Upon Accounting for the Impact of Isoenzyme Loss, Gene Deletion Costs Anticorrelate with Their Evolutionary Rates.
System-level metabolic network models enable the computation of growth and metabolic phenotypes from an organism's genome. In particular, flux balance approaches have been used to estimate the contribution of individual metabolic genes to organismal fitness, offering the opportunity to test whether such contributions carry information about the evolutionary pressure on the corresponding genes. Previous failure to identify the expected negative correlation between such computed gene-loss cost and sequence-derived evolutionary rates in Saccharomyces cerevisiae has been ascribed to a real biological gap between a gene's fitness contribution to an organism "here and now" and the same gene's historical importance as evidenced by its accumulated mutations over millions of years of evolution. Here we show that this negative correlation does exist, and can be exposed by revisiting a broadly employed assumption of flux balance models. In particular, we introduce a new metric that we call "function-loss cost", which estimates the cost of a gene loss event as the total potential functional impairment caused by that loss. This new metric displays significant negative correlation with evolutionary rate, across several thousand minimal environments. We demonstrate that the improvement gained using function-loss cost over gene-loss cost is explained by replacing the base assumption that isoenzymes provide unlimited capacity for backup with the assumption that isoenzymes are completely non-redundant. We further show that this change of the assumption regarding isoenzymes increases the recall of epistatic interactions predicted by the flux balance model at the cost of a reduction in the precision of the predictions. In addition to suggesting that the gene-to-reaction mapping in genome-scale flux balance models should be used with caution, our analysis provides new evidence that evolutionary gene importance captures much more than strict essentiality.


Synergistic protective effect of N-acetylcysteine and taurine against cisplatin-induced nephrotoxicity in rats.
Cisplatin (cis-diaminedichloroplatinum II; CDDP) is an effective anticancer drug, but it has limitations because of its nephrotoxicity. This study investigates the protective effect of N-acetylcysteine (NAC) and taurine (TAU), both individually and in combination, against CDDP nephrotoxicity in rats. For this purpose, 48 male rats were assigned into eight groups (n=6) as follows: 1) control group, 2) NAC group, 3) TAU group, 4) NAC-TAU group, 5) CDDP group, 6) CDDP-NAC group, 7) CDDP-TAU group, and 8) CDDP-NAC-TAU group. Cisplatin was administered as a single intraperitoneal injection at a concentration of 6 mg/kg. Three days after CDDP administration, NAC (50 mg/kg) and/or TAU (50 mg/kg) were administered three times weekly for four consecutive weeks. Kidney function markers in serum, urinary glucose and protein, as well as oxidant and antioxidant parameters in renal tissue were assessed. Administration of CDDP significantly elevated urinary glucose and protein, as well as serum creatinine, urea, and uric acid. Moreover, CDDP enhanced lipid peroxidation and suppressed the major enzymatic antioxidants in the kidney tissue. Treatment with NAC or TAU protected against the alterations in the serum, urine, and renal tissue when used individually along with CDDP. Furthermore, a combined therapy of both was more effective in ameliorating CDDP-induced nephrotoxicity, which points out to their synergistic effect.


Training groups, encounter groups, sensitivity groups and group psychotherapy.
Descriptions and comparison of group therapies and the new group procedures (training groups and sensitivity groups-an outgrowth of the so-called Laboratory Movement methods of the mid-1930's) have been provided for the better understanding of non-psychiatric physicians. A group leader must have proper training and must help his group in its search for its avowed goals, whether he is a group therapist, a sensitivity trainer, or anyone else interested in utilizing group processes.Those goals are either the therapeutic benefit of the individual, as defined in group psychotherapy, or a better understanding of how one functions in groups, as in T-groups or the other group processes in the area of sensitive living. All group situations contain powerful tools which must be handled with proper respect. When so handled by experienced leaders, the individuals involved can achieve their goals in these group experiences.


A study to assess the validity of clinical judgement in determining paediatric dental anxiety and related outcomes of management.
The aim of the present study was to determine the validity of subjective anxiety assessment and the outcomes of management of children receiving operative dental treatment. The study was conducted at the Departments of Sedation and Child Dental Health, Newcastle Dental Hospital, Newcastle upon Tyne, UK. One hundred children and adolescents aged between 8 and 15 years participated in the study. Clinicians subjectively allocated 50 children for treatment with local analgesia alone (low anxiety), and identified 50 children who had the potential to benefit from nitrous oxide and oxygen sedation (high anxiety). Participants then completed the State-Trait Anxiety Inventory for Children (STAIC), the Venham Picture Test (VPT) and the Child Fear Survey Schedule-Dental Subscale (CFSS-DS). A global rating scale classified behaviour during dental treatment. State anxiety and dental fear prior to treatment were significantly higher in children allocated to receive inhalation sedation (P = 0.004 and P = 0.005, respectively). There was no significant difference in trait anxiety or post-treatment state anxiety between the two groups (P = 0.69 and P = 0.06, respectively). Only 11% displayed 'negative' behaviour during treatment: 82% of this group represented those allocated to receive sedation. Children receiving inhalation sedation were significantly more anxious prior to treatment than children receiving treatment with local analgesia alone. The findings support the subjective assessment of anxiety in children; however, objective anxiety measures may assist clinicians in identifying specific fears, which may ultimately aid patient management.


[Photo-induced release of calcium ions frog retina photoreceptor membranes in media of different ionic composition].
Two methods: labelled Ca45 and Ca++-selective electrode served to assess the Ca++ release during illumination of the rod outer segments in the frog retina. The maximal release (8--10 M Ca++/M bleached rhodopsin) occurred in monovalent cations--free medium (100 MM tris--HCl, 5 mM MgCl2, 5 mM ATP, pH--7.5), when at least 50% of visual pigment was bleached. The addition of Na+ or K+ toincubation medium decreased the photoinduced release to 0.06--0.142 M Ca++/M bleached rhodopsin or completely suppressed it. The role of Ca++ as a messenger during the excitation of photoreceptor is discussed.


NuSAP, a mitotic RanGTP target that stabilizes and cross-links microtubules.
Nucleolar and spindle-associated protein (NuSAP) was recently identified as a microtubule- and chromatin-binding protein in vertebrates that is nuclear during interphase. Small interfering RNA-mediated depletion of NuSAP resulted in aberrant spindle formation, missegregation of chromosomes, and ultimately blocked cell proliferation. We show here that NuSAP is enriched on chromatin-proximal microtubules at meiotic spindles in Xenopus oocytes. When added at higher than physiological levels to Xenopus egg extract, NuSAP induces extensive bundling of spindle microtubules and causes bundled microtubules within spindle-like structures to become longer. In vitro reconstitution experiments reveal two direct effects of NuSAP on microtubules: first, it can efficiently stabilize microtubules against depolymerization, and second, it can cross-link large numbers of microtubules into aster-like structures, thick fibers, and networks. With defined components we show that the activity of NuSAP is differentially regulated by Importin (Imp) alpha, Impbeta, and Imp7. While Impalpha and Imp7 appear to block the microtubule-stabilizing activity of NuSAP, Impbeta specifically suppresses aspects of the cross-linking activity of NuSAP. We propose that to achieve full NuSAP functionality at the spindle, all three importins must be dissociated by RanGTP. Once activated, NuSAP may aid to maintain spindle integrity by stabilizing and cross-linking microtubules around chromatin.


Surface-Modified Ta3N5 Nanocrystals with Boron for Enhanced Visible-Light-Driven Photoelectrochemical Water Splitting.
Photocatalysts for water splitting are the core of renewable energy technologies, such as hydrogen fuel cells. The development of photoelectrode materials with high efficiency and low corrosivity has great challenges. In this study, we report new strategy to improve performance of tantalum nitride (Ta3N5) nanocrystals as promising photoanode materials for visible-light-driven photoelectrochemical (PEC) water splitting cells. The surface of Ta3N5 nanocrystals was modified with boron whose content was controlled, with up to 30% substitution of Ta. X-ray photoelectron spectroscopy revealed that boron was mainly incorporated into the surface oxide layers of the Ta3N5 nanocrystals. The surface modification with boron increases significantly the solar energy conversion efficiency of the water-splitting PEC cells by shifting the onset potential cathodically and increasing the photocurrents. It reduces the interfacial charge-transfer resistance and increases the electrical conductivity, which could cause the higher photocurrents at lower potential. The onset potential shift of the PEC cell with the boron incorporation can be attributed to the negative shift of the flat band potential. We suggest that the boron-modified surface acts as a protection layer for the Ta3N5 nanocrystals, by catalyzing effectively the water splitting reaction.


Lifetime treatment contact and delay in treatment seeking after first onset of a mental disorder.
This study examined lifetime treatment contact and delays in treatment seeking, including rates for receipt of helpful treatment, after the onset of specific mental disorders and evaluated factors that predicted treatment seeking and delays in treatment seeking. Data were from the Netherlands Mental Health Survey and Incidence Study-2, a nationally representative, face-to-face survey of the general population aged 18-64 (N=6,646). DSM-IV diagnoses, treatment contact, and respondents' perception of treatment helpfulness were assessed with the Composite International Diagnostic Interview 3.0. The proportion of respondents with lifetime mental disorders who made lifetime treatment contact ranged from 6.5% to 56.5% for substance use disorders and from 75.3% to 91.4% for mood disorders. Delays in initial treatment contact varied among persons with mood disorders (median=0 years), substance use disorders (0-4 years), impulse-control disorders (4-8 years), and anxiety disorders (0-19 years). The proportion of respondents who received helpful treatment ranged from 33.5% for substance use disorders to 69.5% for mood disorders. Men, older cohorts, and respondents with younger age at onset of the disorder generally were more likely to have no lifetime treatment contact, to have longer treatment delay, and to have not received helpful treatment. There was substantial variation in lifetime treatment contact and delays in initial treatment contact by mental disorder. Lifetime treatment contact, delays in treatment seeking, and receipt of helpful treatment did not vary by educational level.


