3D printed models ensure success for robot-guided spinal surgery

Using a 3D printed model, French surgeons have performed the world's first robot guided minimally invasive surgery on a scoliosis-affected child's spine. Dr. François Deroussen, Prof. Richard Gouron, and Dr. Michel Lefranc together with anaesthetists from Amiens-Picardie University Hospital performed the operation with the help of Med Tech's ROSA robot to align and guide the […]

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The interplay of hippocampus and ventromedial prefrontal cortex in memory-based decision making

Episodic memory and value-based decision making are two central and intensively studied research domains in cognitive neuroscience, but we are just beginning to understand how they interact to enable memory-based decisions. The two brain regions that have been associated with episodic memory and value-based decision making are the hippocampus and the ventromedial prefrontal cortex, respectively. In this review article, we first give an overview of these brain–behavior associations and then focus on the mechanisms of potential interactions between the hippocampus and ventromedial prefrontal cortex that have been proposed and tested in recent neuroimaging studies. Based on those possible interactions, we discuss several directions for future research on the neural and cognitive foundations of memory-based decision making.

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Discovering historical rainfall erosivity with a parsimonious approach: A case study in Western Germany

An in-depth analysis of the interannual variability of storms is required to detect changes in soil erosive power of rainfall, which can also result in severe on-site and off-site damages. Evaluating long-term rainfall erosivity is a challenging task, mainly because of the paucity of high-resolution historical precipitation observations that are generally reported at coarser temporal resolutions (e.g., monthly to annual totals). In this paper we suggest overcoming this limitation through an analysis of long-term processes governing rainfall erosivity with an application to datasets available the central Ruhr region (Western Germany) for the period 1701–2011. Based on a parsimonious interpretation of seasonal rainfall-related processes (from spring to autumn), a model was derived using 5-min erosivity data from 10 stations covering the period 1937–2002, and then used to reconstruct a long series of annual rainfall erosivity values. Change-points in the evolution of rainfall erosivity are revealed over the 1760s and the 1920s that mark three sub-periods characterized by increasing mean values. The results indicate that the erosive hazard tends to increase as a consequence of an increased frequency of extreme precipitation events occurred during the last decades, characterized by short-rain events regrouped into prolonged wet spells.

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(31)P and (1)H NMR Studies of the Molecular Organization of Lipids in the Parallel Artificial Membrane Permeability Assay

The parallel artificial membrane permeability assay (PAMPA) has emerged as a widely used primary in vitro screen for passive permeability of potential drug candidates. However, the molecular structure of the permeation barrier (consisting of a filter-supported dodecane-egg lecithin mixture) has never been characterized. Here, we investigated the long-range order of phospholipids in the PAMPA barrier by means of (31)P static solid-state NMR. Diffusion constants of PAMPA membrane components were derived from liquid state NMR and, in addition, drug distribution between the PAMPA lipid phase and buffer (log DPAMPA at pH 7.4) was systematically investigated. Increasing concentration of n-dodecane to the system egg lecithin-water (lamellar phase, Lα) induces formation of inverted hexagonal (Hii) and isotropic phases. At n-dodecane concentrations matching those used in PAMPA (9%, w/v) a purely "isotropic" phase was observed corresponding to lipid aggregates with a diameter in the range 4-7 nm. Drug distribution studies indicate that these reverse micelles facilitate the binding to, and in turn the permeation across, the PAMPA dodecane barrier, in particular for amphiphilic solutes. The proposed model for the molecular architecture and function of the PAMPA barrier provides a fundamental, hitherto missing framework to evaluate the scope but also limitations of PAMPA for the prediction of in vivo membrane permeability.

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Swiss ethnoveterinary knowledge in medicinal plants – a within country comparison of Italian speaking with German speaking regions

Background Ethnoveterinary knowledge in Europe may play an important role as a basis for sustainable treatment options for livestock. Aims of our study were (a) to compare the ethnoveterinary practices of two culturally and sociodemographically different regions of Switzerland, (b) to compare results with earlier ethnoveterinary studies conducted in Switzerland and in adjacent Italian regions and, (c) to evaluate possible reasons for regional differences in European ethnoveterinary medicine. Methods 25 interviews were conducted in 2014 in all Italian speaking regions (ItR) of Switzerland, and 31 interviews were held in five north-western German speaking Cantons (GeC). Semi-structured questionnaires were used to collect detailed information regarding plant species, mode of preparation, dosage, route of administration, category of use, origin of knowledge, frequency of use, and satisfaction with outcomes of the treatments. Results A total of 162 homemade remedies in ItR and 219 in GeC were reported, out of which 125 and 145, respectively, were reported to contain only one plant species (homemade single species herbal remedy report, HSHR). 44 ItR and 43 GeC plant species were reported to treat livestock, of which only a half were used in both regions. For each HSHR, we classified the treatment intention of all use reports (UR), leading to a total of 205 and 219 UR in ItR and GeC respectively. While cattle were the most often treated livestock species in both study regions, in ItR 40% of UR were administered to small ruminants. Main indications in both regions were gastrointestinal diseases and skin afflictions, but in ItR a high number of URs were reported as antiparasitics. URs were mainly handed down from the past generation, but in GeC the source of knowledge for 20% of URs were from courses. Regarding the used plant species, ItR showed a higher concordance with Swiss than Italian studies, but with some differences to all regions. A total of 22 (14 ItR; 8 GeC) plant species in this study have not been reported before in ethnoveterinary studies of Swiss and Italian alpine regions. Conclusions ItR and GeC, show differences and similarities with respect to their own ethnoveterinary practices and earlier Swiss and Italian ethnoveterinary studies. Linguistic, geographical, as well as social and farm-structural conditions influence the regional ethnoveterinary knowledge. However, political borders seem to be more important than language or geographical barriers.

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From medieval land clearing to industrial development: 800 years of human impact history in the Joux Valley (Swiss Jura)

The Joux Valley (Swiss Jura Mountains) has a rather unusual history of human occupation, characterized by tardive but extensive settlement since the Late Middle Ages, followed by an intensive period of industrial development. To estimate the links between human activities and environmental consequences, sediment cores were retrieved in Lake Joux and submitted to a multiproxy analysis (high-resolution photographs, magnetic susceptibility, density, x-ray fluorescence, grain size, organic geochemistry, 14C, 210Pb and 137Cs dating). The diversity of anthropication phases, defined from historical data, is clearly recognized in the lake archive. The record suggests the region was mainly under climatic influence until the end of the 13th century. The growth of settlements in the valley and the associated massive deforestation is recorded by increasing terrestrial inputs, reflecting large-scale soil destabilization, which subsequently persists despite the transition from farming to industrial activities. Autochthonous contributions then dominate the record, both in response to climatic and anthropogenic influences. Construction works conducted at the outlet of the lake affected water flow, sedimentation and aquatic community (macrophytes, ostracods) dynamics. The substantial increase of anthropogenic heavy metals (Fe, Zn, Pb) recorded during the 20th century could reflect the development of the watch-making industry in the area, as well as the use of leaded gasoline. Historical information facilitated interpretation of the observed paleolimnological evolution in the context of varied coexisting human activities. This study highlights the importance of applying an integrated paleolimnological-historical approach in order to establish clear links between well-defined human activities and their subsequent environmental responses through time.

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Viruses, Vol. 9, Pages 272: The Evolutionary History and Spatiotemporal Dynamics of the NC Lineage of Citrus Tristeza Virus

Viruses, Vol. 9, Pages 272: The Evolutionary History and Spatiotemporal Dynamics of the NC Lineage of Citrus Tristeza Virus

Viruses doi: 10.3390/v9100272

Authors: María Benítez-Galeano Matías Castells Rodney Colina

Citrus tristeza virus (CTV) is a major pathogen affecting citrus trees worldwide. However, few studies have focused on CTV's evolutionary history and geographic behavior. CTV is locally dispersed by an aphid vector and long distance dispersion due to transportation of contaminated material. With the aim to delve deeper into the CTV-NC (New Clade) genotype evolution, we estimated an evolution rate of 1.19 × 10−3 subs/site/year and the most common recent ancestor in 1977. Furthermore, the place of origin of the genotype was in the United States, and a great expansion of the population was observed in Uruguay. This expansion phase could be a consequence of the increment in the number of naïve citrus trees in Uruguayan orchards encompassing citrus industry growth in the past years.

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Community-Based Participatory Research for Health: Advancing Social and Health Equity, 3rd Edition

The definitive guide to CBPR concepts and practice, updated and expanded Community-Based Participatory Research for Health: Advancing Health and Social Equity provides a comprehensive reference for this rapidly growing field in participatory and community-engaged research. Hailed as effective by the Centers for Disease Control and Prevention, CBPR and CEnR represent the link between researchers and community and lead to improved public health outcomes Read More...

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Amino acid composition, antioxidant and functional properties of protein hydrolysates from Cucurbitaceae seeds

Abstract

In this study, the effect of enzymatic hydrolysis of globulin fraction of C. moschata (CMH), C. lanatus (CLH) and L. siceraria (LSH) on antioxidant capacity, functional properties, structural and micro-structural properties, as well as amino acid compositions were evaluated. All the hydrolysates exhibited significant antioxidant properties. The essential amino acids content in LSH (92.7 mg/g) was higher than CMH (79.9 mg/g) and CLH (70.5 mg/g). Water absorption capacity (5 g/g), heat stability (89%), emulsifying activity index (98.3 m²/g) and emulsifying stability index (45.1 min) were statistically more significant for LSH as compared to CMH and CLH. In addition, LSH had significantly higher FS and FC at pH 3–9. Among all hydrolysates, LSH showed highest solubility (87.3%) as compared to other hydrolysates. The results suggested that enzymatic hydrolysis improve the antioxidant and functional properties. Thus, the globulin hydrolysates might be served as an innovative source with promising nutritive values, good antioxidant and functional properties. Moreover, these could be used in food and pharmaceutical industries for the development of novel functional foods.

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Development of an evidence-based complex intervention for community rehabilitation of patients with hip fracture using realist review, survey and focus groups

Objectives

To develop an evidence and theory-based complex intervention for improving outcomes in elderly patients following hip fracture.

