The development and initial psychometric evaluation of a measure assessing adherence to prescribed exercise: the Exercise Adherence Rating Scale (EARS).
There is no gold standard for measuring adherence to prescribed home exercise. Self-report diaries are commonly used however lack of standardisation, inaccurate recall and self-presentation bias limit their validity. A valid and reliable tool to assess exercise adherence behaviour is required. Consequently, this article reports the development and psychometric evaluation of the Exercise Adherence Rating Scale (EARS). Development of a questionnaire. Secondary care in physiotherapy departments of three hospitals. A focus group consisting of 8 patients with chronic low back pain (CLBP) and 2 physiotherapists was conducted to generate qualitative data. Following on from this, a convenience sample of 224 people with CLBP completed the initial 16-item EARS for purposes of subsequent validity and reliability analyses. Construct validity was explored using exploratory factor analysis and item response theory. Test-retest reliability was assessed 3 weeks later in a sub-sample of patients. An item pool consisting of 6 items was found suitable for factor analysis. Examination of the scale structure of these 6 items revealed a one factor solution explaining a total of 71% of the variance in adherence to exercise. The six items formed a unidimensional scale that showed good measurement properties, including acceptable internal consistency and high test-retest reliability. The EARS enables the measurement of adherence to prescribed home exercise. This may facilitate the evaluation of interventions promoting self-management for both the prevention and treatment of chronic conditions.


Depletion of 43-kD growth-associated protein in primary sensory neurons leads to diminished formation and spreading of growth cones.
The 43-kD growth-associated protein (GAP-43) is a major protein kinase C (PKC) substrate of growing axons, and of developing nerve terminals and glial cells. It is a highly hydrophilic protein associated with the cortical cytoskeleton and membranes. In neurons it is rapidly transported from the cell body to growth cones and nerve terminals, where it accumulates. To define the role of GAP-43 in neurite outgrowth, we analyzed neurite regeneration in cultured dorsal root ganglia (DRG) neurons that had been depleted of GAP-43 with any of three nonoverlapping antisense oligonucleotides. The GAP-43 depletion procedure was specific for this protein and an antisense oligonucleotide to the related PKC substrate MARCKS did not detectably affect GAP-43 immunoreactivity. We report that neurite outgrowth and morphology depended on the levels of GAP-43 in the neurons in a substrate-specific manner. When grown on a laminin substratum, GAP-43-depleted neurons extended longer, thinner and less branched neurites with strikingly smaller growth cones than their GAP-43-expressing counterparts. In contrast, suppression of GAP-43 expression prevented growth cone and neurite formation when DRG neurons were plated on poly-L-ornithine. These findings indicate that GAP-43 plays an important role in growth cone formation and neurite outgrowth. It may be involved in the potentiation of growth cone responses to external signals affecting process formation and guidance.


A characterization study of some aspects of the adsorption of aqueous Co2+ ions on a natural bentonite clay.
The natural bentonite used in this study contained montmorillonite in addition to low cristobalite. The uptake of aqueous Co(2+) ions was investigated as a function of time, concentration, and temperature. In addition, the change in the interlayer space of montmorillonite was analyzed using XRPD, and the distribution of fixed Co(2+) ions on the heterogeneous clay surface was recorded using EDS mapping. The sorbed amount of Co(2+) appeared to closely follow Freundlich isotherm, with the sorption process showing apparent endothermic behavior. The relevance of the apparent DeltaH(o) values is briefly discussed. Analysis of the Co-sorbed bentonite samples using SEM/EDS showed that the montmorillonite fraction in the mineral was more effective in Co(2+) fixation than the cristobalite fraction. XRPD analysis demonstrated that the interlayer space of montmorillonite was slightly modified at the end of sorption.


Epilepsy in young adults with autism: a prospective population-based follow-up study of 120 individuals diagnosed in childhood.
Little is known about the long-term outcome of epilepsy in autism and the epilepsy characteristics of adults with autism. This prospective population-based study was conducted in an attempt to point out differences on a group basis between adults with autism with or without epilepsy, and to describe the occurrence, the seizure characteristics, and the outcome of epilepsy in autism. One hundred eight of 120 individuals with autism diagnosed in childhood and followed up prospectively for a period of 13-22 years were reevaluated at ages 17-40 years. As adults, the majority had mental retardation and autistic disorder or autistic-like condition. Interviews were performed with the caretakers of 42 of 43 individuals with a history of epilepsy, and their medical records were reviewed. Adults with autism and mental retardation constituted a severely disabled group. On a group basis, both the cognitive level and the adaptive behavior level were lower in the epilepsy group than in the nonepilepsy group (p<0.05). In all, 38% had epilepsy. One third had epilepsy onset before age 2 years. Remission of epilepsy was seen in 16%. Partial seizures with or without secondarily generalized seizures were the dominating seizure type. In a community sample of individuals with autism followed up from childhood through to adult age, one of three had epilepsy since childhood/adolescence. Severe mental retardation and autism are significantly associated with epilepsy, especially in female patients. Seizure frequency has a great impact on the individuals' lives. Specialist medical care is needed in this severely communication-disabled population.


Review of 2022 WHO guidelines on the control and elimination of schistosomiasis.
Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.


Activation of SsoPK4, an Archaeal eIF2α Kinase Homolog, by Oxidized CoA.
The eukaryotic protein kinase (ePK) paradigm provides integral components for signal transduction cascades throughout nature. However, while so-called typical ePKs permeate the Eucarya and Bacteria, atypical ePKs dominate the kinomes of the Archaea. Intriguingly, the catalytic domains of the handful of deduced typical ePKs from the archaeon Sulfolobus solfataricus P2 exhibit significant resemblance to the protein kinases that phosphorylate translation initiation factor 2α (eIF2α) in response to cellular stresses. We cloned and expressed one of these archaeal eIF2α protein kinases, SsoPK4. SsoPK4 exhibited protein-serine/threonine kinase activity toward several proteins, including the S. solfataricus homolog of eIF2α, aIF2α. The activity of SsoPK4 was inhibited in vitro by 3',5'-cyclic AMP (Ki of ~23 µM) and was activated by oxidized Coenzyme A, an indicator of oxidative stress in the Archaea. Activation enhanced the apparent affinity for protein substrates, Km, but had little effect on Vmax. Autophosphorylation activated SsoPK4 and rendered it insensitive to oxidized Coenzyme A.


Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats.
Prolonged treatment with stress levels of corticosterone has been reported to produce changes in the hippocampus. In the experiments reported here, we examined for functional and morphological consequences of this treatment. First, young adult or mid-aged male Long-Evans rats were treated for either 1 or 3 months with corticosterone, at a dose sufficient to mimic the elevated hormone levels observed following exposure to mild stress. Two weeks following the termination of treatment, the animals were tested in the Morris water maze to assess spatial learning. No behavioral deficits were observed after 1 month of treatment. A 3 month treatment period also had no effect in young rats, but produced a learning impairment in the mid-aged rats. We then examined whether the effect of elevated corticosterone in mid-aged animals could be produced by a physiological stressor. Mid-aged rats were maintained for 6 months under conditions of low or high social stress. Six months of exposure to high social stress produced significant spatial learning impairments in the Morris water maze. These effects were absent in high social stress animals that had been previously adrenalectomized (with low-level corticosterone replacement), suggesting that elevated glucocorticoid levels mediate the effects of stress on spatial memory in older animals. In a final experiment, mid-aged rats were treated with corticosterone at levels that mimicked those naturally occurring at the diurnal peak (medium-B: 12-17 micrograms/dl) or in response to stress (high-B: 25-32 micrograms/dl). Only rats exposed to high levels of corticosterone demonstrated impaired performance in the Morris water maze.(ABSTRACT TRUNCATED AT 250 WORDS)


Exercise and sports participation after surgery for congenital heart disease: the European perspective.
The success of surgery for congenital heart disease which has been performed since many years has created a population of patients who require careful follow-up in order to determine their clinical progress and to establish the type and intensity of physical activity which they can safely perform. The authors illustrate the opinion of the European Community regarding children, sport and organizational aspects and also problems concerning the management of pediatric cardiac patients in Europe and Italy. Cardiological and surgical aspects are considered together with the practice of physical activity, with emphasis upon the differences between the various countries. Particular attention is paid to the Italian legislation regarding the certification to participate in competitive or non-competitive sport in such a population of patients. Great importance is given to pediatric cardiac rehabilitation programs which aim at improving the aerobic fitness of patients operated upon for complex congenital heart disease and at illustrating their own cardiovascular limitations so that they can perform physical exercise with the utmost safety.


Differential Impacts of HIV status on short-term fertility desires among couples in Rakai, Uganda.
Fertility desires of female and male partners in current relationships are often correlated. We examined the influence of HIV seropositive status of female and male partners on short-term fertility desires in Rakai, Uganda, a setting with high fertility and HIV infection rates. Participants were couples (15-49 years old) enrolled in the Rakai Community Cohort Study, from 2011 to 2013 (n = 2,291). Cohen's kappa coefficient was used to measure the correlation of female and male partners' short-term fertility desires (measured as 'wanting a child in the next 12 months'), in both total sample and stratified serostatus groups. HIV serostatus and additional characteristics of female and male partners were included in Poisson regression models to estimate the rate ratios (RR) for each partner's short-term fertility desires. Individual and partner characteristics included HIV status, partner HIV status, age in years, partner age in years, educational attainment, number of living children, community of residence, and socioeconomic status (SES). Short-term fertility desires among female and male partners were moderately associated (Kappa = 0.37, p-value<0.001). The association was weakest among female sero-positive and male sero-negative couples (Kappa = 0.29, p-value<0.001). When adjusting for parity and other covariates in the model, women's short-term fertility desires were significantly associated with their positive sero-status regardless of male partners' sero-status (adjRR = 1.58, p<0.001 for F+M-; adjRR = 1.33, p = 0.001 for F+M+; in comparison with F-M-). Men's short-term fertility desires were significantly associated with their positive sero-status, in addition to their female partners' positive sero-status (adjRR = 1.23 with p-value = 0.022 for F-M+; adjRR = 1.42 with p-value<0.001 for F+M-; adjRR = 1.26 with p-value<0.001 for F+M+; in comparison with F-M-). When the differential effect of parity was included in the model, similar associations remained for both female and male partners when the number of living children was small, but largely reduced when the number of living children was large (3 or more). Female and male partners in couple dyads demonstrated moderate agreements about short-term fertility desires. The HIV seropositive status of female partners was most strongly associated with short-term fertility desires of both genders, and this association was even stronger for women who had few or no living children.


