Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174: 10/05/17

Πέμπτη 5 Οκτωβρίου 2017

Review on antioxidants and evaluation procedures

Abstract

Antioxidants are the substances that are capable of counteracting the damaging effects of the physiological process of oxidation occur in animal tissues. These may be nutrients (vitamins and minerals) as well as enzymes (proteins) in our body that assist in chemical reactions. They are believed to play a role in preventing the development of chronic diseases like cancer, diabetes, heart disease, stroke, Alzheimer's disease, rheumatoid arthritis, and cataracts etc. The present review article emphasizes on the various aspects of oxidants and antioxidants viz. definition, types, causes, mechanism, functions, adverse effects along with various in vivo and in vitro models of evaluation of antioxidant activity of new molecule, compounds or any plant or plant part. This review is one of its kinds which will be of great importance for researchers working in this area in search of antioxidant moieties and their biological evaluation.

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Analysis of herbal medicine prescriptions for patients in an academic Korean medical hospital: A cross sectional study of electronic medical records (2010–2013)

Abstract

Objective

To obtain fundamental information for the standardization of herbal medicine in Korea.

Methods

We analyzed the herbal medicine prescription data of patients at the Pusan National University Korean Medicine Hospital from March 2010 to February 2013. We used the Dongui-Bogam (Dong Yi Bao Jian) to classify prescribed herbal medicines.

Results

The study revealed that the most frequently prescribed herbal medicine was 'Liuwei Dihuang Pill (LWDHP, 六味地黄丸)' which was used for invigorating 'Shen (Kidndy)-yin'. 'LWDHP' was most frequently prescribed to male patients aged 50–59, 60–69, 70–79 and 80–89 years, and 'Xionggui Tiaoxue Decoction (XGTXD, 芎归调血饮)' was most frequently prescribed to female patients aged 30–39 and 40–49 years. According to the International Classification of Diseases (ICD) codes, 'Diseases of the musculoskeletal system and connective tissue' showed the highest prevalence. 'LWDHP' and 'XGTXD' was the most frequently prescribed in categories 5 and 3, respectively. Based on the percentage of prescriptions for each sex, 'Ziyin Jianghuo Decoction (滋阴降火汤)' was prescribed to mainly male patients, and 'XGTXD' with 'Guima Geban Decoction (桂麻各半汤)' were prescribed to mainly female patients.

Conclusion

This study analysis successfully determined the frequency of a variety of herbal medicines, and many restorative herbal medicines were identified and frequently administered.

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Effects of electroacupuncture on metabolic changes in motor cortex and striatum of 6-hydroxydopamine-induced Parkinsonian rats

Abstract

Objective

To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model.

Methods

Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance.

Results

Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007).

Conclusions

EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.

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A novel alphapartitivirus detected in Japanese pear

Abstract

Pyrus pyrifolia cryptic virus (PpCV) had been previously reported from Japanese pear (Pyrus pyrifolia). In analyses of Japanese pear, two other double-stranded (ds) RNA molecules (dsRNA4 and 5) were observed along with the three dsRNA segments from PpCV on an electrophoretic profile of isolated dsRNA. When the purified dsRNA sample was deep sequenced by a next-generation sequencer, two de novo assembled contigs corresponding to dsRNA4 and 5, with predicted amino acid sequences showing homologies to the RNA-dependent RNA polymerase and the capsid protein of Rose partitivirus, respectively, were found by BLAST analysis. The relationships between the two contigs and dsRNA4, 5 were confirmed by northern blot analyses with probes amplified using primers designed from the contigs. Terminal sequence analyses by rapid amplification of cDNA ends revealed that dsRNA4 and 5 were 1945 and 1788 bp long, respectively. The 5′ terminal sequences (GUCAAAUU) of dsRNA4 and 5 were conserved. Based on genome size and phylogenetic analyses, the newly found virus is thought to be a member of the genus Alphapartitivirus. Thus, it has been designated as Pyrus pyrifolia partitivirus 2.

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Progression level of extracapsular spread and tumor budding for cervical lymph node metastasis of OSCC

Abstract

Objectives

The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined.

Patients and methods

The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis.

Results

ECS was detected in 216 cases of OSCC and analyzed. The 5-year overall survival and RFS rates of patients with type C, which was microscopically defined as tumor invasion to perinodal fat or muscle tissue, were significantly poor at 40.6 and 37.8%, respectively. The results of a univariate analysis suggested that the prognosis of ECS in OSCC patients is associated with its progression level, particularly type C. The 5-year RFS rate of type C with tumor budding was significantly poor at 31.5%. Type C with tumor budding correlated with local and regional recurrence as well as distant metastasis. In a multivariate analysis, tumor budding was identified as an independent prognostic factor.

Conclusions

These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients.

Clinical relevance

This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients.

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RE: “MODELED AND PERCEIVED EXPOSURE TO RADIOFREQUENCY ELECTROMAGNETIC FIELDS FROM MOBILE-PHONE BASE STATIONS AND THE DEVELOPMENT OF SYMPTOMS OVER TIME IN A GENERAL POPULATION COHORT”

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Progression level of extracapsular spread and tumor budding for cervical lymph node metastasis of OSCC

Abstract

Objectives

Patients and methods

The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis.

Results

Conclusions

These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients.

Clinical relevance

This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients.

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Effects of compound Zhebei Granule (复方浙贝颗粒) combined with doxorubicin on expression of specific surface antigens in mice with transplanted KG-1a cells

Abstract

Objective

To investigate the effects of Compound Zhebei Granule (复方浙贝颗粒, CZG) combined with doxorubicin hydrochloride (adriamycin, ADM) on specific surface antigens in mice with KG-1a transplanted cells.

Methods

A subcutaneous tumor xenograft model was established by injection of the acute myeloid leukemia cell line KG-1a into the axillary flanks of BALB/c-nude mice. Twenty-four tumor bearing mice were divided into 4 groups according to a random number table, including normal saline control group, ADM group, high-dose CZG group, and mid-dose CZG group, with 6 mice in each group. Drug administration occurred on the 14th day after cell inoculation, and normal saline control group mice were gavaged with normal saline at 0.2 mL/10 g every other day. ADM group mice were intraperitoneally injected with ADM 1 mg/kg [conversion of adults, 40 mg/(m²•d)] every other day. High- and mid-dose CZG groups mice were gavaged with CZG at the dose of 8 and 4 g/kg respectively every other day and intraperitoneally injected with ADM (1 mg/kg) every other day. The administration period lasted for 10 days. The tumor xenografts were made into mononuclear cell suspensions after dissection, and the expressions of specific surface antigens, including CD34⁺CD38^-, CD34⁺CD38^-CD123⁺, CD34⁺CD38^-CD96⁺ and CD34⁺CD38^-CD33⁺, in KG-1a cell line tumor xenografts were detected by flow cytometry.

Results

Compared with the control and ADM groups, expression of CD34⁺CD38^- in the two CZG groups was significantly lower (P<0.05). Compared with the control group, expression of CD34⁺CD38^-CD123⁺ in the two CZG groups decreased (P<0.05). The high-dose CZG group showed more obvious outcomes compared with the ADM group (P<0.05). Compared with the control and ADM groups, the expression of CD34⁺CD38^-CD96⁺ and CD34⁺CD38^-CD33⁺ in the two CZG groups decreased (P<0.05).

Conclusions

CZG combined with doxorubicin could reduce the expression of CD34⁺CD38^-, CD34⁺CD38^-CD123⁺, CD34⁺CD38^-CD96⁺ and CD34⁺CD38^-CD33⁺ in KG-1a cell line tumor xenografts, which shows that CZG could target leukemia stem cells and play a role in chemosensitization.

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Recent advances in Chinese medicine for contrast-induced nephropathy

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Effects of electroacupuncture on metabolic changes in motor cortex and striatum of 6-hydroxydopamine-induced Parkinsonian rats

Abstract

Objective

Methods

Results

Conclusions

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Effect of Jiaotai Pill (交泰丸) on intestinal damage in partially sleep deprived rats

Abstract

Objective

To explore the effect and mechanism of Jiaotai Pill (交泰丸, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD).

Methods

Obesity resistant (OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide (LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin (Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes (Cry1 and Cry2) in the intestine were also determined.

Results

The treatment of JTW significantly decreased LPS level in OR rats with PSD (P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting (P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine.

Conclusions

JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.

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Review of Anemone raddeana Rhizome and its pharmacological effects

Abstract

The chemical compositions of Anemone raddeana Rhizome, a kind of traditional Chinese medicine, were reviewed, along with its bioactivity and pharmacological properties and method improvements of extracting and detecting triterpenoid saponins. A. raddeana Rhizome is used to treat neuralgia and rheumatism, and is rich in triterpenoid saponins, most of which are pentacyclic, with oleanane as the nucleus. So far, 37 triterpenoid saponins have been determined from the herb. Its reported bioactivity and pharmacological properties have been described as anticancerous, antimicrobial, anti-inflammatory, analgesic, antipyretic, anticonvulsive, antihistaminic, and sedative. It has also been used for the induction of the humoral immune response and treatment of liver fibrosis in chronic hepatitis. However, the herb also has hemolytic effects and can be toxic, which limits its clinical application. Further studies are needed on the pharmaceutical functions, mechanisms, and immunological responses to contribute to the herb's clinical applications.