Design

Complex-intervention development (Medical Research Council (MRC) framework phase I) using realist literature review, surveys and focus groups of patients and rehabilitation teams.

Setting

North Wales.

Participants

Surveys of therapy managers (n=13), community and hospital-based physiotherapists (n=129) and occupational therapists (n=68) throughout the UK. Focus groups with patients (n=13), their carers (n=4) and members of the multidisciplinary rehabilitation teams in North Wales (n=13).

Results

The realist review provided understanding of how rehabilitation interventions work in the real-world context and three programme theories were developed: improving patient engagement by tailoring the intervention to individual needs; reducing fear of falling and improving self-efficacy to exercise and perform activities of daily living; and coordination of rehabilitation delivery. The survey provided context about usual rehabilitation practice; focus groups provided data on the experience, acceptability and feasibility of rehabilitation interventions. An intervention to enhance usual rehabilitation was developed to target these theory areas comprising: a physical component consisting of six additional therapy sessions; and a psychological component consisting of a workbook to enhance self-efficacy and a patient-held goal-setting diary for self-monitoring.

Conclusions

A realist approach may have advantages in the development of evidence-based interventions and can be used in conjunction with other established methods to contribute to the development of potentially more effective interventions. A rehabilitation intervention was developed which can be tested in a future randomised controlled trial (MRC framework phases II and III).

Trial registration number

ISRCTN22464643, Pre-results.

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Comparison of the cerebroprotective effect of inhalation anaesthesia and total intravenous anaesthesia in patients undergoing cardiac surgery with cardiopulmonary bypass: a systematic review and meta-analysis

Objective

Neurological dysfunction remains a devastating postoperative complication in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), and previous studies have shown that inhalation anaesthesia and total intravenous anaesthesia (TIVA) may produce different degrees of cerebral protection in these patients. Therefore, we conducted a systematic literature review and meta-analysis to compare the neuroprotective effects of inhalation anaesthesia and TIVA.

Design

Searching in PubMed, EMBASE, Science Direct/Elsevier, China National Knowledge Infrastructure and Cochrane Library up to August 2016, we selected related randomised controlled trials for this meta-analysis.

Results

A total of 1485 studies were identified. After eliminating duplicate articles and screening titles and abstracts, 445 studies were potentially eligible. After applying exclusion criteria (full texts reported as abstracts, review article, no control case, lack of outcome data and so on), 13 studies were selected for review. Our results demonstrated that the primary outcome related to S100B level in the inhalation anaesthesia group was significantly lower than in the TIVA group after CPB and 24 hours postoperatively (weighted mean difference (WMD); 95% CI (CI): –0.41(–0.81 to –0.01), –0.32 (–0.59 to –0.05), respectively). Among secondary outcome variables, mini-mental state examination scores of the inhalation anaesthesia group were significantly higher than those of the TIVA group 24 hours after operation (WMD (95% CI): 1.87 (0.82 to 2.92)), but no significant difference was found in arteriovenous oxygen content difference, cerebral oxygen extraction ratio and jugular bulb venous oxygen saturation, which were assessed at cooling and rewarming during CPB.

Conclusion

This study demonstrates that anaesthesia with volatile agents appears to provide better cerebral protection than TIVA for patients undergoing cardiac surgery with CPB, suggesting that inhalation anaesthesia may be more suitable for patients undergoing cardiac surgery.

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Protocol for a pilot, randomised, double-blinded, placebo-controlled trial of prophylactic use of tranexamic acid for preventing postpartum haemorrhage (TAPPH-1)

Introduction

Postpartum haemorrhage (PPH) is the leading cause of maternal morbidity and mortality worldwide. Despite the availability of multiple uterotonic agents, the incidence of PPH continues to rise. Tranexamic acid (TXA) has been shown to be a safe, effective and inexpensive therapeutic option for the treatment of PPH, however, its use prophylactically in mitigating the risk of PPH is unknown. This pragmatic randomised prospective trial assesses the feasibility and safety of administering TXA at the time of delivery for the prevention of PPH.

Methods and analysis

A pilot pragmatic randomised double-blinded placebo-controlled trial will be performed. 58 singleton parturients at term >32 weeks, undergoing either spontaneous vaginal delivery, or caesarean section will be randomised to receive 1 g of TXA or placebo (0.9% saline) intravenously. The primary outcome assessed will be the feasibility of administrating TXA, along with collecting data regarding safety of drug administration. The groups will also be analysed on efficacy of mitigating the onset of PPH and clinically relevant variables. Demographic, feasibility, safety and clinical endpoints will be summarised and the appropriate measures of central tendency and dispersion will be presented.

Ethics and dissemination

This protocol was approved by the Sunnybrook Health Sciences Centre Research Ethics Board (number: 418-2016). The results will be disseminated in a peer-reviewed journal and at scientific meetings.

Trial registration number

NCT03069859; Pre-results.

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Feasibility and acceptability of training community health workers in ear and hearing care in Malawi: a cluster randomised controlled trial

Objective

To assess the feasibility and acceptability of training community health workers (CHWs) in ear and hearing care, and their ability to identify patients with ear and hearing disorders.

Design

Cluster randomised controlled trial (RCT).

Setting

Health centres in Thyolo district, Malawi.

Participants

Ten health centres participated, 5 intervention (29 CHWs) and 5 control (28 CHWs).

Intervention

Intervention CHWs received 3 days of training in primary ear and hearing care, while among control CHWs, training was delayed for 6 months. Both groups were given a pretest that assessed knowledge about ear and hearing care, only the intervention group was given the posttest on the third day of training. The intervention group was given 1 month to identify patients with ear and hearing disorders in their communities, and these people were screened for hearing disorders by ear, nose and throat clinical specialists.

Outcome measures

Primary outcome measure was improvement in knowledge of ear and hearing care among CHWs after the training. Secondary outcome measures were number of patients with ear or hearing disorders identified by CHWs and number recorded at health centres during routine activities, and the perceived feasibility and acceptability of the intervention.

Results

The average overall correct answers increased from 55% to 68% (95% CI 65 to 71) in the intervention group (p<0.001). A total of 1739 patients with potential ear and hearing disorders were identified by CHWs and 860 patients attended the screening camps, of whom 400 had hearing loss (73 patients determined through bilateral fail on otoacoustic emissions, 327 patients through audiometry). Where cause could be determined, the most common cause of ear and hearing disorders was chronic suppurative otitis media followed by impacted wax. The intervention was perceived as feasible and acceptable to implement.

Conclusions

Training was effective in improving the knowledge of CHW in ear and hearing care in Malawi and allowing them to identify patients with ear and hearing disorders. This intervention could be scaled up to other CHWs in low-income and middle-income countries.

Trial registration number

Pan African Clinical Trial Registry (201705002285194); Results.

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Neighbourhood characteristics and mental disorders in three Chinese cities: multilevel models from the World Mental Health Surveys

Objectives

The rapid growth of urban areas in China in the past few decades has introduced profound changes in family structure and income distribution that could plausibly affect mental health. Although multilevel studies of the influence of area-level socioeconomic factors on mental health have become more common in other parts of the world, a study of this sort has not been carried out in Chinese cities. Our objectives were to examine the associations of two key neighbourhood-level variables—median income and percentage of married individuals living in the neighbourhood—with mental disorders net of individual-level income and marital status in three Chinese cities.

Setting

Household interviews in Beijing, Shanghai and Shenzhen, PRC, as part of the cross-sectional World Mental Health Surveys.

Participants

4072 men and women aged 18–88 years.

Primary and secondary outcome measures

Lifetime and past-year internalising and externalising mental disorders.

Results

Each one-point increase in neighbourhood-level percentage of married residents was associated with a 1% lower odds of lifetime (p=0.024) and 2% lower odds of past-year (p=0.008) individual-level externalising disorder, net of individual-level marital status. When split into tertiles, individuals living in neighbourhoods in the top tertile of percentage of married residents had 54% lower odds of a past-year externalising disorder (OR=0.46, 95% CI: 0.24 to 0.87) compared with those in the bottom tertile. Neighbourhood-level marital status was not statistically associated with either lifetime or past-year internalising disorders. Neighbourhood-level income was not statistically associated with odds of either internalising or externalising disorders.

Conclusions

The proportion of married residents in respondents' neighbourhoods was significantly inversely associated with having externalising mental disorders in this sample of Chinese cities. Possible mechanisms for this finding are discussed and related to social causation, social selection and social control theories. Future work should examine these relationships longitudinally.

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Study protocol for a randomised controlled trial: harmonising optimal strategy for treatment of coronary artery stenosis -- coronary intervention with next-generation drug-eluting stent platforms and abbreviated dual antiplatelet therapy (HOST-IDEA) trial

Introduction

We have recently seen the introduction of newer generation drug-eluting stents with ultrathin struts that use advanced polymer technologies. However, the efficacy and safety of these newest stents have not yet been fully explored. In addition, there are still controversies over the optimal duration of dual antiplatelet therapy (DAPT) after stent implantation, particularly for ultrathin stents with the newest polymer technologies.

Methods and analysis

The HOST-IDEA trial is a randomised, open-label, multicentre, non-inferiority trial and the first study to directly compare two of these ultrathin sirolimus-eluting stents: Orsiro stent with biodegradable polymer, and polymer-free Coroflex ISAR (CX-ISAR) stent. This study has a scheme of 2x2 factorial design according to the stent type and DAPT duration (3 vs 12 months). A total of 2152 patients will be randomised and stratified to demonstrate the non-inferiority of CX-ISAR to Orsiro, or of the abbreviated DAPT duration to the conventional 12 months (both in 1:1 ratio). For the comparison of stent type, the primary endpoint is target lesion failure (TLF), which is a composite of cardiac death, target vessel-related myocardial infarction and clinically driven target lesion revascularisation. For the comparison of DAPT duration, the net adverse clinical event is the coprimary endpoint, which is defined as a composite of TLF, definite/probable stent thrombosis and major bleeding.