Paraneoplastic hypercalcemia.
Paraneoplastic syndromes (PNSs) are neoplasm-associated alterations in bodily structure or function or both that occur distant to the tumor. They are an extremely diverse group of clinical aberrations that are associated with the noninvasive actions of the tumor. In many situations, the PNS parallels the underlying malignancy, and therefore, successful treatment of the tumor leads to disappearance of the PNS. Alternatively, recurrence of the PNS after successful treatment signals recurrence of the tumor, and the return of the PNS often significantly precedes the detectable recurrence of the tumor. This is often the case with paraneoplastic hypercalcemia, often referred to as hypercalcemia of malignancy (HM). The most common cause of hypercalcemia in dogs is cancer. Neoplasia is diagnosed in approximately two-thirds of dogs with hypercalcemia vs. approximately one-third in cats. A variety of tumors have been associated with HM. Lymphoma is the most common cause of HM, and the most common anatomical site for dogs with lymphoma-associated HM is the cranial mediastinum. Other tumors associated with HM in dogs and cats include anal sac apocrine gland adenocarcinoma, thyroid carcinoma, multiple myeloma, bone tumors, thymoma, squamous cell carcinoma, mammary gland carcinoma/adenocarcinoma, melanoma, primary lung tumors, chronic lymphocytic leukemia, renal angiomyxoma, and parathyroid gland tumors. As HM is a potential medical emergency, the primary goal in cases of HM is the elucidation of the underlying cause and thereby instituting the appropriate specific therapy.


Incidence and Outcomes of Infectious and Noninfectious Endophthalmitis after Intravitreal Injections for Age-Related Macular Degeneration.
To assess the incidence, cumulative rate, and long-term outcomes of infectious and noninfectious endophthalmitis after intravitreal injections (IVTs) of anti-vascular endothelial growth factor (VEGF) agents. Database study, prospectively designed. Treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) tracked by the Fight Retinal Blindness! (FRB!) registry that commenced anti-VEGF therapy between January 1, 2006, and November 30, 2016. Cumulative rate of endophthalmitis and survival curves were measured using Cox-proportional hazards models. Locally weighted scatterplot smoothing curves were used to display visual acuity (VA). Incidence and cumulative rate of endophthalmitis, and change in VA 12 months after endophthalmitis. Infectious endophthalmitis developed in 18 of 88 150 injections (1/4897 injections [0.020%]; 95% confidence interval [CI], 0.012-0.032) with no difference found between types of anti-VEGF medications (P = 0.896). The cumulative rate of infectious endophthalmitis per patient was 0.055%, 0.183%, 0.360%, 0.360%, 0.555%, and 0.843% after 10, 20, 30, 40, 50, and 60 IVTs, respectively. However, the "risk" of infectious endophthalmitis did not increase with each successive injection (P = 0.202). Noninfectious endophthalmitis developed in 11 of 88 150 injections (1/8013 injections [0.012%]; 95% CI, 0.006-0.022). The cumulative rate of noninfectious endophthalmitis per patient was 0.087% and 0.228% after 10 and 20 IVTs, respectively, and then remained stable up to 60 IVTs. The incidence of noninfectious endophthalmitis was higher for bevacizumab (8/9931, 0.081%) compared with ranibizumab (3/54 776, 0.005%; P = 0.005) and aflibercept (0/23 425; P = 0.016), and no differences were observed between ranibizumab and aflibercept (P = 1.0). The 12-month VA in infectious and noninfectious endophthalmitis was within ±2 lines of before endophthalmitis in 53% and 75% of eyes, respectively; a loss >2 lines was observed in 31% and 25% of eyes, respectively. The incidences of infectious and noninfectious endophthalmitis after IVT were low, and the risk did not increase with each successive injection. We found higher rates of noninfectious endophthalmitis with bevacizumab compared with ranibizumab or aflibercept. Three quarters of cases with infectious and two thirds of cases with noninfectious endophthalmitis retained vision within 10 letters of the pre-endophthalmitis level.


Knowledge, behaviors, attitudes and beliefs of physiotherapists towards the use of psychological interventions in physiotherapy practice: a systematic review.
To systematically review and analyze the literature exploring the knowledge, behaviors, attitudes, and beliefs of physiotherapists towards the use of psychological interventions in their practice. A systematic search was conducted, of articles published between January 1996 and February 2016, using selected electronic databases followed by crosschecking of reference and citation lists. Articles were selected on the basis of the research reported relating to knowledge, behaviors, attitudes or beliefs of physiotherapists towards using a number of different psychological interventions. Quality assessment was conducted by three reviewers independently, and thematic analysis of the included studies was performed. Fifteen studies were included in the analysis. Results indicate that physiotherapists are aware of psychological interventions, are using a variety within practice, and have positive attitudes and beliefs towards their use. However, there are barriers to the incorporation of psychological interventions into their practice, including lack of knowledge, time constraints, and role clarity. The desire for further training was also evident. Notwithstanding the reported awareness and use of psychological interventions in physiotherapy practice, barriers to implementation exist indicating that further research is necessary to address how to effectively equip physiotherapists, to employ such techniques within their scope of practice. Implications for rehabilitation Physiotherapists use and have positive attitudes and beliefs towards a variety of psychological interventions including goal setting, positive, and motivational talk, cognitive behavioral therapy strategies and offering social support. Barriers preventing the incorporation of psychological interventions in practice include, lack of knowledge, time constraints, and role clarity. Despite the use of such interventions, physiotherapists identify the need for further training, to be better equipped to confidently utilize these in practice. These results justify the incorporation of training in psychological interventions in physiotherapist qualifying studies, but also as continued professional development opportunities for physiotherapists currently working in the field.


Circ-0000284 arouses malignant phenotype of cholangiocarcinoma cells and regulates the biological functions of peripheral cells through cellular communication.
Circular RNAs (circRNAs) play a vital role in cancers. Accumulated evidences showed that the physiological condition of cells can be reflected by the circRNAs in the exosomes they secrete, and these exosomal circRNAs can be captured by the receptor cells, thereby inducing a series of cellular responses. We performed qRT-PCR to detect the expression level of circ-0000284 in cholangiocarcinoma cell lines, tissues and plasma exosomes. Then the direct interaction between circ-0000284 and miR-637 was investigated through dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP) assay and Fluorescent in situ hybridization (FISH) assay. Subsequently, EdU (5-ethynyl-2'-deoxyuridine), migration, invasion assay, flow cytometry and nude mouse tumorigenicity assay were adopted to evaluate the effect of circ-0000284 on migration, invasion, proliferation and apoptosis of cholangiocarcinoma cells. Additionally, TEM was conducted to investigate the shape and size of exosomes from cholangiocarcioma and 293T cell lines. Circ-0000284 was evidently elevated in cholangiocarcinoma cell lines, tumor tissues and plasma exosomes. Meanwhile, the high expression of circ-0000284 enhanced the migration, invasion and proliferation abilities of cholangiocarcinoma cells in vivo and in vitro Besides, the levels of circ-0000284 were increased in cholangiocarcinoma cells and exosomes from them. Moreover, exosomes from cholangiocarcinoma cells enhanced circ-0000284 expression and stimulated migration and proliferation of the surrounding normal cells. Our findings suggest that on the one hand circ-0000284 functions as a competitive endogenous RNA to promote cholangiocarcinoma progression, and on the other hand, circ-0000284 can be directly transferred from cholangiocarcinoma cells to surrounding normal cells via exosomes and in this way regulate the biological functions of surrounding normal cells.


Opioid prescribing trends and geographical variation in England, 1998-2018: a retrospective database study.
There is a call for greater monitoring of opioid prescribing in the UK, particularly of strong opioids in chronic pain, for which there is little evidence of clinical benefit. We aimed to comprehensively assess trends and variation in opioid prescribing in primary care in England, from 1998 to 2018, and to assess factors associated with high-dose opioid prescribing behaviour in general practices. We did a retrospective database study using open data sources on prescribing for all general practices in England. For all standard opioids we calculated the number of items prescribed, costs, and oral morphine equivalency to account for variation in strength. We assessed long-term prescribing trends from 1998 to 2017, patterns of geographical variation for 2018, and investigated practice factors associated with higher opioid prescribing. We also analysed prescriptions for long-acting opioids at high doses. Between 1998 and 2016, opioid prescriptions increased by 34% in England (from 568 per 1000 patients to 761 per 1000). After correcting for total oral morphine equivalency, the increase was 127% (from 190 000 mg to 431 000 mg per 1000 population). There was a decline in prescriptions from 2016 to 2017. If every practice prescribed high-dose opioids at the lowest decile rate, 543 000 fewer high-dose prescriptions could have been issued over a period of 6 months. Larger practice list size, ruralness, and deprivation were associated with greater high-dose prescribing rates. The clinical commissioning group to which a practice belongs accounted for 11·7% of the variation in high-dose prescribing. We have developed a publicly available interactive online tool, OpenPrescribing.net, which displays all primary care opioid prescribing data in England down to the individual practice level. Failing to account for opioid strength would substantially underestimate the true increase in opioid prescribing in the National Health Service (NHS) in England. Our findings support calls for greater action to promote best practice in chronic pain prescribing and to reduce geographical variation. This study provides a model for routine monitoring of opioid prescribing to aid targeting of interventions to reduce high-dose prescribing. National Institute for Health Research (NIHR) School of Primary Care Research, NIHR Biomedical Research Centre Oxford, NHS England.


