The present status and developments of laparoscopic surgery for colorectal cancer.
Laparoscopic surgery for colorectal cancer has been shown to be less invasive than open surgery, while maintaining a similar safety level in many clinical trials. Furthermore, there are no significant differences between laparoscopic surgery and open surgery with respect to the long-term outcomes in colon cancer. Thus, laparoscopic surgery has been accepted as one of the standard treatments for colon cancer. In addition, laparoscopic surgery has also achieved favorable outcomes in the treatments of rectal cancer, with many reports showing long-term outcomes comparable to those of open surgery. Furthermore, the magnification in laparoscopy improves visualization in the pelvic cavity and facilitates precise manipulation, as well as providing an excellent educational opportunity. Laparoscopic surgery may be an ideal approach for the treatment of rectal cancer and colon cancer. Recently, two trials showed that, among patients with advanced rectal cancer, the use of laparoscopic surgery as compared with open surgery confirmed to meet the criterion for non-inferiority for long-term outcomes. In addition, new techniques such as single-port and robotic surgery have been introduced for laparoscopic surgery in recent years.


The influence of short-term strength training on health-related quality of life and executive cognitive function.
Strength training has been reported as a potentially useful exercise to improve psychological aspects in the elderly, but its effects remain controversial. This study investigated the effectiveness of strength training conducted twice a week for 12 weeks for improving health-related quality of life (HRQOL) and executive cognitive function. The study was a single-blind randomized controlled trial with assessments before and after intervention. HRQOL and executive function were assessed using the SF-36 Health Status Survey and a computerized neuro-cognitive assessment using task-switch reaction time trials, respectively. Subjects comprised 119 participants > or =65 years old, randomized to either strength training (n=65) or health education classes (controls, n=54). The strength training program was designed to strengthen the large muscle groups most important for functional activities and to improve balance. The effects of the intervention on the eight dimensions of the SF-36 in the control and training groups were analyzed. Only the mental health scale of the SF-36 was significantly improved for the training group compared with controls after 12 weeks. Task-switch reaction time and correct response rate remained unchanged. Short-term strength training might have modest positive effects on HRQOL, although this training period may not be sufficient to affect executive function in relatively healthy older people.


Epidemiology of Heart Failure: A Contemporary Perspective.
Designated as an emerging epidemic in 1997, heart failure (HF) remains a major clinical and public health problem. This review focuses on the most recent studies identified by searching the Medline database for publications with the subject headings HF, epidemiology, prevalence, incidence, trends between 2010 and present. Publications relevant to epidemiology and population sciences were retained for discussion in this review after reviewing abstracts for relevance to these topics. Studies of the epidemiology of HF over the past decade have improved our understanding of the HF syndrome and of its complexity. Data suggest that the incidence of HF is mostly flat or declining but that the burden of mortality and hospitalization remains mostly unabated despite significant ongoing efforts to treat and manage HF. The evolution of the case mix of HF continues to be characterized by an increasing proportion of cases with preserved ejection fraction, for which established effective treatments are mostly lacking. Major disparities in the occurrence, presentation, and outcome of HF persist particularly among younger Black men and women. These disturbing trends reflect the complexity of the HF syndrome, the insufficient mechanistic understanding of its various manifestations and presentations and the challenges of its management as a chronic disease, often integrated within a context of aging and multimorbidity. Emerging risk factors including omics science offer the promise of discovering new mechanistic pathways that lead to HF. Holistic management approaches must recognize HF as a syndemic and foster the implementation of multidisciplinary approaches to address major contributors to the persisting burden of HF including multimorbidity, aging, and social determinants of health.


Global access to infertility care in developing countries: a case of human rights, equity and social justice.
According to WHO data more than 180 million couples in developing countries suffer from primary or secondary infertility. The social stigma of childlessness still leads to isolation and abandonment in many developing countries. Differences between the developed and developing world are emerging because of the different availability in infertility care and different socio-cultural value surrounding procreation and childlessness. Although reproductive health education and prevention of infertility are number one priorities, the need for accessible diagnostic procedures and new reproductive technologies (ART) is very high. The success and sustainability of ART in resource-poor settings will depend to a large extend on our ability to optimise these techniques in terms of availability, affordability and effectiveness. Accessible infertility treatment can only be successfully introduced in developing countries if socio-cultural and economic prerequisites are fulfilled and governments can be persuaded to support their introduction. We have to liaise with the relevant authorities to discuss the strengthening of infertility services, at the core of which lies the integration of infertility, contraceptive and maternal health services within public health care structures. After a fascinating period of more than 30 years of IVF, only a small part of the world population benefits from these new technologies. Time has come to give equitable access to effective and safe infertility care in resource-poor countries as well.


Transmembrane permeability channels in vesicles reconstituted from single species of porins from Salmonella typhimurium.
Aggregates of the "major" outer membrane proteins, "porins," of Salmonella typhimurium form diffusion channels in reconstituted vesicle membranes. The aggregate consists of three species of porins with apparent molecular weights of 34,000, 35,000, and 36,000 when active aggregates are subjected to sodium dodecyl sulfate-acrylamide gel electrophoresis after heating in the presence of sodium dodecyl sulfate (Nakae, J. Biol. Chem. 251:2176-2178, 1976). Single species of porins were isolated by solubilization of membranes and subsequent gel filtration in the presence of sodium dodecyl sulfate from the mutant strains of Salmonella typhimurium that produced only single species of porin. The single species of porins of either 34,000, 35,000, or 36,000 daltons formed diffusion channels when assayed for sucrose permeability in the vesicle membranes reconstituted from porins, phospholipids, and lipopolysaccharides. The exclusion limits of the pores made of single species of porins were not distinguishable from each other and from the exclusion limits of the pores made of the porin aggregates from the wild-type strain, when the permeability of vesicle membranes to radioactive di-, tri-, and tetrasaccharides and to various sizes of radioactive polyethylene glycol was determined. Porin-deficient mutants produced residual amounts of porin amounting to 1 to 5% that produced by the parent strain. This residual porin made diffusion channels when the isolated porins were incorporated into the vesicle membrane and assayed for permeability of saccharides.


Functional connectivity in multiple sclerosis after robotic rehabilitative treatment: A case report.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of central nervous system and it is associated with an impaired motor function status. The efficacy of rehabilitation in promoting functional recovery and increasing quality of life in MS patients has been demonstrated. A 47-year-old woman was diagnosed with relapsing-remitting multiple sclerosis (RRMS) in November 2014 because of left upper limb hypoesthesia and weakness with difficulty in hand manipulation skills (there was a 1-point Expanded Disability Status Scale (EDSS) progression, i.e., 2.5 vs 1.5). Magnetic resonance image (MRI) showed a new frontal right cortical high-signal-intensity lesion. Neurological and MRI examination were suggestive of MS diagnosis. Patient was treated with robotic rehabilitation and evaluated by a Glove Analyzer for fMRI system (GAF). Functional MRI (fMRI) was acquired before and at the end of rehabilitative treatment performed with robotic device (Armeo-power). At the end of the rehabilitation program, most of the behavioral parameters, GAF and fMRI evaluation, showed a significative improvement. Moreover, fMRI showed a significantly increased functional activation within the sensory-motor network in the active, motor task. Our findings suggest a possible restorative effect of robotics on brain networks. Moreover, we may argue that GAF may be a valuable tool in assessing functional recovery after upper limb rehabilitation, especially of associated to fMRI examination.


Granulomatous necrotizing retinochoroiditis caused by Sporotrichum schenkii. Report of a case including immunofluorescence and electron microscopical studies.
A middle-aged man had blurred vision, redness, and pain in the right eye. Ophthalmoscopic examination revealed slowly progressive necrotizing retinitis in the peripheral superonasal quadrant. The clinical impression was toxoplasmic retinochoroiditis, but lesions failed to respond to steroids, pyrimethamine, and sulfonamides. The eye was enucleated and, histopathologically, showed necrotizing granulomatous retinochoroiditis and optic neuritis, numerous cigarshaped, yeast-like organisms located within the necrotic retina and subretinally, and a subretinal asteroid body. Organisms were identified as Sporotrichum schenkii by immunofluorescence techniques. Electron microscopical studies of the fungus disclosed an unusually thickened capsule with a well-developed cell wall, the outer portion of which exhibited a radiating pattern of granular filamentous material. The ability of S schenkii to cause endophthalmitis in a patient without apparent primary infection should be remembered in the differential diagnosis of a cryptogenic, slowly progressive intraocular infection.


[Postoperative hematomas after inguinal hernia repair].
It was done the analysis of the results of 625 open and endoscopic prosthetic and autoplastic hernia repairs made in a planned and emergency basis during the period from 2005 to 2012. The autoplastic group was divided into three subgroups: the plastic by Bassini, Shouldays and Postempski. The prosthesis group was divided into open and endoscopic subgroups. The open prosthesis group was also divided into subgroups in accordance with the options of hernia sac preparation (excised, reseted, untouched) and the reconstruction of the posterior wall of the inguinal canal (without reconstruction, with a single-layer and double-layer plastic). It was noted hematocele scrotum - 19 (3.04%), hematoma of the spermatic cord - 16 (2.56%), wound infiltration with a hemorrhagic component - 13 (2.08%). It was not noted the hemorrhagic complications in the subgroups of open prosthesis without hernia sac preparation. Reducing surgical aggression against inguinal hernias during the operation can reduce the frequency of hematomas. The absence of a clear classification of hematomas brings to difficulties in assessment of the role of specific surgical techniques in the development of postoperative complications after surgery for inguinal hernias.


From DNA damage to mutations: All roads lead to aging.
Damage to the repository of genetic information in cells has plagued life since its very beginning 3-4 billion years ago. Initially, in the absence of an ozone layer, especially damage from solar UV radiation must have been frequent, with other sources, most notably endogenous sources related to cell metabolism, gaining in importance over time. To cope with this high frequency of damage to the increasingly long DNA molecules that came to encode the growing complexity of cellular functions in cells, DNA repair evolved as one of the earliest genetic traits. Then as now, errors during the repair of DNA damage generated mutations, which provide the substrate for evolution by natural selection. With the emergence of multicellular organisms also the soma became a target of DNA damage and mutations. In somatic cells selection against the adverse effects of DNA damage is greatly diminished, especially in postmitotic cells after the age of first reproduction. Based on an abundance of evidence, DNA damage is now considered as the single most important driver of the degenerative processes that collectively cause aging. Here I will first briefly review the evidence for DNA damage as a cause of aging since the beginning of life. Then, after discussing the possible direct adverse effects of DNA damage and its cellular responses, I will provide an overview of the considerable progress that has recently been made in analyzing a major consequence of DNA damage in humans and other complex organisms: somatic mutations and the resulting genome mosaicism. Recent advances in studying somatic mutagenesis and genome mosaicism in different human and animal tissues will be discussed with a focus on the possible mechanisms through which loss of DNA sequence integrity could cause age-related functional decline and disease.