Ethic approval and dissemination

All the institutions involved in this study are required to have ethical approval prior to patient enrolment. This multicentre study will recruit patients through competitive registration, but institutions that have not yet obtained ethical approvals have made it impossible to enrol patients in a centralised web database. The final results will be presented at relevant international conferences and will be materialised in the form of papers.

Trial registration number

NCT02601157; Pre-results.

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Investigating Canadian parents' HPV vaccine knowledge, attitudes and behaviour: a study protocol for a longitudinal national online survey

Introduction

Human papillomavirus (HPV), a sexually transmitted infection, can cause anogenital warts and a number of cancers. To prevent morbidity and mortality, three vaccines have been licensed and are recommended by Canada's National Advisory Committee on Immunisation (for girls since 2007 and boys since 2012). Nevertheless, HPV vaccine coverage in Canada remains suboptimal in many regions. This study will be the first to concurrently examine the correlates of HPV vaccine decision-making in parents of school-aged girls and boys and evaluate changes in parental knowledge, attitudes and behaviours over time.

Methods and analysis

Using a national, online survey utilising theoretically driven constructs and validated measures, this study will identify HPV vaccine coverage rates and correlates of vaccine decision-making in Canada at two time points (August–September 2016 and June–July 2017). 4606 participants will be recruited to participate in an online survey through a market research and polling firm using email invitations. Data cleaning methods will identify inattentive or unmotivated participants.

Ethics and dissemination

The study received research ethics board approval from the Research Review Office, Integrated Health and Social Services University Network for West-Central Montreal (CODIM-FLP-16–219). The study will adopt a multimodal approach to disseminate the study's findings to researchers, clinicians, cancer and immunisation organisations and the public in Canada and internationally.

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Assessment of potential predictors of calretinin and mesothelin to improve the diagnostic performance to detect malignant mesothelioma: results from a population-based cohort study

Objectives

Mesothelin and calretinin are blood-based markers for malignant mesothelioma. The objective of this study was to analyse the markers in plasma samples from cancer-free men and to identify factors influencing their concentrations to minimise false-positive test results when using these markers for the early detection of malignant mesothelioma.

Setting

The present analyses used data and archived blood samples of the population-based Heinz Nixdorf Recall Study among elderly people collected from 2011 to 2014.

Participants

A total of 569 men (median age 70 years) without a malignant disease at the time of blood sampling were selected for these analyses.

Primary and secondary outcome

Mesothelin and calretinin concentration in plasma samples.

Results

We observed 24 mesothelin concentrations ≥1.5 nM (specificity 95.8%, 95% CI 93.8% to 97.2%) and 34 calretinin concentrations ≥1.0 ng/mL (specificity 94.0%, 95% CI 91.7% to 95.7%). Only five men had both markers above these cut-offs. Renal dysfunction and hypertension were major predictors of elevated mesothelin in addition to age. Regarding calretinin, the effect of renal dysfunction was slightly weaker and hypertension was not associated with increased concentrations. However, a diagnosis of cancer after blood collection and bronchial asthma were associated with positive calretinin results.

Conclusions

The combined determination of mesothelin and calretinin results in only few false-positive marker tests. Both markers are mainly influenced by renal dysfunction. The determination of cystatin C concentrations may be informative when interpreting the test results.

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The association between adverse childhood experiences and traumatic brain injury/concussion in adulthood: A scoping review protocol

Introduction

Exposure to adverse childhood experiences (ACEs) is a significant risk factor for physical and mental illnesses later in life. Concussion or traumatic brain injury is a challenging condition where preinjury factors may interact to affect recovery. The association between ACEs and traumatic brain injury/concussion is not well mapped in any previous reviews of the literature. Using a scoping review methodology, the research question that will be addressed is: what is known from the existing literature about the association between ACEs and traumatic brain injury/concussion in adults?

Methods and analysis

The methodological frameworks outlined by Arksey and O'Malley and Levac et al will be used. All original studies in English published since 2007 investigating ACEs and traumatic brain injury/concussion outcomes will be included with no limitations on study type. Literature search strategies will be developed using medical subject headings and text words related to ACEs and traumatic brain injury/concussions. Multiple electronic databases will be searched. Two independent reviewers will screen titles and abstracts for full-text review and full texts for final inclusion. Two independent reviewers will extract data on study characteristics for ACE exposure and traumatic brain injury/concussion outcomes. Extracted data will be summarised quantitatively using numerical counts and qualitatively using thematic analysis.

Dissemination

This review will identify knowledge gaps on the associations between ACEs and traumatic brain injury/concussion and promote further research. Knowledge translation will occur throughout the review process with dissemination of project findings to stakeholders at the local, national and international levels.

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Correction: Attitudes and perceptions of GPs and community pharmacists towards their role in the prevention of bisphosphonate-related osteonecrosis of the jaw: a qualitative study in the North East of England

Sturrock A, Preshaw P, Hayes C, et al. Attitudes and perceptions of GPs and community pharmacists towards their role in the prevention of bisphosphonate-related osteonecrosis of the jaw: a qualitative study in the North East of England. BMJ Open 2017;7:e016047. doi: 10.1136/bmjopen-2017-016047.

The middle initial of author 'Philip Preshaw' is missing from the article. This name should be written 'Philip M Preshaw'.

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STANDING Collaboration: a study protocol for developing clinical standards

Introduction

Despite widespread availability of clinical practice guidelines (CPGs), considerable gaps continue between the care that is recommended ('appropriate care') and the care provided. Problems with current CPGs are commonly cited as barriers to providing 'appropriate care'.

Our study aims to develop and test an alternative method to keep CPGs accessible and up to date. This method aims to mitigate existing problems by using a single process to develop clinical standards (embodied in clinical indicators) collaboratively with researchers, healthcare professionals, patients and consumers. A transparent and inclusive online curated (purpose-designed, custom-built, wiki-type) system will use an ongoing and iterative documentation process to facilitate synthesis of up-to-date information and make available its provenance. All participants are required to declare conflicts of interest. This protocol describes three phases: engagement of relevant stakeholders; design of a process to develop clinical standards (embodied in indicators) for 'appropriate care' for common medical conditions; and evaluation of our processes, products and feasibility.

Methods and analysis

A modified e-Delphi process will be used to gain consensus on 'appropriate care' for a range of common medical conditions. Clinical standards and indicators will be developed through searches of national and international guidelines, and formulated with explicit criteria for inclusion, exclusion, time frame and setting. Healthcare professionals and consumers will review the indicators via the wiki-based modified e-Delphi process. Reviewers will declare conflicts of interest which will be recorded and managed according to an established protocol. The provenance of all indicators and suggestions included or excluded will be logged from indicator inception to finalisation. A mixed-methods formative evaluation of our research methodology will be undertaken.

Ethics and dissemination

Human Research Ethics Committee approval has been received from the University of South Australia. We will submit the results of the study to relevant journals and offer national and international presentations.

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Scorpion bite-induced ischaemic stroke

We report a 54-year-old woman with scorpion bite. After 3 hours of admission, the patient developed sudden onset tachycardia with hypotension. Cardiac evaluation showed raised creatine kinase MB isoenzyme was elevated; ECG and two-dimensional echocardiography findings were suggestive of myocarditis. Subsequently, she developed transient ventricular tachycardia before developing abrupt onset, right hemiplegia, global aphasia and progressive worsening of sensorium 12 hours after the bite. MRI of brain revealed massive left middle cerebral artery (MCA) territory infarct. The magnetic resonance angiography showed non-visualisation of left internal carotid artery (ICA) and MCA. Coagulation parameters were normal. Sudden complete occlusion of left ICA was probably secondary to cardioembolic phenomenon leading to massive infarct. Despite aggressive medical and supportive measures, she clinically worsened rapidly to Glasgow Coma Scale of 3/15 over next 6 hours and succumbed to her illness the next day.

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New understanding of cytokine release and neurological toxicity could help to reduce CAR T-cell side effects

Two new papers provide the most comprehensive data yet reported on side effects of the emerging cancer immunotherapy strategy known as CAR T-cell therapy. Based on their data from 133 adult participants in one clinical trial, the researchers identified...

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Fissure sealants: performance not affected by tooth characteristics

16 studies affect of were included in this review of tooth characteristics on sealant performance. With the exception of lower sealant failure rate on premolars sealants were not affected negatively by mouth side, jaw, or tooth type.

The post Fissure sealants: performance not affected by tooth characteristics appeared first on National Elf Service.

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Improved knowledge of and difficulties in palliative care among physicians during 2008 and 2015 in Japan: Association with a nationwide palliative care education program

BACKGROUND

Palliative care education for health care professionals is a key element in improving access to quality palliative care. The Palliative Care Emphasis Program on Symptom Management and Assessment for Continuous Medical Education (PEACE) was designed to provide educational opportunities for all physicians in Japan. As of 2015, 57,764 physicians had completed it. The objective of this study was to estimate the effects of the program.

METHODS

This study was an analysis of 2 nationwide observational studies from 2008 and 2015. We conducted 2 questionnaire surveys for representative samples of physicians. The measurements used were the Palliative Care Knowledge Test (range, 0-100) and the Palliative Care Difficulties Scale (range, 1-4). Comparisons were made with the unpaired Student t test and with a multivariate linear regression model using 2 cohorts and a propensity score–matched sample.

RESULTS

This study analyzed a total of 48,487 physicians in 2008 and a total of 2720 physicians in 2015. Between 2008 and 2015, physicians' knowledge and difficulties significantly improved on the Palliative Care Knowledge Test with total scores of 68 and 78, respectively (P < .001; effect size, 0.40) and on the Palliative Care Difficulties Scale with total scores of 2.65 and 2.49, respectively (P < .001; effect size, 0.29). Propensity-score matching resulted in 619 untrained physicians matched to 619 trained physicians, and physicians who trained with the PEACE program had a higher knowledge score (74 vs 86; P < .001; effect size, 0.64) and a lower difficulties score (2.6 vs 2.3; P < .001; effect size, 0.42).

CONCLUSIONS

Physicians' knowledge of and difficulties with palliative care improved on a national level. The PEACE program may have contributed to these improvements. Cancer 2017. © 2017 American Cancer Society.