Homeopathy as Boundary Object and Distributed Therapeutic Agency. A Discussion on the Homeopathic Placebo Response.
We discuss homeopathy's placebo effect as the result of a distributed therapeutic agency involving humans, objects, and texts. Homeopathy has been involved in controversies for centuries, and the dispute whether it is therapy or quackery is as lively as ever. Still, homeopathy has retained significant popularity and acceptance within the medical establishment. We bracket the issue of biochemical effectiveness of homeopathic remedies as we only discuss homeopathy's potential to elicit a placebo response within its therapeutic alliance, in virtue of its social, symbolic, and material features. The review is based on literature discussing homeopathic effectiveness, including historical, biographical, sociological, and epistemological perspectives. We build upon research that clarifies the therapeutic relationship, examining its activities and meanings for practitioners and patients. Previous analyses discussing homeopathy's placebo effect stress the importance of the individualized consultation that functions as psychotherapy and generates empathy and hope. We enlarge the discussion, highlighting homeopathy's distributed therapeutic agency across humans, texts, and materials. The historical evolution of homeopathy in relation to biomedicine and science is important to understand its institutional integration into mainstream medicine and its appeal to scientifically minded doctors. Anecdotes of healing and the message of no-harm encourage patients to try homeopathy and hope for the best. The esthetics and ritual of remedies, coupled with computers' scientific legitimacy and time-saving power constitute a material infrastructure of therapeutic persuasion. Through its relation with biomedicine, its doctrine, consultation design, and treatment rituals, homeopathy offers a powerful medium to elicit a placebo response in a therapeutic alliance. By virtue of its proximity and radical difference from the scientific and biomedical enterprises, its material and textual organization, its storytelling and esthetics, homeopathy offers doctors and patients the opportunity and the tools to collaborate, to witness healing, and to hope for success against adversity.


NK3-specific natural killer cells are selectively inhibited by Bw4-positive HLA alleles with isoleucine 80.
Natural killer (NK) cell clones have been previously described which are inhibited by HLA-C alleles with Asn77-Lys80 (NK1-specific cells) or by HLA-C alleles with Ser77-Asn80 (NK2-specific cells). In the present work, the generation of NK cells with HLA-B-related specificities was attempted by stimulation of a Bw4 homozygous responder by a Bw6 homozygous donor. Two NK clones were found, which were inhibited by HLA-Bw4 (but not by HLA-Bw6) allotypes and by some HLA-A allotypes that share the Bw4 public epitope. Inhibition of NK cell-mediated lysis strongly correlated with the presence of an Ile residue at position 80 of the protective allele. These NK cell clones define a new specificity termed NK3.


Comparison of compression screw and perpendicular clamp in ulnar shortening osteotomy.
To biomechanically quantify 2 techniques, compression screw and perpendicular clamp, for generating compression during ulnar shortening osteotomy (USO) in order to promote reliable primary bone healing. Fourteen fresh-frozen cadaveric human forearms were randomly assigned to 1 of 2 groups. Group I (n = 7) underwent USO according to the traditional AO plate fixation technique using a screw placed eccentrically in an oblong hole to generate compression at the osteotomy site. Group II (n = 7) underwent USO with a commercially available USO plating system using a clamp placed perpendicular to the osteotomy site to generate compression. Both techniques involved a 2-mm resection osteotomy performed with cutting jigs to minimize variability and an interfragmentary lag screw to augment compression. A digital pressure sensor measured contact area at the osteotomy site and average pressure in the observed contact area; these values were used to calculate force across the osteotomy site. Measurements were obtained after the following steps: reduction of osteotomy, compression screw placement (group 1 only), lag screw placement, and final construct with all clamps removed. Group II demonstrated significantly greater force than group I, and lag screw placement resulted in significantly increased force independent of fixation technique. The effect of the lag screw on force was maintained after clamp removal. Although technique of fixation did not significantly influence contact area, lag screw placement significantly increased contact area independent of fixation method. However, this effect was not maintained after clamp removal. Average pressure in the observed contact area was not significantly influenced by fixation technique or stage of fixation. Perpendicular clamp compression significantly increased force as compared with traditional compression screw technique, and lag screw placement significantly increased force in both constructs. Larger compressive forces across the osteotomy may promote primary bone union and decrease the rates of delayed union or nonunion.


Subventricular zone neural progenitors protect striatal neurons from glutamatergic excitotoxicity.
The functional significance of adult neural stem and progenitor cells in hippocampal-dependent learning and memory has been well documented. Although adult neural stem and progenitor cells in the subventricular zone are known to migrate to, maintain and reorganize the olfactory bulb, it is less clear whether they are functionally required for other processes. Using a conditional transgenic mouse model, selective ablation of adult neural stem and progenitor cells in the subventricular zone induced a dramatic increase in morbidity and mortality of central nervous system disorders characterized by excitotoxicity-induced cell death accompanied by reactive inflammation, such as 4-aminopyridine-induced epilepsy and ischaemic stroke. To test the role of subventricular zone adult neural stem and progenitor cells in protecting central nervous system tissue from glutamatergic excitotoxicity, neurophysiological recordings of spontaneous excitatory postsynaptic currents from single medium spiny striatal neurons were measured on acute brain slices. Indeed, lipopolysaccharide-stimulated, but not unstimulated, subventricular zone adult neural stem and progenitor cells reverted the increased frequency and duration of spontaneous excitatory postsynaptic currents by secreting the endocannabinod arachidonoyl ethanolamide, a molecule that regulates glutamatergic tone through type 1 cannabinoid receptor (CB(1)) binding. In vivo restoration of cannabinoid levels, either by administration of the type 1 cannabinoid receptor agonist HU210 or the inhibitor of the principal catabolic enzyme fatty acid amide hydrolase, URB597, completely reverted the increased morbidity and mortality of adult neural stem and progenitor cell-ablated mice suffering from epilepsy and ischaemic stroke. Our results provide the first evidence that adult neural stem and progenitor cells located within the subventricular zone exert an 'innate' homeostatic regulatory role by protecting striatal neurons from glutamate-mediated excitotoxicity.


Prostate-specific membrane antigen expression as a predictor of prostate cancer progression.
Distinguishing aggressive prostate cancer from indolent disease represents an important clinical challenge, because current therapy may lead to overtreatment of men with limited disease. The prostate-specific membrane antigen (PSMA) is a membrane-bound glycoprotein that is highly restricted to the prostate. Previously, studies analyzing the expression of PSMA have found an up-regulation in correlation with prostate cancer, particularly in advanced cancer. This association is ideal for an application as a prognostic marker. In the current study, we characterized PSMA expression in a high-risk cohort and evaluated its potential use as predictive marker of prostate-specific antigen (PSA) recurrence. PSMA expression was analyzed by immunohistochemistry using tissue microarrays composed of tumor samples from 450 patients. Protein intensity was recorded using a semiautomated quantitative microscope system (ACIS II; Clarient Chromavision Medical Systems, San Juan Capistrano, CA). PSMA expression levels differed significantly (P < .001) between benign prostatic tissue, localized prostate cancer, and lymph node metastases. Dividing the cohort into high- and low-PSMA expressing cancers based on the median area of positive staining, we found that high PSMA levels were associated with significant increase of PSA recurrence (P = .004). This was independent of clinical parameters such as lymph node tumor burden (lymph node density, >20%; P < .001), extraprostatic extension (P = .017), seminal vesicle invasion (P < .001), and high Gleason score (8-10, P = .006). In a multivariate model, PSMA expression and metastases to pelvic lymph nodes were significantly associated with time to PSA recurrence (HR, 1.4; 95% confidence interval, 1.1-2.8, P = .017; and hazard ratio, 5; 95% confidence interval, 2.6-9.7, P < .001, respectively). In summary, PSMA is independently associated with PSA recurrence in a high-risk cohort and thus might provide insight into the additional use of adjuvant therapy. Validation on other cohorts is required.


De novo hepatitis B infection after liver transplantation: source of disease, incidence, and impact.
New-onset hepatitis B (de novo B) after liver transplantation (OLTX) is an emerging concern. The goals of our study were to determine the incidence and pattern of this infection, to attempt determination of risk factors and the role of immunosuppression, and to review its morbidity/mortality. Over a 10-year period, 1078 OLTX were performed in 956 patients at our institution. Eight hundred twenty-six patients had proven negative hepatitis B surface antigen (HBsAg) before transplantation. Among these, 14 patients (1.7%), 8 women and 6 men, ages 21-59 years (median, 42 years), developed positive HBsAg after transplantation and were defined as de novo B. In 10 of 14 patients (71%), positive HBsAg was revealed during routine annual visits, whereas 4 patients had titer verification prompted by illness. Blood product use (cryoprecipitate, fresh-frozen plasma, platelets, and packed red blood cells) during the transplant hospitalization was similar between groups. Pretransplant hepatitis C infection was more prevalent among the 14 patients with de-novo B (7 of 14, 50% v 129 of 812, 16%; P < or = 05). Hepatitis B vaccine had been given to 12 patients (86%) (but not given to 2) who developed de novo B. Incidence and severity of rejection were similar in both populations, although de novo B patients had more late rejections. Our use of immunosuppressive protocols was the same in both groups. Mean follow-up of the infected patients is 24 (5-51) months. Twelve of these 14 de novo B patients were not clinically ill, with normal or near-normal transaminase levels. One of 14 has died from complications related to hepatic artery revascularization, and another is well after repeat OLTX for biliary strictures. Half of these de novo B patients remain free from viral antigens in their transplanted liver tissue. The high percentage of positive hepatitis C patients who acquire de novo B may indicate a link between these two viral infections and potential risk factor for de novo B. The origins of this infection are most likely multifactorial, needing further study. De novo B after liver transplantation is preliminarily associated with little clinical morbidity and mortality.


Prevention and management of infections in patients without a spleen.
Patients who lack a functioning spleen become vulnerable to sepsis caused by bacteria and, occasionally, protozoa. The risk is higher in children and in those who have had immunosuppressive treatment, and the risk remains lifelong. Overwhelming post-splenectomy infection (OPSI) occurs at an estimated incidence of 0.23-0.42% per year, with a lifetime risk of 5%. Episodes of OPSI are emergencies, requiring immediate parental antibiotics and intensive care; intravenous immunoglobulins may be useful. OPSI carries a mortality of 38-69%. Streptococcus pneumoniae is the commonest infecting organism, accounting for 50-90% of isolates from blood cultures in reported series; it is particularly common in children with sickle cell disease. Less commonly, the infecting organisms are other bacteria, Babesia or Ehrlichia. OPSI may be, to some extent, preventable by several interventions. These are surgical conservation of the spleen; immunization against S. pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis; prophylactic antibiotics; stand-by antibiotics; patient information sheets; and a medical alert bracelet. Asplenic patients living in malaria-endemic areas require optimal prophylaxis. The initial step in prevention of OPSI is the creation of an asplenia register, as many patients are not covered by these simple measures.