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Immunoprotective effects of a hemin-binding peptide derived from hemagglutinin-2 against infection with Porphyromonas gingivalis

Summary

The principal etiologic agent in periodontal disease, Porphyromonas gingivalis, generates cysteine proteases that bind heme with domains such as hemagglutinin-2 (HA2). High-affinity HA2-hemin binding supplies the porphyrin and ferric iron needed for growth and virulence. The DHYAVMISK peptide, recently identified at the hemin-binding site of HA2 inhibits hemin binding. We now evaluate the protective effect of vaccination with DGFPGDHYAVMISK (termed DK) against P. gingivalis using a rat infection model. Rats immunized with DK generated anti-peptide serum IgGs and salivary sIgAs (as measured by ELISA). In a subcutaneous abscess model, the protective effect of immunization was then investigated by measuring abscess size following subcutaneous injection with P. gingivalis. In an oral infection model, a ligature inoculated with P. gingivalis was used to induce periodontitis. The degree of bone erosion, ordinarily provoked by infection, was then evaluated by micro-CT. We found that anti-peptide antibody titers of serum IgGs and salivary sIgAs for rats immunized with DK and adjuvant were significantly higher than for sham immunized rats (injected with adjuvant/PBS alone (P <0.05)). In the subcutaneous abscess model, the DK + adjuvant vaccinated rats recovered faster than sham vaccinated animals, with their abscess sizes significantly smaller (P <0.05). Further, in the experimental periodontitis model, bone loss at the molar palatal side for DK + adjuvant vaccinated rats was significantly lower than for sham vaccinated animals (P <0.05). Collectively, these data demonstrate the potential of (DK) peptide immunization in terms of eliciting an immunoprotective effect against infection with P. gingivalis.

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Metabolic nuclear receptors in periodontal host–microbe interactions and inflammation

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Immunoprotective effects of a hemin-binding peptide derived from hemagglutinin-2 against infection with Porphyromonas gingivalis

Summary

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Two-dimensional (2D) and three-dimensional (3D) models for studying atherosclerosis pathogenesis induced by periodontopathogenic microorganisms

Summary

Epidemiological studies have established a clinical association between periodontal disease and atherosclerosis. Bacteremia and endotoxemia episodes in patients with periodontitis appear to link these two diseases by inducing a body-wide production of cardiovascular markers. The presence of oral bacteria in atherosclerotic lesions in patients with periodontitis suggests that bacteria, or their antigenic components, induce alterations in the endothelium associated with atherosclerosis. Therefore, a causal mechanism explaining the association between both diseases can be constructed using in vitro models. This review presents current experimental approaches based on in vitro cell models used to shed light on the mechanism by which periodontal pathogenic microorganisms, and their antigenic components, induce pro-atherosclerotic endothelial activity. Monolayer cultures of endothelial vascular or arterial cells have been used to assess periodontal pathogenic bacteria and their antigenic compounds and endothelial activation. However, these models are not capable of reflecting the physiological characteristics of the endothelium inside vascularized tissue. Therefore, the shift from two-dimensional (2D) cellular models toward 3D models of endothelial cells resembling an environment close to the physiological environment of the endothelial cell within the endothelium is useful for evaluating the physiological relevance of results, currently obtained from 2D models, regarding the endothelial dysfunction induced by periodontopathogens. The use of in vitro 3D cellular models can also be relevant to the search for therapeutic agents for chronic inflammatory diseases such as atherosclerosis. Here, we present some strategies for the assembly of 3D cultures with endothelial cells, which is useful for the study of periodontopathogen-mediated disease.

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Metabolic nuclear receptors in periodontal host–microbe interactions and inflammation

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Primary Cutaneous CD8+ T-cell Lymphoma, an Indolent and Locally Aggressive Form Mimicking Paronychia.

CD8+ T-cell lymphomas comprise a wide spectrum of lymphomas, many which have yet to be formally classified. We present a case of a 43-year-old woman with an enlarging tumor distal to the distal interphalangeal joint of the fourth finger, compressing the underlying nail matrix. Magnetic resonance imaging showed bony involvement of the underlying distal phalanx. Histology showed a dense epidermotropic and pandermal infiltrate composed of medium-sized, uniformly pleomorphic lymphocytes with cleaved nuclei, which raised the possibility of primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma. However, the patient's clinical photograph was inconsistent with this diagnosis. Other diagnoses, such as primary cutaneous acral CD8+ T-cell lymphoma-a provisional entity, were also considered but did not capture all the features of this patient's lymphoma. We propose to classify this case as a primary cutaneous CD8+ T-cell lymphoma, an indolent and locally aggressive form. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Heterotopic Cutaneous Meningioma: An Unusual Presentation Occurring in a Patient With a Remote History of Intracranial Meningioma.

Meningioma is a neoplasm of the meninges, which usually occurs in intracranial sites. Extracranial meningioma has been frequently reported in the sinonasal tract and skull bone, often as extension of intracranial meningiomas. Isolated heterotopic meningioma without contiguous intracranial lesion is extremely rare. A 56-year-old woman presented in December 2015 with 2 firm subcutaneous scalp masses; one in the left lateral (temporal) and the other in the left superior (parietal) region. The clinical impression was that of lipoma. Pathologic examination revealed an ill-defined proliferation of uniform meningothelial cells in a fibroblastic stroma interspersed within adipose tissue. The excised lesions had similar histologic features. Immunohistochemical stains were performed and the tumor cells were positive for epithelial membrane antigen and negative for S-100. A diagnosis of extracranial meningioma, WHO grade I was made. The patient's medical history was significant for intracranial meningioma of the frontal lobe in October 2007, which was diagnosed as atypical meningioma, WHO grade II. Comparison of the scalp masses to her previous meningioma revealed a distinctly different morphologic pattern. In light of the 8-year interval between the scalp and intracranial meningioma and the difference in histologic grades, it is unlikely that her most recent tumors represent a recurrence or metastasis of the intracranial tumor. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Mixed Lichenoid and Follicular T- and B-Cell Lymphoid Reaction to Red Tattoos With Monoclonal T Cells.

Pseudolymphomatous reactions have been described to occur in tattoos. Most cases have exhibited T-cell predominance and polyclonal T-cell receptor gene rearrangements. One case with monoclonal IgH gene rearrangements progressed into B-cell lymphoma. Lichenoid infiltrates are commonly described but lymphoid follicles much less frequently. We report a case with mixed lichenoid and follicular T- and B-cell reaction to red tattoos. The histopathology and the immunohistochemical studies were constant with a mixed T- and B-cell pseudolymphoma, the IgH gene rearrangement study was polyclonal, but the T-cell receptor gene rearrangement study was monoclonal. The patient who responded to intralesional corticosteroid injections remains under close scrutiny. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Annular Scaly Plaque on the Left Foot.

No abstract available

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Effect of breviscapine on CYP3A metabolic activity in healthy volunteers

Abstract

Objective

The purpose of this study was to investigate the influence of breviscapine on the pharmacokinetics of concomitantly administered midazolam (MID) and its associations with and effects on genetic polymorphism of the gene encoding cytochrome P450 3A5 (CYP3A5) in healthy volunteers.

Methods

The study group comprised 17 healthy volunteers who had been genotyped for CYP3A5*3 prior to start of the study. These volunteers were given daily doses of 120 mg (40 mg, three times a day) of breviscapine or a placebo for 14 days, followed by 7.5 mg midazolam (MID) on day 15. The plasma concentrations of MID and the metabolite 1-hydroxy-midazolam (1-OH-MID) were determined by ultra-performance liquid chromatography-mass spectrometry for up to 12 h after drug administration.

Results

The pharmacokinetics of MID and 1-OH-MID were significantly different between the breviscapine and placebo groups, with a point estimate for MID AUC_(0–12) of 1.56 (90% confidence interval 1.26, 1.87). The pharmacokinetics of MID and 1-OH-MID were not different among the CYP3A5 genotype groups, regardless of whether MID was coadministered with breviscapine or with placebo.

Conclusions

These findings suggest that breviscapine inhibited the metabolism of CYP3A in the volunteers, with no interaction difference among the different CYP3A5 genotypes.

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Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15–55 years of age

Abstract

Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15–25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26–45-year olds and 45–55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15–25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15–55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV.

The HPV-16/18 AS04-adjuvanted vaccine produced a sustained immune response in women aged 15–55 years at vaccination for up to 10 years, with an acceptable safety profile. Study results suggest that women in age groups not targeted by adolescent immunization and catch-up programs may still individually benefit from HPV vaccination.

