Advances in Cardiac Pacing: Arrhythmia Prediction, Prevention and Control Strategies.
Cardiac arrhythmias constitute a tremendous burden on healthcare and are the leading cause of mortality worldwide. An alarming number of people have been reported to manifest sudden cardiac death as the first symptom of cardiac arrhythmias, accounting for about 20% of all deaths annually. Furthermore, patients prone to atrial tachyarrhythmias such as atrial flutter and fibrillation often have associated comorbidities including hypertension, ischemic heart disease, valvular cardiomyopathy and increased risk of stroke. Technological advances in electrical stimulation and sensing modalities have led to the proliferation of medical devices including pacemakers and implantable defibrillators, aiming to restore normal cardiac rhythm. However, given the complex spatiotemporal dynamics and non-linearity of the human heart, predicting the onset of arrhythmias and preventing the transition from steady state to unstable rhythms has been an extremely challenging task. Defibrillatory shocks still remain the primary clinical intervention for lethal ventricular arrhythmias, yet patients with implantable cardioverter defibrillators often suffer from inappropriate shocks due to false positives and reduced quality of life. Here, we aim to present a comprehensive review of the current advances in cardiac arrhythmia prediction, prevention and control strategies. We provide an overview of traditional clinical arrhythmia management methods and describe promising potential pacing techniques for predicting the onset of abnormal rhythms and effectively suppressing cardiac arrhythmias. We also offer a clinical perspective on bridging the gap between basic and clinical science that would aid in the assimilation of promising anti-arrhythmic pacing strategies.


Noise exposures of rail workers at a North American chemical facility.
Both continuous and impact noise exposures of rail yards and railways have been historically understudied. We summarize noise exposures to rail workers at a large chemical facility in North America. Rail workers were surveyed over the course of three 12-hr shifts. Personal noise dosimeters were used to derive a 12-hr time-weighted average (L(AVG)), an 8-hr time-weighted average (L(TWA)), and a percent dose. Peak and maximum sound levels were also recorded during each sampling period. Six workers were sampled on three separate days for a total of 18 full-shift noise samples. Full-shift noise exposures were all below the Occupational Safety and Health Administration's (OSHA) permissible exposure limit (PEL) and action level for a 12-hr workday. Peak impact sound levels exceeded 140 dB in 17 of 18 samples (94%) with a mean peak sound level of 143.9 dB. Maximum continuous sound levels were greater than 115 dBA in 4 of 18 samples (22%) with a mean maximum sound level of 113.1 dBA. The source of peak impact sound levels was a daily exposure to a concussion caused by a sudden break in a freight airline. Rail workers at this facility are at risk of noise induced hearing loss from high impact noise exposures. Peak impact and maximum continuous sound levels can be attenuated through the use of hearing protection or by increasing distances from railroad noise sources.


Annual fish: developmental adaptations for an extreme environment.
Annual fish are freshwater teleosts found in South America and Africa that are exposed to an extremely variable environment. They develop and reproduce in seasonal ponds that dry during the summer eliminating the entire adult population. Remarkably, desiccation-resistant embryos survive in these dry ponds that hatch during the next rainy season when the ponds are recreated. Among vertebrates, they represent one of the most remarkable extremophiles. They share several features with other fish models; however, they exhibit unique traits related to their peculiar life cycle. Epiboly is temporally and spatially uncoupled from organogenesis, and the embryos can undergo reversible developmental arrests (diapauses). These attributes make them a useful model to study diverse topics in developmental biology using a comparative and evolutionary approach. In this article, different aspects related to annual fish biology, taxonomy and phylogenetic considerations, reproductive strategy, and developmental characteristics with special focus on arrests, are summarized. The current challenge is to document and determine the factors that generate such high diversity and unique adaptations of annual fish. To understand this complexity, interdisciplinary approaches are being employed taking into consideration evolutionary biology, ethology, reproductive strategies, regulation of developmental mechanisms, and senescence.