A Water Rehabilitation Program in Patients with Hip Osteoarthritis Before and After Total Hip Replacement.
BACKGROUND Pain associated with coxarthrosis, typically occurring in middle-aged and elderly patients, very commonly causes considerable limitation of motor fitness and dependence on pharmacotherapy. This article provides an assessment of a rehabilitation program with tailored water exercises in patients with osteoarthritis before and after total hip replacement. MATERIAL AND METHODS A total of 192 patients (the mean age 61.03±10.89) suffering from hip osteoarthritis (OA) were evaluated before and after total hip replacement (THR). The clinical study covered measurements of hip active ranges of motion (HAROM) and the forces generated by pelvis stabilizer muscles. Pain intensity was assessed according to analogue-visual scale of pain (VAS) and according to the Modified Laitinen Questionnaire. The patients were divided into 6 groups (4 treatment and 2 control). We compared 2 rehabilitation programs using kinesitherapy and low-frequency magnetic field. One of them also had specially designed exercises in the water. Statistical analysis was carried out at the significance level α=0.05. This was a cross-sectional study. RESULTS A positive effect of water exercises on a number of parameters was found in patients with OA both before and after total hip replacement surgery. We noted a significant reduction of pain (p<0.001), increased ranges of motion and muscle strength, and reduced use of medicines (NASAIDs) (p<0.001). A correlation was found between the degree of degenerative deforming lesions and the effects of the treatment process (p<0.01). CONCLUSIONS 1. The rehabilitation program including water exercises most significantly reduced pain in patients with OA before and after total hip replacement surgery. 2. Inclusion of water exercises in a rehabilitation program can reduce the use of medicines in patient with OA and after THR.


Alcohol Interactive Toxicity Beliefs and ART Non-adherence Among HIV-Infected Current Drinkers in Mbarara, Uganda.
Interactive toxicity beliefs regarding mixing alcohol and antiretroviral therapy (ART) may influence ART adherence. HIV-infected patients in Uganda completed quarterly visits for 1 year, or one visit at 6 months, depending on study randomization. Past month ART non-adherence was less than daily or <100 % on a visual analog scale. Participants were asked if people who take alcohol should stop taking their medications (belief) and whether they occasionally stopped taking their medications in anticipation of drinking (behavior). Visits with self-reported alcohol use and ART use for ≥30 days were included. We used logistic regression to examine correlates of the interactive toxicity belief and behavior, and to determine associations with ART non-adherence. 134 participants contributed 258 study visits. The toxicity belief was endorsed at 24 %, the behavior at 15 %, and any non-adherence at 35 % of visits. In multivariable analysis, the odds of non-adherence were higher for those endorsing the toxicity behavior [adjusted odds ratio (AOR) 2.06; 95 % confidence interval (CI) 0.97-4.36] but not the toxicity belief (AOR 0.63; 95 % CI 0.32-1.26). Clear messaging about maintaining adherence, even if drinking, could benefit patients.


Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-β1/Smad3 pathway.
Keloids, partially considered as benign tumors, are characterized by the overgrowth of fibrosis beyond the boundaries of the wound and are regulated mainly by transforming growth factor (TGF)-β1, which induces the transition of fibroblasts to myofibroblasts. Hypoxia is an important driving force in the development of lung and liver fibrosis by activating hypoxia inducible factor-1α and stimulating epithelial‑mesenchymal transition. However, it is unknown whether and hypoxia can influence human dermal scarring. The aim of this study was to investigate whether hypoxia drives the transition of dermal fibroblasts to myofibroblasts and to clarify the potential transduction mechanisms involved. First, we observed that keloids are a relatively hypoxic tissue. Second, we found that hypoxia drives the transition of normal dermal fibroblasts to a myofibroblast-like phenotype [high expression of α-smooth muscle actin (α-SMA) and collagen I and III]. Finally, hypoxia effectively facilitated the nuclear import of the Smad2 and Smad3 complex, while blockade with the Smad3 inhibitor, SIS3, significantly impaired the expression of hypoxia-induced fibrosis-related molecules. Taken together, to the best of our knowledge, this study demonstrates for the first time that hypoxia facilitates the transition of dermal fibroblasts to myofibroblasts through the activation of the TGF-β1/Smad3 signaling pathway and our findings may provide a potential target for the treatment of keloids.


Molecular genealogy of some nematode taxa as based on cytochrome c and globin amino acid sequences.
We have begun to reconstruct the ancient history of the nematode phylum based on cytochrome c and globin amino acid sequences. The data suggest that the nematode ancestor diverged from a line leading to mammals about 1 billion years ago and that the most recent common ancestor of the extant species Caenorhabditis elegans, Trichostrongylus colubriformis, Nippostrongylus brasiliensis, Ascaris suum, and Pseudoterranova decipiens lived about 550 MY ago. The rhabditids and strongylids emerged as one offshoot of this ancestor, the ascarids as another. Rhabditids and strongylids diverged some 400 MY ago, whereas the genera Trichostrongylus and Nippostrongylus diverged slightly over 200 MY ago. A gene duplication event in the strongylid branch is predicted to have occurred around 250-335 MY ago. There are two globin genes in Nippostrongylus, expressed in anatomically distinct compartments (body and cuticle), and the single sequence from Trichostrongylus is most like the Nippostrongylus body globin gene. A strikingly different duplication event occurred within the same period in the line leading to the extant ascarid genera, creating a single polypeptide containing two globin domains. The genera Ascaris and Pseudoterranova diverged some 150-250 MY ago. Interestingly, the second globin repeat evolved at a faster rate in both species examined. This is possibly related to the acquisition of an unusual carboxyterminal extension, composed of alternating positively and negatively charged residues, that is necessary for the assembly of several monomers into the native polymeric molecules.


Shared and distinct genetic variants in type 1 diabetes and celiac disease.
Two inflammatory disorders, type 1 diabetes and celiac disease, cosegregate in populations, suggesting a common genetic origin. Since both diseases are associated with the HLA class II genes on chromosome 6p21, we tested whether non-HLA loci are shared. We evaluated the association between type 1 diabetes and eight loci related to the risk of celiac disease by genotyping and statistical analyses of DNA samples from 8064 patients with type 1 diabetes, 9339 control subjects, and 2828 families providing 3064 parent-child trios (consisting of an affected child and both biologic parents). We also investigated 18 loci associated with type 1 diabetes in 2560 patients with celiac disease and 9339 control subjects. Three celiac disease loci--RGS1 on chromosome 1q31, IL18RAP on chromosome 2q12, and TAGAP on chromosome 6q25--were associated with type 1 diabetes (P<1.00x10(-4)). The 32-bp insertion-deletion variant on chromosome 3p21 was newly identified as a type 1 diabetes locus (P=1.81x10(-8)) and was also associated with celiac disease, along with PTPN2 on chromosome 18p11 and CTLA4 on chromosome 2q33, bringing the total number of loci with evidence of a shared association to seven, including SH2B3 on chromosome 12q24. The effects of the IL18RAP and TAGAP alleles confer protection in type 1 diabetes and susceptibility in celiac disease. Loci with distinct effects in the two diseases included INS on chromosome 11p15, IL2RA on chromosome 10p15, and PTPN22 on chromosome 1p13 in type 1 diabetes and IL12A on 3q25 and LPP on 3q28 in celiac disease. A genetic susceptibility to both type 1 diabetes and celiac disease shares common alleles. These data suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases.


Validation of the Extreme Experiences Scale (EX2) for Armed Conflict Contexts.
Psychological approaches to the study of armed conflict have focused on analyzing post-traumatic stress outcomes, and on evaluating the intensity of exposure to violent confrontation. Nevertheless, psychometrically valid tools required for measuring these traumatic experiences are scarce To validate the Extreme Experiences scale (EX2) for armed conflict contexts for its use in Colombia, and to provide a framework for validation in conflict contexts around the world This Cross-sectional aims to validate the scale with 187 participants, study of validate with 187 participants, comprising population with high exposure to conflict (former combatants and a set of armed conflict victims) and low conflict-exposed individuals (control group). Structures of two domains and 18 items were confirmed: Direct Extreme Experiences (dEX2) and Indirect Extreme Experiences (iEX2); these dimensions were also validated by expert judgment, producing 14-item version. Good levels of internal consistency were found, with a KR-20 of 0.80 for the 18-item version, and 0.77 for the 14-item. The scale differentiates between population with 'high exposure to conflict' from population with 'low exposure' (dnp > 0.5 and area under the ROC >0.90). The scale scores have significant correlation with some mental health constructs. The EX2 scale has good internal consistency, as well as structural validity with regard to exposed groups. This scale can be potentially validated for its use in countries with armed confrontation history. In future versions, the scale may include additional items in order to improve content validity.


Determination of inhibitor activity of drugs against the COVID-19.
It is the SARS-CoV-2 virus, one of the most significant diseases of today's world. Due to the high transmission of this disease, studies are ongoing to discover an inhibitor drug that can stop this disease. In this study, inhibitory drugs used for many diseases were tried to stop the SARS-CoV-2 virus. In the calculations made, inhibitor molecules for the SARS-CoV-2 virus were calculated by molecular docking method. Inhibitory activities of SARS-CoV-2 virus against spike glycoprotein (PDB ID: 6M0J, 6LZG), main protease (PDB ID: 5RGG, 6WTT), and RNA dependent RNA polymerase (RdRp) (PDB ID: 6YYT, 7BV2) proteins were compared. Then, docking calculations were supported by calculations by MM-PSBA of the inhibitor with the highest activity. Afterwards, it was compared with FDA approved drugs for the SARS-CoV-2 virus. It was found that the Carvedilol molecule was the best against RNA dependent RNA polymerase (RdRp) protein of SARS-CoV-2 (Tab. 4, Fig. 9, Ref. 42).