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Your rights and responsibilities as a patient

In just a few days I will be representing the state of Pennsylvania at the annual meeting of the American Dental Association. As a member dentist I subscribe to a code of ethics.

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Polycythemia

Polycythemia: Too many red blood cells. The opposite of anemia. polycythemia formally exists when the hemoglobin, red blood cell (RBC) count, and total RBC volume are all above normal.

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

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Paxillin binding to the cytoplasmic domain of CD103 promotes cell adhesion and effector functions for CD8+ resident memory T cells in tumors

CD8+/CD103+ tissue resident memory T cells (TRM cells) accumulate in several human solid tumors where they have been associated with a favorable prognosis. However, the role of CD103 - the α subunit of the integrin αEβ7 (also known as CD103) - in the retention and functions of these TRM is undefined. In this report, we investigated the role of CD103 cytoplasmic domain and the focal adhesion-associated protein paxillin (Pxn) in downstream signaling and functional activities triggered through αE/CD103 chain. Binding to immobilized recombinant (r)E-cadherin-Fc of CD103 integrin expressed on tumor-specific CTL clones promotes phosphorylation of Pxn and Pyk2 and binding of Pxn to the αE/CD103 subunit tail. Inhibition of Pxn phosphorylation by the Src inhibitor saracatinib or its knockdown via shRNA dramatically altered adhesion and spreading of freshly isolated CD8+/CD103+ lung-tumor-infiltrating lymphocytes (TIL) and CD103+ tumor-specific CTL clones. Inhibition of Pxn phosphorylation with saracatinib in these CTL clones also severely compromised their functional activities toward autologous tumor cells. Using Jurkat T cells as a model to study CD103 integrin activation, we demonstrated a key role of serine residue S1163 of the αE chain intracellular domain in polarization of CD103 and recruitment of lysosomes and Pxn at the contact zone of T lymphocytes with rE-cadherin-Fc-coated beads. Overall, our results show how Pxn binding to the CD103 cytoplasmic tail triggers αEβ7 integrin outside-in signaling that promotes CD8+ T-cell migratory behavior and effector functions. These results also explain the more favorable prognosis associated with retention of TRM cells in the tumor microenvironment.

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Glutamine addiction in kidney cancer suppresses oxidative stress and can be exploited for real-time imaging

Many cancers appear to activate intrinsic antioxidant systems as a means to counteract oxidative stress. Some cancers, such as clear cell renal cell carcinoma (ccRCC), require exogenous glutamine for growth and exhibit reprogrammed glutamine metabolism, at least in part due to the glutathione pathway, an efficient cellular buffering system that counteracts reactive oxygen species (ROS) and other oxidants. We show here that ccRCC xenograft tumors under the renal capsule exhibit enhanced oxidative stress compared to adjacent normal tissue and the contralateral kidney. Upon glutaminase inhibition with CB-839 or BPTES, the RCC cell lines SN12PM-6-1 (SN12) and 786-O exhibited decreased survival and pronounced apoptosis associated with a decreased GSH/GSSG ratio, augmented nuclear factor erythroid related factor 2 (NRF2), and increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of DNA damage. SN12 tumor xenografts showed decreased growth when treated with CB-839. Furthermore, PET imaging confirmed that ccRCC tumors exhibited increased tumoral uptake of 18F-(2S,4R)4- fluoroglutamine (18F-FGln) compared to the kidney in the orthotopic mouse model. This technique can be utilized to follow changes in ccRCC metabolism in vivo. Further development of these paradigms will lead to new treatment options with glutaminase inhibitors and the utility of PET to identify and manage ccRCC patients who are likely to respond to glutaminase inhibitors in the clinic.-

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DDB2 is a Novel Regulator of Wnt-Signaling in Colon Cancer

Deregulation of the Wnt/β-catenin signaling pathway drives the development of colorectal cancer (CRC) but understanding of this pathway remains incomplete. Here we report that the damage-specific DNA-binding protein DDB2 is critical for β-catenin-mediated activation of RNF43, which restricts Wnt signaling by removing Wnt receptors from the cell surface. Reduced expression of DDB2 and RNF43 was observed in human hyperplastic colonic foci. DDB2 recruited EZH2 and β-catenin at an upstream site in the RNF43 gene, enabling functional interaction with distant TCF4/β-catenin binding sites in the intron of RNF43. This novel activity of DDB2 was required for RNF43 function as a negative feedback regulator of Wnt signaling. Mice genetically deficient in DDB2 exhibited increased susceptibility to colon tumor development in a manner associated with higher abundance of Wnt receptor-expressing cells and greater activation of the downstream Wnt-pathway. Our results identify DDB2 as both a partner and regulator of Wnt signaling with an important role in suppressing colon cancer development.

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Distinct angiogenic changes during carcinogenesis defined by novel label-free dark field imaging in a hamster cheek pouch model

There remain gaps in knowledge concerning how vascular morphology evolves during carcinogenesis. In this study, we imaged neovascularization by label-free dark field microscopy of a DMBA-induced hamster cheek pouch model of oral squamous cell carcinoma (SCC). Wavelength-dependent imaging revealed distinct vascular features at different imaging depths and vessel sizes. Vascular tortuosity increased significantly in high-risk lesions, while diameter decreased significantly in hyperplastic and SCC lesions. Large vessels preserved the same trends seen in the original images, whereas small vessels displayed different trends, with length and diameter increasing during carcinogenesis. Based on these data we developed and validated a classification algorithm incorporating vascular features from different vessel masks. Receiver operator curves generated from the classification results demonstrated high accuracies in discriminating normal and hyperplasia from high-grade lesions (area under the curve>0.95). Overall, these results provided automated imaging of vasculature in the earliest stages of carcinogenesis from which one can extract robust endpoints. The optical toolbox described here is simple, low-cost and portable and can be used in a variety of health care and research settings for cancer prevention and pharmacology research.

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Histone acetyltransferase KAT6A upregulates PI3K/Akt signaling through TRIM24 binding

Lysine acetyltransferase KAT6A is a chromatin regulator that contributes to histone modification and cancer, but the basis of its actions are not well understood. Here we identify a KAT6A signaling pathway that facilitates glioblastoma (GBM) where it is upregulated. KAT6A expression was associated with GBM patient survival. KAT6A silencing suppressed cell proliferation, cell migration, colony formation and tumor development in an orthotopic mouse xenograft model system. Mechanistic investigations demonstrated that KAT6A acetylates lysine 23 of histone H3 (H3K23), which recruits the nuclear receptor binding protein TRIM24 to activate PIK3CA transcription, thereby enhancing PI3K/AKT signaling and tumorigenesis. Overexpressing activated AKT or PIK3CA rescued the growth inhibition due to KAT6A silencing. Conversely, the pan-PI3K inhibitor LY294002 abrogated the growth-promoting effect of KAT6A. Overexpression of KAT6A or TRIM24, but not KAT6A acetyltransferase activity- deficient mutants or TRIM24 mutants lacking H3K23ac binding sites promoted PIK3CA expression, AKT phosphorylation and cell proliferation. Taken together, our results define an essential role of KAT6A in glioma formation, rationalizing its candidacy as a therapeutic target for GBM treatment.

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The Effect of Religious Belief and Forgiveness on Coping with Diabetes

Abstract

We aimed to investigate the relationship of religious beliefs and forgiveness in diabetic patients with various sociodemographic characteristics, emotional problems and glycaemic control. The study comprises 100 patients diagnosed with type 2 DM. We used a data collection form, the Scale of Forgiveness and Religiosity (SFR), Problem Areas in Diabetes Scale (PAID), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI) and the Audit of Diabetes-Dependent Quality of Life (ADDQoL). We also recorded blood glucose and HbA1c test results. A statistically significant relationship was determined only between the scores of the STAI-I and the religious belief scales (r = 0.198, p = 0.049). A statistically significant negative relationship was determined between the forgiveness scale points and the BDI (r = 0.326, p = 0.001), the STAI-II (r = 0.308, p = 0.002) and PAID (r = 0.313, p = 0.001) and a positive correlation with ADDQoL (r = 0.284, p = 0.004). To conclude, forgiveness by patient himself or others reduced the emotional problems which were experienced related to diabetes by reducing stress levels and could increase quality of life.

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Predicting the Happiness of Adolescents Based on Coping Styles and Religious Attitudes

Abstract

The study aimed to predict the happiness of adolescents based on coping styles and religious attitudes. To this end, the correlational research methodology was used. In total, 381 subjects were selected from adolescents of Semnan (Eastern province of Iran), using multistage clustering sampling method. Research tools were Ways of Coping Questionnaire by Lazarus, Golriz and Barahani's Religious Attitude Questionnaire, and Oxford Happiness Questionnaire. Data analysis was performed in SPSS using Pearson's correlation coefficient and multiple regression analysis. Results of Pearson's correlation demonstrated a significant positive relationship between happiness of adolescents and variables of problem-focused coping styles (r = 0.31, P < 0.01) and religious attitudes (r = 0.129, P < 0.05). Meanwhile, a negative significant association was observed between emotion-focused coping styles and happiness (r = −0.184, P < 0.01). Moreover, results of multiple regression analysis indicated that the listed variables explained 17% of the variance of happiness in totality. According to the results, it is recommended that use of problem-focused styles be emphasized in addition to strengthening of religious attitudes to increase the happiness of adolescents.

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PFMG1 promotes osteoblast differentiation and prevents osteoporotic bone loss [Research]

Nacre is a widely used mineral medicine that has been reported to have beneficial effects in bone remodeling without an increase in inflammation. Water-soluble nacre matrix has been demonstrated to be responsible for the effect, yet core active ingredients are unknown. Pinctada fucata mantle gene 1 (PFMG1) was first discovered in the mantle tissue of Pinctada fucata. The protein has 2 EF-hands, a calcium-binding domain. PFMG1 protein can affect the growth of calcium carbonate crystals in vitro. Here, we demonstrate that PFMG1 affects cell-cycle distribution and promotes preosteoblast proliferation. PFMG1 accelerates preosteoblast differentiation and extracellular matrix mineralization. During the differentiation process, PFMG1 increases the expression level of osteoblastic marker genes and activates the Erk signaling pathway. PFMG1 also accelerates calcium crystal aggregation in culture medium and suppresses osteoclast formation. Moreover, PFMG1 prevents bone loss caused by ovariectomy. RNA sequencing analysis demonstrated that PFMG1 stimulates genes that are associated with tissue development and ossification, which indicated new genes that function in bone remodeling. Our findings demonstrate the therapeutic potential of PFMG1 from nacre as a novel medicine for osteoporosis.—Li, L., Wang, P., Hu, K., Wang, X., Cai, W., Ai, C., Liu, S., Wang, Z. PFMG1 promotes osteoblast differentiation and prevents osteoporotic bone loss.