Novel Role of Carbon Monoxide in Improving Neurological Outcome After Cardiac Arrest in Aged Rats: Involvement of Inducing Mitochondrial Autophagy.
Background Dysfunctional mitochondria are associated with neurological injury after cardiac arrest ( CA ). Although carbon monoxide ( CO ) has shown various potential therapeutic effects in preclinical tissue injury models, its mechanism of action in CA remains unclear. We sought to investigate the effects of a novel CO -releasing molecule on cerebral mitochondrial dysfunction and neurological injury after CA . Methods and Results Male Sprague-Dawley rats aged 20 to 22 months were subjected to 6-minute asphyxia CA before receiving CO treatment. Survival, neurologic deficit scores, neuronal death, mitochondrial function, and autophagy were evaluated after the return of spontaneous circulation. Results showed that CO post-treatment increased 3-day survival rate from 25% to 70.83% and reduced neurologic deficit scores. CO also ameliorated CA -induced neuronal apoptosis and necrosis in the cerebral cortex and improved cerebral mitochondrial function by reducing reactive oxygen species, reversing mitochondrial membrane potential depolarization, and preventing cytochrome C release. Furthermore, CO increased mitochondrial autophagy by inducing mitochondrial accumulation of PINK 1 ( PTEN -induced putative kinase 1) and Parkin. Downregulation of PINK 1 with genetic silencing si RNA abolished CO -afforded mitochondrial autophagy. Conclusions Taken together, our results indicate, for the first time, that CO treatment confers neuroprotection against ischemic neurological injury after CA possibly by promoting mitochondrial autophagy.


Randomized Phase III controlled trials of therapy in malignant glioma: where are we after 40 years?
The objective of this study was to review the results of randomized Phase III controlled trials (RCTs) that involve initial treatments of malignant glioma and determine changes in median survival times (MST) over the last 40 years. An electronic database search identified RCTs for patients undergoing initial treatment for supratentorial high-grade malignant glioma. MSTs were analysed with respect to the date that patient accrual to the trial started, to identify the time course of changes in MST. Linear regression was used for statistical analysis. The review included 44 clinical trials that recruited patients between 1966 and 2004. Overall, there was a steady significant improvement in MST for the novel treatment cohorts over this period (r(2) = 0.43, p < 0.001), with MST increasing from around 8 to 15 months. There was also consistent improvement in the MST of the control cohorts, from around 7 months to 14 months, that reached statistical significance (r(2) = 0.41, p < 0.001). However, analysis including a quadratic term revealed a trend towards the rate of improvement in MST decreasing in the last two decades in the control, but not novel treatment, groups. The differences, either positive or negative, in MSTs between the control and novel treatment cohorts, and number of trials performed have all decreased with time. Subgroup analysis of the three most recent clinical trials report statistically significant better outcomes in MST after either >90% or 'complete' tumour resection. Despite tremendous advances in both the understanding of the biology of malignant gliomas and treatments in neuro-oncology, the prognosis for patients with malignant gliomas, although improved, remains very poor. The limitations of this type of analysis, including how trial design can bias outcomes and militate against comparison of trials are discussed.


Multiple infections and the evolution of virulence.
Infections that consist of multiple parasite strains or species are common in the wild and are a major public health concern. Theory suggests that these infections have a key influence on the evolution of infectious diseases and, more specifically, on virulence evolution. However, we still lack an overall vision of the empirical support for these predictions. We argue that within-host interactions between parasites largely determine how virulence evolves and that experimental data support model predictions. Then, we explore the main limitation of the experimental study of such 'mixed infections', which is that it draws conclusions on evolutionary outcomes from studies conducted at the individual level. We also discuss differences between coinfections caused by different strains of the same species or by different species. Overall, we argue that it is possible to make sense out of the complexity inherent to multiple infections and that experimental evolution settings may provide the best opportunity to further our understanding of virulence evolution.


Hierarchical Bayesian inference in the visual cortex.
Traditional views of visual processing suggest that early visual neurons in areas V1 and V2 are static spatiotemporal filters that extract local features from a visual scene. The extracted information is then channeled through a feedforward chain of modules in successively higher visual areas for further analysis. Recent electrophysiological recordings from early visual neurons in awake behaving monkeys reveal that there are many levels of complexity in the information processing of the early visual cortex, as seen in the long-latency responses of its neurons. These new findings suggest that activity in the early visual cortex is tightly coupled and highly interactive with the rest of the visual system. They lead us to propose a new theoretical setting based on the mathematical framework of hierarchical Bayesian inference for reasoning about the visual system. In this framework, the recurrent feedforward/feedback loops in the cortex serve to integrate top-down contextual priors and bottom-up observations so as to implement concurrent probabilistic inference along the visual hierarchy. We suggest that the algorithms of particle filtering and Bayesian-belief propagation might model these interactive cortical computations. We review some recent neurophysiological evidences that support the plausibility of these ideas.