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Inhibition of telomerase activity and induction of apoptosis by Rhodospirillum rubrum L-asparaginase in cancer Jurkat cell line and normal human CD4+ T lymphocytes

Abstract

Rhodospirillum rubrum L-asparaginase mutant _{E149R, V150P, F151T} (RrA) down-regulates telomerase activity due to its ability to inhibit the expression of telomerase catalytic subunit hTERT. The aim of this study was to define the effect of short-term and long-term RrA exposure on proliferation of cancer Jurkat cell line and normal human CD4⁺ T lymphocytes. RrA could inhibit telomerase activity in dose- and time-dependent manner in both Jurkat and normal CD4⁺ T cells. Continuous RrA exposure of these cells resulted in shortening of telomeres followed by cell cycle inhibition, replicative senescence, and development of apoptosis. Complete death of Jurkat cells was observed at the day 25 of RrA exposure while normal CD4⁺ T cells died at the day 50 due to the initial longer length of telomeres. Removal of RrA from senescent cells led to a reactivation of hTERT expression, restoration telomerase activity, re-elongation of telomeres after 48 h of cultivation, and survival of cells. These findings demonstrate that proliferation of cancer and normal telomerase-positive cells can be limited by continuous telomerase inhibition with RrA. Longer telomeres of normal CD4⁺ T lymphocytes make such cells more sustainable to RrA exposure that could give them an advantage during anti-telomerase therapy. These results should facilitate further investigations of RrA as a potent anti-telomerase therapeutic protein.

Long-term exposure to Rhodospirillum rubrum L-asparaginase (RrA) induced telomere shortening and eventual growth arrest and apoptosis in vitro. Telomerase inhibition using RrA may be considered as a promising approach for cancer treatment.

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Restless leg syndrome

Restless leg syndrome: An uncomfortable (creeping, crawling, tingling, pulling, twitching, tearing, aching, throbbing, prickling, or grabbing) sensation in the calves that occurs while sitting or while lying down. The result is an uncontrollable urge to relieve the uncomfortable sensation by
moving the legs. Restless leg syndrome is a common cause of painful legs. The leg pain typically eases with motion of the legs and becomes more noticeable at rest, worsens during the early evening or later at night, and may cause insomnia.

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Shocking the system: AEDs in military resuscitation

Automated external defibrillator (AED) devices have been in routine clinical use since the early 1990s to deliver life-saving shocks to appropriate patients in non-clinical environments. As expectations of survival from out-of-hospital cardiac arrest increase, and evidence incontrovertibly points to reduced timelines as the most crucial factor in achieving return of spontaneous circulation, questions regarding the availability and location of AEDs in the UK military need to be readdressed. This article explores the background of AEDs and reviews their history, life-saving potential and defines current and best practice. It goes on to review the evidence surrounding training and looks to identify knowledge gaps that might be addressed effectively by future research. Finally, it makes recommendations regarding training, availability of AEDs on military bases and locations most likely to deliver good outcomes for military personnel in the future.

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Relationship between 1.5-mile run time, injury risk and training outcome in British Army recruits

Background

1.5-mile run time, as a surrogate measure of aerobic fitness, is associated with musculoskeletal injury (MSI) risk in military recruits. This study aimed to determine if 1.5-mile run times can predict injury risk and attrition rates from phase 1 (initial) training and determine if a link exists between phase 1 and 2 discharge outcomes in British Army recruits.

Method

1.5-mile times from week 1 of initial training and MSI reported during training were retrieved for 3446 male recruits. Run times were examined against injury occurrence and training outcomes for 3050 recruits, using a Binary Logistic Regression and ² analysis.

Results

The 1.5-mile run can predict injury risk and phase 1 attrition rates (²(1)=59.3 p<0.001, ² (1)=66.873 p<0.001). Slower 1.5-mile run times were associated with higher injury occurrence (² (1)=59.3 p<0.001) and reduced phase 1 (² 104.609^ap<0.001) and 2 (² 84.978^ap<0.001) success.

Conclusion

The 1.5-mile run can be used to guide a future standard that will in turn help reduce injury occurrence and improve training success.

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‘Your lack of planning does not constitute my emergency’ – caring for obstetric patients with mental illness

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Pre-operative variables including fitness associated with complications after oesophagectomy

Summary

Oesophagectomy is a technically-demanding operation associated with a high level of morbidity. We analysed the association of pre-operative variables, including those from cardiopulmonary exercise testing, with complications (logistic regression) and survival and length of stay (Cox regression) after scheduled transthoracic oesophagectomy in 273 adults, in isolation and on multivariate testing (maximum Akaike information criterion). On multivariate analysis, any postoperative complication was associated with ventilatory equivalents for carbon dioxide, odds ratio (95%CI) 1.088 (1.02–1.17), p = 0.018. Cardiorespiratory complications were associated with FEV₁ and pre-operative background survival (in an analogous group without cancer), odds ratios (95%CI) 0.55 (0.37–0.80), p = 0.002 and 0.89 (0.82–0.96), p = 0.004, respectively. Survival was associated with the ratio of expected-to-observed ventilatory equivalents for carbon dioxide and predicted postoperative survival, hazard ratios (95%CI) 0.17 (0.03–0.91), p = 0.039 and 0.96 (0.90–1.01), p = 0.076. Length of hospital stay was associated with FVC, hazard ratio (95%CI) 1.38 (1.17–1.63), p < 0.0001.

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Gustavo Olague: Evolutionary computer vision, the first footprints

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Validation of 3D documentation of palatal soft tissue shape, color, and irregularity with intraoral scanning

Abstract

Objectives

The purpose of this study was to assess the feasibility of 3D intraoral scanning for documentation of palatal soft tissue by evaluating the accuracy of shape, color, and curvature.

Materials and methods

Intraoral scans of ten participants' upper dentition and palate were acquired with the TRIOS® 3D intraoral scanner by two observers. Conventional impressions were taken and digitized as a gold standard. The resulting surface models were aligned using an Iterative Closest Point approach. The absolute distance measurements between the intraoral models and the digitized impression were used to quantify the trueness and precision of intraoral scanning. The mean color of the palatal soft tissue was extracted in HSV (hue, saturation, value) format to establish the color precision. Finally, the mean curvature of the surface models was calculated and used for surface irregularity.

Results

Mean average distance error between the conventional impression models and the intraoral models was 0.02 ± 0.07 mm (p = 0.30). Mean interobserver color difference was − 0.08 ± 1.49° (p = 0.864), 0.28 ± 0.78% (p = 0.286), and 0.30 ± 1.14% (p = 0.426) for respectively hue, saturation, and value. The interobserver differences for overall and maximum surface irregularity were 0.01 ± 0.03 and 0.00 ± 0.05 mm.

Conclusions

This study supports the hypothesis that the intraoral scan can perform a 3D documentation of palatal soft tissue in terms of shape, color, and curvature.

Clinical relevance

An intraoral scanner can be an objective tool, adjunctive to the clinical examination of the palatal tissue.

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Sleep problems in prison employees

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Characterizing spatiotemporal variations of chromophoric dissolved organic matter in headwater catchment of a key drinking water source in China

Abstract

Natural surface drinking water sources with the increasing chromophoric dissolved organic matter (CDOM) have profound influences on the aquatic environment and drinking water safety. Here, this study investigated the spatiotemporal variations of CDOM in Fengshuba Reservoir and its catchments in China. Twenty-four surface water samples, 45 water samples (including surface water, middle water, and bottom water), and 15 pore water samples were collected from rivers, reservoir, and sediment of the reservoir, respectively. Then, three fluorescent components, namely two humic-like components (C1 and C2) and a tryptophan-like component (C3), were identified from the excitation-emission matrix coupled with parallel factor analysis (EEM-PARAFAC) for all samples. For spatial distributions, the levels of CDOM and two humic-like components in the reservoir were significantly lower than those in the upstream rivers (p < 0.01), indicating that the reservoir may act as a reactor to partly reduce the levels of exogenous input including CDOM and humic-like matters from the surrounding catchment. For temporal variations, the mean levels of CDOM and three fluorescent components did not significantly change in rivers, suggesting that perennial anthropic activity maybe an important factor impacting the concentration and composition of river CDOM but not the precipitation and runoff. However, these mean values of CDOM for the bulk waters of the reservoir changed markedly along with seasonal variations, indicating that the hydrological processes in the reservoir could control the quality and quantity of CDOM. The different correlations between the fluorescent components and primary water parameters in the river, reservoir, and pore water samples further suggest that the reservoir is an important factor regulating the migration and transformation of FDOM along with the variations of different environmental gradients.

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Seasonal Rhythms: The Role of Thyrotropin and Thyroid Hormones

Thyroid , Vol. 0, No. 0.

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Thyroid Storm: A Japanese Perspective

Thyroid , Vol. 0, No. 0.

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Projecting Survival in Papillary Thyroid Cancer: A Comparison of the Seventh and Eighth Editions of the American Joint Commission on Cancer/Union for International Cancer Control Staging Systems in Two Contemporary National Patient Cohorts

Thyroid , Vol. 0, No. 0.