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Transcription profiling suggests that mitochondrial topoisomerase IB acts as a topological barrier and regulator of mitochondrial DNA transcription [Cell Biology]

Mitochondrial DNA (mtDNA) is essential for cell viability because it encodes subunits of the respiratory chain complexes. Mitochondrial topoisomerase IB (TOP1MT) facilitates mtDNA replication by removing DNA topological tensions produced during mtDNA transcription, but appears to be dispensable. To test whether cells lacking TOP1MT have aberrant mtDNA transcription, we performed mitochondrial transcriptome profiling. To that end, we designed and implemented a customized tiling array, which enabled genome-wide, strand-specific, and simultaneous detection of all mitochondrial transcripts. Our technique revealed that TOP1MT KO mouse cells have a normal processing of the mitochondrial transcripts, but that protein-coding mitochondrial transcripts are elevated. Moreover, we found discrete long noncoding RNAs produced by H-strand transcription and encompassing the noncoding regulatory region of mtDNA in human and murine cells and tissues. Of note, these noncoding RNAs were strongly upregulated in the absence of TOP1MT. In contrast, 7S DNA, produced by mtDNA replication, was reduced in the TOP1MT KO cells. We propose that the long noncoding RNA species in the D-loop region are generated by the extension of H-strand transcripts beyond their canonical stop site and that TOP1MT acts as a topological barrier and regulator for mtDNA transcription and D-loop formation.

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Constitutive role of the Fanconi anemia D2 gene in the replication stress response [Molecular Bases of Disease]

In response to DNA crosslinking damage, the Fanconi anemia (FA) core complex activates the FA pathway by monoubiquitinating Fanconi anemia complementation group D2 (FANCD2) for the initiation of the nucleolytic processing of the DNA crosslinks and stabilization of stalled replication forks. Given that all the classic FA proteins coordinately monoubiquitinate FANCD2, it is unclear why losses of individual classic FA genes yield varying cellular sensitivities to crosslinking damage. To address this question, we generated cellular knockout models of FA core complex components and FANCD2 and found that FANCD2-null mutants display higher levels of spontaneous chromosomal damage and hypersensitivity to replication-blocking lesions than Fanconi anemia complementation group L (FANCL)-null mutants, suggesting that FANCD2 provides a basal level of DNA protection countering endogenous lesions in the absence of monoubiquitination. FANCD2's ubiquitination-independent function is likely involved in optimized recruitment of nucleolytic activities for the processing and protection of stressed replication forks. Our results reveal that FANCD2 has an ubiquitination-independent role in countering endogenous levels of replication stress, a function that is critical for the maintenance of genomic stability.

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Electrostatic lipid-protein interactions sequester the curli amyloid fold on the lipopolysaccharide membrane surface [Protein Structure and Folding]

Curli is a functional amyloid protein in the extracellular matrix of enteric Gram-negative bacteria. Curli is assembled at the cell surface and consists of CsgA, the major subunit of curli, and a membrane-associated nucleator protein, CsgB. Oligomeric intermediates that accumulate during the lag phase of amyloidogenesis are generally toxic, but the underlying mechanism by which bacterial cells overcome this toxicity during curli assembly at the surface remains elusive. Here, we elucidated the mechanism of curli amyloidogenesis and provide molecular insights into the strategy by which bacteria can potentially bypass the detrimental consequences of toxic amyloid intermediates. Using a diverse range of biochemical and biophysical tools involving circular dichroism, fluorescence, Raman spectroscopy, and atomic force microscopy imaging, we characterized the molecular basis of the interaction of CsgB with a membrane-mimetic anionic surfactant as well as with LPS constituting the outer leaflet of Gram-negative bacteria. Aggregation studies revealed that the electrostatic interaction of the positively charged C-terminal region of the protein with a negatively charged head group of surfactant/LPS promotes a protein-protein interaction that results in facile amyloid formation without a detectable lag phase. We also show that CsgB, in the presence of surfactant/LPS, accelerates the fibrillation rate of CsgA by circumventing the lag phase during nucleation. Our findings suggest that the electrostatic interactions between lipid and protein molecules play a pivotal role in efficiently sequestering the amyloid fold of curli on the membrane surface without significant accumulation of toxic oligomeric intermediates.

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Nuclear export factor 3 regulates localization of small nucleolar RNAs [RNA]

Small nucleolar RNAs (snoRNAs) guide chemical modifications of ribosomal and small nuclear RNAs, functions that are carried out in the nucleus. While most snoRNAs reside in the nucleolus, a growing body of evidence indicates that snoRNAs are also present in the cytoplasm and that snoRNAs move between the nucleus and cytoplasm by a mechanism that is regulated by lipotoxic and oxidative stress. Here, in a genome-wide shRNA-based screen we identified nuclear export factor 3 (NXF3) as a transporter that alters the nucleocytoplasmic distribution of box C/D snoRNAs from the ribosomal protein L13a (Rpl13a) locus. Using RNA-sequencing analysis, we show that NXF3 associates not only with Rpl13a snoRNAs, but also with a broad range of box C/D and box H/ACA snoRNAs. Under homeostatic conditions, gain or loss of function of NXF3, but not related family member NXF1, decreases or increases cytosolic Rpl13a snoRNAs, respectively. Furthermore, treatment with the adenylyl cyclase activator forskolin diminishes cytosolic localization of the Rpl13a snoRNAs through a mechanism that is dependent on NXF3, but not NXF1. Our results provide evidence of a new role for NXF3 in regulating the distribution of snoRNAs between the nuclear and cytoplasmic compartments.

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Checkpoint kinase 1-induced phosphorylation of O-linked {beta}-N-acetylglucosamine transferase regulates the intermediate filament network during cytokinesis [Cell Biology]

Checkpoint kinase 1 (Chk1) is a kinase instrumental for orchestrating DNA replication, DNA damage checkpoints, the spindle assembly checkpoint and cytokinesis. Despite Chk1′s pivotal role in multiple cellular processes, many of its substrates remain elusive. Here, we identified O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) as one of Chk1′s substrates. We found that Chk1 interacts with and phosphorylates OGT at Ser-20, which not only stabilizes OGT, but also is required for cytokinesis. Phospho-specific antibodies of OGT-pSer-20 exhibited specific signals at the midbody of the cell, consistent with midbody localization of OGT as previously reported. Moreover, phospho-deficient OGT (S20A) cells attenuated cellular O-GlcNAcylation levels and also reduced phosphorylation of Ser-71 in the cytoskeletal protein vimentin, a modification critical for severing vimentin filament during cytokinesis. Consequently, elongated vimentin bridges were observed in cells depleted of OGT via an siOGT-based approach. Lastly, expression of plasmids resistant to siOGT efficiently rescued the vimentin bridge phenotype, but the OGT-S20A rescue plasmids did not. Our results suggest a Chk1-OGT-vimentin pathway that regulates the intermediate filament network during cytokinesis.

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A chemical and biological toolbox for Type Vd secretion: Characterization of the phospholipase A1 autotransporter FplA from Fusobacterium nucleatum [Lipids]

Fusobacterium nucleatum is an oral pathogen that is linked to multiple human infections and colorectal cancer. Strikingly, F. nucleatum achieves virulence in the absence of large, multi-protein secretion systems (Type I, II, III, IV, and VI) which are widely used by Gram-negative bacteria for pathogenesis. By contrast, F. nucleatum strains contain genomic expansions of Type V secreted effectors (autotransporters) that are critical for host cell adherence, invasion, and biofilm formation. Here we present the first characterization of a F. nucleatum Type Vd phospholipase class A1 autotransporter (strain ATCC 25586, gene FN1704) that we hereby rename Fusobacterium phospholipase autotransporter (FplA). Biochemical analysis of multiple Fusobacterium strains revealed that FplA is expressed as a full-length 85 kDa outer membrane embedded protein, or as a truncated phospholipase domain that remains associated with the outer membrane. While the role of Type Vd secretion in bacteria remains unidentified, we show that FplA binds with high affinity to host phosphoinositide signaling lipids, revealing a potential role for this enzyme in establishing a F. nucleatum intracellular niche. To further analyze the role of FplA we developed an fplA gene knockout strain, which will guide future in vivo studies to determine its potential role in F. nucleatum pathogenesis. In summary, using recombinant FplA constructs we have identified a biochemical toolbox that includes lipid substrates for enzymatic assays, potent inhibitors, and chemical probes to detect, track, and characterize the role of Type Vd secreted phospholipases in Gram-negative bacteria.

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Direct evidence for conformational dynamics in Major Histocompatibility Complex class I molecules [Protein Structure and Folding]

Major histocompatibility complex class I molecules (MHC I) help protect jawed vertebrates by binding and presenting immunogenic peptides to cytotoxic T lymphocytes. Peptides are selected from a large diversity present in the endoplasmic reticulum. However, only a limited number of peptides complement the polymorphic MHC specificity determining pockets in a way that leads to high affinity peptide binding and efficient antigen presentation. MHC I molecules possess an intrinsic ability to discriminate between peptides, which varies in efficiency between allotypes, but the mechanism of selection is unknown. Elucidation of the selection mechanism is likely to benefit future immune-modulatory therapies. Evidence suggests peptide selection involves MHC transiently adopting alternative, presumably higher energy conformations than native peptide-MHC complexes. However, the instability of peptide-receptive MHC has hindered characterisation of such conformational plasticity. To investigate the dynamic nature of MHC we refolded MHC proteins with peptides that can be hydrolysed by UV light, and thus released. We compared the resultant peptide-receptive MHC molecules with non-hydrolysed peptide-loaded MHC complexes by monitoring the exchange of hydrogen for deuterium in solution. We found differences in hydrogen-deuterium exchange between peptide-loaded and peptide-receptive MHC that were negated by the addition of peptide to peptide-receptive MHC molecules. Peptide hydrolysis caused significant increases in hydrogen-deuterium exchange in sub-regions of the peptide-binding domain, and smaller increases elsewhere, including in the α3 domain and the non-covalently associated β2-microglobulin molecule, demonstrating long-range dynamic communication. Comparing two MHC allotypes revealed allotype-specific differences in hydrogen-deuterium exchange, consistent with the notion that MHC I plasticity underpins peptide selection.