Epstein-Barr viral DNA: infectivity for human placental cells.
Purified DNA of Epstein-Barr virus (EBV) is regularly infectious by means of the "calcium" method of transfection. Cultured human placental cells exposed to EBV DNA of two transforming strains, FF41 and B95, produce virus that is capable of converting normal B lymphocytes into established cell lines. After treatment with EBV (FF41) DNA and EBV (HR-1) DNA the placental cells display antigens associated with the productive viral cycle. The placental cells have not developed foci or other signs of morphologic transformation.


Neighborhood Socioeconomic Status and Cognitive Trajectories in a Diverse Longitudinal Cohort.
Although individual-level socioeconomic status is associated with poor outcomes, less is known regarding how the social context might affect cognitive outcomes. We examined the effect of neighborhood socioeconomic status (NSES) on baseline cognitive function and trajectories of decline. The sample (N = 480) came from a longitudinal cohort recruited to study cognitive function. Mixed effects models examined the influence of NSES on baseline and rate of change in executive function, semantic memory, and episodic memory. NSES was positively associated with semantic memory scores at baseline, but not with executive function or episodic memory in adjusted models, nor was it associated with cognitive change in longitudinal analyses. In exploratory analyses, for individuals with dementia, those with higher NSES declined faster in executive function and semantic memory than did those with lower NSES. Results suggest that NSES has limited effects independent of personal characteristics; however, findings showed a complex relation of NSES and decline, with NSES effects observed only for individuals with dementia. Results are discussed in the context of cognitive reserve. Clinical assessments of individuals who present with cognitive impairment might benefit from an understanding of the neighborhood context from which patients come.


Catastrophic head and neck injuries in judo players in Japan from 2003 to 2010.
Few studies have documented catastrophic head and neck injuries in judo, but these injuries deserve greater attention. To determine the features of catastrophic head and neck injuries in judo. Descriptive epidemiological study. This study was based on the accident reports submitted to the All Japan Judo Federation's System for Compensation for Loss or Damage. A total of 72 judo injuries (30 head, 19 neck, and 23 other injuries) were reported between 2003 and 2010. The investigated parameters were mechanism of injury, age at time of injury, length of judo experience, diagnosis, and outcome. Among head injuries, 27 of 30 (90%) occurred in players younger than 20 years of age. The relationship between age, mechanism, and location of injury was more relevant when players younger than 20 years incurred head injury while being thrown (P = .0026). Among neck injuries, 13 of 19 (68%) occurred in players with more than 36 months of experience. The relationship between experience, mechanism, and location of injury was more relevant when experienced players incurred neck injury while executing an offensive maneuver (P = .0294). Acute subdural hematoma was diagnosed in 94% of head injuries. The outcomes of head injury were as follows: 15 players died; 5 were in a persistent vegetative state; 6 required assistance because of higher brain dysfunction, hemiplegia, or aphasia; and 4 had full recovery. Among neck injuries, 18 players were diagnosed with cervical spine injury, 11 of whom had fracture-dislocation of the cervical vertebra; there was also 1 case of atlantoaxial subluxation. The outcomes of neck injury were as follows: 7 players had complete paralysis, 7 had incomplete paralysis, and 5 had full recovery. Neck injuries were associated with having more experience and executing offensive maneuvers, whereas head injuries were associated with age younger than 20 years and with being thrown.


Chest pain syndromes in pregnancy.
Chest pain syndromes in pregnancy include numerous catastrophic cardiovascular events. Acute myocardial infarction, aortic dissection, pulmonary embolism, and amniotic fluid embolism are the most important causes of nonobstetric mortality and morbidity in pregnancy. Each of these could result in poor maternal and fetal outcomes if not diagnosed and treated in a timely fashion. However, their diagnosis and management is limited by fetal risks of diagnostic procedures, dangers of pharmacotherapy and interventions that have neither been widely studied nor validated. This article reviews the current literature on epidemiology, risk factors, pathogenesis, diagnosis, and management of 4 potentially lethal chest pain syndromes in pregnancy.