Arts and creativity interventions for improving health and wellbeing in older adults: a systematic literature review of economic evaluation studies.
As the population ages, older people account for a larger proportion of the health and social care budget. A significant body of evidence suggests that arts and creativity interventions can improve the physical, mental and social wellbeing of older adults, however the value and/or cost-effectiveness of such interventions remains unclear. We systematically reviewed the economic evidence relating to such interventions, reporting our findings according to PRISMA guidelines. We searched bibliographic databases (MEDLINE, EMBASE, Econlit and Web of Science and NHSEED), trial registries and grey literature. No language or temporal restrictions were applied. Two screening rounds were conducted independently by health economists experienced in systematic literature review. Methodological quality was assessed, and key information extracted and tabulated to provide an overview of the published literature. A narrative synthesis without meta-analysis was conducted. Only six studies were identified which provided evidence relating to the value or cost-effectiveness of arts and creativity interventions to improve health and wellbeing in older adults. The evidence which was identified was encouraging, with five out of the six studies reporting an acceptable probability of cost-effectiveness or positive return on investment (ranging from £1.20 to over £8 for every £1 of expenditure). However, considerable heterogeneity was observed with respect to study participants, design, and outcomes assessed. Of particular concern were potential biases inherent in social value analyses. Despite many studies reporting positive health and wellbeing benefits of arts and creativity interventions in this population, we found meagre evidence on their value or cost-effectiveness. Such evidence is costly and time-consuming to generate, but essential if innovative non-pharmacological interventions are to be introduced to minimise the burden of illness in this population and ensure efficient use of public funds. The findings from this review suggests that capturing data on the value and/or cost-effectiveness of such interventions should be prioritised; furthermore, research effort should be directed to developing evaluative methods which move beyond the confines of current health technology assessment frameworks, to capture a broader picture of 'value' more applicable to arts and creativity interventions and public health interventions more generally. CRD42021267944 (14/07/2021).


Refractive error and visual impairment in private school children in Ghana.
To assess the prevalence of refractive error and visual impairment in private school children in Ghana. A random selection of geographically defined classes in clusters was used to identify a sample of school children aged 12 to 15 years in the Ashanti Region. Children in 60 clusters were enumerated and examined in classrooms. The examination included visual acuity, retinoscopy, autorefraction under cycloplegia, and examination of anterior segment, media, and fundus. For quality assurance, a random sample of children with reduced and normal vision were selected and re-examined independently. A total of 2454 children attending 53 private schools were enumerated, and of these, 2435 (99.2%) were examined. Prevalence of uncorrected, presenting, and best visual acuity of 20/40 or worse in the better eye was 3.7, 3.5, and 0.4%, respectively. Refractive error was the cause of reduced vision in 71.7% of 152 eyes, amblyopia in 9.9%, retinal disorders in 5.9%, and corneal opacity in 4.6%. Exterior and anterior segment abnormalities occurred in 43 (1.8%) children. Myopia (at least -0.50 D) in one or both eyes was present in 3.2% of children when measured with retinoscopy and in 3.4% measured with autorefraction. Myopia was not significantly associated with gender (P = 0.82). Hyperopia (+2.00 D or more) in at least one eye was present in 0.3% of children with retinoscopy and autorefraction. The prevalence of reduced vision in Ghanaian private school children due to uncorrected refractive error was low. However, the prevalence of amblyopia, retinal disorders, and corneal opacities indicate the need for early interventions.


Signal stratification of autoantibody levels in serum samples and its application to the early detection of lung cancer.
Further signal stratification for the EarlyCDT®-Lung test should facilitate interpretation of the test, leading to more precise interventions for particular patients. Samples were measured for the presence of autoantibodies to seven tumor-associated antigens (TAAs) (p53, NY-ESO-1, CAGE, GBU4-5, SOX2, MAGE A4, and HuD). In addition to the current test cut-offs (determined using a previously reported Validation case-control sample set, set A; n=501), new high and low cut-offs were set in order to maximize the test's positive and negative predictive values (PPV and NPV, respectively). All three sets of cut-offs were applied to two confirmatory datasets: (I) the case-control set B (n=751), and (II) Population-derived set C (n=883), and all three datasets combined (n=2,135). For the Validation dataset, cancer/non-cancer positivity for current cut-offs was 41%/9% (PPV =0.109, 1 in 9). The high positive stratum improved this to 25%/2% (PPV =0.274, 1 in 4). The low negative stratum improved this to 8%/23% (NPV =0.990, 1 in 105). This provides a 25-fold difference in lung cancer probability between the highest and lowest groups. The test performs equally well in subjects who fulfilled the entry risk criteria for the National Lung Screening Trial (NLST) and subjects who did not meet the NLST criteria. The EarlyCDT®-Lung test has been converted to a four-stratum test by the addition of high and low sets of cut-offs: patients are thus stratified into four risk categories. This stratification will enable personalization of subsequent screening and treatment programs for high risk individuals or patients with lung nodules.


The effect of taxation on tobacco consumption and public revenues in Lebanon.
Tobacco consumption rates in Lebanon are among the highest worldwide. The country ratified the Framework Convention on Tobacco Control in 2005. A law was passed in 2011 which regulates smoking in closed public spaces, bans advertising, and stipulates larger warnings. Despite international evidence confirming that increasing taxation on tobacco products lowers tobacco consumption, no such policy has yet been adopted: a cigarette pack costs on average US$1.50. To date no studies in Lebanon have addressed the welfare and public finance effects of increasing taxes on tobacco products. Using the 2005 national survey of household living conditions, we estimate an almost ideal demand system to generate price elasticities of demand for tobacco. Using estimated elasticities and a conservative scenario for expected smuggling, we simulate the consumption and tax revenue effects of a change in the price of tobacco under various tax schemes. Increasing taxes on all tobacco products so as to double the price of imported cigarettes would lower their consumption by 7% and consumption of domestically produced cigarettes by over 90%. Young adults (ages 15-30) are more sensitive: consumption would drop by 9% for imported cigarettes and by 100% for domestic cigarettes. Government revenues would increase by approximately 52%. The estimated elasticities indicate that an increase in taxes on all tobacco products would lead to a reduction in consumption and an increase in government revenue. Evidence from Lebanon on the effectiveness of increased taxation may help initiate national debate on the need to raise taxes.


A metanalysis to evaluate the effects of substrate sources on the nutritional performance of black soldier fly larvae: implications for sustainable poultry feed.
This meta-analysis presents an evaluation of substrate sources and their impact on the growth performance of black soldier fly (BSF) larva. The database, compiled from Google Scholar, PubMed, and Science Direct, focuses on data concerning substrate sources, environmental conditions, and the performance parameters of BSF. Seven types of substrates were analyzed, including Feed Waste, Manure, Fruits, Mix, Animal Source, Fermentation Residue, and Food Waste. The Feed Waste group demonstrated the highest DM content, while the highest CP content was found in the Animal Source group. Higher CP and DM content were found in larva meal from Fermentation Residues and Feed Waste diets, respectively. Higher survival rates were observed in BSF larvae fed on Feed Waste, Fermentation Residues, Food Waste, Fruits, Mix, and Manure substrates compared to Vegetable and Animal Source substrates. Fresh larval weight was lower when Manure was used as a feed substrate than in the Animal Source, Feed Waste, and Vegetable substrates. The prepupal Wet Weight was highest in BSF larvae fed on Animal Source, surpassing those fed on Fermentation Residue, Manure, and Vegetable substrates. Substrate CP content exhibited a positive relationship with fresh larva weight, prepupal wet weight, dry larval weight; larval length, mortality until prepupal, protein conversion, feed conversion ratio, food consumption, substrate reduction rate bioconversion ratio, waste reduction index, and efficiency conversion of digested feed in BSF larva. In conclusion, our findings underline that the source and composition of substrates are correlated to the nutritional composition and conversion efficiency of BSF larva meal.


Variant Creutzfeldt-Jakob [corrected] disease: the second case in Portugal and in the same geographical region.
We present the second variant Creutzfeldt-Jacob patient in the same district of northwest Portugal as was previously reported. A 14-year-old previously healthy girl had unexplained pain in the left leg, as well as psychiatric disturbances. This was shortly followed by progressive cognitive impairment, ataxia and generalised choreoatethosis. Neuropsychological assessment revealed severe frontal and medial temporal dysfunction, the posterior cortices being spared. An electroencephalogram was normal. CSF 14.3.3 protein was slightly positive. Magnetic resonance imaging showed the "hockey stick sign" and hyperintensities in the periaquedutal grey matter and in the right parietal cortex, the last with restriction to water molecule movement. SPECT revealed perfusion defects in the left frontotemporal and right parietal regions. PRNP gene sequencing showed no mutations, the patient being homozygous to methionine in codon 129. Five months after onset, immunocytochemical and immunoblotting analysis confirmed deposition of prion protein and a PrP4t electrophoretic pattern. The patient never travelled outside Portugal or received blood transfusions. She had surgical herniorrhaphy in 1998 (when catgut was used) and 2003. This is the second case in Portugal in a 2-year period and 20 km apart from each other, with no known common exposure apart from ingestion of cow meat. We discuss these case peculiarities and underline its epidemiological significance.


