fluid aspirated was significantly lower in the axillary drainage group (0.00 ml; 0.00 - 270.00) compared to the no drain group (522.50 ml; 130.00 - 1148.75). The median number of aspirations performed during conservative breast cancer treatment was significantly lower in the drainage group (0.5; 0.0 - 4.0) compared to the no drain group (5.0; 3.0 - 7.0). The total volume of serous fluid produced (the volume of fluid obtained from drainage added to the volume of aspirated fluid) was similar in the two groups. Regarding complications, two cases (2.4%) of wound dehiscence occurred in the drainage group compared to 13 cases (13.5%) in the group in which drainage was not performed, with this difference being statistically significant. Rates of infection, necrosis and hematoma were similar in both groups. CONCLUSION: Safety rates were similar in both study groups; hence, axillary dissection can feasibly be performed without drainage. However, more needle aspirations could be required, and there could be more cases of wound dehiscence in patients who do not undergo auxiliary drainage.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vJ8d3Y
via IFTTT

Abnormal diastolic function underlies the different beneficial effects of cardiac resynchronization therapy on ischemic and non-ischemic cardiomyopathy

OBJECTIVES: To investigate the association between diastolic function and the different beneficial effects of cardiac resynchronization therapy in patients with heart failure due to different causes. METHODS: The 104 enrolled patients were divided into an ischemic cardiomyopathy group (n=27) and a non-ischemic cardiomyopathy group (n=77) according to the cause of heart failure. Before implantation, left ventricular diastolic function was evaluated in all patients using echocardiography. After six months of follow-up, the beneficial effects of cardiac resynchronization therapy were evaluated using a combination of clinical symptoms and echocardiography parameters. RESULTS: The ischemic cardiomyopathy group included significantly more patients with restrictive filling than the non-ischemic cardiomyopathy group. The response rate after the implantation procedure was significantly higher in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Degrees of improvement in echocardiography parameters were significantly greater in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Multivariate regression analysis showed that a restrictive filling pattern was an independent factor that influenced responses to cardiac resynchronization therapy. CONCLUSIONS: This study again confirmed that the etiology of heart failure affects the beneficial effects of cardiac resynchronization therapy and a lower degree of improvement in ventricular systolic function and remodelling was observed in ischemic cardiomyopathy patients than in non-ischemic cardiomyopathy patients. In addition, systolic heart failure patients with severe diastolic dysfunction had poor responses to cardiac resynchronization therapy. Ischemic cardiomyopathy patients exhibited more severe diastolic dysfunction than non-ischemic cardiomyopathy patients, which may be a reason for the reduced beneficial effect of cardiac resynchronization therapy.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wC7Lkh
via IFTTT

The diagnostic value of narrow-band imaging for early and invasive lung cancer: a meta-analysis

This study aimed to compare the ability of narrow-band imaging to detect early and invasive lung cancer with that of conventional pathological analysis and white-light bronchoscopy. We searched the PubMed, EMBASE, Sinomed, and China National Knowledge Infrastructure databases for relevant studies. Meta-disc software was used to perform data analysis, meta-regression analysis, sensitivity analysis, and heterogeneity testing, and STATA software was used to determine if publication bias was present, as well as to calculate the relative risks for the sensitivity and specificity of narrow-band imaging vs those of white-light bronchoscopy for the detection of early and invasive lung cancer. A random-effects model was used to assess the diagnostic efficacy of the above modalities in cases in which a high degree of between-study heterogeneity was noted with respect to their diagnostic efficacies. The database search identified six studies including 578 patients. The pooled sensitivity and specificity of narrow-band imaging were 86% (95% confidence interval: 83-88%) and 81% (95% confidence interval: 77-84%), respectively, and the pooled sensitivity and specificity of white-light bronchoscopy were 70% (95% confidence interval: 66-74%) and 66% (95% confidence interval: 62-70%), respectively. The pooled relative risks for the sensitivity and specificity of narrow-band imaging vs the sensitivity and specificity of white-light bronchoscopy for the detection of early and invasive lung cancer were 1.33 (95% confidence interval: 1.07-1.67) and 1.09 (95% confidence interval: 0.84-1.42), respectively, and sensitivity analysis showed that narrow-band imaging exhibited good diagnostic efficacy with respect to detecting early and invasive lung cancer and that the results of the study were stable. Narrow-band imaging was superior to white light bronchoscopy with respect to detecting early and invasive lung cancer; however, the specificities of the two modalities did not differ significantly.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vJ1h6Q
via IFTTT

Osteointegration of porous absorbable bone substitutes: A systematic review of the literature