Nutrition, illness, and injury in aquatic sports.
In this review, we outline key principles for prevention of injury and illness in aquatic sports, detail the epidemiology of injury and illness in aquatic athletes at major international competitions and in training, and examine the relevant scientific evidence on nutrients for reducing the risk of illness and injury. Aquatic athletes are encouraged to consume a well-planned diet with sufficient calories, macronutrients (particularly carbohydrate and protein), and micronutrients (particularly iron, zinc, and vitamins A, D, E, B6, and B12) to maintain health and performance. Ingesting carbohydrate via sports drinks, gels, or sports foods during prolonged training sessions is beneficial in maintaining energy availability. Studies of foods or supplements containing plant polyphenols and selected strains of probiotic species are promising, but further research is required. In terms of injury, intake of vitamin D, protein, and total caloric intake, in combination with treatment and resistance training, promotes recovery back to full health and training.


Confounding by dietary factors in case-control studies on the efficacy of cancer screening in Japan.
Evaluation of cancer screening using case-control studies is less valid in comparison to randomized controlled trails, due to the intrusion of a possible self-selection bias in the former. The randomized controlled trial approach, however, may be difficult in developed countries where mass cancer screening programs are already being performed nationally. Accordingly, case-control studies are often performed instead of randomized controlled trials. In case-control studies, no reports could be found in the literature using dietary habit, an important influencing factor in carcinogenesis, as an adjusting item. We surveyed nutrition and food intake status through a nutrition survey using the weighing method, and smoking prevalence and alcohol consumption with questionnaires in the general population in northern Japan, in subjects over 30 years of age. We then compared these results among non-participants and participants in cancer screening programs, and evaluated how any differences between the two groups might affect the results of case-control studies. Non-participants had a significantly lower intake of vegetables, carotene, vitamin C, and dietary fiber, which are thought to be beneficial factors in the prevention of carcinogenesis. Non-participants had a significantly higher cigarette smoking prevalence than participants. In relation to the intake of vegetables, a difference between participants and non-participants was evident, as proper adjustment for vegetable intake led to an odds ratio closer to the null value. The value of the odds ratio will probably not decrease, but it might increase when other dietary factors or smoking are taken into consideration.


Sexual orientation of women does not affect outcome of fertility treatment with donated sperm.
Is there a difference in fertility between heterosexual women and lesbians undergoing sperm donation? Women undergoing treatment with donated sperm are equally fertile regardless of sexual orientation. Lesbians have an increased prevalence of smoking, obesity, sexually transmitted diseases and, possibly, polycystic ovary syndrome, all factors known to affect fertility. Previous studies on sperm donation inseminations (D-IUI) show conflicting results regarding pregnancy outcome. This is a national study of 171 lesbians and 124 heterosexual women undergoing sperm donation both as D-IUI (lesbian n = 438, heterosexual n = 298) and as embryo transfers (ET) after IVF with donated sperm (lesbians n = 225, heterosexuals n = 230) during 2005-2010. All clinics in Sweden offering sperm donation recruited patients. Differences in patients' medical history, treatment results and number of treatments to live birth were analyzed using independent samples t-test, Pearson's χ(2) test or Fisher's exact probability test. 71.8% of heterosexuals and 69.0% of lesbians had a child after treatment. The mean number of treatments was 4.2 for heterosexual women and 3.9 for lesbians. The total live birth rate, regardless of treatment type, was 19.7% for heterosexuals and 19.5% for lesbians. For D-IUI, the live birth rate was 12.8% for heterosexuals and 16.0% for lesbians and the live birth rate for all IVF embryo transfers (fresh and thawed cycles) was 28.7% for heterosexuals and 26.2% for lesbians. There were no differences in live birth rate between the groups for each of the different types of insemination stimulations (natural cycle; clomiphene citrate; FSH; clomiphene citrate and FSH combined). Nor was there a difference in live birth rate between the groups for either fresh or thawed embryo transfer. There was no difference between the proportions of women in either group or the number of treatments needed to achieve a live birth. Heterosexuals had a higher prevalence of smokers (9.2%), uterine polyps (7.2%) or previous children (11.3%) than lesbians (smokers 2.8%, P = 0.03; polyps 1.8%, P = 0.03; child 2.5%, P = 0.003). This study is limited to women living in stable relationships undergoing treatment with donated sperm in a clinical setting and may not apply to single women or those undergoing home inseminations. These results may influence healthcare policy decisions as well as increase the quality of clinical care and medical knowledge of healthcare professionals. The data also have important implications for individuals regarding screening, infertility diagnostic procedures and treatment types offered to heterosexuals and lesbians seeking pregnancy through sperm donation. Funding was granted by the Stiftelsen Familjeplaneringsfonden i Uppsala; the Swedish Research Council for Health, Working Life and Welfare; and the Marianne and Marcus Wallenberg Foundation. The authors report no conflicts of interest.