"Women Are Better Than Men"-Public Beliefs on Gender Differences and Other Aspects in Multitasking.
Reports in public media suggest the existence of a stereotype that women are better at multitasking than men. The present online survey aimed at supporting this incidental observation by empirical data. For this, 488 participants from various ethnic backgrounds (US, UK, Germany, the Netherlands, Turkey, and others) filled out a self-developed online-questionnaire. Results showed that overall more than 50% of the participants believed in gender differences in multitasking abilities. Of those who believed in gender differences, a majority of 80% believed that women were better at multitasking. The main reasons for this were believed to be an evolutionary advantage and more multitasking practice in women, mainly due to managing children and household and/or family and job. Findings were consistent across the different countries, thus supporting the existence of a widespread gender stereotype that women are better at multitasking than men. Further questionnaire results provided information about the participants' self-rated own multitasking abilities, and how they conceived multitasking activities such as childcare, phoning while driving, and office work.


Beyond the binding site: in vivo identification of tbx2, smarca5 and wnt5b as molecular targets of CNBP during embryonic development.
CNBP is a nucleic acid chaperone implicated in vertebrate craniofacial development, as well as in myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) human muscle diseases. CNBP is highly conserved among vertebrates and has been implicated in transcriptional regulation; however, its DNA binding sites and molecular targets remain elusive. The main goal of this work was to identify CNBP DNA binding sites that might reveal target genes involved in vertebrate embryonic development. To accomplish this, we used a recently described yeast one-hybrid assay to identify DNA sequences bound in vivo by CNBP. Bioinformatic analyses revealed that these sequences are G-enriched and show high frequency of putative G-quadruplex DNA secondary structure. Moreover, an in silico approach enabled us to establish the CNBP DNA-binding site and to predict CNBP putative targets based on gene ontology terms and synexpression with CNBP. The direct interaction between CNBP and candidate genes was proved by EMSA and ChIP assays. Besides, the role of CNBP upon the identified genes was validated in loss-of-function experiments in developing zebrafish. We successfully confirmed that CNBP up-regulates tbx2b and smarca5, and down-regulates wnt5b gene expression. The highly stringent strategy used in this work allowed us to identify new CNBP target genes functionally important in different contexts of vertebrate embryonic development. Furthermore, it represents a novel approach toward understanding the biological function and regulatory networks involving CNBP in the biology of vertebrates.


Hollow carbon nanobubbles: monocrystalline MOF nanobubbles and their pyrolysis.
While bulk-sized metal-organic frameworks (MOFs) face limits to their utilization in various research fields such as energy storage applications, nanoarchitectonics is believed to be a possible solution. It is highly challenging to realize MOF nanobubbles with monocrystalline frameworks. By a spatially controlled etching approach, here, we can achieve the synthesis of zeolitic imidazolate framework (ZIF-8) nanobubbles with a uniform size of less than 100 nm. Interestingly, the ZIF-8 nanobubbles possess a monocrystalline nanoshell with a thickness of around 10 nm. Under optimal pyrolytic conditions, the ZIF-8 nanobubbles can be converted into hollow carbon nanobubbles while keeping their original shapes. The structure of the nanobubble enhances the fast Na+/K+ ion intercalation performance. Such remarkable improvement cannot be realized by conventional MOFs or their derived carbons.


Working around hierarchy: Resident and medical assistant teaming.
In health care, hierarchy can facilitate getting work done efficiently. It can also hinder performance by suppressing valuable contributions from lower-positioned individuals. Team-based care could mitigate negative effects by creating space for all team members to contribute their unique expertise. This article sought to understand how resident-medical assistant (MA) dyads interacted before and after primary care clinics transitioned to team-based care. We also studied how they negotiated changes in interpersonal dynamics given the challenge these changes presented to hierarchical norms. We conducted two qualitative interview studies, with 37 residents and 30 MAs at primary care clinics transitioning to team-based care. Interviews were transcribed, coded, and analyzed together using a thematic networks approach and focused coding. An intervention that promoted teamwork prompted resident-MA dyads to change their interactions to counter traditional hierarchy. Residents increasingly asked MAs questions about patient care, and MAs initiated interactions and volunteered ideas more frequently. We also found that MAs and residents expressed some discomfort with the hierarchical ambiguity that their new interactions produced and used alternate scripts to buffer this discomfort and to collaborate as teammates despite formal hierarchy. Among resident-MA dyads, a team-based care intervention changed interpersonal dynamics by blurring hierarchical lines and shifting traditional boundaries in ways that were uncomfortable for both groups. They were able to work around discomfort by using new scripts that downplayed the threat to hierarchy. Organizational structures that encourage greater interprofessional collaboration may neutralize barriers that formal hierarchy in medicine can pose for effective teamwork, but this process can also bring social discomfort. Our findings suggest that health care professionals may use microlevel strategies, such as alternative scripts, to overcome formal hierarchies without openly engaging them. Together, new organizational structures and interaction techniques can help professionals work around hierarchy and improve team performance.


Association of fat to lean mass ratio with metabolic dysfunction in women with polycystic ovary syndrome.
Are differences in metabolic dysfunction between polycystic ovary syndrome (PCOS) and control women related to differences in their fat to lean mass (F/L) ratio? Compared with controls of similar body mass index (BMI), women with PCOS demonstrate adverse body composition characterized by increased whole body fat relative to lean mass (i.e. a higher F/L ratio), which is associated with differences in metabolic dysfunction between the two groups. Previous studies examining body composition and insulin resistance (IR) in PCOS have yielded conflicting results. Excess total fat mass (i.e. fat mass index [fat BMI]) correlates with IR, whereas increased total lean mass (i.e. lean BMI) has been associated with higher insulin sensitivity. However, the role of the F/L ratio, which integrates the antagonistic effects of both fat and lean mass depots, on IR in PCOS, has not been investigated. We conducted a prospective cross-sectional study of 120 women between the ages of 22-44 years to study the relation of the F/L ratio with measures of insulin action and secretion in both steady and dynamic states. Sixty PCOS (by NIH, 1990 criteria) and 60 control (age, race and BMI-matched) women were prospectively studied for body composition (by bioelectrical impedance analysis [BIA]) and basal IR and insulin secretion by the homeostasis model assessment (HOMA-IR and HOMA-%β-cell function, respectively) in a tertiary care academic referral center. A subset of 12 PCOS and 12 matched control women also underwent a modified frequently sampled intravenous glucose tolerance test (FSIVGTT) to determine glucose uptake and insulin secretion in dynamic state. Our results indicate that women with PCOS demonstrated greater degrees of hyperandrogenism, and higher waist-to-hip ratio (WHR), %body fat, fat BMI, F/L, fasting insulin levels, and HOMA-IR and HOMA-%β-cell values, than controls. In models adjusted for WHR and free testosterone and diagnostic groups, fasting insulin levels, HOMA-IR, and HOMA-%beta cell function were positively related to the F/L ratio. A positive relationship was also found in both study groups between F/L and the FSIVGTT measures insulin sensitivity (Si) and acute insulin response to glucose (AIRg). The F/L tended to negatively correlate with glucose effectiveness or non-insulin-mediated glucose transport (Sg) only in PCOS women. Regional tissue sub-compartments, which have been shown to have potential independent associations with metabolic variables, cannot be determined by bioelectrical impedance analysis (BIA). The current results suggest that BIA could be used to assess F/L in place of dual energy X-ray absorptiometry (DXA) in research protocols, and that F/L could possibly be used as an alternative to WHR as a surrogate marker of metabolic dysfunction in clinical practice. This work was supported by grants R01-DK073632 and R01-HD29364 from the NIH and an endowment of the Helping Hand of Los Angeles, Inc. (to R.A.). The authors have no competing interests to declare. Not applicable.


Immediate versus delayed surgery for hip fractures in the elderly patients: a protocol for a systematic review and meta-analysis.
Hip fractures are a major public health problem in elderly populations and are accompanied by high-mortality rates. Whether timing of surgery has an impact on morbidity and mortality has been discussed controversially, numerous studies suggest that the delay of surgery can significantly increase the risk of morbidity and mortality; others report that achieving a stable medical condition is more important than early surgery. The goal of our systematic review is to assess the impact of timing of surgery on health outcomes in patients aged 60 years or older with acute hip fracture. In addition, we will investigate differences in beneficial or harmful effects of timing of surgery in subgroups of patients based on demographic characteristics, physical status, and the use of anticoagulant medications. We will systematically search MEDLINE via Ovid, the Cochrane Library, Embase, PubMed, and clinical trial registries (from 1997 to 2017). In addition, we will search reference lists of pertinent reviews, archives of annual meetings of orthopaedic societies, and contact experts. We will include randomized controlled trials and non-randomized studies assessing the impact of timing of surgery after hip fracture in patients 60 years or older, published in English or German. Our outcomes of interest include health outcomes such as mortality, perioperative complications, functional capacity, and quality of life. We plan to perform meta-analyses if we have at least three sufficiently similar studies. If data are sufficient, we will conduct subgroup-analyses testing for differences between age groups, sex, patients' physical status as assessed with ASA (American Society of Anesthesiologists) scores, and the use of anticoagulation. Since this is the first systematic review on this topic since 2010, our findings will help to inform clinical practice guidelines concerning timing of surgery in hip fractures. Furthermore, our findings could contribute to define an optimal time period for surgery for different groups of patients with acute hip fracture. PROSPERO 2017 CRD42017058216.


Dystonic opisthotonus: a "red flag" for neurodegeneration with brain iron accumulation syndromes?
Back arching was reported in one of the very first patients with neurodegeneration with brain iron accumulation syndrome (NBIAs) published in 1936. However, recent reports have mainly focused on the genetic and imaging aspects of these disorders, and the phenotypic characterization of the dystonia has been lost. In evaluating patients with NBIAs in our centers, we have observed that action-induced dystonic opisthotonus is a common and characteristic feature of NBIAs. Here, we present a case series of patients with NBIAs presenting this feature demonstrated by videos. We suggest that dystonic opisthotonus could be a useful "red flag" for clinicians to suspect NBIAs, and we discuss the differential diagnosis of this feature. This would be particularly useful in identifying patients with NBIAs and no iron accumulation as yet on brain imaging (for example, as in phospholipase A2, group IV (cytosolic, calcium-independent) [PLA2G6]-related disorders), and it has management implications.