Caregiving experiences and health conditions of women veteran and non-veteran caregivers.
Unique experiences, for example, trauma, of women veteran caregivers may create differences in the caregiving experience and may be associated with health concerns. We examined caregiving factors and health concerns in women veteran caregivers compared to non-veteran women (civilian) caregivers, and identified variables associated with being a woman veteran caregiver. We conducted secondary data analyses using data from a multistate survey to examine sociodemographics, the caregiver experience (relationship to recipient, duration as caregiver, hours of care provided, area help is needed, and greatest difficulty faced as a caregiver); emotional support; life satisfaction; lifestyle behaviors; general, physical, and mental health; and chronic conditions in women informal caregivers. Of women caregivers, more veteran caregivers provided activities of daily living (ADL) help (33%) than non-veteran caregivers (21%; p = .02). There were no differences in years as a caregiver, hours of care provided, or the relationship to the recipient. Poor sleep and poor mental health were experienced by more women veteran caregivers (vs. non-veteran), but physical health, general health, and chronic condition prevalence did not differ. Women veteran caregivers had twofold greater odds of being Black, never married, college educated, and providing ADL assistance. Odds of obesity were lower for women veteran caregivers relative to other women caregivers. Women veteran caregivers experience health concerns, including sleeplessness, poor mental health, and some chronic conditions. Our cohort were young women, yet had concerns that may be exacerbated by being a veteran and assuming a caregiver role. Comprehensive services to support their needs as veteran patients and as caregivers are needed.


Two novel compounds from the root bark of Morus alba L.
Chemical investigation of the root bark of Morus alba led to the isolation of a new flavone, dioxycudraflavone A (1) and a new 2-arylbenzofuran, 5-hydroxyethyl moracin M (2), together with seven known compounds namely sanggenon V (3), morusin (4), morusignin L (5), licoflavone C (6), moracin C (7), alfafuran (8) and mulberrofuran G (9). The structure elucidation of these compounds was based on analyses of spectroscopic data including 1D, 2D NMR and HR-ESI-MS. All compounds were evaluated for the α-glucosidase inhibitory and cytotoxic activities. Compounds 2-4, 8 and 9 exhibited strong α-glucosidase inhibitory activities with IC50 less than 10 μM, while only 4 and 9 showed moderate cytotoxic effects against lung cancer cells.


Profiling of healthy and asthmatic airway smooth muscle cells following interleukin-1β treatment: a novel role for CCL20 in chronic mucus hypersecretion.
Chronic mucus hypersecretion (CMH) contributes to the morbidity and mortality of asthma, and remains uncontrolled by current therapies in the subset of patients with severe, steroid-resistant disease. Altered cross-talk between airway epithelium and airway smooth muscle cells (ASMCs), driven by pro-inflammatory cytokines such as interleukin (IL)-1β, provides a potential mechanism that influences CMH. This study investigated mechanisms underlying CMH by comparing IL-1β-induced gene expression profiles between asthma and control-derived ASMCs and the subsequent paracrine influence on airway epithelial mucus production in vitroIL-1β-treated ASMCs from asthmatic patients and healthy donors were profiled using microarray analysis and ELISA. Air-liquid interface (ALI)-cultured CALU-3 and primary airway epithelial cells were treated with identified candidates and mucus production assessed.The IL-1β-induced CCL20 expression and protein release was increased in ASMCs from moderate compared with mild asthmatic patients and healthy controls. IL-1β induced lower MIR146A expression in asthma-derived ASMCs compared with controls. Decreased MIR146A expression was validated in vivo in bronchial biopsies from 16 asthmatic patients versus 39 healthy donors. miR-146a-5p overexpression abrogated CCL20 release in ASMCs. CCL20 treatment of ALI-cultured CALU-3 and primary airway epithelial cells induced mucus production, while CCL20 levels in sputum were associated with increased levels of CMH in asthmatic patients.Elevated CCL20 production by ASMCs, possibly resulting from dysregulated expression of the anti-inflammatory miR-146a-5p, may contribute to enhanced mucus production in asthma.


[Superficial cervical plexus block in ear surgery: A case report].
The aim of this study was to share our experience with the application of a superficial cervical plexus block in the ear operation of a 59-year-old male patient. The superficial cervical plexus provides sensory innervation of the superficial structures of the anterolateral neck, ear, and shoulder. Ultrasound-guided cervical plexus block may be an alternative method for both anesthesia and analgesia in ear surgery.


Income inequality, social cohesion, and class relations: a critique of Wilkinson's neo-Durkheimian research program.
Wilkinson's "income inequality and social cohesion" model has emerged as a leading research program in social epidemiology. Public health scholars and activists working toward the elimination of social inequalities in health can find several appealing features in Wilkinson's research. In particular, it provides a sociological alternative to former models that emphasize poverty, health behaviors, or the cultural aspects of social relations as determinants of population health. Wilkinson's model calls for social explanations, avoids the subjectivist legacy of U.S. functionalist sociology that is evident in "status" approaches to understanding social inequalities in health, and calls for broad policies of income redistribution. Nevertheless, Wilkinson's research program has characteristics that limit its explanatory power and its ability to inform social policies directed toward reducing social inequalities in health. The model ignores class relations, an approach that might help explain how income inequalities are generated and account for both relative and absolute deprivation. Furthermore, Wilkinson's model implies that social cohesion rather than political change is the major determinant of population health. Historical evidence suggests that class formation could determine both reductions in social inequalities and increases in social cohesion. Drawing on recent examples, the authors argue that an emphasis on social cohesion can be used to render communities responsible for their mortality and morbidity rates: a community-level version of "blaming the victim." Such use of social cohesion is related to current policy initiatives in the United States and Britain under the New Democrat and New Labor governments.


Hypofractionated Radiotherapy Dose Scheme and Application of New Techniques Are Associated to a Lower Incidence of Radiation Pneumonitis in Breast Cancer Patients.
Purpose: Radiation pneumonitis (RP) is one of the most severe toxicities experienced by patients with breast cancer after radiotherapy (RT). RT fractionation schemes and techniques for breast cancer have undergone numerous changes over the past decades. This study aimed to investigate the incidence of RP as a function of such changes in patients with breast cancer undergoing RT and to identify dosimetric markers that predict the risk of this adverse event. Methods and Materials: We identified 1,847 women with breast cancer who received adjuvant RT at our institution between 2015 and 2017. The RT technique was individually tailored based on each patient's clinicopathological features. Deep inspiration breath hold technique or prone positioning were used for patients who underwent left whole-breast irradiation for cardiac sparing, while those requiring regional lymph node irradiation underwent volumetric-modulated arc therapy (VMAT). Results: Of 1,847 patients who received RT, 21.2% received the conventional dose scheme, while 78.8% received the hypofractionated dose scheme (mostly 40 Gy in 15 fractions). The median follow-up period was 14.5 months, and the overall RP rate was 2.1%. The irradiated organ at risk was corrected concerning biologically equivalent dose. The ipsilateral lung V30 in equivalent dose in 2 Gy (EQD2) was the most significant dosimetric factor associated with RP development. Administering RT using VMAT, and hypofractionated dose scheme significantly reduced ipsilateral lung V30. Conclusions: Application of new RT techniques and hypofractionated scheme significantly reduce the ipsilateral lung dose. Our data demonstrated that ipsilateral lung V30 in EQD2 is the most relevant dosimetric predictor of RP in patients with breast cancer.


Longitudinal study of inflammatory markers and psychopathology in schizophrenia.
Schizophrenia is associated with abnormal levels of blood inflammatory markers, which may be correlated with levels of psychopathology. Few previous studies have explored whether baseline inflammatory marker levels predict longitudinal changes in psychopathology. In the present study, we explored this association in a cohort of patients with schizophrenia. We investigated inflammatory markers and psychopathology after 3, 6, and 12 months of antipsychotic treatment for subjects with baseline and follow-up data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial. Linear regression models, controlling for multiple potential confounding factors, were used to investigate these associations. There was a significant decrease in monocyte, ICAM, and adiponectin levels between baseline and 12 months. Higher baseline blood interleukin-6 (IL-6) predicted greater reduction in PANSS total and general subscale scores at 3 and 6 months, and PANSS negative subscale scores at 3 months (β = -0.10 to -0.16, p < 0.05 for each). Higher baseline blood leptin levels predicted greater reduction in PANSS total, negative and general subscale scores at 6 months (β = -0.09 to -0.11, p < 0.05 for each). In post-hoc analyses, associations between baseline IL-6 levels and symptom reduction were strongest in patients treated with either ziprasidone or quetiapine. Changes in blood inflammatory markers were generally not associated with changes in psychopathology. Our findings provide additional support that measuring blood inflammatory markers may be relevant to the clinical care of patients with schizophrenia. Specifically, these markers may help guide selection of antipsychotic treatment towards more personalized medicine approaches for patients with schizophrenia.


Ultrahigh Penetration and Retention of Graphene Quantum Dot Mesoporous Silica Nanohybrids for Image Guided Tumor Regression.
So far, near-infrared (NIR) light responsive nanostructures have been well-defined in cancer nanomedicine. However, poor penetration and retention in tumors are the limiting factors. Here, we report the ultrahigh penetration and retention of carbanosilica (graphene quantum dots, GQDs embedded mesoporous silica) in solid tumors. After NIR light exposure, quick (0.5 h) emission from the tumor area is observed that is further retained up to a week (tested up to 10 days) with a single dose administration of nanohybrids. Emissive and photothermally active GQDs and porous silica shell (about 31% drug loading) make carbanosilica a promising nanotheranostic agent exhibiting 68.75% tumor shrinking compared to without NIR light exposure (34.48%). Generated heat (∼52 °C) alters the permeability of tumor enhancing the accumulation of nanotheranostics into the tumor environment. Successive tumor imaging ensures the prolonged follow-up of image guided tumor regression due to synergistic therapeutic effect of nanohybrids.


Use of hyperbaric oxygen therapy in Hong Kong.
The Recompression Treatment Centre on Stonecutters Island has been operating in Hong Kong for more than 5 years and has been used to treat a variety of diving-related and other conditions by means of hyperbaric oxygen therapy. Up to the end of December 1997, 295 treatment sessions had been conducted for 39 patients. This article reviews the usefulness of and indications for hyperbaric oxygen therapy.