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Disruption of amyloid precursor protein ubiquitination selectively increases amyloid beta (A{beta}) 40 levels via presenilin 2-mediated cleavage [Neurobiology]

Amyloid plaques, a neuropathological hallmark 1 of Alzheimer's disease (AD), are largely 2 composed of amyloid beta (Aβ) peptide, derived 3 from cleavage of amyloid precursor protein 4 (APP) by β- and γ-secretases. The endosome is 5 increasingly recognized as an important 6 crossroad for APP and these secretases, with 7 major implications for APP processing and 8 amyloidogenesis. Among various 9 posttranslational modifications affecting APP 10 accumulation, ubiquitination of cytodomain 11 lysines may represent a key signal controlling 12 APP endosomal sorting. Here, we show that 13 substitution of APP C-terminal lysines with 14 arginine disrupts APP ubiquitination and that an 15 increase in the number of substituted lysines 16 tends to increase APP metabolism. An APP 17 mutant lacking all C-terminal lysines underwent 18 the most pronounced increase in processing, 19 leading to accumulation of both secreted and 20 intracellular Aβ40. Artificial APP ubiquitination 21 with rapalog-mediated proximity inducers 22 reduced Aβ40 generation. A lack of APP C- 23 terminal lysines caused APP redistribution from 24 endosomal intraluminal vesicles (ILVs) to the 25 endosomal limiting membrane, with subsequent 26 decrease in APP C-terminal fragment (CTF) 27 content in secreted exosomes, but had minimal 28 effects on APP lysosomal degradation. Both the 29 increases in secreted and intracellular Aβ40 were 30 abolished by depletion of presenilin 2 (PSEN2), 31 recently shown to be enriched on the endosomal 32 limiting membrane compared with PSEN1. Our 33 findings demonstrate that ubiquitin can act as a 34 signal at five cytodomain-located lysines for 35 endosomal sorting of APP. They further suggest 36 that disruption of APP endosomal sorting 37 prevents its sequestration in ILVs and results in 38 PSEN2-mediated processing of a larger pool of 39 APP-CTF on the endosomal membrane.

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The molecular mechanism of N-acetylglucosamine side-chain attachment to the Lancefield group A Carbohydrate in Streptococcus pyogenes [Glycobiology and Extracellular Matrices]

In many Lactobacillales species (i.e. lactic acid bacteria), peptidoglycan is decorated by polyrhamnose polysaccharides that are critical for cell envelope integrity and cell shape and also represent key antigenic determinants. Despite the biological importance of these polysaccharides, their biosynthetic pathways have received limited attention. The important human pathogen, Streptococcus pyogenes, synthesizes a key antigenic surface polymer-the Lancefield group A carbohydrate (GAC). GAC is covalently attached to peptidoglycan and consists of a polyrhamnose polymer, with N-acetylglucosamine (GlcNAc) side chains, which is an essential virulence determinant. The molecular details of the mechanism of polyrhamnose modification with GlcNAc are currently unknown. In this report, using molecular genetics, analytical chemistry and mass spectrometry analysis, we demonstrated that GAC biosynthesis requires two distinct undecaprenol-linked GlcNAc-lipid intermediates: GlcNAc-pyrophosphoryl-undecaprenol (GlcNAc-P-P-Und) produced by the GlcNAc-phosphate transferase GacO and GlcNAc-phosphate-undecaprenol (GlcNAc-P-Und) produced by the glycosyltransferase GacI. Further investigations revealed that the GAC polyrhamnose backbone is assembled on GlcNAc-P-P-Und. Our results also suggested that a GT-C glycosyltranferase, GacL, transfers GlcNAc from GlcNAc-P-Und to polyrhamnose. Moreover, GacJ, a small membrane-associated protein, formed a complex with GacI and significantly stimulated its catalytic activity. Of note, we observed that GacI homologs perform a similar function in Streptococcus agalactiae and Enterococcus faecalis. In conclusion, the elucidation of GAC biosynthesis in S. pyogenes reported here enhances our understanding of how other Gram-positive bacteria produce essential components of their cell wall.

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Understanding DNA replication by the bacteriophage T4 replisome [DNA and Chromosomes]

The T4 Replisome has provided a unique opportunity to investigate the intricacies of DNA replication. We present a comprehensive review of this system focusing on: its eight proteins composition, their individual and synergistic activities, and assembly in vitro and in vivo into a replisome capable of coordinated leading/lagging strand DNA synthesis. We conclude with a brief comparison to other replisomes with emphasis on how coordinated DNA replication is achieved.

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Commentary on observations on our article – Re: Seroprevalence of sexually transmitted diseases (herpes, chlamydia, and syphilis) in pregnant women in Warri, Nigeria

Favour Osazuwa

CHRISMED Journal of Health and Research 2017 4(4):288-288



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Calvarial tuberculosis presenting as multiple osteolytic soft tissue lesions

Reddy Ravikanth, Sunil Mathew, Robert Patrick Selvam

CHRISMED Journal of Health and Research 2017 4(4):278-279

Primary tuberculosis (TB) of the skull is a very rare entity scantily described in literature with 0.2%–1.3% of cases. The different radiological forms of calvarial TB described are - circumscribed lesions of the sclerotic and lytic type and diffuse TB of the cranium. Treatment for skull TB includes antituberculous therapy along with appropriate surgical intervention. Here, we present a case of calvarial TB presenting as multiple osteolytic soft tissue lesions.

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Assessment of antibiotic prescribing pattern in pediatric patients: A cross-sectional hospital-based survey

Bhupalam Pradeepkumar, Tawfeek Alameri, Goruntla Narayana, Y Padmanabha Reddy, Jinka Dasaratha Ramaiah

CHRISMED Journal of Health and Research 2017 4(4):235-237

Background: Irrational usage of antibiotics increases the risk for the antimicrobial resistance, leads to increase morbidity, mortality, and economic burden for health care. India is a lower-middle income developing country in south Asia that has high potential for overuse and misuse of antibiotics and has less public awareness of antimicrobial resistance. The World Health Organization (WHO) developed the prescribing indicators to measure the rational usage of drugs in primary care and to assess the prescribing pattern of antibiotics. Aim: The aim of the study was to assess the prescribing pattern of antibiotics in pediatric patients of Anantapur district, Andhra Pradesh, India. Subjects and Methods: A cross-sectional and prospective study was carried out in private pediatric specialty hospitals in urban areas of Anantapur district. Sample size was calculated using single population proportion formula. A total number of 845 pediatric in-patients were included for the study. Patients' demographic characters, diagnosis, and drugs prescribed were recorded in a prestructured and validated data collection form. Results: An average of 3.53 drugs prescribed per patient encounter, which was higher than WHO prescribed indicator standard value 2. The present study reveals that the percentage of encounters with antibiotics was 50.05% (423), which was higher than WHO standard (20.0-26.8%). Among 423 antibiotic prescriptions, 23.43% (198) prescribed with generic names and 91.48% antibiotics were prescribed from essential drug formulary list. Conclusion: Prescription patterns and usage of antibiotics in this study was inappropriate in comparing our results with WHO prescribing indicators. Effective interventions are required to reduce inappropriate antibiotic prescriptions.

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Milestones of dental history

Rajesh Mahant, S Vineet Agrawal, Sonali Kapoor, Isha Agrawal

CHRISMED Journal of Health and Research 2017 4(4):229-234

Since ages, human beings suffer from the dental problems. With the journey as time elapsed the person treating the teeth changed (i.e., from barbers and monks to present dentists), equipment changed (i.e., from bow drills to airotor and laser handpieces), materials changed (i.e., from ground mastic alum/honey to tooth colored composite and ceramics). There has been drastic change in treatment planning from extraction to the conservation of teeth and from manual restoration to computerized restorations computer-aided design/computer-aided manufacturing. Thus, this review is an attempt to have an insight into major milestones of the dental timeline.

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Validation of Kvaal's and Cameriere's methods of age estimation in people of Marathwada origin

Maneesha Das, Abhishek Singh Nayyar, Neetu Punhani, Harsha Puri, Rakesh Rohilla, KV Chalapathi, B Anand Babu

CHRISMED Journal of Health and Research 2017 4(4):238-247

Context: Aging, in forensic context, is necessary both for the dead and the living. Kvaal et al. introduced a method of age estimation by indirectly measuring secondary dentin deposition on radiographs. Cameriere et al., later, put forth a method based on radiographic estimation of pulp/tooth area ratio (AR) in specific teeth of the dentition. Aim: The purpose of the present study was to assess the validity of Kvaal's and Cameriere's methods of age estimation in a specific populace of Marathwada origin. Materials and Methods: A total number of 110 patients aged between 15 and 75 years were selected and the variables P = complete pulp length/root length (from enamel-cementum junction [ECJ]-root apex), r = complete pulp length/complete tooth length, a = complete pulp length/root width at ECJ level, b = pulp/root width at midpoint level between ECJ level and mid-root level, and c = pulp/root width at mid-root level; and pulp/tooth AR were recorded as devised in Kvaal's and Cameriere's methods of age estimation, respectively. Statistical Analysis: Statistical analysis was performed with SPSS (version 10.5) package. Mean comparison of morphological variables was carried out using Student's t-test. Intra- and inter-observer reproducibility of measurements was studied using the concordance correlation coefficient. Results: Of all the morphological variables, variables P, r, mean (M), length (L), and pulp/tooth AR of Kvaal's and Cameriere's methods correlated significantly with age with variable P correlating the best among them. Conclusion: Variables associated with width ratios rather than length ratios of Kvaal's and Cameriere's methods correlated best with chronological age in the populace of Marathwada origin.