TNF-alpha is a predictor of insulin resistance in human pregnancy.
Historically, insulin resistance during pregnancy has been ascribed to increased production of placental hormones and cortisol. The purpose of this study was to test this hypothesis by correlating the longitudinal changes in insulin sensitivity during pregnancy with changes in placental hormones, cortisol, leptin, and tumor necrosis factor (TNF)-alpha. Insulin resistance was assessed in 15 women (5 with gestational diabetes mellitus [GDM] and 10 with normal glucose tolerance) using the euglycemic-hyperinsulinemic clamp procedure, before pregnancy (pregravid) and during early (12-14 weeks) and late (34-36 weeks) gestation. Body composition, plasma TNF-alpha, leptin, cortisol, and reproductive hormones (human chorionic gonadotropin, estradiol, progesterone, human placental lactogen, and prolactin) were measured in conjunction with the clamps. Placental TNF-alpha was measured in vitro using dually perfused human placental cotyledon from five additional subjects. Compared with pregravid, insulin resistance was evident during late pregnancy in all women (12.4 +/- 1.2 vs. 8.1 +/- 0.8 10(-2) mg. kg(-1) fat-free mass. min(-1). microU(-1). ml(-1)). TNF-alpha, leptin, cortisol, all reproductive hormones, and fat mass were increased in late pregnancy (P < 0.001). In vitro, most of the placental TNF-alpha (94%) was released into the maternal circulation; 6% was released to the fetal side. During late pregnancy, TNF-alpha was inversely correlated with insulin sensitivity (r = -0.69, P < 0.006). Furthermore, among all of the hormonal changes measured in this study, the change in TNF-alpha from pregravid to late pregnancy was the only significant predictor of the change in insulin sensitivity (r = -0.60, P < 0.02). The placental reproductive hormones and cortisol did not correlate with insulin sensitivity in late pregnancy. Multivariate stepwise regression analysis revealed that TNF-alpha was the most significant independent predictor of insulin sensitivity (r = -0.67, P < 0.0001), even after adjustment for fat mass by covariance (r = 0.46, P < 0.01). These observations challenge the view that the classical reproductive hormones are the primary mediators of change in insulin sensitivity during gestation and provide the basis for including TNF-alpha in a new paradigm to explain insulin resistance in pregnancy.


A new technique to acquire additional liver volume for left lobe graft in living donor liver transplantation.
Left lobe graft is an ideal option to minimize potential risk for the donor in adult living-donor liver transplantation (LDLT). However, its use is restricted due to size limitations. The purpose of this study was to determine the impact of a new technique for the acquisition of additional liver volume for left lobe graft. Three donors underwent left hepatic lobectomy by exploiting a new technique as follows: a demarcation line was marked by clamping the right first Glisson's pedicle. A parenchymal transection plane was located 1 cm right side from the demarcation line and just on the left side of the right anterior Glisson's pedicle. A part of the anterior segment added to the left lobe graft by this procedure belonged to right anterior segment by preoperative CT. The preoperative volumetry of the liver was performed using the 3D-CT software, which was able to calculate total liver volume and the volume of each vessel's territories. Additional liver volume was calculated by preoperative CT scan and defined as part of the perfusion area by the right anterior portal branch. Blood perfusion of the additional liver area was postoperatively assessed by dynamic CT, and graft outcome was also evaluated. An additional gain ranged from 40 mL to 51 mL (mean 41.8 mL). GV/SLV was 35.7, 60.0, and 41.0%. The rate of additional volume in GV/SLV ranged from 7.2-8.4% (mean 7.6%). All grafts functioned well. The CT scan performed on early postoperative period confirmed excellent blood perfusion the additional segment. No complication attributable to small-for-size graft was noted. This new technique for left lobe graft harvesting proved a promising approach to gain additional volume, thereby avoiding small-for-size graft in adult LDLT.