The Role of Exercise in the Quality of Life in Patients After Pancreatectomy: A Prospective Randomized Controlled Trial.
Pancreatic resection is still a challenging operation characterised by high morbidity. The quality of life in patients after pancreatectomy is a critical outcome. The aim of our trial is to prove whether or not exercise has any benefit to the life of these patients. The study was an open-label, randomized clinical trial. The patients were selected according to the Consolidated Standard of Reporting Trials criteria. The study was registered at the International Standard Randomized Controlled Trial registry (ISRCTN) with the study ID ISRCTN1087174. The study was approved by the Bioethics and Deontology Committee, Medical School of Aristotle University, Thessaloniki (ref: 166/29.10.2015). Once the allocation and the follow-up were completed, 21 patients in the exercise group and 22 in the control group were analyzed. There was no statistical difference between the two groups regarding co-morbidities and disease characteristics; however, the quality of life and the total status of health were superior in the exercise group. Exercise can improve the quality of life in patients after complex operations like pancreatectomy.


Is primary surgery for locally advanced/metastatic breast cancer a better choice than chemotherapic treatment?
A part of the literature supports the undoubtful advantage of neoadjuvant chemotherapy on the overall survival and for the possibility of surgical conservative treatment in locally advanced tumours after downstaging. Other authors report that primitive tumour's surgical removal at first, improves survival in cases with locally advanced /metastatic disease. The advantages were improvement of patient's health status, removal of a reservoir of neoplastic cell neoangiogenic cytokines and growth factors,and cytoreduction. Aim of this study is to evaluate the effectiveness on the survival of a primary surgical treatment of the locally advanced tumours comparing two homogeneous groups. In the first group (GROUP 1) 40 patients were enrolled with stage III A, III B,IV tumours and were treated with primary surgery. The second group (GROUP 2) was made up of 40 patients with similar stage treated with neoadjuvant chemotherapy. The surgical treatment had the intention to remove the entire primary tumour. After a median follow up of 48,2 months,22,5 % of GROUP 1 died and 30 % of GROUP 2. The average survival of patients in GROUP 1 was 27,1 months while in GROUP 2 there was an average survival of 16,8 months. In conclusion surgical treatment plays a key role in the treatment of advanced/metastatic disease and is an independent factor associated with survival.


Lipid lowering effect of antioxidant alpha-lipoic Acid in experimental atherosclerosis.
Accumulating data demonstrated that hypercholesterolemia and oxidative stress play an important role in the development of atherosclerosis. In the present study, a protective activity of alpha-lipoic acid; a metabolic antioxidant in hypercholesterolemic-induced animals was investigated. Eighteen adult male New Zealand White (NZW) rabbit were segregated into three groups labelled as group N, HCD and ALA (n = 6). Group N (normal control) was fed with normal chow, the rest (HCD and ALA) were fed with 100 g/head/day of 1% cholesterol rich diet to induce hypercholesterolemia. Four point two mg/body weight of alpha lipoic acid was concomintantly supplemented to the ALA group. Drinking water was given ad-libitum. The study was designed for 10 weeks. Blood sampling was taken from the ear lobe vein at the beginning, week 5 and week 10. Plasma was prepared for lipid profile estimation and microsomal lipid peroxidation index indicated with malondialdehyde (MDA) formation. At the end of the experiment, the animals were sacrificed and the aorta were excised for intimal lesion analysis. The plasma total cholesterol (TC) and low density lipoprotein (LDL) levels were found to be significantly low in ALA group compared to that of the HCD group (p<0.05). Similarly, low level of MDA (p<0.05) in ALA group was observed compared to that of the HCD group showing a significant reduction of lipid peroxidation activity. Histomorphometric intimal lesion analysis of the aorta showing less of atheromatous plaque formation in alpha lipoic acid supplemented group (p<0.05) compared to HCD group. These findings suggested that alpha lipoic acid posses a dual lipid lowering and anti-atherosclerotic properties indicated with low plasma TC and LDL levels and reduction of athero-lesion formation in hypercholesterolemic-induced rabbits.


The familial aggregation of Alzheimer's disease: an epidemiological review.
This report reviews current data on the familial aggregation of Alzheimer's disease (AD). Single pedigree reports indicate that in few families AD is inherited as an autosomal dominant single gene disorder. Family studies show that first-degree relatives of AD patients have a higher lifetime incidence of AD than the general population or groups of nondemented subjects. Case-control studies indicate that the risk of developing AD is significantly higher for subjects with family members affected by dementia than for those without. The concordance rate in monozygotic twin pairs was found to be much lower than expected from an autosomal dominant disease. These data are inconclusive; however, they suggest that in future etiologic studies 3 types of AD should be considered separately: autosomal dominant, familial, and sporadic. Subclassification of AD by type of occurrence generates groups of patients which are probably more homogeneous regarding etiology.


Chronic musculoskeletal pain predicted hospitalisation due to serious medical conditions in a 10 year follow up study.
The aim was to examine if self reported chronic regional pain (CRP) and chronic widespread pain (CWP) predicted inpatient care due to serious medical conditions such as cerebrovascular diseases, ischemic heart diseases, neoplasms and infectious diseases in a general population cohort over a ten year follow-up period. A ten-year follow up of a cohort from the general adult population in two health care districts with mixed urban and rural population in the south of Sweden, that in 1995 participated in a survey on health and musculoskeletal pain experience. Information on hospitalisation for each subject was taken from the regional health care register. Multiple logistic regression analyses were used to study the associations between chronic musculoskeletal pain and different medical conditions as causes of hospitalisation. A report of CRP (OR = 1.6; p < 0.001) or CWP ( OR = 2.1; p < 0.001) predicted at least one episode of inpatient care over a ten year period, with an increased risk in almost all diagnostic subgroups, including cerebrovascular diseases, ischemic heart diseases, and infectious diseases. There was however no increased risk of hospitalisation due to neoplasms. The presence of especially CWP was associated with hospital inpatient care due to several serious medical disorders. This may imply a general vulnerability to different medical conditions that has to be addressed in the assessment and management of subjects with chronic musculoskeletal pain.


The release of catecholamines by an endogenous factor that inhibits neuronal Na+,K(+)-ATPase.
It is known that the inhibition of Na+,K(+)-ATPase induces neurotransmitter release in several experimental models. In this laboratory it was previously observed that a brain soluble fraction separated by Sephadex G-50 (peak II) is able to inhibit Na+,K(+)-ATPase but not other membrane-bound enzymes. The object of the present study was to test the effect of brain peak II fraction on neurotransmitter content of the pineal nerves synaptic vesicles. Uninjected rats and rats injected 30 min before with 5-hydroxydopamine (30 mg per kg,i.p.) were used. 5-hydroxydopamine produces a false neurotransmitter whose presence in the synaptic vesicles is visualized after fixation with glutaraldehyde-osmium as an electron dense material with the electron microscope which fills totally or partially the vesicles. In uninjected rats the osmiophilia and the chromaffin reaction of the electron dense core were studied. The pineal glands were incubated in Tyrode solution without calcium in the presence and absence of peak II at room temperature and processed for electron microscopy. When the glands from rats pretreated with 5-hydroxydopamine were incubated with peak II a significant decrease in the number of vesicles totally stained was observed. This indicates a reduction in false neurotransmitter content, specially in the matrix of the synaptic vesicles. In the presence of an aged peak II, which does not inhibit Na+,K(+)-ATPase, this effect on the synaptic vesicles was not observed. When the glands from uninjected rats were incubated with peak II no changes in the osmiophilia and the chromaffin reaction of the synaptic vesicles were found. The osmiophilia and the chromaffin reaction of the cores marks the monoamines storage site (catechol and indoleamines in the pineal nerves). These results are coherent with the idea of a relationship between the inhibition of Na+,K(+)-ATPase activity and the release of a pool of neurotransmitter stored in the nerve endings.


The molecular impact of pigment epithelium-derived factor, PEDF, on lung cancer cells and the clinical significance.
Pigment epithelium-derived factor (PEDF) is an endogenous protein factor that has been shown to act as anti-angiognesis factor. The present study aimed to determine the direct biological effects of PEDF on lung cancer cells and deduce a clinical relevance in patients with lung cancer, major cause of death worldwide in which the knowledge of PEDF remains poor. We constructed a mammalian expression system for human PEDF produced recombinant PEDF (rhPEDF) protein from 3T3 cells. The expression of PEDF was examined using SDS-PAGE and Western blot analysis. Using the rhPEDF protein, we investigated the biological function of PEDF in the lung cancer cells as well as endothelial cells. PEDF expression levels were assessed in a cohort of human lung cancer specimen (77 pairs of matched normal and tumour tissues), in association with patient clinical variables and survival, using quantitative analysis of PEDF. In vitro, we found that administration of rhPEDF on two lung cancer cell lines (A549 and SK-MES1) significantly reduced tumour cell growth (P<0.05) with no significant effect on the growth of vascular cell line (HECV). We also found that rhPEDF significantly decreased lung cancer motility and adhesion to extracellular matrix (Matrigel) when compared with the control cells (P<0.05). We showed that reduced PEDF levels in lung cancer tissues significantly correlated with lymph node metastasis and an overall poor prognosis in the lung cancer patients. PEDF suppresses the growth and motility of lung cancer cells and has a significant correlation with the clinical outcome of the patients. These results contribute to our understanding of the molecular mechanisms of PEDF and indicates a potential prognostic and therapeutic impact of PEDF in lung cancer.