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Capturing the Asc1p/RACK1 microenvironment at the head region of the 40S ribosome with quantitative BioID in yeast [Research]

The Asc1 protein of Saccharomyces cerevisiae is a scaffold protein at the head region of ribosomal 40S that links mRNA translation to cellular signaling. In this study, proteins that co-localize with Asc1p were identified with proximity-dependent Biotin IDentification (BioID), an in vivo labeling technique described here for the first time for yeast. Biotinylated Asc1p-birA*-proximal proteins were identified and quantitatively verified against controls applying SILAC and mass spectrometry. The mRNA-binding proteins Sro9p and Gis2p appeared together with Scp160p, each providing ribosomes with nuclear transcripts. The cap-binding protein eIF4E (Cdc33p) and the eIF3/a-subunit (Rpg1p) were identified reflecting the encounter of proteins involved in the initiation of mRNA translation at the head region of ribosomal 40S. Unexpectedly, a protein involved in ribosome preservation (the clamping factor Stm1p), the deubiquitylation complex Ubp3p-Bre5p, the RNA polymerase II degradation factor 1 (Def1p), and transcription factors (Spt5p, Mbf1p) co-localize with Asc1p in exponentially growing cells. For Asc1R38D, K40Ep, a variant considered to be deficient in binding to ribosomes, BioID revealed its predominant ribosome localization. Glucose depletion replaced most of the Asc1p co-localizing proteins for additional ribosomal proteins, suggesting a ribosome aggregation process during early nutrient limitation, possibly concomitant with ribosomal subunit clamping. Overall, the characterization of the Asc1p microenvironment with BioID confirmed and substantiated our recent findings that the β-propeller broadly contributes to signal transduction influencing phosphorylation of co-localizing proteins (e.g. of Bre5p), and by that might affect nuclear gene transcription and the fate of ribosomes.

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Arrhythmogenic Cardiomyopathy: the Guilty Party in Adipogenesis

Abstract

Arrhythmogenic cardiomyopathy (ACM) is a genetic cardiac condition characterized by the replacement of the ventricular myocardium with fibro-fatty tissue, by arrhythmias and sudden death. Adipogenesis in ACM is considered an aberrant remodeling following myocardial loss. Which cell type(s) is (are) responsible for the adipose replacement is still matter of debate. A systematic overview of the different cells that have been, over time, considered as main players in adipose replacement is provided. The comprehension of the cellular component giving rise to arrhythmogenic cardiomyopathy substrate defects may represent both an essential tool for mechanistic studies of disease pathogenesis and a novel possible therapeutic target.

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Adenosine receptors differentially regulate type 2 cytokine production by IL-33-activated bone marrow cells, ILC2s, and macrophages [Research]

Group 2 innate lymphoid cells (ILC2s) represent a rapid source of type 2 cytokines, such as IL-5 and IL-13, and play an important role in orchestrating type 2 immune response. Adenosine is an endogenous purine nucleoside, a catabolite of ATP that binds and activates ≥1 of 4 transmembrane G protein–coupled cell-surface adenosine receptors (ARs)—A₁, A_2A, A_2B, and A₃. Here, we studied the role of ARs in the regulation of cytokine production by ILC2s. We found that A_2BARs suppress the production of both IL-5 and IL-13 by ILC2s, whereas A_2AARs augment IL-5 production and fail to affect IL-13 release. Combined stimulation of all ARs led to the suppression of both IL-5 and IL-13 production, which indicated that A_2BARs dominate A_2AARs. Both pre- and post-transcriptional processes may be involved in the AR modulation of ILC2 IL-5 and IL-13 production. Thus, we identify adenosine as a novel negative regulator of ILC2 activation.—Csóka, B., Németh, Z. H., Duerr, C. U., Fritz, J. H., Pacher, P., Haskó, G. Adenosine receptors differentially regulate type 2 cytokine production by IL-33–activated bone marrow cells, ILC2s, and macrophages.

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Studies in genetically modified mice implicate maternal HDL as a mediator of fetal growth [Research]

Studies in humans have shown a direct association between maternal plasma cholesterol concentrations and infant birthweight. Similarly, previous studies in our laboratory have shown that chow-fed mice lacking apolipoprotein (apo) A-I, the major protein in HDL, have low HDL-cholesterol (HDL-C) concentrations and smaller fetuses in midgestation. In the current study, we measured fetal weights in mice with varying levels of apoA-I gene dose (knockout, wild-type, and transgenic) and examined metabolic pathways known to affect fetal growth. As expected, we found the differences in apoA-I expression led to changes in HDL particle size and protein cargo as well as plasma cholesterol concentrations. Fetal masses correlated directly with maternal plasma cholesterol and apoA-I concentrations, but placental masses and histology did not differ between groups of mice. There was no significant difference in glucose or amino acid transport to the fetus or in expression levels of the glucose (glucose transporter 1 and 2) or amino acid (sodium-coupled neutral amino acid transporter 1 and 2) transporters in whole placentas, although there was a trend for greater uptake of both nutrients in the whole fetal unit (fetus + placenta) of mice with greater apoA-I levels; significant differences in transport rates occurred when mice without apoA-I (knockout) vs. mice with apoA-I (wild-type and transgenic) were compared. Glucose tolerance tests were improved in the mice with the highest level of apoA-I, suggesting increased insulin-induced uptake of glucose by tissues of apoA-I transgenic mice. Thus, maternal HDL is associated with fetal growth, an effect that is likely mediated by plasma cholesterol or other HDL-cargo, including apolipoproteins or complement system proteins. A direct role of enhanced glucose and/or amino acid transport cannot be excluded.—Rebholz, S. L., Melchior, J. T., Davidson, W. S., Jones, H. N., Welge, J. A., Prentice, A. M., Moore, S. E., Woollett, L. A. Studies in genetically modified mice implicate maternal HDL as a mediator of fetal growth.

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Hersintuzumab: A novel humanized anti-HER2 monoclonal antibody induces potent tumor growth inhibition

Summary

Humanized monoclonal antibodies (mAbs) against HER2 including trastuzumab and pertuzumab are widely used to treat HER2 overexpressing metastatic breast cancers. These two mAbs recognize distinct epitopes on HER2 and their combination induces a more potent blockade of HER2 signaling than trastuzumab alone. Recently, we have reported characterization of a new chimeric mAb (c-1T0) which binds to an epitope different from that recognized by trastuzumab and significantly inhibits proliferation of HER2 overexpressing tumor cells. Here, we describe humanization of this mAb by grafting all six complementarity determining regions (CDRs) onto human variable germline genes. Humanized VH and VL sequences were synthesized and ligated to human γ1 and κ constant region genes using splice overlap extension (SOE) PCR. Subsequently, the humanized antibody designated hersintuzumab was expressed and characterized by ELISA, Western blot and flow cytometry. The purified humanized mAb binds to recombinant HER2 and HER2-overexpressing tumor cells with an affinity comparable with the chimeric and parental mouse mAbs. It recognizes an epitope distinct from those recognized by trastuzumab and pertuzumab. Binding of hersintuzumab to HER2 overexpressing tumor cells induces G1 cell cycle arrest, inhibition of ERK and AKT signaling pathways and growth inhibition. Moreover, hersintuzumab could induce antibody-dependent cell cytotoxicity (ADCC) on BT-474 cells. This new humanized mAb is a potentially valuable tool for single or combination breast cancer therapy.

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Characterization of Chinese white-flesh peach cultivars based on principle component and cluster analysis

Abstract

The purpose of this study was to gain insights into the variations in quality characteristics of white-flesh peach fruits. Eighteen cultivars of north of China were investigated. The quality evaluation indicators, including color, physico-chemical and nutritional attributes were measured. Analysis of variance revealed that all the indicators showed significant differences among the cultivars, except edible rate. Principal Component Analysis (PCA) conducted to distinguish the indicators among cultivars, suggested that the most important factors affecting the peach quality could be reduced into nine principal components. Crude fiber content, glucose content, peel-b*, TA, moisture content, pulp-firmness, quinic content, shikimic content and edible rate could be regarded as the characteristic indicators for PC1, PC2, PC3,PC4, PC5, PC6, PC7, PC8 and PC9, respectively. Cluster analysis classified the different cultivars into five main groups on the basis of the measured quality evaluation indicators, and the results were in good accordance with PCA results.

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Thermodynamic and kinetics study of phenolics degradation and color of yacon ( Smallanthus sonchifolius ) microparticles under accelerated storage conditions

Abstract

This study aimed to investigate the kinetics and thermodynamic of the phenolics degradation and the kinetics of degradation of the total color difference of yacon juice microcapsules produced by spray drying using Gum Arabic and polydextrose as wall materials. The degradation of the microcapsule was evaluated by accelerated tests under controlled conditions at 35 and 45 °C, and relative humidity of 75 and 90%, for 35 days. Degradation of phenolics followed the first order model and the degradation constant was in the range of 0.0124–0.0209 days⁻¹. The microparticles with gum Arabic were more stable than those with polydextrose for all conditions studied, with longer half-lives. Both wall materials showed similar thermodynamic characteristics, indicating similar mechanism of degradation of phenolics. With respect to the color parameters, the first order model adjusted to data of the total color difference, and no significant differences were observed for the conditions studied.