Biomaterials' structural characteristics and the addition of osteoinductors influence the osteointegration capacity of bone substitutes. This study aims to identify the characteristics of porous and resorbable bone substitutes that influence new bone formation. An Internet search for studies reporting new bone formation rates in bone defects filled with porous and resorbable substitutes was performed in duplicate using the PubMed, Web of Science, Scielo, and University of São Paulo Digital Library databases. Metaphyseal or calvarial bone defects 4 to 10 mm in diameter from various animal models were selected. New bone formation rates were collected from the histomorphometry or micro-CT data. The following variables were analyzed: animal model, bone region, defect diameter, follow-up time after implantation, basic substitute material, osteoinductor addition, pore size and porosity. Of 3,266 initially identified articles, 15 articles describing 32 experimental groups met the inclusion criteria. There were no differences between the groups in the experimental model characteristics, except for the follow-up time, which showed a very weak to moderate correlation with the rate of new bone formation. In terms of the biomaterial and structural characteristics, only porosity showed a significant influence on the rate of new bone formation. Higher porosity is related to higher new bone formation rates. The influence of other characteristics could not be identified, possibly due to the large variety of experimental models and methodologies used to estimate new bone formation rates. We suggest the inclusion of standard control groups in future experimental studies to compare biomaterials.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wCqsV4
via IFTTT

Hypoxia reduces mature hERG channels through calpain up-regulation [Research]

Human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium current (I_Kr) potassium channel, which is important for cardiac repolarization. Impairment of hERG function is the primary cause of acquired long QT syndrome, which predisposes individuals to cardiac arrhythmias and sudden death. Patients with hypoxia due to conditions such as cardiac ischemia or obstructive sleep apnea display increased incidence of cardiac arrhythmias and sudden death. We sought to understand the mechanisms that underlie hypoxia-associated cardiac arrhythmias. Using cell biology and electrophysiologic techniques, we found that hypoxic culture of hERG-expressing human embryonic kidney (HEK) cells and neonatal rat cardiomyocytes reduced hERG current/I_Kr and mature ERG channel expression with a concomitant increase in calpain expression. Calpain was actively released into the extracellular milieu and degraded cell-surface hERG. In contrast to hERG, the ether-a-go-go (EAG) channel was not reduced by hypoxic culture. By making chimeric channels between hERG and EAG, we identified that hypoxia-induced calpain degraded hERG by targeting its extracellular S5-pore linker. The scorpion toxin BeKm-1, which is known to selectively bind to the S5-pore linker of hERG, prevented hypoxia-induced hERG reduction. Our data provide novel information about hypoxia-mediated hERG dysfunction and may have biological and clinical implications in hypoxia-associated diseases.—Lamothe, S. M., Song, W., Guo, J., Li, W., Yang, T., Baranchuk, A., Graham, C. H., Zhang, S. Hypoxia reduces mature hERG channels through calpain up-regulation.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2folV5c
via IFTTT

Worcestershire hospital trust told to make urgent improvements

A hospital trust in the West Midlands has been issued with a warning notice to make urgent improvements, after inspectors found that it had become standard practice to treat emergency patients in the...

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2fmWLUC
via IFTTT

Voice-Specialized Speech-Language Pathologist's Criteria for Discharge from Voice Therapy

No standard protocol exists to determine when a patient is ready and able to be discharged from voice therapy. The aim of the present study was to determine what factors speech-language pathologists (SLPs) deem most important when discharging a patient from voice therapy. A second aim was to determine if responses differed based on years of voice experience.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uAWf7A
via IFTTT

Does Microscope Assistance in Cold Steel Tonsillectomy Reduce the Risk of Postoperative Hemorrhage? Results of a Prospective Cohort Study

Background. Posttonsillectomy hemorrhage (PTH) is the most feared complication. Dissection near the tonsillar capsule under microscopic view () could be assumed to decrease PTH compared to traditional tonsillectomy (). Methods. In this study, patients were evaluated with respect to the need for surgical control (R/N: return/no return to theater (RTT): the day of surgery or thereafter ). The findings at resection site and pain were measured. Results. 869 patients were included (183 ; 686 ). PTH requiring RTT was not seen in the group on the day of surgery (R0) while PTH requiring RTT subsequently (R1) was seen in 1.1% of the cases. In the group, hemorrhages without a need for surgical control were observed in 0.6% (N0) and 3.4% (N1), respectively. The corresponding rates for were as follows: R0, 0.3%; R1, 1.7%; N0, 0.6%; and N1, 3.6% (). Postoperative edema and local infection at resection site were proven to be predictive of PTH (). Conclusion. Microscope assistance in tonsillectomy did not statistically have an influence on the PTH even though there was a trend towards lower PTH rate in the group. Benefit for was observed in high-volume and long experienced surgeons.

from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2vfQT3u
via IFTTT

Comparison between autogenous iliac bone and freeze-dried bone allograft for repair of alveolar clefts in the presence of plasma rich in growth factors: A randomized clinical trial

This study aimed to compare the effectiveness of alveolar cleft repair using iliac bone and freeze-dried bone allograft (FDBA) in the presence of plasma rich in growth factors (PRGF).