Characteristics of suicide attempts in young people undergoing treatment for first episode psychosis.
Understanding the characteristics of suicide attempts in people undergoing treatment for first episode psychosis (FEP) may have implications for risk management at a service level and local suicide prevention strategies. Although studies have focused on identifying individual-level risk factors for suicide attempts in this patient group, none have yet conducted an in-depth profile of suicide attempts. The aim of the present study was to examine the characteristics of suicide attempts in young people during the initial 18 months of treatment for FEP. A retrospective medical record audit study of a cohort of patients accepted for treatment at a specialist FEP service between 1/12/2002 and 30/11/2005. Of 607 patients, 73 (12%) attempted suicide during treatment. Of these 73, most (72.6%) attempted suicide on one occasion. The majority of attempts (85.3%) occurred when patients were treated as outpatients and were in regular contact with the service. Suicide attempts tended to be impulsive (77.6%), triggered by interpersonal conflict or distress due to psychotic symptoms. Two thirds involved self-poisoning, usually by overdose of prescribed medications. All inpatient suicide attempts were by hanging or strangulation. Individuals infrequently sought help immediately before or after the attempt; if help-seeking occurred, informal sources of support were contacted. To reduce the number of suicide attempts among individuals treated for FEP, psychiatric services could consider: restricting the amount of medication prescribed per purchase; individualised suicide risk management plans for all newly admitted patients, including those who do not appear to be at risk; stringent reviews of inpatient psychiatric units for potential ligature points; providing information and psycho-education for significant others in recognition and response to suicide risk; fostering patients' problem solving and conflict resolution skills; and regular risk assessment and close monitoring of patients, particularly during the high risk period of 3 months after a suicide attempt.


Inflammatory dietary potential is associated with vitamin depletion and gut microbial dysbiosis in early pregnancy.
Pregnancy alters many physiological systems, including the maternal gut microbiota. Diet is a key regulator of this system and can alter host inflammation. Multiple perinatal disorders have been associated with inflammation, maternal metabolic alterations, and gut microbiota dysbiosis, including gestational diabetes mellitus, preeclampsia, preterm birth, and mood disorders. However, the effects of high inflammatory diets on the gut microbiota during pregnancy has yet to be fully explored. To use a systems-based approach to characterize associations among dietary inflammatory potential, a measure of diet quality, and the gut microbiome during pregnancy. Forty-nine pregnant persons were recruited prior to 16 weeks of gestation. Participants completed a food frequency questionnaire (FFQ) and provided fecal samples. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) from FFQ data. Fecal samples were analyzed using 16S rRNA amplicon sequencing. Differential taxa abundance with respect to DII score were identified, and microbial metabolic potential was predicted using PICRUSt2. Inflammatory diets were associated with decreased vitamin and mineral intake and dysbiotic gut microbiome structure and metabolism. Gut microbial compositional differences revealed a decrease in short chain fatty acid producers such as g_ Faecalibacterium, upregulation of vitamin B12 synthesis, methylglyoxal detoxification, galactose metabolism and multi drug efflux systems in pregnant individuals with increased DII scores. Dietary inflammatory potential was associated with depletion of vitamins & minerals and gut microbiota metabolic dysregulation.


Using twitter in health professional education: a case study.
The vast majority of health care students, providers, and organizations utilize social media to access and share information. However, there is little research exploring integration of social media into health professional education. This case study describes how the social media site Twitter was used in a first-year physical therapy professionalism course to teach, support, and model professional online communication. Twitter was used for discussion and sharing among 36 doctor of physical therapy (DPT) students enrolled in a first-year professionalism course. Participants completed four Twitter assignments. Outcome measures included student surveys of overall social media use, perceptions of Twitter use in the course, Twitter use during the course, and student engagement measured using a subset of questions from the National Survey of Student Engagement (NSSE). During the course, students posted a total of 337 tweets (mean 9.36 tweets/student). Pre- and post-course surveys showed an increase in academic and professional social media use. Perception of Twitter use in the course was generally positive. There was a small increase in mean NSSE score that was not statistically significant. Using Twitter in a physical therapy professionalism course was a positive experience for students and was associated with increased academic and professional social media use. Future studies are needed to determine whether deliberate teaching of social media as a professional technology competency will result in meaningful increases in professional online engagement and improved digital professionalism in health professional students and providers.


Economic evaluation of pneumococcal conjugate vaccination in The Gambia.
Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7), but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars) per disability-adjusted life year (DALY) averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Assuming 90% coverage, a program using a 9-valent PCV (PCV9) would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine), compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Based on the information available now, infant PCV vaccination would be expected to reduce pneumococcal diseases caused by S. pneumoniae in The Gambia. Assuming a cost-effectiveness threshold of three times GDP per capita, all PCVs examined would be cost-effective at the tentative Advance Market Commitment (AMC) price of $3.5 per dose. Because the cost-effectiveness of a PCV program could be affected by potential serotype replacement or herd immunity effects that may not be known until after a large scale introduction, type-specific surveillance and iterative evaluation will be critical.


Changes in strength over a 2-year period in professional rugby union players.
The purpose of this study was to assess the magnitude of upper and lower body strength changes in highly trained professional rugby union players after 2 years of training. An additional purpose was to examine if the changes in strength were influenced by the starting strength level, lean mass index (LMI), or chronological age. This longitudinal investigation tracked maximal strength and body composition over 3 consecutive years in 20 professional rugby union athletes. Maximal strength in the bench press and back squat and body composition was assessed during preseason resistance training sessions each year. The athletes completed a very rigorous training program throughout the duration of this study consisting of numerous resistance, conditioning and skills training sessions every week. The primary findings of this study were as follows: (a) Maximal upper and lower body strength was increased by 6.5-11.5% after 2 years of training (p = 0.000-0.002 for bench press; p = 0.277-0.165 for squat); (b) magnitude of the improvement was negatively associated with initial strength level (r = -0.569 to -0.712, p ≤ 0.05); (c) magnitude of improvement in lower body maximal strength was positively related to the change in LMI (an indicator of hypertrophy; r = 0.692-0.880, p ≤ 0.05); and (d) magnitude of improvement was not associated with the age of professional rugby union athletes (r = -0.068 to -0.345). It appears particularly important for training programs to be designed for continued muscle hypertrophy in highly trained athletes. Even in professional rugby union athletes, this must be achieved in the face of high volumes of aerobic and skills training if strength is to be increased.


Adaptive and maladaptive perfectionism, adult attachment, and big five personality traits.
The author examined the role of anxiety and avoidance dimensions of attachment and Big Five personality traits in adaptive and maladaptive dimensions of perfectionism among 604 (377 male, 227 female) Turkish university students. The results of 2 separate multiple regression analyses yielded that adaptive perfectionism was significantly predicted by conscientiousness, openness, and extraversion. Maladaptive perfectionism was significantly predicted by the neuroticism, anxiety, and avoidance dimensions of attachment. The authors discuss the implications, limitations, and future directions for research.


Fractures of the middle third of the tibia treated with a functional brace.
It generally is accepted that fractures of the tibia located in the proximal and distal thirds tend to angulate more than midshaft fractures when treated with intramedullary nails. We therefore compared the angular deformities and final shortening of 434 closed fractures located in the middle third of the tibia treated with a functional brace with those in fractures in the proximal and distal thirds treated in the same manner. Ninety-seven percent in the middle third healed with 8 degrees or less angulation in the mediolateral plane, which was a higher percentage than we had experienced in distal and proximal third fractures treated with this method. Nonunions occurred in four (0.9%) fractures. We found correlations between initial shortening, final shortening, initial displacement, final displacement, and time to brace with initial angulation and final angulation in the mediolateral and anteroposterior planes. The overall mean final shortening of the fractures located in the middle third was 4.3 mm. These experiences suggest satisfactory results can be obtained in most instances using a functional brace for management of closed fractures of the middle third of the tibia. Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.


Entomological surveys of malaria in Khammouane Province, Lao PDR, in 1999 and 2000.
Anopheline mosquitos and their relation to malaria transmission were studied 3 times: in July and August, 1999; in December, 1999; and in August and September, 2000. The studies took place in the malaria endemic villages of Khammouane Province, southeast of Lao PDR. A total of 28 species were collected using human and animal bait. Human bait attracted predominantly Anopheles dirus and An. minimus, which were identified as vectors by the detection of sporozoites by dissection, PCR, and enzyme-linked immunosorbent assays for Plasmodium falciparum and P. vivax. The vectorial capacity of An. dirus was 0.009-0.428, while that of An. minimus was 0.048-0.186. The inoculation rate of An. dirus was 0.052-0.137 (Boualapha; August, 2000). An. nivipes and its sister species, An. philippinensis, were principally zoophilic, although a considerable number of the females were also attracted to human bait in the villages of the paddy field areas. An. philippinensis infected with oocysts of P. vivax was detected in a specimen collected by animal bait. These two species were considered as vectors in Khammouane Province. Four species, An. notanandai, An. sawadwongporni, An. willmori, and An. hodgkini, had not been recored before in Lao PDR. Information is provided on host preference and the nocturnal biting activities of common species and the incidence of malaria in the study areas.


Membrane protein analysis by two-dimensional immunoelectrophoresis.
Water-soluble membrane proteins may be analyzed by a new, rapid technique that combines electrophoresis on high-resolution sodium dodecyl sulfate (SDS) polyacrylamide gels and immunoelectrophoresis. After separation in the first dimension by electrophoresis in SDS, the proteins are subjected to a second electrophoresis at right angles through a two-layered buffered agarose gel. They first pass through a layer containing Lubrol PX which forms complexes with free SDS and then into an antiserum layer where antigen-antibody precipitates form. Precipitin arcs appear at positions corresponding to the antigens separated in the first dimension. The effectiveness of the technique was demonstrated with frog and cattle opsins, human erythrocyte membrane proteins, and their rabbit antiserums and for several water soluble proteins. By this method two fundamental parameters, molecular weight and antigenicity, may be readily used for analysis of membrane proteins.


A rapid expression and purification condition screening protocol for membrane protein structural biology.
Membrane proteins control a large number of vital biological processes and are often medically important-not least as drug targets. However, membrane proteins are generally more difficult to work with than their globular counterparts, and as a consequence comparatively few high-resolution structures are available. In any membrane protein structure project, a lot of effort is usually spent on obtaining a pure and stable protein preparation. The process commonly involves the expression of several constructs and homologs, followed by extraction in various detergents. This is normally a time-consuming and highly iterative process since only one or a few conditions can be tested at a time. In this article, we describe a rapid screening protocol in a 96-well format that largely mimics standard membrane protein purification procedures, but eliminates the ultracentrifugation and membrane preparation steps. Moreover, we show that the results are robustly translatable to large-scale production of detergent-solubilized protein for structural studies. We have applied this protocol to 60 proteins from an E. coli membrane protein library, in order to find the optimal expression, solubilization and purification conditions for each protein. With guidance from the obtained screening data, we have also performed successful large-scale purifications of several of the proteins. The protocol provides a rapid, low cost solution to one of the major bottlenecks in structural biology, making membrane protein structures attainable even for the small laboratory.