The socioeconomic determinants of cancer.
This paper provides a synthesis on socioeconomic inequalities in cancer incidence, mortality and survival across countries and within countries, with particular focus on the Italian context; the paper also describes the underlying mechanisms documented for cancer incidence, and reports some remarks on policies to tackle inequalities.From a worldwide perspective, the burden of cancer appears to be particularly increasing in developing countries, where many cancers with a poor prognosis (liver, stomach and oesophagus) are much more common than in richer countries. As in the case of incidence and mortality, also in cancer survival we observe a great variability across countries. Different studies have suggested a possible impact of health care on the social gradients in cancer survival, even in countries with a National Health System providing equitable access to care.In developed countries, there is increasing awareness of social inequalities as an important public health issue; as a consequence, there is a variety of strategies and policies being implemented throughout Europe. However, recent reviews emphasize that present knowledge on effectiveness of policies and interventions on health inequalities is not sufficient to offer a robust and evidence-based guide to the choice and design of interventions, and that more evaluation studies are needed.The large disparities in health that we can measure within and between countries represent a challenge to the world; social health inequalities are avoidable, and their reduction therefore represents an achievable goal and an ethical imperative.


Species-specific effects of single sensillum ablation on mating position in Drosophila.
Dipteran insects show a wide range of species-specific mating positions. Interspecific transitions from one position to another may reflect sexual or natural selection, or be pleiotropic consequences of other genetic changes. Like many cyclorrhaphan flies, Drosophila species mate with the male on the back of the female, positioned centrally. Mechanosensory sensilla on the male genitalia of three species of the melanogaster species sub-group of Drosophila have species-specific effects on mating position and on courtship success: ablation of a single pair of bristles on the genital claspers of D. melanogaster males halved homotypic mating success, and unilateral ablation produced a contralateral asymmetry in the male's mating posture. Ablation of mechanoreceptors on the male genital lateral plate affected mating posture less radically and had no effect on mating frequency. Surprisingly, ablation of sensilla on the claspers of D. simulans and D. sechellia males showed no effect on homotypic mating. A similar result was found for D. melanogaster x D. simulans hybrid males. The existence of major differences in the sensory bases of mating position and copulation success in closely related species shows how differing mating positions may have evolved and underlines the need for detailed functional studies in studying the evolution of insect genitalia: homologous structures may serve different functions in different species.


Screening of electrocatalytic materials for hydrogen evolution.
A general scheme for high-throughput screening of electrocatalysts is presented. By systematically exploiting a collection of theoretical and experimental materials databases, supplemented with quantum mechanical calculations, it locates systems that meet a set of pre-imposed selection criteria. As an example, the scheme is used to identify a binary "substrate-overlayer" electrocatalytic system for the hydrogen evolution reaction. The best catalysts found in this screening are based on Cu and W. The hydrogen evolution activity of W-Cu catalysts is evaluated by means of cyclic voltammetry. It turns out to be considerably more active than any of its constituents, pure W and Cu.


Is suicide ideation a surrogate endpoint for geriatric suicide?
The present study explored the validity of treating suicide ideation as a surrogate endpoint that can serve as a proxy for suicide in clinical intervention research with suicidal seniors. Two criteria; that suicide ideation is modulated by the proposed intervention and that modulation of suicide ideation leads to a quantitative reduction in suicide rates, were the focus of this review. A series of literature searches of the PsychINFO and Medline databases were conducted on the terms geriatric, elderly, seniors, suicide, self-destruction, clinical, randomized, trial, treatment, intervention , and ideation . Articles were analyzed if they provided sufficient information to examine whether an intervention effectively led to a reduction in suicide ideation among seniors. Two hundred and eight articles were considered for potential inclusion in this study, with 19 articles meeting final inclusion criteria. The articles reviewed were divided into three broad categories: articles supporting suicide ideation as a surrogate endpoint for geriatric suicide ( n = 6); those not supporting this hypothesis ( n = 1); and those providing insufficient information to test the hypothesis ( n = 12). The present analysis provided modest evidence for suicide ideation as a surrogate endpoint for geriatric suicide, due, in part, to a paucity of randomized controlled trials of treatment interventions for suicidal seniors, thus demonstrating a clear need for research in this area. Implications of utilizing surrogate endpoints in suicide research are discussed.


Peer mentoring for core medical trainees: uptake and impact.
To assess the uptake and impact of a peer mentoring scheme for core medical trainees on both mentors and mentees. All second year core medical trainees in the Southwest London Training programme in September 2012 were invited to mentor a first year core medical trainee. In parallel, all first year core medical trainees were invited to be mentored. Both potential mentors and mentees were asked to submit personal statements, to attend a three-session mentoring training programme and to be matched into mentoring pairs. The impact of the mentoring scheme on trainees' behaviour and outlook was assessed through questionnaires distributed at the start and at the end of the year. 31 of 72 (43%) core medical trainees submitted personal statements and 40 of 72 (56%) attended training sessions. 42 trainees (58%) participated in the scheme (21 mentor/mentee pairs were established). Of the trainees who participated, 23 of 42 (55%) completed the end of year questionnaire. Participating trainees viewed the scheme positively. Reported benefits included changes in their behaviour and acquiring transferable skills that might help them in later career roles, such as an educational supervisor. The end of year questionnaire was sent to all trainees and 10 responded who had not participated. They were asked why they had not participated and their reasons included lack of time, lack of inclination and a desire for more senior mentors. Their suggestions for improvement included more structured sessions to allow the mentor/mentee pairs to meet. This simple peer mentoring scheme was popular despite busy workloads and benefited all concerned. It is a simple effective way of supporting doctors. More work is needed to improve training for mentors and to improve access to mentoring.


Use of Health-Related Apps and Telehealth in Adults with Epilepsy in Germany: A Multicenter Cohort Study.
Background: Telehealth can improve the treatment of chronic disorders, such as epilepsy. Telehealth prevalence and use increased during the coronavirus disease 2019 (COVID-19) pandemic. However, familiarity with and use of telehealth and health-related mobile applications (apps) by persons with epilepsy remain unknown. Methods: We investigated telehealth use, demographics, and clinical variables within the multicenter Epi2020 cross-sectional study. Between October and December 2020, adults with epilepsy completed a validated questionnaire, including individual questions regarding knowledge and use of apps and telehealth. Results: Of 476 included individuals (58.2% women; mean age 40.2 ± 15.4 years), 41.6% reported using health-related apps. Health apps were used more frequently (pedometer 32.1%, exercise app 17.6%) than medical apps (health insurance 15.1%, menstrual apps 12.2%) or apps designed for epilepsy (medication reminders 10.3%, seizure calendars 4.6%). Few used seizure detectors (i.e., apps as medical devices 1.9%) or mobile health devices (fitness bracelet 11.3%). A majority (60.9%) had heard the term telehealth, 78.6% of whom had a positive view. However, only 28.6% had a concrete idea of telehealth, and only 16.6% reported personal experience with telehealth. A majority (55%) would attend a teleconsultation follow-up, and 41.2% would in a medical emergency. Data privacy and availability were considered equally important by 50.8%, 21.8% considered data privacy more important, and 20.2% considered data availability more important. Current health-related app use was independently associated with younger age (p = 0.003), higher education (p < 0.001), and subjective COVID-19-related challenges (p = 0.002). Persistent seizure occurrence (vs. seizure freedom ≥12 months) did not affect willingness to use teleconsultations on multivariable logistic regression analysis. Conclusions: Despite positive telehealth views, few persons with epilepsy in Germany are familiar with specific apps or services. Socioeconomic factors influence telehealth use more than baseline epilepsy characteristics. Telehealth education and services should target socioeconomically disadvantaged individuals to reduce the digital care gap. German Clinical Trials Register (DRKS00022024; Universal Trial Number: U1111-1252-5331).


Personality dimensions of patients can change during the course of parkinson's disease.
Studies assessing personality dimensions by the "Temperament and Character Inventory" (TCI) have previously found an association between Parkinson's disease (PD) and lower Novelty Seeking and higher Harm Avoidance scores. Here, we aimed to describe personality dimensions of PD patients with motor fluctuations and compare them to a normative population and other PD populations. All PD patients awaiting Deep Brain Stimulation (DBS) answered the TCI before neurosurgery. Their results were compared to those of historical cohorts (a French normative population, a de novo PD population, and a PD population with motor fluctuations). Most personality dimensions of our 333 included PD patients with motor fluctuations who are candidates for DBS were different from those of the normative population and some were also different from those of the De Novo PD population, whereas they were similar to those of another population of PD patients with motor fluctuations. During the course of PD, personality dimensions can change in parallel with the development of motor fluctuations, either due to the evolution of the disease and/or dopaminergic treatments.


Assessment of the control measures of the Category A diseases of the Animal Health Law: prohibitions in restricted zones and risk-mitigating treatments for products of animal origin and other materials.
EFSA received a mandate from the European Commission to assess the effectiveness of prohibitions of certain activities in restricted zones, and of certain risk mitigation treatments for products of animal origin and other materials with respect to diseases included in the Category A list in the Animal Health Law (Regulation (EU) 2016/429). This opinion belongs to a series of opinions where other disease-specific control measures have been assessed. In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of (i) prohibiting the movements of certain products, notably germinal products (semen, oocytes, embryos and hatching eggs), products of animal origin and animal by-products and feed of plant origin, hay and straw, and (ii) risk mitigation treatments for products of animal origin. In terms of semen, oocytes, embryos and hatching eggs, it was agreed that there was a lack of evidence particularly for embryos and oocytes reflected in a varying degree of uncertainty, whether these commodities could potentially contain the pathogen under consideration. The scenario assessed did not consider whether the presence of pathogen would lead to infection in the recipient animal. In terms of animal products, certain animal by-products and movement of feed of plant origin and straw, the assessment considered the ability of the commodity to transmit disease to another animal if exposed. For most pathogens, products were to some degree considered a risk, but lack of field evidence contributed to the uncertainty, particularly as potential exposure of ruminants to meat products is concerned. In terms of the risk mitigating treatments, recommendations have been made for several of these treatments, because the treatment description is not complete, the evidence is poor or inconclusive, or the evidence points to the treatment being ineffective.


Microplastic Exposure Assessment in Aquatic Environments: Learning from Similarities and Differences to Engineered Nanoparticles.
Microplastics (MPs) have been identified as contaminants of emerging concern in aquatic environments and research into their behavior and fate has been sharply increasing in recent years. Nevertheless, significant gaps remain in our understanding of several crucial aspects of MP exposure and risk assessment, including the quantification of emissions, dominant fate processes, types of analytical tools required for characterization and monitoring, and adequate laboratory protocols for analysis and hazard testing. This Feature aims at identifying transferrable knowledge and experience from engineered nanoparticle (ENP) exposure assessment. This is achieved by comparing ENP and MPs based on their similarities as particulate contaminants, whereas critically discussing specific differences. We also highlight the most pressing research priorities to support an efficient development of tools and methods for MPs environmental risk assessment.