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Antenatally diagnosed alobar holoprosencephaly: A report of two cases

CR Srinivasa Babu, Inampudi Vineel, Arjun Prakash, Y Ravi Kumar

CHRISMED Journal of Health and Research 2017 4(4):283-285

Holoprosencephaly is a complex developmental abnormality of the brain arising from the failure of cleavage of the prosencephalon. The condition termed "holoprosencephaly" includes cyclopia, cebocephaly, ethmocephaly, and median cleft. We present two cases of antenatally diagnosed alobar holoprosencephaly with multiple associations, which were confirmed after termination of pregnancy. One of them had a proboscis and a single midline eye. The other had multiple facial abnormalities such as hypotelorism, median cleft lip and palate, and preauricular skin tag.

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Virulence property, phylogenetic background, and resistance pattern of Escherichia coli isolates from wound infections

Arindam Chakraborty, Vishwas Saralaya, Prabha Adhikari, Shalini Shenoy

CHRISMED Journal of Health and Research 2017 4(4):248-252

Aims: The aim of the present study was to characterize the E. coli isolates from surgical wounds, traumatic wounds, and from foot ulcers on the basis of virulence and drug resistance. Subjects and Methods: A total of forty E. coli strains isolated from wound infections were studied. Phylogenetic background, virulence factors (VFs), and antibiotic resistance profiles were determined by phenotypic and genotypic methods. Correlation between phylogenetic groups, VFs, and drug resistance pattern were analyzed. Results: Analysis of virulence gene possession among the isolates indicated that a maximum number were carrying the fimH (39 strains; 97.5%) gene, followed by iutA (27; 67.5%), papC (16; 4%), hlyA (5; 12.5%), cnf1 ( 5; 12.5%), and neuC (1; 2.5%), respectively. The phylogroups B2 (32.5%) and D (42.5%) were more common. Thirty isolates (75%) were found to be positive for extended-spectrum β-lactamase genes. CIT type of plasmid-mediated AmpC was seen only in 6 (15%) isolates. Most effective antibiotics were carbapenem and sulfamethoxazole-trimethoprim groups of drugs. Conclusions: Our findings indicate that adherence factors and iron uptake systems are two of the more important CFs expressed by such isolates, and such strains are also observed to exhibit a higher degree of drug resistance. Carbapenems and co-trimoxazole may be considered as reliable and successful alternative medications for these isolates.

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Recommendations to promote safe and effective use of contraceptives: World Health Organization

Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava, Jegadeesh Ramasamy

CHRISMED Journal of Health and Research 2017 4(4):291-291



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Hemophilia treatment center: A stratification model for developing countries: A pilot study from India

M Joseph John, Naveen Kakkar, Amrith Mathew, Chepsy C Philip, Tanuja Tanuja, Ramandeep Kaur, Jasprit Singh, Scott Dunkley

CHRISMED Journal of Health and Research 2017 4(4):253-258

Background: Hemophilia center, treatment center (TC), hemophilia TC (HTC), and Hemophilia Comprehensive Care Center (CCC) are terminologies used to describe centers caring for persons with hemophilia (PWH). These are based on their capability to provide multidisciplinary care and laboratory services. Widely described are the European HTCs (EHTCs) and the European Hemophilia CCCs (EHCCCs). However, most centers in developing countries providing care for PWH have variable clinical expertise and laboratory facilities, which do not qualify for the existing models. Materials and Methods: This cross-sectional study was done to evaluate the laboratory and clinical care facilities available in HTCs in India. The survey questionnaire was sent to 62 HTCs in India. Laboratory and clinical care facilities were categorized based on a predefined stratification model. Level IV being the minimum and Level I the maximum were used to define clinical and laboratory facilities. Results: Fifty-two (85%) centers responded representing 17 states in India. Only 28 HTCs had attached laboratory services. Although all the centers cared for acute bleeds, only half managed chronic joint disease (Level III) while one-sixth could perform surgeries (Level II). Only one-third of the laboratories had instituted quality control measures and performed factor assays. Only four centers qualified for EHTC criteria and two for the EHCCC criteria. Conclusion: This HTC stratification model provides assessment and differentiation of the clinical and laboratory services. It allows an individual HTC to identify the standard of care and provides a framework for objectively planning, implementing, and evaluating its services.

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When chronic ischemia in thalassemia mimics leukodystrophy: Case report with review of literature

Sukriti Kumar, Manish Gutch

CHRISMED Journal of Health and Research 2017 4(4):275-277

We present magnetic resonance imaging (MRI) brain picture of a 10-month-old child suffering from thalassemia major. The picture had changes that mimicked leukodystrophy. However, on taking detailed clinical history, the MRI picture fitted well into the chronic hemolytic anemia pathology, and the changes could be explained and corroborated with studies in the literature.

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Minimally invasive therapy of upside-down stomach: A single-center experience

Radek Vrba, Cestmir Neoral, Rene Aujesky, Martin Stasek, Linda Bebarova, Petr Janda, Tereza Vrbova, Tomas Bohanes, Katherine Vomackova, Martin Lovecek

CHRISMED Journal of Health and Research 2017 4(4):259-263

Introduction: The aim of this study is to evaluate short-term and long-term outcomes of minimally invasive therapy in Type IV hiatal hernia (upside-down stomach). Patients and Methods: A retrospective study of 58 consecutively operated patients with Type IV hiatal hernia between 1998 and 2015 was conducted. Short-term outcome was evaluated using Clavien-Dindo classification and long-term outcomes using phone survey and subjective assessment of patients at least 1 year following surgery. Results: Laparoscopic hiatoplasty was performed in all patients, with gastropexy in 55.2%, fundoplication in 39.6%, and combination of fundoplication and gastropexy in 5.2%. Complications were observed in 6.9%. Two early reoperations (within 30 days) due to acute reherniation were necessary. Adverse events occurred in seven cases – pleural opening and peroperative bleeding. Three patients were reoperated laparoscopically 2–17 months after the first surgery due to receiving partial stomach herniation. In 67.2% of patients, long-term subjective quality of life assessment was available. Eighty percent of them were completely satisfied, without recurrence of preoperative symptoms. Conclusion: Elective laparoscopic surgery of hiatal hernia Type IV is a safe procedure, which has all the benefits of minimally invasive therapy with favorable short- and long-term results.

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One-step apexification of blunderbass canal using biodentin

Vinaya Susan Varghese, Veerendra Uppin, Nirmal Kurian

CHRISMED Journal of Health and Research 2017 4(4):280-282

Apexification is a treatment protocol well recognized and accepted by clinicians worldwide for the management of an immature tooth with necrotic pulp. With the advent of newer biomimetic and bioactive materials in the market, these treatment protocols have succeeded in achieving more predictable, successful treatment outcomes. The case report details the successful treatment of a 33-year-old male patient with nonvital maxillary central incisor that had open apex, with biodentine for apexification procedure, and 1-year follow-up exhibiting progressive involution of periapical radiolucency and satisfactory healing of the periapical tissues.

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Hot iron rods branding, its complications: Still continue in central India

Seema Mahant, CM Reddy, Supriya Mahant, MP Singh

CHRISMED Journal of Health and Research 2017 4(4):264-267

Introduction: The middle of the 20th century has often been described as a golden age of scientific advancement and miraculous medical breakthroughs. In spite of a lot of awareness and many health education programs, still some traditional treatment exists in many places in our country including Central India. In some villages of Madhya Pradesh, many horrifying therapies such as iron rods branding are well known for a few common diseases such as ascites, headache, pneumonia, common cold, or hernia. Bruise marks can be seen on the bodies of a majority of villagers. Main reasons behind such therapy are lack of money for medical treatment, lack of medical facilities, and the unwillingness of medical officers to stay in small villages. Besides this, illiteracy compels them to follow old customs and practices. All these strengthen the faith of villagers in such treatments. It is all due to lack of education and proper awareness. Many female patients come to hospital with complications of iron rods branding suggest that despite being educated, strong cultural beliefs forces people to undergo branding as a treatment of many common diseases in India even in the 21st century. Aims and Objectives: To study the reasons and complications of hot iron branding. Materials and Methods: Sample size was 30. Thirty patients with old, healed (within 1 year), or recent scars of iron branding were included in the study. Patients were evaluated for the sociodemographic details and the information of underlying disease, pattern of lesions, and complications of branding. Results: Hot iron branding is still carrying on as traditional treatment in Central India. It is commonly seen in females of age 20–50 years. It is mostly found in illiterate patients of low socioeconomic status who have chronic disease and chronic pain. Conclusion: Skin branding which still has therapeutic uses in some cultural societies have severe medical complications in Central India.

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Imaging in neurosarcoidosis

Reddy Ravikanth

CHRISMED Journal of Health and Research 2017 4(4):286-287



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Management of periradicular lesion using calcium sulfate graft: An unique case report

Arnav Mukherji

CHRISMED Journal of Health and Research 2017 4(4):268-271

Failure to root canal treatment can be attributed to inadequate treatment. Although highest standards are followed, still failure is inevitable. In most of the cases, the endodontic failure results from persistent or secondary intraradicular infection. Extraradicular infections may also be implicated in the failure of some cases. Paraendodontic surgery is warranted in periapical diseases treatment, when traditional endodontic therapy does not obtain satisfactory outcomes. The objective of this case report is to report a clinical case where an apicoectomy was indicated due to failure in conventional endodontic treatment followed by unconventional bone grafting using calcium sulfate.