Probing hot spots at protein-ligand binding sites: a fragment-based approach using biophysical methods.
Mapping interactions at protein-ligand binding sites is an important aspect of understanding many biological reactions and a key part of drug design. In this paper, we have used a fragment-based approach to probe "hot spots" at the cofactor-binding site of a model dehydrogenase, Escherichia coli ketopantoate reductase. Our strategy involved the breaking down of NADPH (Kd = 300 nM) into smaller fragments and the biophysical characterization of their binding using WaterLOGSY NMR spectroscopy, isothermal titration calorimetry (ITC), and inhibition studies. The weak binding affinities of fragments were measured by direct ITC titrations under low c value conditions. The 2'-phosphate and the reduced nicotinamide groups were found to contribute a large part of the binding energy. A combination of ITC and site-directed mutagenesis enabled us to locate the fragments at separate hot spots on opposite ends of the cofactor-binding site. This study has identified structural determinants for cofactor recognition that represent a blueprint for future inhibitor design.


Albuminuria and estimated glomerular filtration rate as predictors of diabetic end-stage renal disease and death.
We investigated predictive value of albuminuria and estimated GFR (eGFR) for ESRD in Pima Indians with type 2 diabetes. Beginning in 1982, 2420 diabetic Pima Indians ≥18 years old were followed until they developed ESRD or died or until December 31, 2005. Individuals were classified at baseline by urinary albumin-to-creatinine ratio (ACR) and by eGFR, calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. Predictors of ESRD and mortality were examined by proportional hazards regression. During a mean follow-up of 10.2 years, 287 individuals developed ESRD. Incidence of ESRD among individuals with macroalbuminuria (ACR ≥ 300 mg/g) was 9.3 times that of those with normoalbuminuria (ACR < 30 mg/g), controlled for age, gender, and duration of diabetes. Incidence among individuals with eGFR 15 to 29 ml/min per 1.73 m(2) was 81.9 times that of those with eGFR 90 to 119 ml/min per 1.73 m(2). Models that combined albuminuria and eGFR added significant predictive information about risk of ESRD or death compared with models containing eGFR or albuminuria alone. The hazard ratio for ESRD associated with a 10-ml/min per 1.73 m(2) lower eGFR was 1.36, whereas that associated with an increase in albuminuria category was 2.69; corresponding hazard ratios for death were 1.15 and 1.37. These results suggest that incorporation of quantitative information about albuminuria into staging systems based on eGFR adds significant prognostic information about risk for diabetic ESRD and death.


Assessing the accuracy of octanol-water partition coefficient predictions in the SAMPL6 Part II log P Challenge.
The SAMPL Challenges aim to focus the biomolecular and physical modeling community on issues that limit the accuracy of predictive modeling of protein-ligand binding for rational drug design. In the SAMPL5 log D Challenge, designed to benchmark the accuracy of methods for predicting drug-like small molecule transfer free energies from aqueous to nonpolar phases, participants found it difficult to make accurate predictions due to the complexity of protonation state issues. In the SAMPL6 log P Challenge, we asked participants to make blind predictions of the octanol-water partition coefficients of neutral species of 11 compounds and assessed how well these methods performed absent the complication of protonation state effects. This challenge builds on the SAMPL6 p[Formula: see text] Challenge, which asked participants to predict p[Formula: see text] values of a superset of the compounds considered in this log P challenge. Blind prediction sets of 91 prediction methods were collected from 27 research groups, spanning a variety of quantum mechanics (QM) or molecular mechanics (MM)-based physical methods, knowledge-based empirical methods, and mixed approaches. There was a 50% increase in the number of participating groups and a 20% increase in the number of submissions compared to the SAMPL5 log D Challenge. Overall, the accuracy of octanol-water log P predictions in SAMPL6 Challenge was higher than cyclohexane-water log D predictions in SAMPL5, likely because modeling only the neutral species was necessary for log P and several categories of method benefited from the vast amounts of experimental octanol-water log P data. There were many highly accurate methods: 10 diverse methods achieved RMSE less than 0.5 log P units. These included QM-based methods, empirical methods, and mixed methods with physical modeling supported with empirical corrections. A comparison of physical modeling methods showed that QM-based methods outperformed MM-based methods. The average RMSE of the most accurate five MM-based, QM-based, empirical, and mixed approach methods based on RMSE were 0.92 ± 0.13, 0.48 ± 0.06, 0.47 ± 0.05, and 0.50 ± 0.06, respectively.


[ROLE OF LEPTIN IN THE FORMATION OF SECONDARY AMENORRHEA IN ADOLESCENT GIRLS].
In order to understand the role of leptin in the formation of secondary amenorrhea (SA) during puberty, 78 girls aged from 13 to 17 years with SA and 74 girls of the same age with regular menstrual cycle have been examined with the estimation of body mass index (BMI) and hormonal/metabolic state. The obtained data show a strong connection between leptin level, BMI and parameters of energetic metabolic state (insulin; HOMA index); regression analysis results indicated the participation of leptin in steroidogenesis. Odds ratio (OR) values indicated an important role of leptin in the formation of SA during body weight deficit and normal BMI. It has been found that various clinical types of SA have different patterns of leptin influence.


Cardiac Pulsatile Helical Deformation of the Thoracic Aorta Before and After Thoracic Endovascular Aortic Repair of Type B Dissections.
Type B aortic dissections propagate with either achiral (nonspiraling) or right-handed chiral (spiraling) morphology, have mobile dissection flaps, and are often treated with thoracic endovascular aortic repair (TEVAR). We aim to quantify cardiac-induced helical deformation of the true lumen of type B aortic dissections before and after TEVAR. Retrospective cardiac-gated computed tomography (CT) images before and after TEVAR of type B aortic dissections were used to construct systolic and diastolic 3-dimensional (3D) surface models, including true lumen, whole lumen (true+false lumens), and branch vessels. This was followed by extraction of true lumen helicity (helical angle, twist, and radius) and cross-sectional (area, circumference, and minor/major diameter ratio) metrics. Deformations between systole and diastole were quantified, and deformations between pre- and post-TEVAR were compared. Eleven TEVAR patients (59.9±4.6 years) were included in this study. Pre-TEVAR, there were no significant cardiac-induced deformations of helical metrics; however, post-TEVAR, significant deformation was observed for the true lumen proximal angular position. Pre-TEVAR, cardiac-induced deformations of all cross-sectional metrics were significant; however, only area and circumference deformations remained significant post-TEVAR. There were no significant differences of pulsatile deformation from pre- to post-TEVAR. Variance of proximal angular position and cross-sectional circumference deformation decreased after TEVAR. Pre-TEVAR, type B aortic dissections did not exhibit significant helical cardiac-induced deformation, indicating that the true and false lumens move in unison (do not move with respect to each other). Post-TEVAR, true lumens exhibited significant cardiac-induced deformation of proximal angular position, suggesting that exclusion of the false lumen leads to greater rotational deformations of the true lumen and lack of true lumen major/minor deformation post-TEVAR means that the endograft promotes static circularity. Population variance of deformations is muted after TEVAR, and dissection acuity influences pulsatile deformation while pre-TEVAR chirality does not. Description of thoracic aortic dissection helical morphology and dynamics, and understanding the impact of thoracic endovascular aortic repair (TEVAR) on dissection helicity, are important for improving endovascular treatment. These findings provide nuance to the complex shape and motion of the true and false lumens, enabling clinicians to better stratify dissection disease. The impact of TEVAR on dissection helicity provides a description of how treatment alters morphology and motion, and may provide clues for treatment durability. Finally, the helical component to endograft deformation is important to form comprehensive boundary conditions for testing and developing new endovascular devices.


High fat diet-induced modifications in membrane lipid and mitochondrial-membrane protein signatures precede the development of hepatic insulin resistance in mice.
Excess lipid intake has been implicated in the pathophysiology of hepatosteatosis and hepatic insulin resistance. Lipids constitute approximately 50% of the cell membrane mass, define membrane properties, and create microenvironments for membrane-proteins. In this study we aimed to resolve temporal alterations in membrane metabolite and protein signatures during high-fat diet (HF)-mediated development of hepatic insulin resistance. We induced hepatosteatosis by feeding C3HeB/FeJ male mice an HF enriched with long-chain polyunsaturated C18:2n6 fatty acids for 7, 14, or 21 days. Longitudinal changes in hepatic insulin sensitivity were assessed via the euglycemic-hyperinsulinemic clamp, in membrane lipids via t-metabolomics- and membrane proteins via quantitative proteomics-analyses, and in hepatocyte morphology via electron microscopy. Data were compared to those of age- and litter-matched controls maintained on a low-fat diet. Excess long-chain polyunsaturated C18:2n6 intake for 7 days did not compromise hepatic insulin sensitivity, however, induced hepatosteatosis and modified major membrane lipid constituent signatures in liver, e.g. increased total unsaturated, long-chain fatty acid-containing acyl-carnitine or membrane-associated diacylglycerol moieties and decreased total short-chain acyl-carnitines, glycerophosphocholines, lysophosphatidylcholines, or sphingolipids. Hepatic insulin sensitivity tended to decrease within 14 days HF-exposure. Overt hepatic insulin resistance developed until day 21 of HF-intervention and was accompanied by morphological mitochondrial abnormalities and indications for oxidative stress in liver. HF-feeding progressively decreased the abundance of protein-components of all mitochondrial respiratory chain complexes, inner and outer mitochondrial membrane substrate transporters independent from the hepatocellular mitochondrial volume in liver. We assume HF-induced modifications in membrane lipid- and protein-signatures prior to and during changes in hepatic insulin action in liver alter membrane properties - in particular those of mitochondria which are highly abundant in hepatocytes. In turn, a progressive decrease in the abundance of mitochondrial membrane proteins throughout HF-exposure likely impacts on mitochondrial energy metabolism, substrate exchange across mitochondrial membranes, contributes to oxidative stress, mitochondrial damage, and the development of insulin resistance in liver.