[Ultrasound controlled follicle puncture in the "2 instrument technic"].
The authors present a new instrumentarium for ultrasonically guided transabdominal-transvesical follicular puncture. Permanent sonographic imaging of the puncture cannula and precise puncturing without being impeded by the resistance of the abdominal wall are provided by an attachment functioning as an adjustable target device developed for the soundhead of the sector scanner DIASONICS DS 1 and by introduction of a trocar with a puncture cannula sliding within the trocar at low resistance ("two-instruments technique"). In 12 women, 47 follicles were punctured, 30 human oocytes were collected, 12 embryos transferred and two pregnancies achieved after in vitro fertilisation (twins in one woman, a single child in another).


G protein-coupled receptor-associated sorting protein 1 regulates the postendocytic sorting of seven-transmembrane-spanning G protein-coupled receptors.
The largest superfamily of membrane proteins that translate extracellular signals into intracellular messages are the 7-transmembrane-spanning (7TM) G protein-coupled receptors (GPCR). One of the ways in which their activity is controlled is by the process of desensitization and endocytosis, whereby agonist-activated receptors are rapidly and often reversibly silenced through removal from the cell surface. Indeed, following endocytosis, individual receptors can be sorted differentially between recycling endosomes and lysosomes, which controls the reversibility of the silencing. Thus, endocytosis can either serve as a mechanism for receptor resensitization by delivering receptors back to the plasma membrane or facilitate receptor downregulation by serving as the first step towards targeting the receptors to lysosomes for degradation. The sorting of receptors to the lysosomal pathway can be facilitated by interaction with an array of accessory proteins. One of these proteins is the GPCR-associated sorting protein 1 (GASP-1), which specifically targets several 7TM-GPCR to the lysosomal pathway after endocytosis. Furthermore, GASP-1 was recently found to directly affect the signaling capacity of a 7TM-GPCR. Importantly, the in vivo relevance of GASP-1-dependent receptor sorting has also begun to be verified in animal models. Here, we summarize the recent advances in elucidating GASP-1-dependent receptor sorting functions and their potential implications in vivo.


Capitellar Fractures in Children and Adolescents: Classification and Early Results of Treatment.
There has been limited published information regarding capitellar fractures in the pediatric population. The purpose of this investigation was to characterize capitellar fracture patterns in children and adolescents and to assess early clinical and radiographic treatment outcomes. A retrospective analysis of 37 children and adolescents with capitellar fractures presenting to a tertiary pediatric hospital from 2004 to 2014 was performed. The mean patient age at the time of injury was 11.8 years. Medical records and radiographs were evaluated for fracture pattern, treatment, healing, and complications. Fractures were categorized on the basis of prevailing patterns of injury, and a classification system is proposed that aids in treatment decision-making. Thirty-two patients had follow-up of at least 6 weeks and were included for assessment of treatment outcomes. The mean follow-up was 12.3 months. Three predominant capitellar fracture patterns were identified. Type-I fractures (n = 25) were anterior shear injuries. Nondisplaced anterior shear fractures were successfully treated with cast immobilization. Displaced anterior shear fractures were treated with open reduction and internal fixation, with good results in a majority of patients. Of the 21 patients with Type-Ib fractures eligible for analysis, 6 (29%) required a secondary surgical procedure for loss of motion related to soft-tissue contracture, osteonecrosis, implant prominence, and/or intra-articular loose bodies. Type-II fractures (n = 9) were posterolateral shear injuries, typically associated with ulnohumeral dislocations. Among 5 patients with displaced fractures and adequate follow-up, 3 patients were treated nonoperatively and had poor results, with loss of elbow motion or mechanical symptoms, and 2 patients were treated surgically and achieved good functional restoration. Type-III fractures (n = 3) were acute chondral shear injuries, which achieved full restoration of motion after surgical treatment. A classification of pediatric capitellar fractures is proposed, guiding treatment and prognosis. Nondisplaced fractures heal successfully with cast immobilization. Good results may be expected with surgical fixation of displaced Type-I fractures (anterior shear). Type-II fractures (posterolateral shear) and Type-III fractures (chondral shear) are more subtle; advanced imaging and timely surgical management for displaced injuries are recommended to optimize clinical results. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Physical fitness effect on bone mass is mediated by the independent association between lean mass and bone mass through adolescence: a cross-sectional study.
We studied 278 adolescents (169 females) aged 13.0-18.5 years to elucidate whether an independent effect of physical fitness and lean mass in the differences between male and female bones can be detected. Lean and fat masses and bone mineral content (BMC) were measured with DXA. Physical fitness was evaluated with six different tests included in the EUROFIT test battery (flexibility, isometric, dynamic and endurance strength, speed, and cardiovascular fitness). To test the independent relationship between physical fitness and bone mass, multiple regression analysis was applied, including lean mass, age, and Tanner development as covariates. The males had a 43% lower fat mass and 40% and 16% higher lean mass and total BMC compared with the females (all P < 0.05). After adjustment for differences in body size and lean mass, the females exhibited a 7.4% higher BMC than the males (P < 0.05). The multiple regression analysis showed that lean mass had an independent relationship with bone mass (P < 0.001), explaining 67% of the total variance in whole-body BMC. In males, change in R (2) was 0.658 for hand grip and 0.035-0.151 for the rest of physical fitness-related variables; but 0.019-0.042 in females (all P-0.001); however, the independent relationships between physical fitness and bone disappeared after controlling for lean mass. In conclusion, it is likely the differences between male and female in bone mass could be explained by differences in lean mass and physical fitness.


An analysis of stereotypical motor movements and cardiovascular coupling in individuals on the autism spectrum.
One of the core diagnostic features of autism spectrum disorder (ASD) is engagement in stereotypical motor movements, although the etiology of this repetitive behavior is unknown. Since the 1960s, it has been hypothesized that stereotypical motor movements serve a homeostatic regulation function, and thereby a putative coupling mechanism to cardiovascular arousal. However, to date, surprisingly few reports explicitly assess cardio-somatic coupling and stereotypical motor movements. The present exploratory study investigates coupling of stereotypical body rocking and hand flapping to heart rate and heart rate variability (HRV) in a convenience sample (n = 10) of children and young adults with moderate to profound ASD. Motor movements were recorded via video and three-axis accelerometry, and simultaneous electrocardiographic signals were obtained to determine cardiovascular indices at or around the onset of naturalistically occurring stereotypy. Analysis of the heart rate revealed both repetitive body rocking and hand flapping in particular were found to associate with a strikingly similar cardiovascular pattern of acceleration and deceleration unrelated to physical demands associated with the movements themselves. Furthermore, neither type of stereotypical movement provoked directional change in heart rate variability. The implications of these results and opportunities for future research are discussed.


Pharmacological Tools to Modulate Autophagy in Neurodegenerative Diseases.
Considerable evidences suggest a link between autophagy dysfunction, protein aggregation, and neurodegenerative diseases. Given that autophagy is a conserved intracellular housekeeping process, modulation of autophagy flux in various model organisms have highlighted its importance for maintaining proteostasis. In postmitotic cells such as neurons, compromised autophagy is sufficient to cause accumulation of ubiquitinated aggregates, neuronal dysfunction, degeneration, and loss of motor coordination-all hallmarks of neurodegenerative diseases. Reciprocally, enhanced autophagy flux augments cellular and organismal health, in addition to extending life span. These genetic studies not-withstanding a plethora of small molecule modulators of autophagy flux have been reported that alleviate disease symptoms in models of neurodegenerative diseases. This review summarizes the potential of such molecules to be, perhaps, one of the first autophagy drugs for treating these currently incurable diseases.


Back in black: melanin-rich skin colour associated with increased net diversification rates in birds.
Evolutionary biologists have long been interested in understanding the factors that promote diversification in organisms, often focussing on distinct and/or conspicuous phenotypes with direct effects on natural or sexual selection such as body size and plumage coloration. However, multiple traits that potentially influence net diversification are not conspicuous and/or might be concealed. One such trait, the dark, melanin-rich skin concealed beneath the feathers, evolved more than 100 times during avian evolution, frequently in association with white feathers on the crown and UV-rich environments, suggesting that it is a UV-photoprotective adaptation. Furthermore, multiple species are polymorphic, having both light and dark skin potentially aiding occupation in different UV radiation environments. As such these polymorphisms are predicted to occur in species with large latitudinal variation in their distribution. Furthermore, by alleviating evolutionary constraints on feather colour, the evolution of dark skin may promote net diversification. Here, using an expanded dataset on bird skin coloration of 3033 species we found that more than 19% of species had dark skin. In contrast to our prediction, dark skinned birds have smaller distribution ranges. Furthermore, both dark skin and polymorphism in skin coloration promote net diversification. These results suggest that even concealed traits can influence large scale evolutionary events such as diversification in birds.


The Interleukin-1 Balance During Encephalitis Is Associated With Clinical Severity, Blood-Brain Barrier Permeability, Neuroimaging Changes, and Disease Outcome.
Encephalitis is parenchymal brain inflammation, commonly due to herpes simplex virus (HSV). Key host inflammatory mediators and their relationship to blood-brain barrier (BBB) permeability, neuroimaging changes, and disease outcome are poorly understood. We measured levels of 38 mediators in serum (n = 78) and cerebrospinal fluid (n = 37) specimens from patients with encephalitis, including 17 with disease due to HSV infection. Outcome measures were Glasgow coma and outcome scores; CSF to serum albumin ratio, reflecting BBB permeability; and, in patients with HSV infection, magnetic resonance imaging-based temporal lobe volume. Serum interleukin 1 receptor antagonist (IL-1RA) levels were elevated in patients with a good outcome (P= .004). Among patients infected with HSV, the ratio of CSF IL-1β to IL-1RA was associated with a worse outcome (P= .009); a ratio of ≥0.55 pg/mL had high specificity and sensitivity for a poor outcome (100% and 83%;P= .015). Temporal lobe volume had a negative correlation with serum IL-1RA level (P= .012) and a positive correlation with serum IL-1α level (P= .0003) and CSF IL-1β level (P= .007). A normal coma score was associated with an elevated interleukin 10 (IL-10) level in serum specimens from HSV-infected patients (P= .007) and CSF specimens from all patients (P= .016); the IL-10 level correlated inversely with BBB permeability (P= .005). A proinflammatory cytokine response is associated with greater clinical severity, BBB permeability, and neuroimaging damage during encephalitis. IL-1 antagonists should be investigated as adjunctive treatment in encephalitis.