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Effect of soaking and germination on physicochemical and functional attributes of horsegram flour

Abstract

Horsegram is an underutilized pulse, traditionally used for treating various disorders like kidney stones, diabetes and joint pain. The present study was undertaken to optimize the soaking and germination conditions, to decrease the anti-nutritional factors and at the same time maintaining the nutritional properties of horsegram. Horsegram seeds were soaked for 6, 12 and 18 h followed by germination for 0, 24 and 48 h under different illumination conditions i.e., light and dark respectively. The soaked and germinated samples were dried in laboratory drier at 55 °C until constant moisture was achieved and was further analyzed for various quality attributes. Almost all the physicochemical and functional characteristics were significantly affected by both soaking and germination, whereas, germination done in light and dark conditions, exerted significant effect on the ascorbic acid content, total protein, total phenols, antioxidant activity and tannin content only. Based on the quality attributes, it was found that treatment having 18 h soaking and 48 h germination in the presence of light was the best where maximum decrease in the anti-nutritional factors was observed. Moreover, there was an increase in ascorbic acid, total protein content and a decrease in the anti-nutritional factors such as oxalate and tannin content. Thus, it is concluded that 18 h soaking and 48 h germination in the presence of light can be considered as the optimum conditions to increase the nutritional content of horsegram flour, which can further be utilized for the preparation of different value-added food products.

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Effect of different ripening stages on walnut kernel quality: antioxidant activities, lipid characterization and antibacterial properties

Abstract

Packing tissue between and around the kernel halves just turning brown (PTB) is a phenological indicator of kernel ripening at harvest in walnuts. The effect of three ripening stages (Pre-PTB, PTB and Post-PTB) on kernel quality characteristics, mineral composition, lipid characterization, sensory analysis, antioxidant and antibacterial activity were investigated in fresh kernels of indigenous numbered walnut selection of Kashmir valley "SKAU-02". Proximate composition, physical properties and sensory analysis of walnut kernels showed better results for Pre-PTB and PTB while higher mineral content was seen for kernels at Post-PTB stage in comparison to other stages of ripening. Kernels showed significantly higher levels of Omega-3 PUFA (C18:3ⁿ³) and low n6/n3 ratio when harvested at Pre-PTB and PTB stages. The highest phenolic content and antioxidant activity was observed at the first stage of ripening and a steady decrease was observed at later stages. TBARS values increased as ripening advanced but did not show any significant difference in malonaldehyde formation during early ripening stages whereas it showed marked increase in walnut kernels at post-PTB stage. Walnut extracts inhibited growth of Gram-positive bacteria (B. cereus, B. subtilis, and S. aureus) with respective MICs of 1, 1 and 5 mg/mL and gram negative bacteria (E. coli, P. and K. pneumonia) with MIC of 100 mg/mL. Zone of inhibition obtained against all the bacterial strains from walnut kernel extracts increased with increase in the stage of ripening. It is concluded that Pre-PTB harvest stage with higher antioxidant activities, better fatty acid profile and consumer acceptability could be preferred harvesting stage for obtaining functionally superior walnut kernels.

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Effects of dough mixing time before adding konjac glucomannan on the quality of noodles

Abstract

In this study, effects of 5% konjac glucomannan (KGM) blended with low-protein flour at different dough mixing duration on the properties of dough and noodles were investigated. To prepare the KGM noodle samples, 5% KGM was added after low-protein flour mixed with water for 0, 2 and 4 min, respectively. The three samples above were defined as T₀ KGM, T₂ KGM and T₄ KGM noodle samples, respectively. The results revealed that the elastic modulus (G′) and viscous modulus (G″) of dough both increased with extending dough mixing time before adding KGM. T₄ KGM samples showed the least cooking loss. Textural properties including hardness, cohesiveness and tensile strength of KGM noodles had a tendency to increase with a longer dough mixing time before adding KGM. Microstructure of dough and noodles confirmed that a longer dough mixing time before adding KGM made microstructure more compact with a thickened gluten matrix. The sensory quality of the T₂ KGM and T₄ KGM samples was better than that of the T₀ KGM samples.

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An epoxide hydrolase secreted by Pseudomonas aeruginosa decreases mucociliary transport and hinders bacterial clearance from the lung

The opportunistic pathogen Pseudomonas aeruginosa colonizes the lungs of susceptible individuals by deploying virulence factors targeting host defenses. The secreted CFTR inhibitory factor (Cif) dysregulates the endocytic recycling of CFTR and thus reduces CFTR abundance in host epithelial membranes. We have postulated that the decrease in ion secretion mediated by Cif would slow mucociliary transport and decrease bacterial clearance from the lungs. To test this hypothesis, we explored the effects of Cif in cultured epithelia and in the lungs of mice. We developed a strategy to interpret the "hurricane-like" motions observed in reconstituted cultures and identified a Cif-mediated decrease in the velocity of mucus transport in vitro. Presence of Cif also increased the number of bacteria recovered at two time points in an acute mouse model of pneumonia generated by P. aeruginosa. Furthermore, recent work has demonstrated an inverse correlation between the airway concentrations of Cif and 15-epi lipoxin A₄, a pro-resolving lipid mediator important in host defense and the resolution of pathogen-initiated inflammation. Here, we observe elevated levels of 15-epi lipoxin A₄ in the lungs of mice infected with a strain of P. aeruginosa that expresses only an inactive form of cif, as compared to those mice infected with wild type P. aeruginosa. Together these data support Cif's inclusion on the list of virulence factors that assist P. aeruginosa in colonizing and damaging the airways of compromised patients. Further, this study establishes techniques that enable our groups to explore the underlying mechanisms of Cif's effects during respiratory infection.

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The use of proper statistical techniques for research studies with small samples.

In this editorial we discuss the appropriateness of various statistical methods for use with small sample sizes. We review the assumptions and limitations of these methods and provide our recommendations for figures and statistical tests.

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Evaluation of a SPLUNC1-Derived Peptide for the Treatment of Cystic Fibrosis Lung Disease

In cystic fibrosis (CF) lungs, epithelial Na+ channel (ENaC) hyperactivity causes a reduction in airway surface liquid (ASL) volume, leading to decreased mucocilliary clearance and lung damage. Inhibition of ENaC is an attractive therapeutic option. However, ENaC antagonists have failed clinically due to off-target renal effects. The S18 peptide is a naturally occurring short palate lung and nasal epithelial clone 1 (SPLUNC1)-derived ENaC antagonist that restores ASL height for up to 24 h in CF human bronchial epithelial cultures. However, its efficacy and safety in vivo are unknown. To interrogate the potential clinical efficacy of S18, we assessed its safety and efficacy using airway cultures and animal models. S18-mucus interactions were tested using super resolution microscopy, quartz crystal microbalance with dissipation and confocal microscopy. Human and murine airway cultures were used to measure ASL height. Off-target effects were assessed in conscious mice and anesthetized rats. Morbidity and mortality were assessed in the βENaC-Tg mouse model. Restoration of normal mucus clearance was measured in CFTR(inh)-172 challenged sheep. We found that S18 does not interact with mucus and rapidly penetrated dehydrated CF mucus. Compared to amiloride, an early generation ENaC antagonist, S18 displayed a superior ability to slow ASL absorption, reverse CFTR(inh)-172-induced reduction of mucus transport and reduce morbidity and mortality in the βENaC-Tg mouse, all without inducing any detectable signs of renal toxicity. These data suggest that S18 is the first naturally occurring ENaC antagonist to show improved preclinical efficacy in animal models of CF with no signs of renal toxicity.

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Acidosis Exacerbates in vivo IL-1-Dependent Inflammatory Responses and Neutrophil Recruitment During Pulmonary Pseudomonas aeruginosa Infection

Acidic microenvironments commonly occur at sites of inflammation and bacterial infections. In the context of a Pseudomonas aeruginosa infection, we previously demonstrated that acidosis enhances the cellular proinflammatory IL-1β response in vitro. However, how pH alterations affect in vivo IL-1β responses and subsequent IL-1 driven inflammation during infection with P. aeruginosa is unclear. We report herein that acidosis enhances in vivo IL-1β production and downstream IL-1R-dependent responses during infection with P. aeruginosa in models of acute pneumonia and peritonitis. Importantly, we demonstrate that infection with P. aeruginosa within an acidic environment leads to an enhanced production of a subset of proinflammatory cytokines, including CXCL1, IL-6 and CCL2, and increased neutrophil recruitment. Furthermore, with the use of IL-1R1-deficient mice, we identify the contribution of the IL-1 signaling pathway to the acidosis-enhanced inflammatory response and pathology. These data provide insights into the potential benefit of pH regulation during bacterial infections to control disease progression and immunopathology.