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujt3lY
via IFTTT

Cementoblastoma: an updated analysis of 258 cases reported in the literature

To investigate the recurrence rate of cementoblastomas for different variables aside from the clinical/radiologic features.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vHKOip
via IFTTT

Unraveling the interactions of the physiological reductant flavodoxin with the different conformations of the Fe protein in the nitrogenase cycle [Protein Structure and Folding]

Nitrogenase reduces dinitrogen (N2) to ammonia in biological nitrogen fixation. The nitrogenase Fe protein cycle involves a transient association between the reduced, MgATP-bound Fe protein and the MoFe protein and includes electron transfer, ATP hydrolysis, release of Pi , and dissociation of the oxidized, MgADP-bound Fe protein from the MoFe protein. The cycle is completed by reduction of oxidized Fe protein and nucleotide exchange. Recently, a kinetic study of the nitrogenase Fe protein cycle involving the physiological reductant flavodoxin reported a major revision of the rate-limiting step from MoFe protein and Fe protein dissociation, to release of Pi . Since the Fe protein cannot interact with flavodoxin and the MoFe protein simultaneously, knowledge of the interactions between flavodoxin and the different nucleotide states of the Fe protein is critically important for understanding the Fe protein cycle. Here, we used time-resolved limited proteolysis and chemical cross-linking to examine nucleotide-induced structural changes in the Fe protein and their effects on interactions with flavodoxin. Differences in proteolytic cleavage patterns and chemical cross-linking patterns were consistent with known nucleotide-induced structural differences in the Fe protein and indicated that MgATP-bound Fe protein resembles the structure of the Fe protein in the stabilized nitrogenase complex structures. Docking models and cross-linking patterns between the Fe protein and flavodoxin revealed that the MgADP-bound state of the Fe protein has the most complementary docking interface with flavodoxin compared with the MgATP-bound state. Together, these findings provide new insights into the control mechanisms in protein-protein interactions during the Fe protein cycle.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vHJL1V
via IFTTT

Efficient reduction of CO2 by the molybdenum-containing formate dehydrogenase from Cupriavidus necator (Ralstonia eutropha). [Molecular Biophysics]

The ability of the FdsABG formate dehydrogenase from Cupriavidus necator (formerly known as Ralstonia eutropha) to catalyze the reverse of the physiological reaction, the reduction of CO2 to formate utilizing NADH as electron donor, has been investigated. Contrary to previous studies of this enzyme, we demonstrate that it is in fact effective in catalyzing the reverse reaction, with a kcat of 11 ± 0.4 s-1. We also quantify the stoichiometric accumulation of formic acid as the product of the reaction and demonstrate that the observed kinetic parameters for catalysis in the forward and reverse reaction are thermodynamically consistent, complying with the expected Haldane relationships. Finally, we demonstrate the reaction conditions necessary for gauging the ability of a given formate dehydrogenase or other CO2-utilizing enzyme to catalyze the reverse direction so as to avoid false negative results. In conjunction with our earlier studies on the reaction mechanism of this enzyme (Niks et al. (2016) J. Biol. Chem. 291, 1162- 1174), and on the basis of the present work we conclude that all molybdenum- and tungsten-containing formate dehydrogenases and related enzymes likely operate via a simple hydride transfer mechanism and are effective in catalysing the reversible interconversion of CO2 and formate under the appropriate experimental conditions.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ujt35s
via IFTTT

Site-specific inhibition of the SUMO-conjugating enzyme Ubc9 selectively impairs SUMO chain formation [Enzymology]

Posttranslational modifications by small ubiquitin-like modifiers (SUMOs) regulate many cellular processes, including genome integrity, gene expression, and ribosome biogenesis. The E2-conjugating enzyme Ubc9 catalyzes the conjugation of SUMOs to ϵ-amino groups of lysine residues in target proteins. Attachment of SUMO moieties to internal lysines in Ubc9 itself can further lead to the formation of polymeric SUMO chains. Mono- and poly-SUMOylations of target proteins provide docking sites for distinct adapter and effector proteins important for regulating discrete SUMO-regulated pathways. However, molecular tools to dissect pathways depending on either mono- or poly-SUMOylation are largely missing. Using a protein-engineering approach, we generated high-affinity SUMO2 variants by phage display that bind the backside of Ubc9 and function as SUMO-based Ubc9 inhibitors (SUBINs). Importantly, we found that distinct SUBINs primarily inhibit poly-SUMO chain formation, while mono-SUMOylation is not impaired. Proof-of-principle experiments demonstrated that in a cellular context, SUBINs largely prevent heat shock-triggered poly-SUMOylation. Moreover, SUBINs abrogated arsenic-induced degradation of promyelocytic leukemia protein. We propose that the availability of the new chain-selective SUMO inhibitors reported here will enable thorough investigation of poly-SUMO-mediated cellular processes, such as DNA damage responses and cell cycle progression.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uj1xFq
via IFTTT