Mode-locked 1.93 microm thulium fiber laser with a carbon nanotube absorber.
We report a ring-cavity thulium fiber laser mode locked with a single-wall carbon nanotube absorber used in transmission. A carboxymethyl cellulose polymer film with incorporated carbon nanotubes synthesized by the arc discharge method has an absorption coinciding with in the amplification bandwidth of a Tm-doped fiber. This laser is pumped by an erbium fiber laser at 1.57 microm wavelength and produces a 37 MHz train of mode-locked 1.32 ps pulses at 1.93 microm wavelength with an average output power of 3.4 mW.


Oncologic Outcomes and Predictors in Patients with Stage PT3aNxM0 Renal Cell Carcinoma Following Radical Nephrectomy.
The objective of this study is to evaluate oncologic outcomes in patients with PT3aNxM0 renal cell carcinoma following radical nephrectomy and also to investigate these outcomes in each specific subgroup of PT3a renal cell carcinoma and to determine predictive factors of recurrence, metastasis, and mortality. In this retrospective cohort study, we included 94 patients with stage PT3a renal cell carcinoma who had undergone radical nephrectomy from 2011 to 2016. All patients who had survived had at least 60 months of follow-up. Demographic and clinical data were collected; univariable and multivariable Cox proportional hazards regression analysis was performed to identify predictors of metastasis, recurrence, and cancer-related mortality. Patients' mean age was 58.07 ± 11.17 years and 62/94 (65.9%) were male. The mean follow-up time was 48.1 ± 25.5 months. Forty-three patients (45.7%) had experienced cancer-related mortality. The mean cancer-specific survival time was 60.94 months and the mean metastasis-free and local recurrence-free survival times were 57.06 and 88.72 months, respectively. Metastasis and local recurrence had occurred in 42 (44.6%) and 4 (4.25%) patients, respectively. After performing multivariate analysis, higher nuclear Fuhrman's grade (P < .001) and simultaneous involvement of the renal vein and perinephric fat (P < .001) were found to be predictive of cancerrelated mortality. Advanced nuclear Fuhrman's grade was the only independent predictor of metastasis (P=.001). Based on our results, advanced nuclear Fuhrman's grade and sarcomatoid change can independently predict mortality in patients with stage PT3aNxM0 renal cell carcinoma. Close monitoring during the follow-up period is recommended in patients with the mentioned risk factors.


Clinical factors indicating the presence of malignant lymphoma before lymph node dissection.
Lymph node swelling in the neck is one of the initial symptoms of malignant lymphoma (ML). The present study showed that clinical factors including higher age, higher level of maximum standardized uptake value (SUV-max) of positron-emission tomography, elevated serum lactate dehydrogenase (LDH), and elevated serum soluble interleukin-2 receptor (sIL-2R) were all useful indicators to suggest the diagnosis of ML, so may be helpful in the selection of patients for lymph node dissection. Lymph node dissection is essential for the diagnosis of ML. The factors important for the diagnosis of ML were investigated, to establish surgical indicators. Preoperative data including age, number and side of lymph nodes, SUV-max, serum LDH, serum sIL-2R, and size of lymph nodes were obtained from medical records. The cut-off level for each factor was calculated using the Youden Index for logistic regression analysis. Multivariate logistic regression analysis showed that the following factors were associated with ML: higher age (≥ 53 years), higher level of SUV-max (≥ 9.0), elevated serum LDH (≥ 203 U/L), elevated serum sIL-2R (≥ 2590 U/ml), with odds ratios of 3.7, 4.9, 3.7, and 11.9, respectively.


Cognitive behavioural components in physiotherapy management of chronic whiplash associated disorders (WAD)--a randomised group study.
Different types of integrated management programmes have lately been introduced in the treatment of Whiplash Associated Disorders (WAD). In this study regular primary care physiotherapy and physiotherapy management with integrated components of cognitive-behavioural origin was compared in an experimental group study. The predictive value of self-efficacy was also addressed. In all thirty-three patients with chronic WAD were included in the trial. Results revealed no significant differences between groups in self-ratings of disability or pain intensity. However, among the self-reported benefits of treatment, patients in the experimental group reported significantly less pain than did the comparison group. At three months follow-up the experimental group also reported better performance of daily activities. Between group differences in the coping repertoire were found at pre-, post-and three-month follow-up. Generally, patients with high self-efficacy reported less use of 'maladaptive' and passive coping style than less self-efficient subjects at all times. In conclusion cognitive behavioural components can be useful in physiotherapy treatment for patients with chronic WAD, but their contributions are not yet fully understood. Self-efficacy is related to patients' use of different coping styles. Positive long-term outcomes in WAD-patients could therefore be improved by boosting self-efficacy and by teaching patients to use active, adaptive coping strategies.


Fragile X-related proteins regulate mammalian circadian behavioral rhythms.
Fragile X syndrome results from the absence of the fragile X mental retardation 1 (FMR1) gene product (FMRP). FMR1 has two paralogs in vertebrates: fragile X related gene 1 and 2 (FXR1 and FXR2). Here we show that Fmr1/Fxr2 double knockout (KO) and Fmr1 KO/Fxr2 heterozygous animals exhibit a loss of rhythmic activity in a light:dark (LD) cycle, and that Fmr1 or Fxr2 KO mice display a shorter free-running period of locomotor activity in total darkness (DD). Molecular analysis and in vitro electrophysiological studies suggest essentially normal function of cells in the suprachiasmatic nucleus (SCN) in Fmr1/Fxr2 double KO mice. However, the cyclical patterns of abundance of several core clock component messenger (m) RNAs are altered in the livers of double KO mice. Furthermore, FXR2P alone or FMRP and FXR2P together can increase PER1- or PER2-mediated BMAL1-Neuronal PAS2 (NPAS2) transcriptional activity in a dose-dependent manner. These data collectively demonstrate that FMR1 and FXR2 are required for the presence of rhythmic circadian behavior in mammals and suggest that this role may be relevant to sleep and other behavioral alterations observed in fragile X patients.


Cloned stromal cell lines derived from human Whitlock/Witte-type long-term bone marrow cultures.
We report a human bone marrow culture technique that initially parallels the murine Whitlock/Witte culture system. As in the murine system, B cells predominate over other cell types, and all differentiation stages from pre-B to plasma cell are observed. Although these human long-term cultures pass through stages resembling phases I to III of murine Whitlock/Witte cultures, no outgrowth of nonadherent cells was seen after cultures had reached the "crisis" phase unless Epstein-Barr virus (EBV)-transformants appeared. The stromal cells persisted well beyond crisis, but they could not be maintained and passaged as cell lines, limiting their use in molecular analysis. Transfection of these stromal cells with plasmid DNA containing the simian virus 40 (SV40) early region yielded 124 cloned cell lines. Analysis of these lines showed that all expressed SV40 large T antigen, but they retained most phenotypic markers found on non-transformed stromal cells. When adherent and T-cell-depleted bone marrow cells were cultured on either nontransformed stromal layers or transformed cell lines they proliferated actively and soon yielded predominantly lymphoid nonadherent populations. Moreover, prolonged survival of acute lymphoblastic leukemia cells of pre-B phenotype was regularly achieved on both normal and transformed adherent cell layers. Although the liquid culture system favored lymphocytes, transformed stroma supported colony formation by both human and murine hemopoietic progenitors when marrow was added in agar medium. This was not explained by colony-stimulating factor (CSF) production, because striking heterogeneity in the levels of granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) secretion by the lines was noted. Some lines that did not produce detectable CSF demonstrated good support of fresh bone marrow growth and acute lymphoblastic leukemia (ALL) cell survival. The heterogeneity of these cell lines and their capacity to support hemopoiesis suggest that they will be useful in studying the molecular basis of in vitro lymphohemopoiesis in man.


Genome-wide transcriptome analysis of the plant pathogen Xanthomonas identifies sRNAs with putative virulence functions.
The Gram-negative plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria (Xcv) is an important model to elucidate the mechanisms involved in the interaction with the host. To gain insight into the transcriptome of the Xcv strain 85-10, we took a differential RNA sequencing (dRNA-seq) approach. Using a novel method to automatically generate comprehensive transcription start site (TSS) maps we report 1421 putative TSSs in the Xcv genome. Genes in Xcv exhibit a poorly conserved -10 promoter element and no consensus Shine-Dalgarno sequence. Moreover, 14% of all mRNAs are leaderless and 13% of them have unusually long 5'-UTRs. Northern blot analyses confirmed 16 intergenic small RNAs and seven cis-encoded antisense RNAs in Xcv. Expression of eight intergenic transcripts was controlled by HrpG and HrpX, key regulators of the Xcv type III secretion system. More detailed characterization identified sX12 as a small RNA that controls virulence of Xcv by affecting the interaction of the pathogen and its host plants. The transcriptional landscape of Xcv is unexpectedly complex, featuring abundant antisense transcripts, alternative TSSs and clade-specific small RNAs.


APOL1 renal risk variants are associated with obesity and body composition in African ancestry adults: An observational genotype-phenotype association study.
While increased obesity prevalence among persons of African ancestry (AAs) compared to persons of European ancestry (EAs) is linked to social, environmental and behavioral factors, there are no gene variants that are common and significantly associated with obesity in AA populations. We sought to explore the association between ancestry specific renal risk variants in the apolipoprotein L1 (APOL1) gene with obesity related traits in AAs.We conducted a genotype-phenotype association study from 3 electronic medical record linked cohorts (BioMe Biobank, BioVU, nuGENE); randomized controlled trials (genetic testing to understand and address renal disease disparities) and prospective cohort study (Jackson Heart Study). We analyzed association of APOL1 renal risk variants with cross-sectional measures of obesity (average body mass index (BMI), and proportion of overweight and obesity) and with measures of body composition (in Jackson Heart Study).We had data on 11,930 self-reported AA adults. Across cohorts, mean age was from 42 to 49 years and percentage female from 58% to 75.3%. Individuals who have 2 APOL1 risk alleles (14% of AAs) have 30% higher obesity odds compared to others (recessive model adjusted odds ratio 1.30; 95% confidence interval 1.16-1.41; P = 2.75 × 10-6). An additive model better fit the association, in which each allele (47% of AAs) increases obesity odds by 1.13-fold (adjusted odds ratio 1.13; 95% confidence interval 1.07-1.19; P = 3.07 × 10-6) and increases BMI by 0.36 kg/m2 (∼1 kg, for 1.7 m height; P = 2 × 10-4). APOL1 alleles are not associated with refined body composition traits overall but are significantly associated with fat free mass index in women [0.30 kg/m2 increment per allele; P = .03].Thus, renal risk variants in the APOL1 gene, found in nearly half of AAs, are associated with BMI and obesity in an additive manner. These variants could, either on their own or interacting with environmental factors, explain a proportion of ethnic disparities in obesity.