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ATP catabolism by tissue non-specific alkaline phosphatase contributes to development of ARDS in influenza-infected mice.

Influenza A viruses are highly contagious respiratory pathogens that are responsible for significant morbidity and mortality worldwide on an annual basis. We have shown previously that influenza infection of mice leads to increased ATP and adenosine accumulation in the airway lumen. Moreover, we demonstrated that A1-adenosine receptor activation contributes significantly to influenza-induced acute respiratory distress syndrome (ARDS). However, we found that development of ARDS in influenza-infected mice does not require catabolism of ATP to adenosine by ecto-5'-nucleotidase (CD73). Hence, we hypothesized that increased adenosine generation in response to infection is mediated by tissue non-specific alkaline phosphatase (TNAP), which is a low-affinity, high-capacity enzyme that catabolizes nucleotides in a non-specific manner. In the current study, we found that whole lung and BALF TNAP expression and alkaline phosphatase enzymatic activity increased as early as 2 days post infection (d.p.i.) of C57BL/6 mice with 10,000 pfu/mouse of influenza A/WSN/33 (H1N1). Treatment at 2 and 4 d.p.i. with a highly-specific quinolinyl-benzenesulfonamide TNAP inhibitor (TNAPi) significantly reduced whole lung alkaline phosphatase activity at 6 d.p.i. but did not alter TNAP gene or protein expression. TNAPi treatment attenuated hypoxemia, lung dysfunction, histopathology, and pulmonary edema at 6 d.p.i. without impacting viral replication. Treatment also improved epithelial barrier function and attenuated cellular and humoral innate immune responses to influenza infection. These data indicate that TNAP inhibition can attenuate influenza-induced ARDS by reducing inflammation and fluid accumulation within the lung. They also further emphasize the importance of adenosine generation for development of ARDS in influenza-infected mice.

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Intranasal administration of recombinant progranulin inhibits bronchial smooth muscle hyperresponsiveness in mouse allergic asthma

Progranulin (PGRN) is a growth factor with multiple biological functions, and has been suggested as an endogenous inhibitor of TNFα-mediated signaling. TNFα is believed as one of the important mediators of the pathogenesis of asthma, including airway hyperresponsiveness (AHR). In the present study, effects of recombinant PGRN on the TNFα-mediated signaling and the antigen-induced hyper-contractility were examined in bronchial smooth muscles (BSMs) both in vitro and in vivo. Cultured human BSM cells (hBSMCs) and male BALB/c mice were used. The mice were sensitized and repeatedly challenged with ovalbumin antigen. Animals also received intranasal administrations of recombinant PGRN into the airways 1 hour before each antigen inhalation. In hBSMCs, PGRN inhibited both the degradation of IB-α (an index of NF-B activation) and the up-regulation of RhoA (a contractile machinery-associated protein that contributes to the BSM hyperresponsiveness) induced by TNFα, indicating that PGRN has an ability to inhibit TNFα-mediated signaling also in the BSM cells. In BSMs of the repeatedly antigen-challenged mice, an augmented contractile responsiveness to acetylcholine with an up-regulation of RhoA was observed: both the events were ameliorated by the pretreatments with PGRN intranasally. Interestingly, a significant decrease in the PGRN expression was found in the airways of the repeatedly antigen-challenged mice than those of control animals. In conclusion, exogenously applied PGRN into the airways ameliorated the antigen-induced BSM hyperresponsiveness, probably by blocking TNFα-mediated response. Increasing PGRN levels might be a promising therapeutic for the AHR in allergic asthma.

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Pyruvate dehydrogenase complex (PDC) subunits moonlight as interaction partners of phosphorylated STAT5 in adipocytes and adipose tissue [Gene Regulation]

STAT5 proteins play a role in adipocyte development and function, but their specific functions are largely unknown. To this end, we used an unbiased MS-based approach to identify novel STAT5-interacting proteins. We observed that STAT5A bound the E1β and E2 subunits of the pyruvate dehydrogenase complex (PDC). Whereas STAT5A typically localizes to the cytosol or nucleus, PDC normally resides within the mitochondrial matrix where it converts pyruvate to acetyl-CoA. We employed affinity purification and immunoblotting to validate the interaction between STAT5A and PDC subunits in murine and human cultured adipocytes, as well as in adipose tissue. We found that multiple PDC subunits interact with hormone-activated STAT5A in a dose- and time-dependent manner that coincides with tyrosine phosphorylation of STAT5. Using subcellular fractionation and immunofluorescence microscopy, we observed that PDC-E2 is present within the adipocyte nucleus where it associates with STAT5A. Since STAT5A is a transcription factor, we used chromatin immunoprecipitation (ChIP) to assess PDC's ability to interact with STAT5 DNA-binding sites. These analyses revealed that PDC-E2 is bound to a STAT5-binding site in the promoter of the STAT5 target gene cish (cytokine inducible SH2 containing protein). We have demonstrated a compelling interaction between STAT5A and PDC subunits in adipocytes under physiological conditions. There is previous evidence that PDC localizes to cancer cell nuclei where it plays a role in histone acetylation. On the basis of our ChIP data and these previous findings, we hypothesize that PDC may modulate STAT5's ability to regulate gene expression by controlling histone or STAT5 acetylation.

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Permeant-specific gating of connexin 30 hemichannels [Membrane Biology]

Gap junctions confer interconnectivity of the cytoplasm in neighboring cells via docking of two connexons expressed in each of the adjacent membranes. Undocked connexons, referred to as hemichannels, may open and connect the cytoplasm with the extracellular fluid. The hemichannel configuration of connexins (Cxs) displays isoform-specific permeability profiles that are not directly determined by the size and charge of the permeant. To further explore Ca2+-mediated gating and permeability features of connexin hemichannels, we heterologously expressed Cx30 hemichannels in Xenopus laevis oocytes. The sensitivity toward divalent cation-mediated gating differed between small atomic ions (current) and fluorescent dye permeants, indicating that these permeants are distinctly gated. Three aspartate residues in Cx30 (D50, D172 and D179) have previously been implicated in the Ca2+ sensitivity of other hemichannel isoforms. While the aspartate at position D50 was indispensable for divalent cation-dependent gating of Cx30 hemichannels, substitutions of the two other residues had no significant effect on gating, illustrating differences in the gating mechanisms between connexin isoforms. Using the substituted-cysteine accessibility method (SCAM), we evaluated the role of possible pore-lining residues in the permeation of ions and ethidium through Cx30 hemichannels. Of the cysteine-substituted residues, interaction of a proposed pore-lining cysteine at position 37 with the positively charged compound [2-(trimethylammonium)ethyl] methane thiosulfonate bromide (MTS-ET) increased Cx30-mediated currents, with unperturbed ethidium permeability. In summary, our results demonstrate that the permeability of hemichannels is regulated in a permeant-specific manner, and underscores that hemichannels are selective rather than non-discriminating and freely-diffusable pores.

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The Hippo pathway regulator KIBRA promotes podocyte injury by inhibiting YAP signaling and disrupting actin cytoskeletal dynamics [Cell Biology]

Kidney podocytes represent a key constituent of the glomerular filtration barrier. Identifying the molecular mechanisms of podocyte injury and survival is important for better understanding and management of kidney diseases. KIBRA (KIdney BRAin protein), an upstream regulator of the Hippo signaling pathway encoded by the Wwc1 gene, shares the pro-injury properties of its putative binding partner dendrin and antagonizes the pro-survival signaling of the downstream Hippo pathway effector YAP (Yes-associated protein) in Drosophila and MCF10A cells. We recently identified YAP as an essential component of the glomerular filtration barrier that promotes podocyte survival by inhibiting dendrin pro-apoptotic function. Despite these recent advances, the signaling pathways that mediate podocyte injury remain poorly understood. Here we tested the hypothesis that similar to its role in other model systems, KIBRA promotes podocyte injury. We found increased expression of KIBRA and phosphorylated YAP (P-YAP) protein in glomeruli of patients with biopsy-proven focal segmental glomerulosclerosis (FSGS). KIBRA/WWc1 overexpression in murine podocytes promoted LATS kinase phosphorylation, leading to subsequent YAP S127 phosphorylation, YAP cytoplasmic sequestration, and reduction in YAP target gene expression. Functionally, KIBRA overexpression induced significant morphological changes in podocytes including disruption of the actin cytoskeletal architecture and reduction of focal adhesion size and number, all of which were rescued by subsequent YAP overexpression. Conversely, constitutive KIBRA knockout mice displayed reduced P-YAP and increased YAP expression at baseline. These mice were protected from acute podocyte foot process effacement following protamine sulfate perfusion. KIBRA knockdown podocytes were also protected against protamine-induced injury. These findings suggest an important role for KIBRA in the pathogenesis of podocyte injury and the progression of proteinuric kidney disease.