Herbivory Increases Fruit Set in Silene latifolia: A Consequence of Induced Pollinator-Attracting Floral Volatiles?
Although the effect of herbivory on plant reproduction has been investigated in some detail, little is known about how herbivores affect floral signalling. Here, we investigated the effect of foliar herbivory by the African Cotton Leafworm (Spodoptera littoralis) on floral signalling and fruit set in the White Campion (Silene latifolia). We found no effects of herbivory on floral traits involved in visual signalling (flower number, corolla diameter, calyx length, petal length) or in amount of nectar produced. However, Spodoptera-infested plants emitted higher amounts of the two floral volatiles, (Z)-3-hexenyl acetate and β-ocimene, than control plants. Open pollinated, infested plants also were found to produce more fruits than control plants, but only with nocturnal pollinators. Experimental addition of the two induced floral volatiles to non-infested Silene flowers also led to the production of more fruits with nocturnal pollination. This suggests that higher fruit production in herbivore-infested plants was caused by increased nocturnal pollinator attraction, mediated by the induced floral emission of these two volatiles. Our results show that the effects of herbivory on plant reproductive success are not necessarily detrimental, as plants can compensate herbivory with increased investment in pollinator attraction.


Patient reactions to a web-based cardiovascular risk calculator in type 2 diabetes: a qualitative study in primary care.
Use of risk calculators for specific diseases is increasing, with an underlying assumption that they promote risk reduction as users become better informed and motivated to take preventive action. Empirical data to support this are, however, sparse and contradictory. To explore user reactions to a cardiovascular risk calculator for people with type 2 diabetes. Objectives were to identify cognitive and emotional reactions to the presentation of risk, with a view to understanding whether and how such a calculator could help motivate users to adopt healthier behaviours and/or improve adherence to medication. Qualitative study combining data from focus groups and individual user experience. Adults with type 2 diabetes were recruited through website advertisements and posters displayed at local GP practices and diabetes groups. Participants used a risk calculator that provided individualised estimates of cardiovascular risk. Estimates were based on UK Prospective Diabetes Study (UKPDS) data, supplemented with data from trials and systematic reviews. Risk information was presented using natural frequencies, visual displays, and a range of formats. Data were recorded and transcribed, then analysed by a multidisciplinary group. Thirty-six participants contributed data. Users demonstrated a range of complex cognitive and emotional responses, which might explain the lack of change in health behaviours demonstrated in the literature. Cardiovascular risk calculators for people with diabetes may best be used in conjunction with health professionals who can guide the user through the calculator and help them use the resulting risk information as a source of motivation and encouragement.


Blood pressure and left ventricular hypertrophy in patients on different peritoneal dialysis regimens.
To examine the relation between the results of ambulatory 24-hour blood pressure monitoring (ABPM) and left ventricular mass index (LVMI), then to find the independent determinant for left ventricular hypertrophy (LVH) in peritoneal dialysis (PD) patients. Finally, to evaluate the differences in the clinical and cardiovascular characteristics between patients on continuous ambulatory PD (CAPD) and continuous cyclic PD (CCPD). An open, nonrandomized, cross-sectional study. Divisions of nephrology and cardiology in a medical center. Thirty-two uremic patients on maintenance PD therapy (22 patients on CAPD, and 10 on CCPD) without anatomical heart disease or history of receiving long-term hemodialysis. Home blood pressure (BP) and office BP were measured using the Korotkoff sound technique by sphygmomanometer. ABPM was employed for continuous measurement of BP. Echocardiography was performed for measurement of cardiac parameters and calculation of LVMI. Multivariate logistic regression analysis was performed for independent determinant of LVH in PD patients. The differences in clinical and cardiovascular characteristics between CAPD and CCPD patients were compared. Simple regression analysis showed positive correlations between LVMI and the duration of hypertension, ambulatory nighttime BP/BP load/BP load > 30%, serum phosphate, calcium-phosphate product, ultrafiltration (UF) volume, and percentage of UF volume during the nighttime. A negative correlation was noted between LVMI and dipping. In multiple regression analysis, the duration of hypertension was the only variable linked to LVMI. In multivariate logistic regression analysis, only ambulatory nighttime systolic BP load > 30% had an independent association with LVH. There were correlations between office/home BP and ambulatory 24-hour BP. In addition, CCPD patients had higher LVMI, UF volume during the nighttime, and percentage of UF volume during the nighttime than those of CAPD patients. In this study, ambulatory nighttime systolic BP load > 30% had an independent association with LVH. Office and home BP measurements were correlated with ABPM in PD patients. The result that CCPD patients had a higher LVMI than CAPD patients may be due to a relative volume overload during the daytime in CCPD patients.