Opioids modulate stress-induced proenkephalin gene expression in the hypothalamus of transgenic mice: a model of endogenous opioid gene regulation by exogenous opioids.
Stressful stimuli strongly induce proenkephalin gene expression within the paraventricular nucleus (PVN) of the hypothalamus. A human proenkephalin-beta-galactosidase fusion gene has previously been shown to give correct phenotypic expression and appropriate stress regulation within the hypothalamus of transgenic mice; this model provides high sensitivity, cellular resolution, and ready quantification of levels of proenkephalin gene expression. Here we describe use of this transgenic model to study modulation of stress-regulated gene expression in the PVN by opiates. Acute or subacute morphine administration prior to a hypertonic saline stress produced marked superinduction of transgene expression compared with hypertonic saline stress alone. In contrast, chronic morphine administration decreased basal expression of the transgene, and inhibited stress-induced expression of the transgene. The endogenous proenkephalin mRNA was induced in parallel with the transgene as demonstrated by in situ hybridization; the immediate-early gene c-fos was also regulated in parallel with the transgene. These data suggest that acute or subacute morphine administration sensitizes proenkephalin neurons within the PVN and other regions of the hypothalamus to stress and that chronic morphine administration desensitizes this response. Because the molecular mechanisms regulating the expression of the transgene are well understood, this model provides a useful tool for investigating cellular and molecular effects of opioids on the hypothalamus.


Cyclometalated ruthenium complexes with carboxylated ligands from a combined experimental/computational perspective.
The syntheses and characterization of nine new cyclometalated ruthenium complexes are reported. These structures consist of Ru(ii) with bipyridine and phenylpyridine ligands which are substituted with ester or carboxylate groups. Two of the complexes were extensively studied and their properties were compared to those of two previously reported structures. The identities of the compounds were confirmed by NMR, HR-MS and single crystal XRD, and the electronic properties were investigated by UV-Vis spectroscopy. DFT and TD-DFT calculations showed that the intense absorbances in the visible region of the spectrum of these cyclometalated complexes are due to electronic excitations to virtual orbitals located on the carboxylated ligands. These results indicate that the compounds are promising candidates as sensitizers for more efficient photocatalysis with sunlight. Further, the carboxylate groups should facilitate their use as linkers in metal-organic frameworks.


An Archaean heavy bombardment from a destabilized extension of the asteroid belt.
The barrage of comets and asteroids that produced many young lunar basins (craters over 300 kilometres in diameter) has frequently been called the Late Heavy Bombardment (LHB). Many assume the LHB ended about 3.7 to 3.8 billion years (Gyr) ago with the formation of Orientale basin. Evidence for LHB-sized blasts on Earth, however, extend into the Archaean and early Proterozoic eons, in the form of impact spherule beds: globally distributed ejecta layers created by Chicxulub-sized or larger cratering events4. At least seven spherule beds have been found that formed between 3.23 and 3.47 Gyr ago, four between 2.49 and 2.63 Gyr ago, and one between 1.7 and 2.1 Gyr ago. Here we report that the LHB lasted much longer than previously thought, with most late impactors coming from the E belt, an extended and now largely extinct portion of the asteroid belt between 1.7 and 2.1 astronomical units from Earth. This region was destabilized by late giant planet migration. E-belt survivors now make up the high-inclination Hungaria asteroids. Scaling from the observed Hungaria asteroids, we find that E-belt projectiles made about ten lunar basins between 3.7 and 4.1 Gyr ago. They also produced about 15 terrestrial basins between 2.5 and 3.7 Gyr ago, as well as around 70 and four Chicxulub-sized or larger craters on the Earth and Moon, respectively, between 1.7 and 3.7 Gyr ago. These rates reproduce impact spherule bed and lunar crater constraints.


Alternating Hemiplegia of Childhood: Pharmacological treatment of 30 Italian patients.
Alternating Hemiplegia of Childhood (AHC) is a severe disorder. Several drugs have been administered as prophylaxis for paroxysmal attacks, however, no therapy is completely effective. Our aim is to review the pharmacological data related to the prophylactic and acute treatment of a cohort of 30 patients (16M, 14F, age range 5-42years) and to correlate them with the clinical and genetic data collected through the Italian Biobank and Clinical Registry for AHC. Flunarizine was the most commonly used long-term treatment in the cohort; it reduced duration and frequency of attacks in 50% of patients and decreased intensity in 32.1%. In younger patients, flunarizine seemed significantly more effective in reducing intensity. We found no correlation between the effectiveness of flunarizine and genotype, or between developmental outcome and duration of treatment. In particular, 3 of our patients affected by E815K mutation presented rapid neurological deterioration despite ongoing treatment. Among the other administered prophylactic therapies, few proved to be effective (benzodiazepines, niaprazine, acetazolamide, melatonin, olanzapine, ketogenic diet). No clear rationale exists regarding their use, but these therapies may work by reducing the triggering factors. The presented data are retrospective, but they are aimed at filling a gap given the rarity of the disease and the lack of randomized and controlled studies. Besides their usefulness in clarifying the pathophysiology of the disease, prospective studies involving larger cohorts of ATP1A3 mutated AHC patients are needed to provide a rationale for testing other molecules.


Subpicosecond solitons in an actively mode-locked fiber laser.
Experimental results are presented for a study of the stability regime of an actively mode-locked polarizationmaintaining fiber ring laser used as a memory. Observations indicate that the pulse widths in the memory can be reduced (by soliton effects) by a factor of approximately 4.4 below the pulse widths predicted by standard active mode-locking theory. Stability regions for the solitons are mapped and compared with theoretical predictions.


Clan, language, and migration history has shaped genetic diversity in Haida and Tlingit populations from Southeast Alaska.
The linguistically distinctive Haida and Tlingit tribes of Southeast Alaska are known for their rich material culture, complex social organization, and elaborate ritual practices. However, much less is known about these tribes from a population genetic perspective. For this reason, we analyzed mtDNA and Y-chromosome variation in Haida and Tlingit populations to elucidate several key issues pertaining to the history of this region. These included the genetic relationships of Haida and Tlingit to other indigenous groups in Alaska and Canada; the relationship between linguistic and genetic data for populations assigned to the Na-Dene linguistic family, specifically, the inclusion of Haida with Athapaskan, Eyak, and Tlingit in the language family; the possible influence of matrilineal clan structure on patterns of genetic variation in Haida and Tlingit populations; and the impact of European entry into the region on the genetic diversity of these indigenous communities. Our analysis indicates that, while sharing a "northern" genetic profile, the Haida and the Tlingit are genetically distinctive from each other. In addition, Tlingit groups themselves differ across their geographic range, in part due to interactions of Tlingit tribes with Athapaskan and Eyak groups to the north. The data also reveal a strong influence of maternal clan identity on mtDNA variation in these groups, as well as the significant influence of non-native males on Y-chromosome diversity. These results yield new details about the histories of the Haida and Tlingit tribes in this region.


miCloud: A Plug-n-Play, Extensible, On-Premises Bioinformatics Cloud for Seamless Execution of Complex Next-Generation Sequencing Data Analysis Pipelines.
The availability of low-cost small-factor sequencers, such as the Illumina MiSeq, MiniSeq, or iSeq, have paved the way for democratizing genomics sequencing, providing researchers in minority universities with access to the technology that was previously only affordable by institutions with large core facilities. However, these instruments are not bundled with software for performing bioinformatics data analysis, and the data analysis can be the main bottleneck for independent laboratories or even small clinical facilities that consider adopting genomic sequencing for medical applications. To address this issue, we have developed miCloud, a bioinformatics platform that enables genomic data analysis through a fully featured data analysis cloud, which seamlessly integrates with genome sequencers over the local network. The miCloud can be easily deployed without any prior bioinformatics expertise on any computing environment, from a laboratory computer workstation to a university computer cluster. Our platform not only provides access to a set of preconfigured RNA-Seq and CHIP-Seq bioinformatics pipelines, but also enables users to develop or install new preconfigured tools from the large selection available on open-source online Docker container repositories. The miCloud built-in analysis pipelines are also integrated with the Visual Omics Explorer framework (Kim et al., 2016), which provides rich interactive visualizations and publication-ready graphics from the next-generation sequencing data. Ultimately, the miCloud demonstrates a bioinformatics approach that can be adopted in the field for standardizing genomic data analysis, similarly to the way molecular biology sample preparation kits have standardized laboratory operations.


HIF-1 and c-Src mediate increased glucose uptake induced by endothelin-1 and connexin43 in astrocytes.
In previous work we showed that endothelin-1 (ET-1) increases the rate of glucose uptake in astrocytes, an important aspect of brain function since glucose taken up by astrocytes is used to supply the neurons with metabolic substrates. In the present work we sought to identify the signalling pathway responsible for this process in primary culture of rat astrocytes. Our results show that ET-1 promoted an increase in the transcription factor hypoxia-inducible factor-1α (HIF-1α) in astrocytes, as shown in other cell types. Furthermore, HIF-1α-siRNA experiments revealed that HIF-1α participates in the effects of ET-1 on glucose uptake and on the expression of GLUT-1, GLUT-3, type I and type II hexokinase. We previously reported that these effects of ET-1 are mediated by connexin43 (Cx43), the major gap junction protein in astrocytes. Indeed, our results show that silencing Cx43 increased HIF-1α and reduced the effect of ET-1 on HIF-1α, indicating that the effect of ET-1 on HIF-1α is mediated by Cx43. The activity of oncogenes such as c-Src can up-regulate HIF-1α. Since Cx43 interacts with c-Src, we investigated the participation of c-Src in this pathway. Interestingly, both the treatment with ET-1 and with Cx43-siRNA increased c-Src activity. In addition, when c-Src activity was inhibited neither ET-1 nor silencing Cx43 were able to up-regulate HIF-1α. In conclusion, our results suggest that ET-1 by down-regulating Cx43 activates c-Src, which in turn increases HIF-1α leading to the up-regulation of the machinery required to take up glucose in astrocytes. Cx43 expression can be reduced in response not only to ET-1 but also to various physiological and pathological stimuli. This study contributes to the identification of the signalling pathway evoked after Cx43 down-regulation that results in increased glucose uptake in astrocytes. Interestingly, this is the first evidence linking Cx43 to HIF-1, which is a master regulator of glucose metabolism.