Wolf-like or dog-like? A comparison of gazing behaviour across three dog breeds tested in their familiar environments.
Human-directed gazing, a keystone in dog-human communication, has been suggested to derive from both domestication and breed selection. The influence of genetic similarity to wolves and selective pressures on human-directed gazing is still under debate. Here, we used the 'unsolvable task' to compare Czechoslovakian Wolfdogs (CWDs, a close-to-wolf breed), German Shepherd Dogs (GSDs) and Labrador Retrievers (LRs). In the 'solvable task', all dogs learned to obtain the reward; however, differently from GSDs and LRs, CWDs rarely gazed at humans. In the 'unsolvable task', CWDs gazed significantly less towards humans compared to LRs but not to GSDs. Although all dogs were similarly motivated to explore the apparatus, CWDs and GSDs spent a larger amount of time in manipulating it compared to LRs. A clear difference emerged in gazing at the experimenter versus owner. CWDs gazed preferentially towards the experimenter (the unfamiliar subject manipulating the food), GSDs towards their owners and LRs gazed at humans independently from their level of familiarity. In conclusion, it emerges that the artificial selection operated on CWDs produced a breed more similar to ancient breeds (more wolf-like due to a less-intense artificial selection) and not very human-oriented. The next step is to clarify GSDs' behaviour and better understand the genetic role of this breed in shaping CWDs' heterospecific behaviour.


Pro-Choice Versus Pro-Life: The Relationship Between State Abortion Policy and Child Well-Being in the United States.
In the United States, pro-choice supporters contend that the desire of pro-life supporters to protect the life of the fetus ends at birth and that thereafter they ignore the health and well-being of infants and children. This study examines the question of whether infants and children fare better in U.S. states that have the most restrictive abortion laws. Eighteen indicators of infant/child health, family, economic, and educational status are analyzed. The empirical evidence finds that states with the most antiabortion policies are also the same states that have significantly lower indicators of infant/child well-being. This supports the contention by pro-choice supporters that efforts by pro-life supporters to protect the life of the fetus end at birth.


Measles immunity among community hospital employees.
To define measles immunity rates among employees at 2 hospitals during a community outbreak in 1990. Cohort survey using enzyme-linked immunosorbent assay (ELISA) and questionnaire. Two community hospitals. Seventy-six percent of 2,060 employees. Seven percent (115/1566) of participants lacked ELISA-defined measles immunity. Among employees whose ages were known, 14% (64/467) of those born after 1956 and 5% (50/1086) of those born before 1957 lacked serologic evidence of immunity. Fifty-eight percent of the susceptible persons had substantial patient contact. With ELISA results as the reference for immunity, the predictive value of an undocumented positive history of measles disease or vaccination was 95%; the predictive value of a negative history of both was 52%. Measles developed in 7 employees. A substantial number of hospital employees lacked ELISA-defined measles immunity, including many who had patient contact or who had been born before 1957. Undocumented disease and vaccination histories were not adequate predictors of serologic status. This study supports the recommendations and suggestions of the Immunization Practices Advisory Committee that hospitals should require documented evidence of measles immunity from employees who have patient contact.


Evaluating the Performance of De Novo Assembly Methods for Venom-Gland Transcriptomics.
Venom-gland transcriptomics is a key tool in the study of the evolution, ecology, function, and pharmacology of animal venoms. In particular, gene-expression variation and coding sequences gained through transcriptomics provide key information for explaining functional venom variation over both ecological and evolutionary timescales. The accuracy and usefulness of inferences made through transcriptomics, however, is limited by the accuracy of the transcriptome assembly, which is a bioinformatic problem with several possible solutions. Several methods have been employed to assemble venom-gland transcriptomes, with the Trinity assembler being the most commonly applied among them. Although previous evidence of variation in performance among assembly software exists, particularly regarding recovery of difficult-to-assemble multigene families such as snake venom metalloproteinases, much work to date still employs a single assembly method. We evaluated the performance of several commonly used de novo assembly methods for the recovery of both nontoxin transcripts and complete, high-quality venom-gene transcripts across eleven snake and four scorpion transcriptomes. We varied k-mer sizes used by some assemblers to evaluate the impact of k-mer length on transcript recovery. We showed that the recovery of nontoxin transcripts and toxin transcripts is best accomplished through different assembly software, with SDT at smaller k-mer lengths and Trinity being best for nontoxin recovery and a combination of SeqMan NGen and a seed-and-extend approach implemented in Extender as the best means of recovering a complete set of toxin transcripts. In particular, Extender was the only means tested capable of assembling multiple isoforms of the diverse snake venom metalloproteinase family, while traditional approaches such as Trinity recovered at most one metalloproteinase transcript. Our work demonstrated that traditional metrics of assembly performance are not predictive of performance in the recovery of complete and high quality toxin genes. Instead, effective venom-gland transcriptomic studies should combine and quality-filter the results of several assemblers with varying algorithmic strategies.


Influence of sulfobutylether-beta-cyclodextrin on the stability of S- and R- omeprazole.
Omeprazole (OME), a proton pump inhibitor used to treat acid reflux disease and gastric ulcers presents a formulation challenge due to its rapid decomposition at acidic and neutral pHs. Thus, the aim of this project was to investigate whether interaction with sulfobutylether-beta-cyclodextrin (Captisol-CD) could improve omeprazole stability and provide more efficient oral liquid formulations. A stability-indicating high performance liquid chromatography assay allowed for the quantitation of S- and R-forms of OME in the presence and absence of Captisol-CD. The developed method was validated to discriminate between OME and its degradation products and used to describe the kinetic model of OME at different pH values over a period of 36 days. Calculated degradation constants (k(obs)), were directly correlated with the H(+) concentrations of the solutions regardless of whether the omeprazole was complexed with the Captisol-CD or not. Moreover, the pH-rate profile curve indicated that in all cases, maximum stability was achieved at pH 11. Though it was anticipated that interaction of OME with Captisol-CD might increase the relative stability of OME at a lower pH, the cavity of the cyclodextrin was too small to allow the inclusion to occur. However the R-isomer of OME, both in the presence or absence of the cyclodextrin appeared to be slightly less stable than the corresponding S-form at the same pH conditions.


decapentaplegic is a direct target of dTcf repression in the Drosophila visceral mesoderm.
Drosophila T cell factor (dTcf) mediates transcriptional activation in the presence of Wingless signalling and repression in its absence. Wingless signalling is required for the correct expression of decapentaplegic (dpp), a Transforming Growth Factor (beta) family member, in parasegments 3 and 7 of the Drosophila visceral mesoderm. Here we demonstrate that a dpp enhancer element, which directs expression of a reporter gene in the visceral mesoderm in a pattern indistinguishable from dpp, has two functional dTcf binding sites. Mutations that reduce or eliminate Wingless signalling abolish dpp reporter gene expression in parasegment 3 and reduce it in parasegment 7 while ectopic expression of Wingless signalling components expand reporter gene expression anteriorly in the visceral mesoderm. However, mutation of the dTcf binding sites in the dpp enhancer results in ectopic expression of reporter gene expression throughout the visceral mesoderm, with no diminution of expression in the endogenous sites of expression. These results demonstrate that the primary function of dTcf binding to the dpp enhancer is repression throughout the visceral mesoderm and that activation by Wingless signalling is probably not mediated via these dTcf binding sites to facilitate correct dpp expression in the visceral mesoderm.


[Pseudomonas pneumonia--an important differential pulmonary infiltration diagnosis in AIDS].
Bacterial pneumonias are the most common pulmonary complication in HIV-infected patients. Up to now, H. influenzae and S. pneumoniae have been described as the most important germs. Within a period of 4 years we diagnosed 15 cases of pneumonia caused by P. aeruginosa. All patients were in HIV stage C3; 3F, 12M; median age 34 (24-54) years; median CD4 count 10 (0-130) microliters. Except for 3 nosocomial pneumonias, all others were community-acquired. Only 3 patients had neutropenia < 1000/microliter; 7 were intravenous drug abusers. Morphologically there were 6 cases of abscess pneumonia, in 3 of which pleural drainage was necessary because of pyopneumothorax. 4 patients showed bilateral infiltrates that could not be differentiated from those of P. carinii pneumonia. Our diagnosis was based on quantitative cultures of broncho-alveolar lavage fluid (9 cases, two of them with concurrent positive blood cultures/positive cultures of the pleural fluid), pleural puncture (one case), sputum in pneumonias responding only to antipseudomonas therapy (3 cases), and autopsy (2 cases). 8 patients died of pseudomonas pneumonia within 1-3 months despite therapy. 7 patients received pseudomonas-specific combination therapy, but all died after median 9 (4-15) months of the underlying illness. In 3 cases recurrent pseudomonas pneumonia could be documented bacteriologically. We conclude that in HIV-infected patients pneumonia caused by P. aeruginosa is a significant and severe pulmonary complication.