Measuring physical activity in children and adolescents for dietary surveys: practicalities, problems and pitfalls.
Physical inactivity is an important risk factor for many chronic diseases and contributes to obesity and poor mental well-being. The present paper describes the main advantages and disadvantages, practical problems, suggested uses, and future developments regarding self-reported and objective data collection in the context of dietary surveys. In dietary surveys, physical activity is measured primarily to estimate energy expenditure. Energy expenditure surveillance is important for tracking changes over time, particularly given the debates over the role of the relative importance of energy intake and expenditure changes in the aetiology of obesity. It is also important to assess the extent of underreporting of dietary intake in these surveys. Physical activity data collected should include details on the frequency, duration and relative intensity of activity for each activity type that contributes considerably to overall activity and energy expenditure. Problems of validity and reliability, associated with inaccurate assessment, recall bias, and social desirability bias, are well-known; children under 10 years cannot report their activities accurately. However, despite such limitations, questionnaires are still the dominant method of physical activity assessment in dietary surveys due to their low cost and relatively low participant burden. Objective, time-stamped measures that monitor heart rate and/or movement can provide more comprehensive, quantitative assessment of physical activity but at greater cost and participant burden. Although overcoming many limitations of questionnaires, objective measures also have drawbacks, including technical, practical and interpretational issues.


Complex Transcriptional Profiles of the PPP1R12A Gene in Cells of the Circulatory System as Revealed by In Silico Analysis and Reverse Transcription PCR.
The myosin light chain phosphatase target subunit 1 (MYPT1), encoded by the PPP1R12A gene, is a key component of the myosin light chain phosphatase (MLCP) protein complex. MYPT1 isoforms have been described as products of the cassette-type alternative splicing of exons E13, E14, E22, and E24. Through in silico analysis of the publicly available EST and mRNA databases, we established that PPP1R12A contains 32 exons (6 more than the 26 previously reported), of which 29 are used in 11 protein-coding transcripts. An in silico analysis of publicly available RNAseq data combined with validation by reverse transcription (RT)-PCR allowed us to determine the relative abundance of each transcript in three cell types of the circulatory system where MYPT1 plays important roles: human umbilical vein endothelial cells (HUVEC), human saphenous vein smooth muscle cells (HSVSMC), and platelets. All three cell types express up to 10 transcripts at variable frequencies. HUVECs and HSVSMCs predominantly express the full-length variant (58.3% and 64.3%, respectively) followed by the variant skipping E13 (33.7% and 23.1%, respectively), whereas in platelets the predominant variants are those skipping E14 (51.4%) and E13 (19.9%), followed by the full-length variant (14.4%). Variants including E24 account for 5.4% of transcripts in platelets but are rare (<1%) in HUVECs and HSVSMCs. Complex transcriptional profiles were also found across organs using in silico analysis of RNAseq data from the GTEx project. Our findings provide a platform for future studies investigating the specific (patho)physiological roles of understudied MYPT1 isoforms.


miR-375- and miR-1-Regulated Coxsackievirus B3 Has No Pancreas and Heart Toxicity But Strong Antitumor Efficiency in Colorectal Carcinomas.
Coxsackievirus B3 (CVB3) has strong oncolytic activity in colorectal carcinoma but it also infects the pancreas and the heart. To improve the safety of the virus, here we investigated whether pancreas and cardiac toxicity can be prevented by insertion of target sites (TS), which are complementary to miR-375 and miR-1 into the viral genome. Although miR-375 and miR-1 are abundantly expressed in the pancreas and in the heart, respectively, their expression levels are low in colorectal carcinomas, which allows the carcinomas to be selectively attacked. To investigate the importance of the microRNAs, two viruses were engineered, H3N-375TS containing only miR-375TS and H3N-375/1TS containing miR-375TS and miR-1TS. In vitro, both viruses replicated in and lysed colorectal carcinoma cells, similar to a nontargeted control virus H3N-39TS, whereas they were strongly attenuated in cell lines transiently or endogenously expressing the corresponding microRNAs. In vivo, the control virus H3N-39TS induced strong infection of the pancreas and the heart, which led to fatal disease within 4 days after a single intratumoral virus injection in mice xenografted with colorectal DLD-1 cell tumors. In contrast, three intratumoral injections of H3N-375TS or H3N-375/1TS failed to induce virus-induced sickness. In the animals, both viruses were completely ablated from the pancreas and H3N-375/1TS was also ablated from the heart, whereas the cardiac titers of H3N-375TS were strongly reduced. Long-term investigations of the DLD-1 tumor model confirmed lack of virus-induced adverse effects in H3N-375TS- and H3N-375/1TS-treated mice. There was no mortality, and the pancreas and the heart were free of pathological alterations. Regarding the therapeutic efficiency, the treated animals showed high and long-lasting H3N-375TS and H3N-375/1TS persistence in the tumor and significantly slower tumor growth. These data demonstrate that miR-375- and miR-1-mediated virus detargeting from the pancreas and heart is a highly effective strategy to prevent toxicity of oncolytic CVB3.