A Prime/Boost Vaccine Regimen Alters the Rectal Microbiome and Impacts Immune Responses and Viremia Control Post-Simian Immunodeficiency Virus Infection in Male and Female Rhesus Macaques.
An efficacious human immunodeficiency virus (HIV) vaccine will likely require induction of both mucosal and systemic immune responses. We compared the immunogenicity and protective efficacy of two mucosal/systemic vaccine regimens and investigated their effects on the rectal microbiome. Rhesus macaques were primed twice mucosally with replication-competent adenovirus type 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinants and boosted twice intramuscularly with ALVAC-SIV recombinant plus SIV gp120 protein or with DNA for SIV genes and rhesus interleukin-12 plus SIV gp120 protein. Controls received empty Ad5hr vector and alum adjuvant only. Both regimens elicited strong, comparable mucosal and systemic cellular and humoral immunity. Prevaccination rectal microbiomes of males and females differed and significantly changed over the course of immunization, most strongly in females after Ad5hr immunizations. Following repeated low-dose intrarectal SIV challenges, both vaccine groups exhibited modestly but significantly reduced acute viremia. Male and female controls exhibited similar acute viral loads; however, vaccinated females, but not males, exhibited lower levels of acute viremia, compared to same-sex controls. Few differences in adaptive immune responses were observed between the sexes. Striking differences in correlations of the rectal microbiome of males and females with acute viremia and immune responses associated with protection were seen and point to effects of the microbiome on vaccine-induced immunity and viremia control. Our study clearly demonstrates direct effects of a mucosal SIV vaccine regimen on the rectal microbiome and validates our previously reported SIV vaccine-induced sex bias. Sex and the microbiome are critical factors that should not be overlooked in vaccine design and evaluation.IMPORTANCE Differences in HIV pathogenesis between males and females, including immunity postinfection, have been well documented, as have steroid hormone effects on the microbiome, which is known to influence mucosal immune responses. Few studies have applied this knowledge to vaccine trials. We investigated two SIV vaccine regimens combining mucosal priming immunizations and systemic protein boosting. We again report a vaccine-induced sex bias, with female rhesus macaques but not males displaying significantly reduced acute viremia. The vaccine regimens, especially the mucosal primes, significantly altered the rectal microbiome. The greatest effects were in females. Striking differences between female and male macaques in correlations of prevalent rectal bacteria with viral loads and potentially protective immune responses were observed. Effects of the microbiome on vaccine-induced immunity and viremia control require further study by microbiome transfer. However, the findings presented highlight the critical importance of considering effects of sex and the microbiome in vaccine design and evaluation.


Adult testosterone treatment but not surgical disruption of vomeronasal function augments male-typical sexual behavior in female mice.
It was recently reported that female mice lacking a functional vomeronasal organ (VNO) displayed male-typical sexual behavior indiscriminately toward female and male conspecifics. These results have been cited as showing that a circuit controlling male-typical sex behavior exists in both sexes, with its activation in females being tonically inhibited by VNO signaling, independent of adult sex hormones. We further assessed this hypothesis while controlling the endocrine status of female mice in which VNO function was surgically disrupted. In experiment 1, VNO-lesioned (VNOx) female mice showed no more mounting or pelvic-thrusting behavior toward an estrous female or a castrated, urine-swabbed male (presented simultaneously) than sham-operated (VNOi) females. This was true when subjects were either ovary-intact or ovariectomized and treated with estradiol, estradiol plus progesterone, or testosterone. In experiment 2, female mice given accessory olfactory bulb lesions or a sham lesion displayed equivalent frequencies of male sex behaviors when given testosterone after ovariectomy. In experiment 3, VNOx and VNOi females displayed equivalent frequencies of male sex behaviors toward an estrous female or a castrated male (presented in separate tests), again, when given testosterone after ovariectomy. Our results confirm early reports that adult testosterone can stimulate appreciable male-typical sex behavior in female mice. However, we failed to corroborate the recent claim that VNO signaling normally inhibits the activity of neural circuitry controlling the expression of male-typical mating behavior by female mice.


Nitrite generation and antioxidant effects during neutrophil apoptosis.
Neutrophil apoptosis is important for the resolution of airway inflammation in a number of lung diseases. Inflammatory mediators, endogenous reactive oxygen and nitrogen species, and intracellular and extracellular antioxidants may all influence neutrophil apoptosis. This study investigated the involvement of these factors during apoptosis of neutrophils cultured in vitro. Neutrophils undergoing spontaneous apoptosis in culture as assessed by annexin V binding generated significant amounts of nitrite. Incubation with agonistic anti-Fas monoclonal antibody or tumor necrosis factor-alpha (TNF-alpha) enhanced neutrophil apoptosis at 6 h, although it decreased nitrite accumulation. Although granulocyte-macrophage colony-stimulating factor significantly reduced neutrophil apoptosis, this was also associated with decreased nitrite accumulation. In contrast, inhibition of apoptosis at 16 h by dibutyryl cyclic adenosine monophosphate was associated with increased nitrite accumulation. Exogenous glutathione (GSH) or N-acetylcysteine significantly enhanced neutrophil apoptosis at 6 h and stimulated the production of H(2)O(2), which may mediate apoptosis through intracellular hydroxyl radical production. Intracellular GSH concentrations decreased in neutrophils undergoing apoptosis, and this was more marked in neutrophils treated with anti-Fas or TNF-alpha. These results suggest a causal association between reduced endogenous nitric oxide production, reduced intracellular GSH, and Fas- and TNF-alpha-mediated neutrophil apoptosis, whereas enhanced neutrophil survival mediated by dibutyryl cyclic adenosine monophosphate is associated with increased nitrite generation and maintenance of intracellular GSH. The interaction of endogenous reactive oxygen species with extracellular antioxidants such as GSH could also contribute to the complex processes regulating neutrophil apoptosis and hence the resolution of inflammation in the lung.


Flumequine in Atlantic salmon Salmo salar: disposition in fish held in sea water versus fresh water.
14C-labeled flumequine was administered as a single oral (5 mg kg(-1), 86 microCi kg(-1)) or intravenous (5 mg kg(-1), 82 microCi kg(-1)) dose to Atlantic salmon Salmo salar held in sea water or in fresh water. The absorption, tissue distribution and elimination were determined by means of liquid scintillation counting and whole-body autoradiography. The drug was rapidly absorbed and extensively distributed in all groups of fish. Radiolabeled compound was present in blood and muscle for more than 8 wk in the freshwater groups. In the seawater groups, however, no radioactivity was detected in the blood and muscle after 4 d and 2 wk, respectively. It was concluded that flumequine was eliminated at a substantially higher rate from Atlantic salmon in sea water than in fresh water.


Normal range of spinal mobility for healthy young adult Turkish men.
Anthropometric characteristics may vary among human populations, especially with differences in race. The aim of the present study is to find normal values of some measures (chest expansion, Schober's test and modified Schober's test) frequently used in the assessment of patients with ankylosing spondylitis, in young adult Turkish men. Initial recruitment identified 2,925 healthy male participants aged 20-30 years, and the final study sample included 1,982 of them. Participants joined the research from all cities except one in Turkey. The measurements of chest expansion, Schober's test, and modified Schober's test were performed by the same researcher using a plastic measuring tape. The mean (±standard error) values of the chest expansion, Schober's test, and modified Schober's test were 6.11 (±0.02), 5.62 (±0.02), and 7.78 (±0.02) cm, respectively. The estimated normal lower bounds for chest expansion, Schober's test, and modified Schober's test may be between 3.71-3.86 cm, 3.86-3.97 cm, and 5.46-5.60 cm, respectively, for young adult Turkish men. No correlation was found between height and spinal mobility. The normal values for spinal mobility in this sample of healthy young adult Turkish men differed from those reported for other young adult male populations (chest expansion ≥5 cm, Schober's test >5 cm, modified Schober's test >7 cm). It is thus useful to consider nationality in interpreting results of spinal mobility tests.


Radiosurgery to reduce the risk of first hemorrhage from brain arteriovenous malformations.
It remains unclear whether or not and to what extent stereotactic radiosurgery can reduce the risk of first intracranial hemorrhage from brain arteriovenous malformations. We performed a retrospective observational investigation of 500 patients with arteriovenous malformations who were treated with gamma knife radiosurgery. The risk of first hemorrhage was analyzed using the Cox proportional-hazards model with age at radiosurgery and angiographic obliteration included as time-dependent covariates. Three periods were defined: from birth to radiosurgery (before radiosurgery); from radiosurgery to angiographic obliteration (latency period); and from angiographic obliteration to end of the follow-up period (after obliteration). Hemorrhage was documented before radiosurgery in 318 patients (median observation period, 30.0 yr), during the latency period in 11 patients (median observation period, 2.2 yr), and after obliteration in two patients (median observation period, 5.5 yr). Compared with the period before radiosurgery, the risk of hemorrhage decreased by 86% after obliteration (hazard ratio, 0.14; 95% confidence interval, 0.03-0.55; P = 0.005), whereas the reduction observed during the latency period was not statistically significant (hazard ratio, 0.56; 95% confidence interval, 0.31-1.04; P = 0.07). Irrespective of obliteration, the risk of hemorrhage decreased by 62% after radiosurgery (hazard ratio, 0.38; 95% confidence interval, 0.22-0.67; P = 0.001). Similar results were observed when the 33 patients who had undergone previous therapy were excluded from the analysis. Stereotactic radiosurgery significantly reduces the risk of first hemorrhage from brain arteriovenous malformations. The extent of the decrease might be greater if angiography indicates the evidence of obliteration.