Quantifying enzyme activity in living cells [Enzymology]

For over a century enzymatic activity is studied in vitro, assuming similar activity in the crowded cellular milieu. Here, we determined in real time the catalytic activity of TEM1-β-lactamase inside living cells and compared the values to those obtained in vitro. We found the apparent in vivo catalytic efficiency, kcat/KM, to be lower than in vitro, with significant cell-to-cell variability. Surprisingly, the results show that inside the cell the apparent catalytic efficiency decreases and KM increases with increasing enzyme concentration. To rationalize these findings we measured enzyme and substrate diffusion rates in the cell and found the later to be slower than expected. Simulations showed that for attenuated diffusion the substrate flux becomes rate limiting, explaining why reaction rates in vivo can be independent on enzyme concentrations. The octanol/water partition of the substrate is 4.5, which is in the range of FDA approved drugs. This suggests substrate limited reaction rates to be common. These findings indicate that in vitro data cannot be simply extrapolated to the crowded in vivo environment.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vHKLTL
via IFTTT

The 19S proteasome is directly involved in the regulation of heterochromatin spreading in fission yeast [DNA and Chromosomes]

Cumulative evidence suggests that non-proteolytic functions of the proteasome are involved in transcriptional regulation, mRNA export and ubiquitin-dependent histone modification, and thereby modulate the intracellular levels of regulatory proteins implicated in controlling key cellular functions. To date, the non-proteolytic roles of the proteasome have been mainly investigated in euchromatin; their effects on heterochromatin are largely unknown. Here, using fission yeast as a model, we randomly mutagenized the subunits of the 19S proteasome subcomplex, and sought to uncover a direct role of the proteasome in heterochromatin regulation. We identified a non-proteolytic allele, rpt4-1. Experiments performed using rpt4-1 cells revealed that the proteasome is involved in the regulation of heterochromatin spreading to prevent its uncontrolled invasion into neighboring euchromatin regions. Intriguingly, the phenotype of the non-proteolytic rpt4-1 mutant resembled that of epe1Δ cells, which lack the Epe1 protein that counteracts heterochromatin spreading. Both mutants exhibited variegated gene-silencing phenotypes across yeast colonies, spreading of heterochromatin, bypassing of the requirement for RNAi in heterochromatin formation at the outer repeat region (otr), and upregulation of RNA polymerase II. Further analysis revealed Mst2, another factor that antagonizes heterochromatin spreading, may function redundantly with Rpt4. These observations suggest that the 19S proteasome may be involved in modulating the activities of Epe1 and Mst2. In conclusion, our findings indicate that the proteasome appears to have a heterochromatin-regulating function that is independent of its canonical function in proteolysis.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uj24af
via IFTTT

The 3-hydroxyacyl-CoA dehydratases HACD1 and HACD2 exhibit functional redundancy and are active in a wide range of fatty acid elongation pathways [Metabolism]

Differences among fatty acids (FAs) in chain length and number of double bonds create lipid diversity. FA elongation proceeds via a four-step reaction cycle, in which the 3-hydroxyacyl-CoA dehydratases HACD1-4 catalyze the third step. However, the contribution of each HACD to 3-hydroxyacyl-CoA dehydratase activity in certain tissues or in different FA elongation pathways remains unclear. HACD1 is specifically expressed in muscles and is a myopathy-causative gene. Here, we generated Hacd1 KO mice and observed that these mice had reduced body and skeletal muscle weights. In skeletal muscle, HACD1 mRNA expression was by far the highest among the HACDs. However, we observed only a ~40% reduction in HACD activity and no changes in membrane lipid composition in Hacd1 KO skeletal muscle, suggesting that some HACD activities are redundant. Moreover, when expressed in yeast, both HACD1 and HACD2 participated in saturated and monounsaturated FA elongation pathways. Disruption of HACD2 in the haploid human cell line HAP1 significantly reduced FA elongation activities toward both saturated and unsaturated FAs, and HACD1 HACD2 double disruption resulted in a further reduction. Overexpressed HACD3 exhibited weak activity in saturated and monounsaturated FA elongation pathways, and no activity was detected for HACD4. We therefore conclude that HACD1 and HACD2 exhibit redundant activities in a wide range of FA elongation pathways, including those for saturated to polyunsaturated FAs, with HACD2 being the major 3-hydroxyacyl-CoA dehydratase. Our findings are important for furthering the understanding of the molecular mechanisms in FA elongation and diversity.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vHKJv7
via IFTTT