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A simple and versatile system for the ATP-dependent assembly of chromatin [Methods and Resources]

Chromatin is the natural form of DNA in the eukaryotic nucleus, and is the substrate for diverse biological phenomena. The functional analysis of these processes would ideally be carried out with nucleosomal templates that are assembled with customized core histones, DNA sequences, and chromosomal proteins. Here we report a simple, reliable, and versatile method for the ATP-dependent assembly of evenly-spaced nucleosome arrays. This minimal chromatin assembly system comprises the Drosophila nucleoplasmin-like protein (dNLP) histone chaperone, the imitation switch (ISWI) ATP-driven motor protein, core histones, template DNA, and ATP. The dNLP and ISWI components were synthesized in bacteria, and each protein could be purified in a single step by affinity chromatography. We show that the dNLP-ISWI system can be used with different DNA sequences, linear or circular DNA, bulk genomic DNA, recombinant or native Drosophila core histones, native human histones, the linker histone H1, the non-histone chromosomal protein HMGN2, and the core histone variants H3.3 and H2A.V. The dNLP-ISWI system should be accessible to a wide range of researchers and enable the assembly of customized chromatin with specifically desired DNA sequences, core histones, and other chromosomal proteins.

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Inhibition of the transforming growth factor-{beta}/SMAD cascade mitigates the anti-neurogenic effects of the carbamate pesticide carbofuran [Neurobiology]

The widely used carbamate pesticide carbofuran causes neurophysiological and neurobehavioral deficits in rodents and humans and therefore poses serious health hazards around the world. Previously, we reported that gestational carbofuran exposure has detrimental effects on hippocampal neurogenesis, the generation of new neurons from neural stem cells (NSC), in offspring. However, the underlying cellular and molecular mechanisms for carbofuran-impaired neurogenesis remain unknown. Herein, we observed that chronic carbofuran exposure from gestational day 7 to postnatal day 21 altered expression of genes and transcription factors and levels of proteins involved in neurogenesis and the TGF-β pathway (i.e. TGF-β; SMAD-2,3, and 7; and SMURF-2) in the rat hippocampus. We found that carbofuran increases TGF-β signaling (i.e. increased phosphorylated SMAD-2/3 and reduced SMAD-7 expression) in the hippocampus, which reduced NSC proliferation because of increased p21 levels and reduced cyclin-D1 levels. Moreover, the carbofuran-altered TGF-β signaling impaired neuronal differentiation (of BrdU/DCX+ and BrdU/NeuN+ cells), increased apoptosis and neurodegeneration in the hippocampus. Blockade of the TGF-β pathway with the specific inhibitor SB431542 and via SMAD-3 siRNA prevented carbofuran mediated inhibition of neurogenesis both in hippocampal NSC culture and the hippocampus, suggesting the specific involvement of this pathway. Of note, both in vitro and in vivo studies indicated that TGF-β pathway attenuation reverses carbofuran's inhibitory effects on neurogenesis and associated learning and memory deficits. These results suggest that carbofuran inhibits NSC proliferation and neuronal differentiation by altering TGF-β signaling. We conclude that TGF-β may represent a potential therapeutic target against carbofuran-mediated neurotoxicity and neurogenesis disruption.

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3-sulfo-galactosyl dependent adhesion of Escherichia coli HS Multivalent Adhesion Molecule is attenuated by sulfatase activity [Molecular Bases of Disease]

Bacterial adhesion to host receptors is an early and essential step in bacterial colonization, and the nature of adhesin-receptor interactions determines bacterial localization and thus the outcome of these interactions. Here, we determined the host receptors for the Multivalent Adhesion Molecule (MAM) from the gut commensal E. coli HS (MAMHS), which contains an array of seven mammalian cell entry (MCE) domains. The MAMHS adhesin interacted with a range of host receptors, through recognition of a shared 3-O-sulfo-galactosyl moiety. This functional group is also found in mucin, a component of the intestinal mucus layer and thus one of the prime adherence targets for commensal E. coli. Mucin gels impeded the motility of E. coli by acting as a physical barrier, and the barrier effect was enhanced by specific interactions between mucin and MAMHS in a sulfation-dependent manner. Desulfation of mucin by pure sulfatase or the sulfatase-producing commensal Bacteroides thetaiotaomicron decreased binding of E. coli to mucin and increased the attachment of bacteria to the epithelial surface, via interactions with surface-localized sulfated lipid and protein receptors. Together, our results demonstrate that the E. coli adhesin MAMHS facilitates retention of a gut commensal by attachment to mucin. They further suggest that the amount of sulfatase secreted by mucin-foraging bacteria such as B. thetaiotaomicron, inhabiting the same niche, may affect the capacity of the mucus barrier to retain commensal E. coli.

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Defining the interaction of the protease CpaA with its type II secretion-chaperone CpaB and its contribution to virulence in Acinetobacter species [Microbiology]

Acinetobacter baumannii, A. nosocomialis, and A. pittii are a frequent cause of multi-drug resistant, healthcare-associated infections. Our previous work demonstrated that A. nosocomialis M2 possesses a functional Type II secretion system (T2SS) that is required for full virulence. Further, we identified the metallo-endopeptidase CpaA, which had been previously shown to cleave human factor V and deregulate blood coagulation, as the most abundant Type II-secreted effector protein. We also demonstrated that its secretion is dependent on CpaB, a membrane-bound chaperone. In this study, we show that CpaA expression and secretion is conserved across several medically-relevant Acinetobacter species. Additionally, we demonstrate that deletion of cpaA results in attenuation of A. nosocomialis M2 virulence in moth and mouse models. The virulence defects resulting from the deletion of cpaA were comparable to those observed upon abrogation of T2SS activity. The virulence defects resulting from the deletion of cpaA are comparable to those observed upon abrogation of T2SS activity. We also show that CpaA and CpaB strongly interact, forming a complex in a 1 to 1 ratio. Interestingly, deletion of the N-terminal transmembrane domain of CpaB results in robust secretion of CpaA and CpaB, indicating that the transmembrane domain is dispensable for CpaA secretion and likely functions to retain CpaB inside the cell. Limited proteolysis of spheroplasts revealed that the C-terminal domain of CpaB is exposed to the periplasm, suggesting that this is the site where CpaA and CpaB interact in vivo. Lastly, we show that CpaB does not abolish the proteolytic activity of CpaA against human Factor V. We conclude that CpaA is, to the best of our knowledge, the first characterized, bona-fide virulence factor secreted by Acinetobacter species.

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Activation of the phospholipid scramblase TMEM16F by nanosecond pulsed electric field (nsPEF) facilitates its diverse cytophysiological effects [Membrane Biology]

Nanosecond pulsed electric fields (nsPEFs) are emerging as a novel modality for cell stimulation and tissue ablation. However, the downstream protein effectors responsible for nsPEF bioeffects remain to be established. Here we demonstrate that nsPEFs activate TMEM16F, (or anoctamin 6), a protein functioning as a Ca2+-dependent phospholipid scramblase and Ca2+-activated chloride channel. Using confocal microscopy and patch-clamp recording, we investigated the relevance of TMEM16F activation for several bioeffects triggered by nsPEF, including phosphatidylserine (PS) externalization, nanopore-conducted currents, membrane blebbing, and cell death. In HEK 293 cells treated with a single 300-ns pulse of 25.5 kV/cm, Tmem16f expression knockdown and TMEM16F-specific inhibition decreased nsPEF-induced PS exposure by 49% and 42%, respectively. Moreover, the Tmem16f silencing significantly decreased Ca2+-dependent chloride channel currents activated in response to the nanoporation. Tmem16f expression also affected nsPEF-induced cell blebbing, with only 20% of the silenced cells developing blebs compared with 53% of the control cells. This inhibition of cellular blebbing correlated with a 25% decrease in cytosolic free Ca2+ transient at 30 s after nanoporation. Finally, in TMEM16F-overexpressing cells, a train of 120 pulses (300 ns, 20 Hz, 6 kV/cm) decreased cell survival to 34% compared with 51% in control cells (*p < 0.01). Taken together, these results indicate that TMEM16F activation by nanoporation mediates and enhances the diverse cellular effects of nsPEFs.

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Protein Kinase A induced internalization of Slack channels from the neuronal membrane occurs by Adaptor Protein-2/Clathrin mediated endocytosis [Cell Biology]

The sodium-activated potassium (KNa) channel Kcnt1 (Slack) is abundantly expressed in nociceptor (pain sending) neurons of the dorsal root ganglion (DRG), where they transmit the large outward conductance IKNa and arbitrate membrane excitability. Slack channel expression at the DRG membrane is necessary for their characteristic firing accommodation during maintained stimulation, and reduced membrane channel density causes hyperexcitability. We have previously shown that in a pro-inflammatory state, a decrease in membrane channel expression leading to reduced Slack-mediated IKNa expression underlies DRG sensitization. An important component of the inflammatory milieu, Protein Kinase A (PKA) internalizes Slack channels from the DRG membrane, reduces IKNa and produces DRG hyperexcitability when activated in cultured primary DRG neurons. Here, we show that this PKA-induced retrograde trafficking of Slack channels also occurs in intact spinal cord slices and that it is carried out by Adaptor Protein-2 (AP-2) via clathrin mediated endocytosis (CME). We provide mass spectrometric and biochemical evidence of an association of native neuronal AP-2 adaptor proteins with Slack channels, facilitated by a di-leucine motif housed in the cytoplasmic Slack C-terminus that binds AP-2. By creating a competitive peptide blocker of AP-2-Slack binding, we demonstrated that this interaction is essential for clathrin recruitment to the DRG membrane, Slack channel endocytosis and DRG hyperexcitability after PKA activation. Together, these findings uncover AP-2 and clathrin as players in Slack channel regulation. Given Slack's significant role in nociceptive neuronal excitability, the AP-2 CME trafficking mechanism may enable targeting of peripheral and possibly, central neuronal sensitization.