Insulin fine-tunes self-renewal pathways governing naive pluripotency and extra-embryonic endoderm.
Signalling downstream of Activin/Nodal (ActA) and Wnt can induce endoderm differentiation and also support self-renewal in pluripotent cells. Here we find that these apparently contradictory activities are fine-tuned by insulin. In the absence of insulin, the combination of these cytokines supports endoderm in a context-dependent manner. When applied to naive pluripotent cells that resemble peri-implantation embryos, ActA and Wnt induce extra-embryonic primitive endoderm (PrE), whereas when applied to primed pluripotent epiblast stem cells (EpiSC), these cytokines induce gastrulation-stage embryonic definitive endoderm. In naive embryonic stem cell culture, we find that insulin complements LIF signalling to support self-renewal; however, when it is removed, LIF, ActA and Wnt signalling not only induce PrE differentiation, but also support its expansion. Self-renewal of these PrE cultures is robust and, on the basis of gene expression, these cells resemble early blastocyst-stage PrE, a naive endoderm state able to make both visceral and parietal endoderm.


Mitochondria in the flight muscles of insects. III. Mitochondrial cytochrome c in relation to the aging and wing beat frequency of flies.
1. In the present study a correlation has been sought between aging, flight muscle mitochrondria (sarcosomes), cytochrome c, and flight ability in the blowfly, Phormia regina. 2. During the 1st week of adult life, individual sarcosomes increase in mass from 2.7 x 10(-7) microg. dry weight at the time of emergence, to 8.5 x 10(-7) microg. by the 7th day. During this period of growth, the number of sarcosomes per fly (6.7 x 10(8)) remains constant. When mature, the sarcosomes account for 32.6 per cent of the total muscle dry weight, or close to 40 per cent on a wet weight basis. 3. It appears probable that the high content of flight muscle cytochromes is entirely localized in the sarcosomes. The cytochromes continue to be synthesized and increase in titer within the sarcosomes for 7 days after adult emergence. 4. As determined spectroscopically, the various cytochrome components at all times maintain a constant ratio both to one another and to the sarcosomal dry weight. This suggests the possibility that the cytochrome system may be synthesized as a single entity. 5. The wing-beat frequency of Drosophila funebris and Phormia varies with the age of these flies, being lowest at the time of emergence and maximum after the 6th day. 6. The relations between wing-beat frequency, respiration during flight, and sarcosomal cytochrome c content are discussed. On the basis of some likely assumptions it is calculated that the cytrochrome c turnover number is over 5,000, and that the cytochrome c turns over once for every two wing-beat cycles.


Incidence and phenotypical variation of outer retina-associated hyperreflectivity in macular telangiectasia type 2.
Macular telangiectasia type 2 (MacTel) is a neurodegenerative disease resulting in photoreceptor loss. Optical coherence tomography (OCT) reveals outer retina-associated hyperreflectivity (ORaH) as part of this process. The purpose of this study was to describe the incidence and phenotypical variation of ORaH. Different parameters of ORaH were analysed: OCT characteristics (Spectralis SD-OCT), correlation with vascular changes (OCT angiography; OCTA 3×3 mm Optovue) and correlation with hyperpigmentation (autofluorescence/fundus images). ORaH was also evaluated regarding the grade of severity of photoreceptor loss (Disease Severity Scale). Of 220 eyes with MacTel type 2, 106 demonstrated ORaH. On OCT, the size, the extension into the inner retina and the contact with retinal pigment epithelium (RPE) of the ORaH were variable. On OCTA neovascularisation (NV) in the outer retina (OR) was present at the location of the ORaH in 97.6%. Increasing size of NV correlated with progressive photoreceptor loss. In 86.6% with NV, the flow signals were visible between the OR and the choriocapillaris. In 85.7%, the ORaH was associated with hyperpigmentation on autofluorescence and fundus colour images. The presence of ORaH is associated with increasing photoreceptor loss and disease severity. In these more advanced cases of the present study, a variable presentation of ORaH in respect to size and form was seen, but in most cases, ORaH was in contact to the RPE. Additionally, ORaH was associated with hyperpigmentation and OR NV on OCTA. These results are consistent with the concept of ORaH representing fibrovascular OR-NV with RPE proliferation after contact with the RPE.


[Central Type Squamous Cell Lung Cancer Incidentally Found by the Treatment of Pneumothorax;Report of a Case].
A 69-year-old man who arrived at our hospital by ambulance with dyspnea was diagnosed with pneumothorax. The chest was drained, but the left lung failed to expand due to air leakage. A pulmonary fistula in the left lower lobe identified by video-assisted thoracic surgery was repaired. Postoperative chest radiography showed inadequate expansion of the left upper lobe. Bronchoscopy revealed an obstruction of the left upper bronchus that was pathologically diagnosed as squamous cell carcinoma. Enhanced computed tomography revealed a central tumor with atelectasis of the left upper lobe, and a stained node in the left lower lobe. Clinical T4N1M0 stage III A lung cancer was confirmed. The patient was treated with concurrent chemoradiotherapy. It was likely that the lung cancer in the upper bronchus caused the atelectasis, leading secondary expansion of the lower lobe and the rupture of a bulla.


3-Methyl-4,5-dihydro-oxepine, polyoxygenated seco-cyclohexenes and cyclohexenes from Uvaria flexuosa and their anti-inflammatory activity.
The phytochemical investigation of the methanolic extract of Uvaria flexuosa (Annonaceae) leaves led to the isolation of seven compounds including, 3-methyl-4,5-dihydro-oxepine (flexuvaroxepine A), four polyoxygenated seco-cyclohexene (flexuvarin A-D) and two polyoxygenated cyclohexene (flexuvarol A-B) derivatives, together with four known flavones. The structures of the isolated compounds were elucidated using different spectroscopic techniques. A plausible biogenetic route of the new compounds was discussed. The anti-inflammatory activity of the isolated compounds was evaluated by superoxide anion generation and elastase release assays. Among the tested compounds, flexuvarol B and chrysin showed the most potent anti-inflammatory effect by inhibiting superoxide anion generation and elastase release from human neutrophils in response to fMLP with IC50 2.25-5.55μM. Moreover, 5-hydroxy-6,7-dimethoxy-flavone showed selective inhibitory activity on superoxide anion generation (IC50=1.19±0.34μM).


High-resolution ultrasound and MRI in the evaluation of pectoralis major injuries.
The pectoralis major muscle is the largest muscle of the anterior chest wall. The primary function of the muscle is to adduct and internally rotate the arm at the shoulder. The pectoralis major muscle is broken down into two main components or "heads" based upon muscle fiber origin: clavicular and sternal. Pectoralis major muscle injury results from direct trauma or indirect force overload. The inferior sternal head fibers are the most commonly torn. The pectoralis major tendon most commonly is torn at the humeral insertion. Magnetic resonance imaging and high-resolution ultrasound have value in diagnosing pectoralis major muscle injury and help guide clinical and surgical management. Non-operative versus operative management of pectoralis major tears is dependent upon accurate diagnosis of tear location and severity on imaging. Operative management is recommended for tears at the humeral insertion and for musculotendinous junction tears with severe cosmetic/functional deformity. The indications for surgical intervention have been further expanded to complete intra-tendinous tears, defined as the mid-tendon substance between the myotendinous junction and humeral insertion, and those located at the sternal head/posterior lamina. This paper reviews normal pectoralis major anatomy and the spectrum of injury on magnetic resonance imaging and ultrasound. The importance of regional anatomical landmarks in assessing for pectoralis major muscle injury will be described. Other pathologies, such as tumor and infection, can also affect the pectoralis major muscle and key imaging features will be discussed to help differentiate these entities. Operative and non-operative management of pectoralis major muscle injury is described with examples of pectoralis major repair on post-operative imaging.


Desmosterol in brain is elevated because DHCR24 needs REST for Robust Expression but REST is poorly expressed.
Cholesterol synthesis in the fetal brain is inhibited because activity of DHCR24 (24-dehydrocholesterol reductase) is insufficient, causing concentrations of the precursor desmosterol to increase temporarily to 15-25% of total sterols at birth. We demonstrate that failure of DHCR24 to be adequately upregulated during periods of elevated cholesterol synthesis in the brain results from the presence in its promoter of the repressor element 1 (RE1) nucleotide sequence that binds the RE1-silencing transcription factor (REST) and that REST, generally reduced in neural tissues, uncharacteristically but not without precedent, enhances DHCR24 transcription. DHCR24 and REST mRNA levels are reduced 3- to 4-fold in fetal mouse brain compared to liver (p < 0.001). Chromatin immunoprecipitation assays suggested that REST binds to the human DHCR24 promoter in the vicinity of the predicted human RE1 sequence. Luminescent emission from a human DHCR24 promoter construct with a mutated RE1 sequence was reduced 2-fold compared to output from a reporter with wild-type RE1 (p < 0.005). Silencing REST in HeLa cells resulted in significant reductions of DHCR24 mRNA (2-fold) and DHCR24 protein (4-fold). As expected, relative concentrations of Δ(24)-cholesterol precursor sterols increased 3- to 4-fold, reflecting the inhibition of DHCR24 enzyme activity. In contrast, mRNA levels of DHCR7 (sterol 7-dehydrocholesterol reductase), a gene essential for cholesterol synthesis lacking an RE1 sequence, and concentrations of HMGR (3-hydroxy-3-methyl-glutaryl-CoA reductase) enzyme protein were both unaffected. Surprisingly, a dominant negative fragment of REST consisting of just the DNA binding domain (about 20% of the protein) and full-length REST enhanced DHCR24 expression equally well. Furthermore, RE1 and the sterol response element (SRE), the respective binding sites for REST and the SRE binding protein (SREBP), are contiguous. These observations led us to hypothesize that REST acts because it is bound in close proximity to SREBP, thus amplifying its ability to upregulate DHCR24. It is likely that modulation of DHCR24 expression by REST persisted in the mammalian genome either because it does no harm or because suppressing metabolically active DHCR24 while providing abundant quantities of the multifunctional sterol desmosterol during neural development proved useful.