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The public health implications of mycetoma: A neglected tropical disease

Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava, Jegadeesh Ramasamy

CHRISMED Journal of Health and Research 2017 4(4):289-290



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Emphysematous pyelonephritis within a horseshoe kidney

Amit Tuli, Faireena Singh, Kim Jacob Mammen

CHRISMED Journal of Health and Research 2017 4(4):272-274

Association of emphysematous pyelonephritis (EPN) with horseshoe kidney is rare. It is a life-threatening condition with variable mortality. Historically, the treatment consisted of early nephrectomy. One such patient managed conservatively by placement of percutaneous drainage (PCD) and appropriate antibiotic coverage, is reported. This patient responded well to the conservative approach of treatment by insertion of PCD under computed tomography guidance. Hence, insertion of PCDs is an effective way of treating EPN.

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Springboard program: A ray of hope for the empowerment of victims of child marriage in Yemen

Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava, Jegadeesh Ramasamy

CHRISMED Journal of Health and Research 2017 4(4):292-292



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Synchronous HPV-Related Cancer of Bilateral Tonsils Detected Using Transoral Endoscopic Examination with Narrow-Band Imaging

Background. The incidence of human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing worldwide. HPV is reported in approximately 50% cases of OPSCC in Japan. However, there are few reports of synchronous bilateral HPV-positive tonsillar carcinoma, and, in almost all those cases, carcinoma was detected using positron emission tomography/computed tomography and/or bilateral tonsillectomy. Methods and Results. We report the case of a 63-year-old male with bilateral tonsillar carcinoma detected using transoral endoscopic examination with narrow-band imaging (NBI). A biopsy of the bilateral tonsils revealed squamous cell carcinoma, which was demonstrated to be HPV-related using in situ hybridization and p16 immunohistochemistry. The patient was diagnosed as synchronous bilateral tonsillar carcinoma: T1 (2) N2b M0. He was treated with induction chemotherapy, bilateral radical tonsillectomy with neck dissection, and radiotherapy. Conclusion. To our knowledge, this is the first report of a synchronous bilateral tonsillar carcinoma detected using transoral NBI in the outpatient setting. Early diagnosis without the inspection under general anesthesia is beneficial for the patients with lymph node metastasis from unknown primary lesion.

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Can acute-phase response biomarkers differentiate infection from inflammation postpediatric cardiac surgery?

Bana Agha Nasser, Abdu Rahman Mesned, Mohamad Tageldein, Mohamed S Kabbani, Nada Siddig Sayed

Avicenna Journal of Medicine 2017 7(4):182-188

Background: Infection is a common serious complication postpediatric cardiac surgery. Diagnosis of infection after cardiopulmonary bypass (CPB) is difficult in the presence of surgical stress, hemodynamic instability, and inflammatory reaction. Aim: The purpose of this study is to investigate the value of available inflammatory biomarkers and its validity to differentiate infection from inflammation postpediatric cardiac surgery and to find the trend and the change in the level of these biomarkers shortly after cardiac surgery. Methods: We conducted a prospective study that included all children who underwent cardiac surgery in Prince Sultan Cardiac Centre-Qassim from November 2013 to October 2015. C-reactive protein, erythrocyte sedimentation rate, white blood cell count, and neutrophil count were measured for all patients presurgery, 4 consecutive days postsurgery, and predischarge. Patients were divided into two groups (the infected and the noninfected group). We compared the level of biomarkers between both groups. Then, we further analyzed the effects of CPB and preoperative steroid on postoperative inflammatory biomarker levels. Collected data were then reviewed and analyzed. Results: There were 134 pediatric cardiac patients included during the study period. Group 1 (bacterial negative culture group) had 125 cases and Group 2 (bacterial positive culture group) had nine cases. We found no statistically significant difference in inflammatory biomarker elevation between both groups. Only Group 2 had higher (RACHS) Risk adjustment for congenital heart surgery score, more ventilator days, and more drop in platelet count on the 2nd and 3rd postoperative days in comparison with the noninfected group 1. Both groups of patients who were in on and off CPB had the same level of inflammatory biomarkers with no significant differences. Giving corticosteroid preoperatively did not affect the trend of biomarker elevation and made no difference when it was compared to the group of patients who did not receive corticosteroid before surgery. Conclusion: Common inflammatory biomarkers cannot differentiate between infection and inflammation within the first 5 days postpediatric cardiac surgery as these reflect the inflammatory process rather than infection. Trend is more important than single reading.

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Metastatic breast cancer: Endocrine therapy landscape reshaped

Mohamad Adham Salkeni, Samantha June Hall

Avicenna Journal of Medicine 2017 7(4):144-152

Endocrine therapy (ET) of hormone receptor (HR)-positive and human epidermal growth factor receptor 2-(HER2)-negative metastatic breast cancer (MBC) historically focused on estrogen deprivation and antagonism. The identification of several intracellular pathways promoting resistance to antiestrogen therapy led to the introduction of novel endocrine drug combinations that reformed treatment schema and expanded therapeutic options. There is no doubt that efforts to overcome or delay resistance to ET are fruiting, particularly with the introduction of cyclin-dependent kinase 4/6 inhibitors such as palbociclib and ribociclib, and mechanistic target of rapamycin inhibitors such as everolimus. Although still considered incurable by currently available treatment modalities, many patients with MBC nowadays enjoy several years of good quality life coupled with decent tumor control. The diversity of therapies and unusual pattern of side effects can be quite perplexing to the treating physician. The sequence of variable agents and management of side effects, in addition to the timing of initiation of cytotoxic chemotherapy, is among the challenges faced by oncologists. In this review, we shed a spotlight on mechanisms of resistance to ET, and provide a review of landmark studies that have recently reshaped the landscape of treatment options for patients with metastatic HR-positive, HER2-negative MBC. A suggested treatment strategy for newly diagnosed patients is also discussed herein.

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Gluten-free diet among school-age children in Olmsted County, Minnesota

Eyad Almallouhi, Imad Absah

Avicenna Journal of Medicine 2017 7(4):171-175

Objective: To assess the prevalence of gluten-free diet (GFD) among school-age children in Olmsted County, Minnesota, and compare it with the prevalence of celiac disease (CD) in the same age group. Methods: We performed a population-based study in Olmsted County using a survey to collect information from the six school districts in the county for the academic year 2014–2015. The survey contained questions to (1) assess the prevalence of GFD among school-age children in the public schools of Olmsted County; (2) assess the prevalence of CD among school-age children in Olmsted County; and (3) determine the indications for GFD in these children. We used the infrastructure of the Rochester Epidemiology Project (REP) to calculate the prevalence of CD in children aged 4–18 years in December 2014. Results: Using the REP data, we identified sixty patients with CD in the county aged 4–18 years; the prevalence of CD among school students in 2014 was 193.6/100,000. The prevalence of GFD in Olmsted County children, however, was higher, at 265/100,000 according to the survey from the school districts. The prevalence of GFD was highest in Rochester, the largest city. GFD was more common among children in secondary schools. Conclusion: According to our study, there are more children on GFD than the actual cases of CD in Olmsted County during the study period. This finding could be related to an increased number of children without CD who are following GFD for other indications.

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Adnexal masses in pregnancy: An updated review

Abdullah M Hakoun, Iyad AbouAl-Shaar, Khaled J Zaza, Hussam Abou-Al-Shaar, Mohammad Nour A. Salloum

Avicenna Journal of Medicine 2017 7(4):153-157

Adnexal masses in pregnancy are not commonly encountered. The majority of these masses are discovered incidentally during routine follow-up. However, some of these masses become symptomatic due to their size, location, and impingement of adjacent structures. Several diagnostic modalities can be utilized for the detection of adnexal masses with different sensitivity and specificity rates. The differential diagnosis of adnexal masses discovered during pregnancy is broad and includes both benign and malignant lesions. The management of such lesions has been a subject of debate for years with no consensus regarding the best management plan. Tumor size, site, and the trimester of mass detection are all crucial in management. In this account, we review adnexal masses discovered in pregnancy, the diagnostic modalities utilized for detecting these lesions, their differential diagnosis, and management strategies.

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Minimizing nocebo effect: Pragmatic approach

Majed Chamsi-Pasha, Mohammed Ali Albar, Hassan Chamsi-Pasha

Avicenna Journal of Medicine 2017 7(4):139-143

The nocebo effect, the inverse of the placebo effect, is a well-established phenomenon, yet under-appreciated. It refers to nonpharmacological, harmful, or undesirable effects occurring after active or inactive therapy. The frequency of adverse events can dramatically increase by informing patients about the possible side effects of the treatment, and by negative expectations on the part of the patient. Patients who were told that they might experience sexual side effects after treatment with β-blocker drugs reported these symptoms between three and four times more often than patients in a control group who were not informed about these symptoms. Nocebo effect has been reported in several neurological diseases such as migraine, epilepsy, multiple sclerosis, Parkinson's disease and neuropathic pain, and in patients with depression. The investigation of the biological and theoretical underpinning of the nocebo phenomenon is at an early stage, and more research is required. Physicians need to be aware of the influence of nocebo phenomenon and be able to recognize it and minimize its effects.

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Cardiac manifestations of Familial Mediterranean fever

Ahmad Alsarah, Osama Alsara, Heather S Laird-Fick

Avicenna Journal of Medicine 2017 7(4):158-163

Familial Mediterranean fever (FMF) is autoinflammatory disorder characterized by sporadic attacks of fever, peritonitis, pleuritis, and arthritis. It is mainly seen in patients from Mediterranean origins, but it is now reported more frequently in Europe and North America due to immigration. To analyze the data on the cardiovascular manifestations in FMF patients, we searched PubMed using the terms "Familial Mediterranean Fever" or "FMF" in combination with other key words including "cardiovascular diseases" "pericardial diseases" "atherosclerosis" "coronary artery diseases" "cardiomyopathy" "pulmonary hypertension" or "valvular diseases." suggested several mechanisms to explain the cardiac involvements in FMF including the ongoing inflammation and the amyloid deposits in the heart and vessels' walls at the advanced stages of FMF. The course of these manifestations varies widely, but it can associate with poor prognosis in some cases such as with pulmonary hypertension. Interestingly, Colchicine, which is the cornerstone therapy of FMF, plays a vital role in treating and preventing some of these disorders. In this article, In this article, we will discuss the incidence, pathophysiology, and prognosis of the various cardiac manifestations affecting FMF patients.

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