Healthcare resource utilization among patients with cold agglutinin disease in Denmark.
Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia that may manifest in complement-mediated chronic hemolytic anemia, profound fatigue, and transient agglutination-mediated circulatory symptoms. This study compared the healthcare resource utilization (HRU) of patients with CAD with a matched non-CAD comparison cohort using national Danish health registry data. All cases of CAD were identified from 1 January 1999 to 30 June 2016, in the Danish National Patient Registry using the International Classification of Diseases, Tenth Revision, discharge diagnosis codes. A subcohort of patients with primary CAD was identified based on the absence of secondary predisposing concomitant diseases. CAD cases were matched to individuals without CAD from the general population based on birth year, sex, and 19 disease categories of the Charlson Comorbidity Index. Comparative analyses assessed inpatient hospitalizations, outpatient clinic visits, emergency room visits, transfusion use, and expensive drug use between cohorts 6 months before and 12 months after the admission date of the first hospital visit with CAD diagnosis (index date). A total of 104 patients with CAD were matched to 1003 comparison cohort members. Throughout the 12 months after the index date, patients with CAD were more likely to have at least one inpatient hospitalization (odds ratio [OR], 3.9; 95% confidence interval [CI], 2.5-6.0), outpatient clinic visit (OR, 17.2; 95% CI, 6.8-43.1), and blood transfusion (OR, 93.0; 95% CI, 33.3-259.8) than matched comparisons. HRU was similarly higher among patients with CAD than matched comparisons during the 6 months before the index date. Findings were similar among patients with primary CAD. Characterization of HRU among European patients with CAD has not previously been conducted. This study shows that patients with CAD utilize significant resources in Denmark. Increased HRU uses among patients with CAD before diagnosis presents opportunities for earlier diagnosis and management.


Punishment sensitivity modulates the processing of negative feedback but not error-induced learning.
Accumulating evidence suggests that individual differences in punishment and reward sensitivity are associated with functional alterations in neural systems underlying error and feedback processing. In particular, individuals highly sensitive to punishment have been found to be characterized by larger mediofrontal error signals as reflected in the error negativity/error-related negativity (Ne/ERN) and the feedback-related negativity (FRN). By contrast, reward sensitivity has been shown to relate to the error positivity (Pe). Given that Ne/ERN, FRN, and Pe have been functionally linked to flexible behavioral adaptation, the aim of the present research was to examine how these electrophysiological reflections of error and feedback processing vary as a function of punishment and reward sensitivity during reinforcement learning. We applied a probabilistic learning task that involved three different conditions of feedback validity (100%, 80%, and 50%). In contrast to prior studies using response competition tasks, we did not find reliable correlations between punishment sensitivity and the Ne/ERN. Instead, higher punishment sensitivity predicted larger FRN amplitudes, irrespective of feedback validity. Moreover, higher reward sensitivity was associated with a larger Pe. However, only reward sensitivity was related to better overall learning performance and higher post-error accuracy, whereas highly punishment sensitive participants showed impaired learning performance, suggesting that larger negative feedback-related error signals were not beneficial for learning or even reflected maladaptive information processing in these individuals. Thus, although our findings indicate that individual differences in reward and punishment sensitivity are related to electrophysiological correlates of error and feedback processing, we found less evidence for influences of these personality characteristics on the relation between performance monitoring and feedback-based learning.


Independent and complementary methods for large-scale structural analysis of mammalian chromatin.
The fundamental building block of chromatin, the nucleosome, occupies 150 bp of DNA in a spaced arrangement that is a primary determinant in regulation of the genome. The nucleosomal organization of some regions of the human genome has been described, but mapping of these regions has been limited to a few kilobases. We have explored two independent and complementary methods for the high-throughput analysis of mammalian chromatin structure. Through adaptations to a protocol used to map yeast chromatin structure, we determined sites of nucleosomal protection over large regions of the mammalian genome using a tiling microarray. By modifying classical primer extension methods, we localized specific internucleosomally cleaved mammalian genomic sequences using a capillary electrophoresis sequencer in a manner that allows high-throughput nucleotide-resolution characterization of nucleosome protection patterns. We developed algorithms for the automated and unbiased analysis of the resulting data, a necessary step toward large-scale analysis. We validated these assays using the known positions of nucleosomes on the mouse mammary tumor virus LTR, and additionally, we characterized the previously unreported chromatin structure of the LCMT2 gene. These results demonstrate the effectiveness of the combined methods for reliable analysis of mammalian chromatin structure in a high-throughput manner.


Towards malaria control and elimination in Ghana: challenges and decision making tools to guide planning.
Ghana is classified as being in the malaria control phase, according to the global malaria elimination program. With many years of policy development and control interventions, malaria specific mortality among children less than 5 years old has declined from 14.4% in 2000 to 0.6% in 2012. However, the same level of success has not been achieved with malaria morbidity. The recently adopted 2015-2020 Ghana strategic action plan aims to reduce the burden of malaria by 75.0%. Planning and policy development has always been guided by evidence from field studies, and mathematical models that are able to investigate malaria transmission dynamics have not played a significant role in supporting policy development. The objectives of this study are to describe the malaria situation in Ghana and give a brief account of how mathematical modelling techniques could support a more informed malaria control effort in the Ghanaian context. A review is carried out of some mathematical models investigating the dynamics of malaria transmission in sub-Saharan African countries, including Ghana. The applications of these models are then discussed, considering the gaps that still remain in Ghana for which further mathematical model development could be supportive. Because of the collaborative approach adopted in their development, some model examples Ghana could benefit from are also discussed. Collaboration between malaria control experts and modellers will allow for more appropriate mathematical models to be developed. Packaging these models with user-friendly interfaces and making them available at various levels of malaria control management could help provide the decision making tools needed for planning and a platform for monitoring and evaluation of interventions in Ghana.


Accuracy and confidence of Gd-EOB-DTPA enhanced MRI and diffusion-weighted imaging alone and in combination for the diagnosis of liver metastases.
To evaluate the accuracy and confidence in diagnosing liver metastases using combined gadolinium-EOB-DTPA (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI)/diffusion-weighted imaging (DWI) in comparison to Gd-EOB-DTPA enhanced MRI and DWI alone. Forty-three patients (age, 58 ± 13 years) with 89 liver lesions (28 benign, 61 malignant) underwent liver MRI for suspected liver metastases. Three image sets (DWI, Gd-EOB-DTPA and combined Gd-EOB-DTPA/DWI) in combination with unenhanced T1- and T2-weighted images were reviewed by three readers. Detection rates of focal liver lesions were assessed and diagnostic accuracy was evaluated by calculating the areas under the receiver-operating-characteristics curve (AUC). Confidence in diagnosis was evaluated on a 3-point scale. Histopathology and imaging follow-up served as the standard of reference. Detection of liver lesions and confidence in final diagnosis for all readers were significantly higher for the combined Gd-EOB-DTPA/DWI dataset than for DWI. The combination of DWI and Gd-EOB-DTPA rendered a significantly higher confidence in final diagnosis (2.44 vs. 2.50) than Gd-EOB-DTPA alone for one reader. For two readers, accuracy in diagnosis of liver metastases was significantly higher for Gd-EOB-DTPA/DWI (AUCs of 0.84 and 0.83) than for DWI datasets (AUCs of 0.73 and 0.72). Adding DWI to Gd-EOB-DTPA did not significantly increase diagnostic accuracy as compared to Gd-EOB-DTPA imaging alone. Addition of DWI sequences to Gd-EOB-DTPA enhanced MRI did not significantly increase diagnostic accuracy as compared to Gd-EOB-DTPA enhanced MRI alone in the diagnosis of liver metastases. However, the increase in diagnostic confidence might justify acquisition of DWI sequences in a dedicated MRI protocol.


Association Study between 5-HT1A Receptor Gene C(-1019)G Polymorphism and Panic Disorder in a Korean Population.
Serotonergic dysfunction is quite evident in panic disorder. We investigated whether the C(-1019)G polymorphism of 5-HT1A receptor gene may play a role in the pathogenesis of panic disorder in a Korean population. The 5-HT1A receptor genotype for the single nucleotide polymorphism (SNP) C(-1019)G was analyzed in 94 patients and 111 healthy controls. The severity of the patients' symptoms was examined using the Spielberger State-Trait Anxiety Inventory (STAI), Panic Disorder Severity Scale (PDSS), Anxiety sensitivity index (ASI), Acute Panic Inventory (API) and Hamilton's Rating Scale for Anxiety (HAM-A). The distribution of the genotypes of the C/G polymorphism did not differ significantly from those predicted by Hardy-Weinberg equilibrium in patients as well as the controls. No association between the C(-1019)G polymorphism and panic disorder was detected in either the allele frequency or genotype distribution. There was no significant association with genotype distribution in the panic disorder with agoraphobia. However, there was a significant difference of symptom severity between C/C, C/G, and G/G genotype or between C and G allele in panic disorder patients without agoraphobia. PDSS scores were significantly higher in subjects with the G/G genotype or with G allele in patients without agoraphobia, not in total patients or patients with agoraphobia. Although there were no significant differences in the genotype and allele distributions, we found a significant association between panic symptom severity and the serotonin 1A receptor gene. This result suggests that the serotonin 1A receptor and serotonin may play a role in the pathogenesis of panic disorder.