Adjusted hypervolemic hemodilution in acute ischemic stroke.
We prospectively randomized 47 patients with acute ischemic stroke of the middle cerebral artery of less than 24 hours' duration to either adjusted hypervolemic hemodilution or control treatment and followed them up for 90 days. Rapid hemodilution to a target hematocrit of 30-35% as monitored with bedside determinations was achieved by using infusions of dextran 40, venesections, and infusions of additional crystalloid solution when necessary. There was no difference in the death rate between the two treatment groups. Of these 47 patients, 37 (19 in the hemodilution group and 18 in the control group) could be followed up for the entire study period of 3 months. The relative improvement in neurologic function from day 1 to days 8, 21, and 90 was significantly better in the hemodilution group than in the control group. In accordance, special tests for fine motor control of the paretic arm disclosed better performance in the hemodilution group. The frequency of patients with severe disability was significantly lower in the hemodilution group on days 8 and 21. Plasma viscosity (measured in 11 patients) was not affected by infusions of dextran 40. Vigorous hypervolemic hemodilution in patients with acute ischemic stroke is well tolerated and improves early neurologic outcome with an effect lasting at least 3 months.


Lifetime Prevalence and Determinants of Suicidal Ideation and Attempt Among All Patients Living with HIV/AIDS in Hiwot Fana Specialized Hospital, Harar, Ethiopia, 2020.
Suicide is a psychiatric emergency and the second leading cause of death among youths. Suicide risk is 7 to 36 times greater among PLWHA as compared to the general population. This study was aimed at determining the prevalence of suicide and its associated factors among PLWHA and attendings at Hiwot Fana Specialized University Hospital, Ethiopia, 2020. We conducted a cross-sectional study on 412 randomly selected respondent PLWHA and attendingz at Hiwot Fana Specialized University Hospital from February 1-March 1, 2020. The interviewers administered a structured questionnaire consisting of the World Health Organization Composite International Diagnostic Interview (CIDI) tool to measure suicidality. We used the clinical records to collect clinical variables of the respondents. We used simple logistic regression ≤ 0.25 at p-value ≤ 0.25 and multiple logistic regression at p-value ≤ 0.05 to identify the predictor variables of the outcome. A total of 412 participants have completed the questionnaire, with a response rate of 97.4%. The majority, 252 (61.2) of the participants were female, while 112 (27.2%) of the respondents were in the age group of 28-37. The prevalence of suicidal ideation and attempt among PLWHA was 24.3% (CI; 20.4, 28.4) and 12.6% (9.5-15.8), respectively. Predictors for suicidal ideation were being in extreme poverty, living alone, widowed, CD4 level less than 250, and current alcohol use, and for suicidal attempt were an urban residence, stage IV HIV, family history of suicide, and depression. Nearly one-fourth of the respondents reported suicidal ideation. So, early screening and working on those identified predictors of suicidality is vital to prevent the mortality of it in PLWHA.


Effects of a commercial herbal-based formula on exercise performance in cyclists.
We examined the effects of a commercially marketed herbal-based formula purported to increase endurance on oxygen consumption (VO2) in 17 competitive category III/IV amateur cyclists [mean (SEM) age: 31.1 (1.8) yr; height: 178.5 (1.8) cm; weight: 77.1 (1.6) kg]. Each cyclist participated in two (pre/post) cycling tests progressing 25 W.4 min(-1) starting at 100 W administered in a randomized, placebo-controlled, double-blind fashion. The second trial was performed 14 d after the ingestion of a manufacturer recommended loading phase (4 d x 6 caps.d(-1)) and a maintenance phase (11 d x 3 caps.d(-1)). Three treatment capsules contained 1000 mg of Cordyceps sinensis (CS-4) and 300 mg Rhodiola rosea root extract as the primary ingredients; 800 mg of other ingredients included calcium pyruvate, sodium phosphate, potassium phosphate, ribose, and adenosine and 200 mcg of chromium. Using a 2 x 2 ANOVA, we observed no significant treatment effect for any between or within group variables including peak VO2 [treatment 4.14 (0.2) L.min(-1); placebo 4.10 (0.2) L.min(-1)], time to exhaustion [treatment 38.47 (1.7) min; placebo 36.95 (1.8) min], peak power output (PO) [treatment 300.00 (12.1) W; placebo 290.63 (12.9) W], or peak heart rate. We also observed no differences for any subpeak exercise variable including the PO eliciting 2 mmol.L(-1) blood lactate (BLa) [treatment 201.00 (18.1) W; placebo 167.50 (19.2) W] and 4 mmol.L(-1) BLa [treatment 235.88 (15.8) W; placebo 244.78 (14.9) W], ventilatory threshold, respiratory compensation point, or Vo2 L.min(-1) gross efficiency at each stage. A 2-wk ingestion schema of a commercial herbal-based formula is insufficient to elicit positive changes in cycling performance.


A super-resolution ultrasound imaging method based on active-modulated super-resolution optical fluctuation imaging.
Super resolution ultrasound imaging (SR-US) methods including super-resolution optical fluctuation imaging (SOFI) have been successfully demonstrated to improve imaging performance of ultrasound (US). However, the imaging quality of US improved by conventional SOFI depends on the probability of microbubbles (MB) appearing in imaging regions. Current SOFI-based ultrasound imaging methods usually fix the probability of MBs, ignoring the effect of probability characteristics, leading to artifacts in high-order SOFI images. Inspired by active-modulated SOFI (AR-SOFI), in this paper, we propose a new method, termed as AR-SOFI-US, for further improving the performance of SR-US, which is achieved by effectively controlling the probabilities of MBs on an appropriate range. Through a series of numerical simulations, we compare the imaging resolution at differing MB probabilities and demonstrate that by controlling the probabilities of MBs when they appear in the imaging regions, incorporating the proposed AR-SOFI-US method, we can improve the spatial resolution of SR-US to a higher degree, especially for the high-order SOFI imaging results.


Realizing the Dream: The Future of Primary Care Research.
Primary care research is central to the successful transformation of care delivery, providing the crucial evidence to overcome the longstanding and widespread threats and challenges to the realization of primary care's full potential. The Agency for Healthcare Research and Quality (AHRQ), as the federal agency specifically charged with conducting and supporting primary care research, plays a pivotal role in supporting the research and generating the evidence needed to advance primary care. Drawing upon decades of AHRQ-supported research studies, extensive stakeholder consultation, and a Primary Care Research Summit held in fall 2020, we discuss the primary care research central to successful primary care transformation and for realizing the vision of a high-performing US health system to effectively serve all Americans and their communities while advancing health equity.Realizing the potential of primary care will require wise investments in primary care research. Newly generated evidence needs to be rapidly incorporated into the design of the delivery system, clinical care, and community interventions. Investments in evidence-informed primary care redesign can catalyze progress to achieving the quintuple aim-improved health outcomes, increased value, better patient and clinician experience, and health equity. Primary care research can provide the evidence to help stem the twin epidemics of clinician burnout and lack of trust in the health system. Actualizing this vision will require a concerted and coordinated effort by policy makers, researchers, clinicians, and community members and a commitment to ensuring people and communities have ready access to primary care.Appeared as Annals "Online First" article.


Ventricular arrhythmias after acute myocardial infarction: a 20-year community study.
Although myocardial infarction (MI) severity is declining, the occurrence of ventricular arrhythmia (VA) after MI and its effect on outcome is unknown. This study was undertaken to examine the frequency and timing of VA and the effect of VA on mortality after MI. Myocardial infarctions recorded between 1979 and 1998 were validated. Baseline characteristics, occurrence of VA, and survival were determined. Ventricular arrhythmias were categorized as primary ventricular fibrillation (VF), nonprimary VF, and ventricular tachycardia (VT). Logistic regression was used to analyze associations between VA and baseline characteristics. Temporal trends were assessed with the Mantel-Haenszel chi2. Survival was analyzed with the Kaplan-Meier method. Proportional hazards regression was used to examine the association between death and occurrence of VA. Among 2317 persons with incident MI, 7.5% experienced VA (3.6% nonprimary VF, 2.1% primary VF, 1.8% VT). Ventricular arrhythmia-associated factors were younger age, female sex, higher Killip class, ST elevation, and atrial fibrillation. Ventricular arrhythmias were associated with increased risk of death at 30 days. Ventricular arrhythmias after MI are relatively common, particularly among persons with more severe MI and no prior history of coronary disease. Over time, the incidence of VF declined, whereas VT did not change. Ventricular arrhythmia after MI was associated with a 6-fold increase in morality. Thus, identification of high-risk MI survivors and prevention of VA could markedly improve outcomes. Further studies are needed to determine the cause of the shift in distribution of VA subtype.


Mechanisms of zero-lag synchronization in cortical motifs.
Zero-lag synchronization between distant cortical areas has been observed in a diversity of experimental data sets and between many different regions of the brain. Several computational mechanisms have been proposed to account for such isochronous synchronization in the presence of long conduction delays: Of these, the phenomenon of "dynamical relaying"--a mechanism that relies on a specific network motif--has proven to be the most robust with respect to parameter mismatch and system noise. Surprisingly, despite a contrary belief in the community, the common driving motif is an unreliable means of establishing zero-lag synchrony. Although dynamical relaying has been validated in empirical and computational studies, the deeper dynamical mechanisms and comparison to dynamics on other motifs is lacking. By systematically comparing synchronization on a variety of small motifs, we establish that the presence of a single reciprocally connected pair--a "resonance pair"--plays a crucial role in disambiguating those motifs that foster zero-lag synchrony in the presence of conduction delays (such as dynamical relaying) from those that do not (such as the common driving triad). Remarkably, minor structural changes to the common driving motif that incorporate a reciprocal pair recover robust zero-lag synchrony. The findings are observed in computational models of spiking neurons, populations of spiking neurons and neural mass models, and arise whether the oscillatory systems are periodic, chaotic, noise-free or driven by stochastic inputs. The influence of the resonance pair is also robust to parameter mismatch and asymmetrical time delays amongst the elements of the motif. We call this manner of facilitating zero-lag synchrony resonance-induced synchronization, outline the conditions for its occurrence, and propose that it may be a general mechanism to promote zero-lag synchrony in the brain.