Incidence and clinical characteristics of ciguatera fish poisoning in Guadeloupe (French West Indies) between 2013 and 2016: a retrospective cases-series.
This retrospective case study analysed the incidence and symptoms of ciguatera fish poisoning (ciguatera) in Guadeloupe (French West Indies) between 2013 and 2016. Cases attending the emergency departments of the two public hospitals and the reports received by the regional health authority in charge of monitoring (ARS) were compiled. Two hundred and thirty-four cases of poisoning were observed, with a mean annual incidence of 1.47/10,000 (95% CI): 1.29-1.66), i.e 5 times higher than the previously reported incidence (1996-2006). The main species described as being responsible for poisoning were fish from the Carangidae family (n = 47) (jack), followed by fish from the Lutjanidae family (n = 27) (snapper), Serranidae family (n = 15) (grouper), Sphyraenidae family (n = 12) (barracuda), and Mullidae family (n = 12) (goatfish). One case of lionfish ciguatera was observed. 93.9% of patients experienced gastrointestinal symptoms, 76.0% presented neurological signs (mainly paresthesia, dysesthesia and pruritus) and 40.3% presented cardiovascular symptoms (bradycardia and/or hypotension). A high frequency (61.4%) of hypothermia (body temperature <36.5 °C) was observed. This study reports for the first time the relatively high frequency of cardiac symptoms and low body temperature. The monitoring of ciguatera poisoning throughout the Caribbean region must be improved, notably after reef disturbance due to Irma and Maria major cyclones.


A case of superior vena cava syndrome caused by Klebsiella pneumoniae.
A 27 yr old man presented with productive cough, fever and manifestations of superior vena cava syndrome. He was an alcoholic but had been in good health until 3 days prior to admission. The physical examination, the chest radiograph and the results of the sputum culture were compatible with Klebsiella pneumoniae pneumonia of the right upper lobe. The superior vena cava scintigram using technetium-99m showed near total occlusion of the superior vena cava, while sputum cytology, chest computed tomography, and bronchoscopy were all negative for malignant aetiology. Antibiotic therapy brought about slow resolution of the pneumonia and also of the superior vena caval obstruction. The follow-up scintigram showed normalized venous flow of the superior vena cava. To our knowledge, this is the first case of superior vena cava syndrome developed in probable association with Klebsiella pneumoniae pneumonia.


Pornography Use, Two Forms of Dehumanization, and Sexual Aggression: Attitudes vs. Behaviors.
Sexual objectification is a common pornographic theme. Research shows that sexual objectification leads to the expression of aggressive attitudes and behaviors toward women. Based on a survey study of 320 male participants, this study re-conceptualizes sexual objectification in terms of two forms of dehumanization. Evidence suggests men's pornography use is positively associated with both forms, but mechanistic dehumanization of women is more associated with aggressive attitudes while animalistic dehumanization is more associated with aggressive behaviors. Findings indicate how objectifying pornography use may relate to aggressive attitudes and behaviors and inform the future education campaigns and interventions to reduce sexual aggression.


A rare collision tumor of squamous carcinoma and small cell carcinoma in esophagus involved with separate lymph nodes: a case report.
We report a case of an esophageal collision tumor composed of squamous cell carcinoma and small cell carcinoma (SmCC). A 66-year-old man complained of chest pain after oral intake for nearly one month. The patient received two cycles of neoadjuvant platinum-based combination chemotherapy and enhanced computed tomography showed a partial response of the tumor. He then underwent a thoracolaparoscopic esophagectomy with extensive mediastinal lymphadenectomy. Two cycles of chemotherapy and prophylactic irradiation of the lymphatic drainage region were sequentially achieved after surgery. The patient has survived for more than 18 months with no evidence of recurrent disease since surgical resection.


[Comprehensive Assessment and Treatment of Cataracts].
Cataract is a global disease that may cause blindness. Due to the slow pace of disease progression, patients often presume incorrectly that their blurred vision is caused by excessive fatigue or lack of sleep. In addition to their role in causing blindness, cataracts that are diagnosed late into their progression are more difficult to treat with corrective surgery. Furthermore, many older individuals believe incorrectly that declines in vision are part of the natural course of aging and accept these declines as inevitable. Reduced vision has a significant and negative effect on quality of life. Although aging is one of the main causes of cataracts, other major factors include common chronic diseases and the side effects of drugs. In addition, lifestyle factors such as diet, activity, and environmental exposure to ultraviolet rays and radiation are factors in cataract development. Surgery is the only treatment for cataracts currently available. Healthcare professionals not only consider a patient's background but also whether surgery may promote quality of life. While preoperative evaluation requires a holistic and comprehensive approach, postoperative care is also important to the overall success of cataract surgery. For example, instructions in topical-drop application, wound assessment, and symptoms of comorbidities are crucial for patients. Therefore, a critical literature review was used in this article to establish a strategy for the holistic evaluation of and perioperative nursing care and prevention strategies for cataracts. In addition, recommendations for the comprehensive assessment of and nursing care for patients with cataracts are provided to healthcare professionals article in hopes of improving the quality of care provided to patients with cataracts.


Implantation Failure Is Associated With Increased α-Inhibin and β-Glycan Gene Expression in Secretory Phase Endometrium: Nested Case-Control Study of Infertile Women Undergoing IVF/Fresh Embryo Transfer.
Embryo implantation involves a complex sequence of events, and a large amount of molecules have been postulated to be involved in the interaction of embryo and endometrium. This study evaluated the endometrial expression of α-inhibin and β-glycan in the mid-secretory phase of women scheduled to in vitro fertilization (IVF) and tested whether these markers are associated with implantation failure. We performed a nested case-control study including 52 women submitted to IVF and embryo transfer, divided into 2 groups: cases with implantation failure (n = 33) and controls with confirmed clinical pregnancy (n = 19). Endometrial α-inhibin and β-glycan gene expression was evaluated in the mid-secretory phase of the natural menstrual cycle immediately before IVF, using real-time polymerase chain reaction. We found a higher gene expression of α-inhibin (fold increase = 2.14 ± 0.32, P < .05) and β-glycan (fold increase = 1.44 ± 0.16, P < .05) in implantation failure patients compared to confirmed clinical pregnancy patients. The areas under the receiver operating characteristics curves for prediction of implantation failure in this context were 0.692 and 0.678 for α-inhibin and β-glycan, respectively. The present results suggest that high expression levels of α-inhibin and β-glycan transcripts in secretory phase endometrium are associated with a lower chance of achieving pregnancy with IVF.


Women's experiences of cervical cellular changes: an unintentional transition from health to liminality?
Cervical cancer screening is a preventive intervention directed towards women to both detect cervical cancer and identify those at risk for developing this disease. It has been argued that participation in screening programmes and early detection situations may lead to new kinds of sickness experiences. This article is based on qualitative phenomenological hermeneutical analysis of interviews with women who have received abnormal Pap smear test results through a population-based outreach screening programme in urban Sweden. The aim of this article is to illuminate the meaning, for the participating women, of the lived experience of receiving notification about an abnormal Pap smear result. The data are presented in terms of two themes: Pap smear for routine and recurrent confirmation of health and unexpected and ambiguous communication about Pap smear results. The findings are discussed as an unintentional transition from confirmation of health to liminality. Whereas medical diagnosis has been discussed as structuring the inchoate, an abnormal Pap smear did not create order for the interviewed women. On the contrary, the notification of an abnormal Pap smear created disorder as the women had expected to be confirmed as healthy but instead neither health nor disease were confirmed or excluded. Even 'simple' technology is shown to have an ontological dimension, with the ability to transform daily taken-for-grantedness of ourselves as primarily healthy to (potentially) unhealthy.


Feasibility of a Global Positioning System to Assess the Spatiotemporal Characteristics of Polo Performance.
The implementation of global positioning systems (GPSs) has become widely supported in a variety of sports, owing to the insight it provides into athlete workloads, training parameters, and playing styles. Despite widely reported use of GPS in equine settings, few studies have quantified the reliability of spatiotemporal characteristics in a dynamic environment of high-intensity gameplay. Owing to the unique game demands of Polo for both riders and horses, this study aimed to assess the interunit reliability between a traditional GPS placement between the shoulder blades and a Polo-specific placement on players' belts, to inform the feasibility of GPS implementation within Polo. GPS data were collected across 37 unique rider-horse interactions. GPS metrics included distance covered, speeds attained, and number of sprints performed. Data were further categorized with respect to equine-specific speed zones. All metrics agreed across multiple reliability measures and were deemed qualitatively reliable (intraclass correlation coefficient > 0.70 and coefficient of variation < 10%), with sprint count displaying 100% agreement between units. Findings suggest the spatiotemporal characteristics of Polo can be reliably measured via GPS through a traditional or belt-based placement, which leaves the decision of GPS placement at riders' discretion.


At the deep end: COVID-19 experiences of Zimbabwean health and care workers in the United Kingdom.
Black, Asian and Minority Ethnic groups (BAME) in the UK were disproportionately affected by the first phase of COVID-19 in terms of exposure, negative health and socio-economic impacts and consequences including recorded deaths. However, aggregate categories like BAME mask internal diversities and differences and limit the scope for understanding why disproportionalities occur and appropriate interventions. This paper responds to calls for disaggregated and in-depth participatory community based research to improve culturally nuanced understanding of health inequalities and COVID-19 impacts. The paper draws from weekly zoom discussions and data from a google-forms on-line survey (n = 103) that the Zimbabwean community conducted to establish and examine COVID-19 experiences of Zimbabwean health and care workers in the UK. Our interpretive approach used MAXQDA software for qualitative data analysis; to code and categorise responses to open ended survey questions. Discursive analysis of this community data shows that health and social care worker experiences included recurrent and widely reported themes such as discrimination in allocation of equipment, moral injury and trauma that may lead to long- term mental health problems. These results confirm diversity of experiences amongst health care professionals when compared to other ethnic groups and by gender. They reinforce the case for monitoring, for after care research and support, including that which draws on community-based capital.


HiTRACE-Web: an online tool for robust analysis of high-throughput capillary electrophoresis.
To facilitate the analysis of large-scale high-throughput capillary electrophoresis data, we previously proposed a suite of efficient analysis software named HiTRACE (High Throughput Robust Analysis of Capillary Electrophoresis). HiTRACE has been used extensively for quantitating data from RNA and DNA structure mapping experiments, including mutate-and-map contact inference, chromatin footprinting, the Eterna RNA design project and other high-throughput applications. However, HiTRACE is based on a suite of command-line MATLAB scripts that requires nontrivial efforts to learn, use and extend. Here, we present HiTRACE-Web, an online version of HiTRACE that includes standard features previously available in the command-line version and additional features such as automated band annotation and flexible adjustment of annotations, all via a user-friendly environment. By making use of parallelization, the on-line workflow is also faster than software implementations available to most users on their local computers. Free access: http://hitrace.org.