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The Phosphatidic Acid-Binding, Polybasic Domain is Responsible for the Differences in the Phosphoregulation of Lipins 1 and 3 [Lipids]

Lipins 1, 2, and 3 are Mg2+-dependent phosphatidic acid phosphatases (PAP) and catalyze the penultimate step of triacylglycerol synthesis. We have previously investigated the biochemistry of lipins 1 and 2 and shown that di-anionic phosphatidic acid (PA) augments their activity and lipid binding, and that lipin 1 activity is negatively regulated by phosphorylation. In the present study, we show that phosphorylation does not affect the catalytic activity of lipin 3 or its ability to associate with PA in vitro. The lipin proteins each contain a conserved polybasic domain (PBD) composed of nine lysine and arginine residues located between the conserved amino- and carboxy-terminal domains. In lipin 1, the PBD is the site of PA binding and sensing of the PA electrostatic charge. The specific arrangement and number of the lysines and arginines of the PBD varies among the lipins. We show that the different PBDs of lipins 1 and 3 are responsible for the presence of phosphoregulation on the former, but not the latter enzyme. To do so, we generated lipin 1 that contained the PBD of lipin 3 and vice versa. The lipin 1 enzyme with the lipin 3 PBD lost its ability to be regulated by phosphorylation but remained downstream of phosphorylation by mTOR. Conversely, the presence of the lipin 1 PBD in lipin 3, subjected the enzyme to negative intramolecular control by phosphorylation. These results indicate a mechanism for the observed differences in lipin phosphoregulation in vitro.

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Metabolomic analysis of insulin resistance across different mouse strains and diets [Metabolism]

Insulin resistance is a major risk factor for many diseases. However, its underlying mechanism remains unclear in part because it is triggered by a complex relationship between multiple factors including genes and the environment. Here we used metabolomics combined with computational methods to identify factors that classified insulin resistance across individual mice derived from three different mouse strains fed two different diets. Three inbred ILSXISS strains were fed high fat or chow diets and subjected to metabolic phenotyping and metabolomics analysis of skeletal muscle. There was significant metabolic heterogeneity between strains, diet and individual animals. Distinct metabolites were changed with insulin resistance, diet and between strains. Computational analysis revealed 113 metabolites that were correlated with metabolic phenotypes. Using these 113 metabolites, combined with machine learning to segregate mice based on insulin sensitivity we identified C22:1-CoA, C2-carnitine and C16-ceramide as the best classifiers. Strikingly, when these three metabolites were combined into one signature, they classified mice based on insulin sensitivity more accurately than each metabolite on its own or other published metabolic signatures. Furthermore, C22:1-CoA, was 2.3-fold higher in insulin resistant mice and correlated significantly with insulin resistance. We have identified a metabolomic signature comprised of three functionally unrelated metabolites that accurately predicts whole body insulin sensitivity across three mouse strains. These data indicate the power of simultaneous analysis of individual, genetic and environmental variance in mice for identifying novel factors that accurately predict metabolic phenotypes like whole body insulin sensitivity.

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The Need for and the Needs of the Direct Care Workforce

As has been noted in these pages repeatedly, the world of long-term services and supports (LTSS) occupies an especially precarious position in American social policy. Along at least three dimensions, it can be seen as a residual world: LTSS addresses vulnerable and often devalued populations, the nature of complexity of chronic illness renders it less attractive to providers than more acute health care needs, and when LTSS is addressed by public policy it is most often through a means-tested and selective public assistance program, Medicaid. Very much caught up in and harmed by this toxic environment are those who do the most demanding work within it: the LTSS direct care workforce.

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Private Pay Home Care: New Models of Access and Service Delivery

Private pay home careNew models of service provisionInformation technologyOn-line registries

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The American Care Landscape: Challenges and Solutions for the 21st Century

CaregivingUniversal Family careUniversal Long-term careWorking Families

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The Changing Policy Landscape of the Direct Care Workforce

Direct careHome careLong-term careHealth workforce

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The Growing Need for Home Care Workers: Improving a Low-Paid, Female-Dominated Occupation and the Conditions of its Immigrant Workers

Care workElder careLow-wage immigrant womenLow-wage workersImmigrant womenWomen of color

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Developing a Quality Direct Care Workforce: Searching for Solutions

Direct care workersHome care aidesCertified nursing assistants

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The Future is Now? On-Demand Health for Long-Term Services and Supports

On-demand healthcareLong-term services & supportsAlzheimer's diseaseTechnology and agingCaregivers

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The British Services Dhaulagiri Medical Research Expedition 2016: a unique military and civilian research collaboration

Introduction

High-altitude environments lead to a significant physiological challenge and disease processes which can be life threatening; operational effectiveness at high altitude can be severely compromised. The UK military research is investigating ways of mitigating the physiological effects of high altitude.

Methods

The British Service Dhaulagiri Research Expedition took place from March to May 2016, and the military personnel were invited to consent to a variety of study protocols investigating adaptation to high altitudes and diagnosis of high-altitude illness. The studies took place in remote and austere environments at altitudes of up to 7500 m.

Results

This paper gives an overview of the individual research protocols investigated, the execution of the expedition and the challenges involved. 129 servicemen and women were involved at altitudes of up to 7500 m; 8 research protocols were investigated.

Conclusions

The outputs from these studies will help to individualise the acclimatisation process and inform strategies for pre-acclimatisation should troops ever need to deploy at high altitude at short notice.

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The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case–control study

Acetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality due to intracranial hypertension (ICH), a result of cerebral edema (CE) and astrocyte swelling. Brain-type fatty ...

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Removal of NO with the hexamminecobalt solution catalyzed by the carbon treated with oxalic acid

Abstract

NO can be removed at the same time with SO₂ by aqueous Co(NH₃)₆²⁺ solution. The reduction of Co(NH₃)₆³⁺ to Co(NH₃)₆²⁺ is catalyzed by activated carbon to regain the NO absorption ability of the scrubbing solution. Oxalic acid solution is explored to change the carbon surface to ameliorate its catalytic capability. The experimental results suggest that the best catalyst is prepared by impregnating the carbon sample in 0.7 mol l⁻¹ oxalic acid solution for 24 h followed by being activated at 600 °C for 5 h under nitrogen atmosphere. After being treated with oxalic acid solution, the surface area and the acidity on the carbon surface increase. The experiments show that the carbon modified with oxalic acid can get a much higher NO removal efficiency than the original carbon.

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Continuous eruption of maxillary teeth and changes in clinical crown length: A 10-year longitudinal study in adult women

Abstract

Background

Continuous physiologic eruption of teeth may become a main aesthetic issue for implants inserted in the maxillary anterior region.

Purpose

To study maxillary tooth vertical changes during a 10 years period by 3-dimensional superimposition of digital dental casts.

Material and methods

Alginate impressions were taken at both baseline and at the 10-year follow-up in a sample of 24 adult Swedish women (average age of 48 years at T0). The upper arch plaster casts were digitized with a 3-dimensional scanner and then superimposed on the palate and the palatal rugae. Occlusal and gingival anatomic structures were digitized for each upper tooth from first molar to first molar. The vertical changes of these structures gave an indication of tooth extrusion and apical or coronal displacement of the gingival margin.

Results

A trend was found for eruption in the anterior region (+0.3 mm on average) while a slight extrusion if not any was found in the first molars and premolars area. Vertical displacement of the gingival margin showed also a positive trend from first molars to incisors. Negative average values, corresponding clinically to gingival recession, were found on first molars (−0.36 mm) and premolars (−0.15 mm), while no displacement was detected in the anteriors. Clinical crown lengths increased in all teeth and it is mainly due to gingival recession for first molars and premolars, while for the incisors the eruption is coupled to a slight equivalent gingival coronal migration.

Conclusions

During a 10-year period, continuous eruption takes place in female adult subjects, especially in the upper incisors area while gingival recession occurred in first molars and premolars area leading to crown length elongation. Implant placement in the anterior area of the maxilla may have an aesthetic impact even in mature adults due to the continuous eruption of the adjacent teeth.

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Αρχειοθήκη ιστολογίου

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Πέμπτη 5 Οκτωβρίου 2017

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