PKC-theta-deficient mice are protected from Th1-dependent antigen-induced arthritis.
T cell effector functions contribute to the pathogenesis of rheumatoid arthritis. PKC-theta transduces the signal from the TCR through activation of transcription factors NF-kappaB, AP-1, and NFAT. We examined the effects of PKC-theta deficiency on two Th1-dependent models of Ag-induced arthritis and found that PKC-theta-deficient mice develop disease, but at a significantly diminished severity compared with wild-type mice. In the methylated BSA model, cellular infiltrates and articular cartilage damage were mild in the PKC-theta-deficient mice as compared with wild-type mice. Quantitation of histopathology reveals 63 and 77% reduction in overall joint destruction in two independent experiments. In the type II collagen-induced arthritis model, we observed a significant reduction in clinical scores (p < 0.01) in three independent experiments and diminished joint pathology (p < 0.005) in PKC-theta-deficient compared with wild-type littermates. Microcomputerized tomographic imaging revealed that PKC-theta deficiency also protects from bone destruction. PKC-theta-deficient CD4(+) T cells show an impaired proliferative response, decreased intracellular levels of the cytokines IFN-gamma, IL-2, and IL-4, and significantly diminished cell surface expression of the activation markers CD25, CD69, and CD134/OX40 on memory T cells. We demonstrate decreased T-bet expression and significantly reduced IgG1 and IgG2a anti-collagen II Ab levels in PKC-theta-deficient mice. Collectively, our results demonstrate that PKC-theta deficiency results in an attenuated response to Ag-induced arthritis, which is likely mediated by the reduced T cell proliferation, Th1/Th2 cell differentiation and T cell activation before and during disease peak.


Transcriptomic analysis of the role of RasGEF1B circular RNA in the TLR4/LPS pathway.
Circular RNAs (circRNAs) have recently emerged as a large class of novel non-coding RNA species. However, the detailed functional significance of the vast majority of them remains to be elucidated. Most functional characterization studies targeting circRNAs have been limited to resting cells, leaving their role in dynamic cellular responses to stimuli largely unexplored. In this study, we focus on the LPS-induced cytoplasmic circRNA, mcircRasGEF1B, and combine targeted mcircRasGEF1B depletion with high-throughput transcriptomic analysis to gain insight into its function during the cellular response to LPS stimulation. We show that knockdown of mcircRasGEF1B results in altered expression of a wide array of genes. Pathway analysis revealed an overall enrichment of genes involved in cell cycle progression, mitotic division, active metabolism, and of particular interest, NF-κB, LPS signaling pathways, and macrophage activation. These findings expand the set of functionally characterized circRNAs and support the regulatory role of mcircRasGEF1B in immune response during macrophage activation and protection against microbial infections.


Inpatient Addiction Consultation for Hospitalized Patients Increases Post-Discharge Abstinence and Reduces Addiction Severity.
Alcohol and drug use results in substantial morbidity, mortality, and cost. Individuals with alcohol and drug use disorders are overrepresented in general medical settings. Hospital-based interventions offer an opportunity to engage with a vulnerable population that may not otherwise seek treatment. To determine whether inpatient addiction consultation improves substance use outcomes 1 month after discharge. Prospective quasi-experimental evaluation comparing 30-day post-discharge outcomes between participants who were and were not seen by an addiction consult team during hospitalization at an urban academic hospital. Three hundred ninety-nine hospitalized adults who screened as high risk for having an alcohol or drug use disorder or who were clinically identified by the primary nurse as having a substance use disorder. Addiction consultation from a multidisciplinary specialty team offering pharmacotherapy initiation, motivational counseling, treatment planning, and direct linkage to ongoing addiction treatment. Addiction Severity Index (ASI) composite score for alcohol and drug use and self-reported abstinence at 30 days post-discharge. Secondary outcomes included 90-day substance use measures and self-reported hospital and ED utilization. Among 265 participants with 30-day follow-up, a greater reduction in the ASI composite score for drug or alcohol use was seen in the intervention group than in the control group (mean ASI-alcohol decreased by 0.24 vs. 0.08, p < 0.001; mean ASI-drug decreased by 0.05 vs. 0.02, p = 0.003.) There was also a greater increase in the number of days of abstinence in the intervention group versus the control group (+12.7 days vs. +5.6, p < 0.001). The differences in ASI-alcohol, ASI-drug, and days abstinent all remained statistically significant after controlling for age, gender, employment status, smoking status, and baseline addiction severity (p = 0.018, 0.018, and 0.02, respectively). In a sensitivity analysis, assuming that patients who were lost to follow-up had no change from baseline severity, the differences remained statistically significant. In a non-randomized cohort of medical inpatients, addiction consultation reduced addiction severity for alcohol and drug use and increased the number of days of abstinence in the first month after hospital discharge.


Safety in numbers: the development of Leapfrog's composite patient safety score for U.S. hospitals.
To develop a composite patient safety score that provides patients, health-care providers, and health-care purchasers with a standardized method to evaluate patient safety in general acute care hospitals in the United States. The Leapfrog Group sought guidance from a panel of national patient safety experts to develop the composite score. Candidate patient safety performance measures for inclusion in the score were identified from publicly reported national sources. Hospital performance on each measure was converted into a "z-score" and then aggregated using measure-specific weights. A reference mean score was set at 3, with scores interpreted in terms of standard deviations above or below the mean, with above reflecting better than average performance. Twenty-six measures were included in the score. The mean composite score for 2652 general acute care hospitals in the United States was 2.97 (range by hospital, 0.46-3.94). Safety scores were slightly lower for hospitals that were publicly owned, rural in location, or had a larger percentage of patients with Medicaid as their primary insurance. The Leapfrog patient safety composite provides a standardized method to evaluate patient safety in general acute care hospitals in the United States. While constrained by available data and publicly reported scores on patient safety measures, the composite score reflects the best available evidence regarding a hospital's efforts and outcomes in patient safety. Additional analyses are needed, but the score did not seem to have a strong bias against hospitals with specific characteristics. The composite score will continue to be refined over time as measures of patient safety evolve.


Telomerase activity reconstituted in vitro with purified human telomerase reverse transcriptase and human telomerase RNA component.
Telomerase is a specialized reverse transcriptase that catalyzes elongation of the telomeric tandem repeat, TTAGGG, by addition of this sequence to the ends of existing telomeres. Human telomerase reverse transcriptase (hTERT) has been identified as a catalytic enzyme involved in telomere elongation that requires telomerase RNA, human telomerase RNA component (hTR), as an RNA template. We established a new method to express and purify soluble insect-expressed recombinant hTERT. The partially purified FLAG-hTERT retained the catalytic activity of telomerase in a complementation assay in vitro to exhibit telomerase activity in telomerase-negative TIG3 cell extract and in a reconstitution assay with FLAG-hTERT and purified hTR in vitro. FLAG-hTERT (D712A) with a mutation in the VDV motif exhibited no telomerase activity, confirming the authentic catalytic activity of FLAG-hTERT. The reconstituted complex of FLAG-hTERT and hTR in vitro was detected by electrophoretic mobility shift assay, and its activity was stimulated by more than 30-fold by TIG3 cell extract. This suggested that some cellular component(s) in the extract facilitated the reconstituted telomerase activity in vitro. Geldanamycin had no effect on the reconstituted activity but partially reduced the stimulated activity of the reconstituted telomerase by the TIG3 cell extract, suggesting that Hsp90 may contribute to the stimulatory effect of the cellular components.


Posterior Urethral Valves with Severe Unilateral Vesicoureteral Reflux in a 3-year-old Boy.
In patients with posterior urethral valves (PUV), severe unilateral vesicoureteral reflux (VUR) is one of the three conditions associated with preservation of renal function. Others are urinary ascites or urinoma in newborns and large congenital bladder diverticula. These conditions most likely provide a pop-off mechanism preventing the development of high intravesical pressure. Only 5% of patients with PUV and an associated pop-off mechanism will develop renal failure as opposed to 40 % of patients with PUV without a protective factor. We present a 3-year-old boy with posterior urethral valves and a severe right unilateral vesicoureteral reflux. He had PUV ablation with Mohan's valvotome and made satisfactory post operative recovery with indication on follow-up of preservation of renal function.


Esophagocutaneous fistula in spinal cord injury: a complication of anterior cervical fusion.
Esophageal perforation can be a difficult management problem in a patient with spinal cord injury. Meticulous history taking and physical examination are essential for diagnosis. A quadriplegic patient with the unusual complication of esophagocutaneous fistula following anterior cervical fusion was admitted to our spinal cord injury service for intensive rehabilitation. Although early surgery is the usual treatment, conservative management with emphasis on local wound care can lead to satisfactory healing of the fistula. Because of the halo vest traction device used to maintain the surgical reduction of the cervical fracture, it was decided to treat the patient's fistula conservatively. Difficulties with feeding, diarrhea, and recurrent drainage that complicated the nonoperative treatment were successfully managed while the patient underwent intensive and comprehensive rehabilitation. The patient was discharged ambulating independently without any orthotic device a day after complete closure of the esophagocutaneous fistula.


Objective Measurement of Physical Activity in Adults With Newly Diagnosed Type 1 Diabetes and Healthy Individuals.
Aims: Physical activity (PA) has many benefits in type 1 diabetes mellitus (type 1 DM). However, PA levels in people with type 1 DM have not previously been measured accurately. We aimed to compare objectively measured PA in adults recently diagnosed with type 1 DM and healthy adults. Methods: Accelerometer data from 65 healthy adults [mean (SD) age 31 (13), 29% men] were compared with data from 50 people with type 1 DM [mean (SD) age 33 (10), 64% men], time since diagnosis <3months, HbA1c 76 ± 25 mmol/mol) in the EXTOD (Exercise for Type 1 Diabetes) pilot study. Briefly, EXTOD investigated the feasibility of recruiting recently diagnosed adults with type 1 DM into a yearlong exercise intervention. Multiple-regression models were used to investigate the association between diabetes status and activity outcomes. Results: Adults recently diagnosed with type 1 DM spent on average a quarter less time in moderate-to-vigorous-physical-activity (MVPA) per day than healthy adults [after adjusting for confounders, predicted values: type 1 DM adults: [mean (SD)] 37.4 mins/day (9.1) Healthy adults: 52.9 mins/day (11.0)]. No difference in MVPA between the groups was seen at the weekend, but adults with type 1 DM spent more time in light physical activity (LPA), and less time in sedentary behavior. Time spent in sedentary or LPA during weekdays did not differ between groups. Summary: Adults recently diagnosed with type 1 DM do less MVPA. Health care workers should encourage these people to engage in more PA. Further studies are needed to assess PA in people with type 1 DM of longer duration.