On the buzzword approach to policy formation.
This article draws attention to an absurd feature of contemporary political life that significantly affects health service policy and calls for an urgent explanation. Policies are formed by a process that privileges rhetoric over reality, producing policies that are conceptualized at a later date. Two influential articles on clinical governance illustrate this phenomenon perfectly. Lack of clarity about its true meaning and nature is a key feature of clinical governance. The lack of clarity allows policy-makers to shift responsibility for the problems of the health service onto the workforce, who are required to interpret the deliberately vague and platitudinous statements of management in order to implement the policy. But management, through the creation of monitoring agencies, reserves the right to determine whether the policy has been correctly interpreted, thus retaining power without responsibility. Government and senior management have abandoned the communicative function of language, eschewing reasoned debate (as characterized by the use of evidence and structured argument), instead employing language exclusively for the purposes of control and manipulation. Those of us still concerned that the future of our essential services should be determined by open and reasonable debate need to discuss urgently how to explain and respond to this appalling situation.


Risk factors for temporary tracheostomy tube placement following surgery to alleviate signs of brachycephalic obstructive airway syndrome in dogs.
OBJECTIVE To identify risk factors for temporary tracheostomy tube placement (TTTP) following surgery for alleviation of signs associated with brachycephalic obstructive airway syndrome (BOAS) in dogs. DESIGN Retrospective case-control study. ANIMALS 122 client-owned dogs with BOAS that underwent surgery to alleviate clinical signs (BOAS surgery). PROCEDURES The medical records database of a veterinary teaching hospital was searched to identify dogs that underwent BOAS surgery from January 2007 through March 2016. Of the 198 dogs identified, 12 required postoperative TTTP (cases); 110 of the remaining 186 dogs were randomly selected as controls. Data regarding signalment and select preoperative, intraoperative, and postoperative variables were extracted from the medical record of each dog. Variables were compared between cases and controls and evaluated for an association with the odds of postoperative TTTP. RESULTS Body condition score, tracheal diameter-to-thoracic inlet ratio, staphylectomy technique, and mortality rate did not differ significantly between cases and controls. The odds of postoperative TTTP increased approximately 30% (OR, 1.3) for each 1-year increase in patient age. Postoperative administration of corticosteroids and presence of pneumonia were also positively associated with the odds of postoperative TTTP. Median duration of hospitalization was significantly longer for cases than controls. CONCLUSIONS AND CLINICAL RELEVANCE Age was positively associated with the odds of TTTP in dogs after BOAS surgery, and TTTP led to prolonged hospitalization. Thus, early identification and intervention may be beneficial for dogs with BOAS. The associations between TTTP and postoperative corticosteroid use or pneumonia were likely not causal, but reflective of patient disease severity.


Transcatheter arterial chemoembolization as primary treatment for hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) in Western populations has historically been associated with poor survival. In this study, we conducted a 7-year retrospective analysis of patients with HCC undergoing transcatheter arterial chemoembolization (TACE) at our institution and examined demographics, outcomes, and complications. During the period of study, 39 patients (25 male [64%], mean age 58 [range 17 to 86]) underwent a total of 78 chemoembolization treatments. During the same time period, an additional 31 patients received supportive care only. The majority of patients had late stage disease (American Joint Committee on Cancer stage III, IVa, or IVb) with no statistical difference noted between the two groups (P = 0.2). However, patients receiving supportive care only had significantly worse hepatic dysfunction by Child's classification (P = 0.005). Twenty-nine patients (74%) had documented cirrhosis, with hepatitis C being the most common cause in 11 of 29 (38%). In patients undergoing TACE, overall actuarial survival was 35%, 20%, and 11% at 1, 2, and 3 years with a median survival of 9.2 months, significantly improved over the group receiving supportive care only (P < 0.0001). Median survival for the group receiving supportive care was less than 3 months. Neither age nor stage had a significant impact on survival. The most common complications of TACE included transient nausea, abdominal pain, vomiting, and fever. TACE is a safe and effective therapeutic option for selected patients with HCC not amenable to surgical intervention.


Complete genome sequence of Halomonas sp. R5-57.
The marine Arctic isolate Halomonas sp. R5-57 was sequenced as part of a bioprospecting project which aims to discover novel enzymes and organisms from low-temperature environments, with potential uses in biotechnological applications. Phenotypically, Halomonas sp. R5-57 exhibits high salt tolerance over a wide range of temperatures and has extra-cellular hydrolytic activities with several substrates, indicating it secretes enzymes which may function in high salinity conditions. Genome sequencing identified the genes involved in the biosynthesis of the osmoprotectant ectoine, which has applications in food processing and pharmacy, as well as those involved in production of polyhydroxyalkanoates, which can serve as precursors to bioplastics. The percentage identity of these biosynthetic genes from Halomonas sp. R5-57 and current production strains varies between 99 % for some to 69 % for others, thus it is plausible that R5-57 may have a different production capacity to currently used strains, or that in the case of PHAs, the properties of the final product may vary. Here we present the finished genome sequence (LN813019) of Halomonas sp. R5-57 which will facilitate exploitation of this bacterium; either as a whole-cell production host, or by recombinant expression of its individual enzymes.


Validity and reliability of GPS for measuring distance travelled in field-based team sports.
The aim of the present study was to examine the effects of movement intensity and path linearity on global positioning system (GPS) distance validity and reliability. One participant wore eight 1-Hz GPS receivers while walking, jogging, running, and sprinting over linear and non-linear 200-m courses. Five trials were performed at each intensity of movement on each 200-m course. One receiver was excluded from analysis due to errors during data collection. The results from seven GPS receivers showed the mean (± s) and percent bias of the GPS distance values on the 200-m linear course were 205.8 ± 2.4 m (2.8%), 201.8 ± 2.8 m (0.8%), 203.1 ± 2.2 m (1.5%), and 205.2 ± 4 m (2.5%) for the walk, jog, run, and sprint trial respectively. Walk and sprint distances were significantly different from jogging and running distances (P < 0.05). The GPS distance values on the 200-m non-linear course were 198.9 ± 3.5 m (-0.5%), 188.3 ± 2 m (-5.8%), 184.6 ± 2.9 m (-7.7%), and 180.4 ± 5.7 m (-9.8%) for the walk, jog, run, and sprint trial respectively; these were significantly lower than those for the corresponding values on the linear course (P < 0.05). Differences between all non-linear movement intensities were significant (P < 0.05). The overall coefficient of variation within and between receivers was 2.6% and 2.8% respectively. Path linearity and movement intensity appear to affect GPS distance accuracy via inherent positioning errors, update rate, and conditions of use; reliability decreases with movement intensity.


Splenic abscess associated with endocarditis.
Refractory or recurrent sepsis in patients with endocarditis may be from splenic abscess. The purpose of this review is to assess this relationship. Of 564 patients treated for documented endocarditis between 1970 and 1990, splenic abscesses developed in 27 patients. The mean age of the 18 men and nine women was 37 years. Etiologic factors included street drugs, dental abscess, and rheumatic fever. Symptoms included fever, myalgia, chills, and dyspnea; the prodrome averaged 2 weeks. Typical signs were heart murmur, left lower-lobe infiltrate, and leukocytosis. Splenomegaly was found in three patients. All patients had valve lesions, which involved the aortic valve alone in 10 patients, the mitral valve alone in eight patients, and multiple valves in nine patients. A splenic defect on computed axial tomographic scan was diagnosed correctly as an abscess in 10 patients, was indeterminant in three patients, and was incorrectly called an infarct in four patients. Thirteen patients died. All 10 patients treated without splenectomy died, including five patients who underwent valvular replacement. In contrast, only three of 17 patients treated by splenectomy with (11 patients) or without (six patients) valvular surgery died. Splenic abscess often accompanies endocarditis. The diagnosis is suspected by refractory fever and confirmed by abdominal computed axial tomography scan. Splenectomy is warranted before or after valvular surgery, depending on the patient's clinical response to antibiotics.


Cerebral Blastomyces dermatitidis infection in a cat.
An 8-year-old domestic shorthair cat was evaluated because of signs of depression, circling, and visual deficits. The cat had no cutaneous lesions, and results of an ophthalmologic examination and thoracic radiography were within reference limits. Computed tomography of the brain revealed a mass lesion involving the right parietal, temporal, and occipital lobes; the mass was in broad-based contact with the skull and smoothly marginated and had strong homogenous enhancement after contrast agent administration. During craniectomy, samples of the mass were collected for cytologic and histopathologic evaluations and microbial culture. A diagnosis of Blastomyces dermatitidis-associated meningoencephalitis with secondary pyogranulomatous inflammation was made. Amphotericin B (0.25 mg/kg [0.11 mg/lb], IV) was administered on alternate days (cumulative dose, 1.75 mg/kg [0.8 mg/lb]). To minimize the risk of nephrotoxicosis, assessments of serum biochemical variables (urea nitrogen and creatinine concentrations) and urinalyses were performed at intervals. The third dose of amphotericin B was postponed 48 hours because the cat became azotemic. The cat subsequently received fluconazole (10 mg/kg [4.5 mg/lb], PO, q 12 h) for 5.5 months. Six months after discontinuation of that treatment, the cat appeared healthy and had no signs of relapse. Brain infection with B dermatitidis is typically associated with widespread disseminated disease. The cat of this report had no evidence of systemic disease. Blastomycosis of the CNS should be considered as a differential diagnosis for brain lesions in cats from areas in which B dermatitidis is endemic.


Avian ecologists and physiologists have different sexual preferences.
Seasonal timing is studied by ecologists and physiologists alike and it is now widely recognized that further integration of these fields is needed for a full understanding of phenology. This is especially true in the light of the impact of global climate change on living organisms. In studies of avian reproduction, one obstacle to this integration is that ecologists and physiologists do not allocate their research efforts equally to males and females. The physiological orchestration of breeding stages has been studied almost exclusively in males, while in avian ecology and evolutionary biology females are more often considered. This sex bias has severe implications: sexes differ in the way they use external cues to organize their life cycles, but often cue in on each other's physiology and behavior. The simultaneous investigation of both males and females within single studies is thus essential. In this review, I begin by illustrating the sex-bias in studies and attempt to explain its origin. I then provide a number of examples in which focusing on a single sex would have resulted in misleading conclusions. Finally, I review some classical studies of female reproductive physiology that have promoted and developed research on the "forgotten-sex".