Pulmonary sequestration.
Pulmonary sequestration is an uncommon congenital abnormality in which nonfunctioning lung tissue is supplied by an anomalous systemic artery. Both the extralobar and intralobar forms probably develop from an accessory lung bud from the primitive foregut. Both forms are situated on the left side in about two-thirds of patients. The anomalous arterial supply usually originates from the descending thoracic aorta, and there may be a large left-to-left or left-to-right shunt through the sequestration. The sequestration may have a fistulous communication with the upper gastrointestinal tract. Congenital anomalies, particularly diaphragmatic hernia, are frequently associated with the extralobar form. Intralobar sequestration occasionally is an incidental finding on roentgenograms of the chest in an asymptomatic patient; however, the disorder is usually symptomatic and the most common presentation is recurrent pulmonary infection. Presentation may be characterized by gastrointestinal symptoms, congestive heart failure, hemoptysis or hemothorax. Extralobar sequestration is usually an incidental finding on routine roentgenograms of the chest or during the management of some other congenital anomaly. Infrequently, extralobar sequestration presents with symptoms similar to those seen with the intralobar form. Roentgenograms of the chest, upper gastrointestinal series and arteriography are the most helpful diagnostic aids. The usual treatment is resection of the sequestration by removal of only the sequestration in patients with the extralobar form and by lobectomy or segmental resection in patients with the intralobar form. The reported results of operation have generally been excellent.


Understanding why people do or do not engage in activities following total joint replacement: a longitudinal qualitative study.
Numerous studies report large and significant improvements in basic mobility and activities of daily living following total hip or knee replacement (TJR). Nevertheless, quantitative research has shown minimal increase in participation in activities that benefit overall health. This study explored why people do or do not engage in activities following hip or knee TJR. This was a longitudinal qualitative study. Sampling was guided by constructivist grounded theory and data collected using open-ended, semi-structured interviews. Participants were recruited using maximum variation sampling based on age, sex and joint replaced (hip or knee). Data were analysed using a constant comparative approach and coded for thematic patterns and relationships from which overarching themes were constructed. Twenty-nine patients participated in interviews prior to, and 8 and 18 months post following TJR. A high degree of variability with regard to participants' return to activities was found and five emergent themes were identified that accounted for this variability. These themes highlight the importance of issues beyond medical factors alone, such as socio-cultural factors that partially determine participants' participation in activity following TJR. Findings suggest that multi-faceted experiences impact participation in activity following TJR. These experiences include changes in identity and lifestyle that preclude a 'return to normal'. There is an urgent need for supports to increase people's activity post-TJR in order to facilitate enhancement of post-surgery levels of engagement. Approaches that take into consideration more personalized interventions may be critical to promoting healthy aging in people with TJR.


Inflammatory Leptomeningeal Cytokines Mediate COVID-19 Neurologic Symptoms in Cancer Patients.
SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction that emerges weeks after the acute respiratory infection. To better understand this pathology, we prospectively analyzed of a cohort of cancer patients with neurologic manifestations of COVID-19, including a targeted proteomics analysis of the cerebrospinal fluid. We find that cancer patients with neurologic sequelae of COVID-19 harbor leptomeningeal inflammatory cytokines in the absence of viral neuroinvasion. The majority of these inflammatory mediators are driven by type II interferon and are known to induce neuronal injury in other disease states. In these patients, levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks after convalescence from acute respiratory infection. These prolonged neurologic sequelae following systemic cytokine release syndrome lead to long-term neurocognitive dysfunction. Our findings suggest a role for anti-inflammatory treatment(s) in the management of neurologic complications of COVID-19 infection.


The Development of Translational Biomarkers as a Tool for Improving the Understanding, Diagnosis and Treatment of Chronic Neuropathic Pain.
Chronic neuropathic pain (CNP) is one of the most significant unmet clinical needs in modern medicine. Alongside the lack of effective treatments, there is a great deficit in the availability of objective diagnostic methods to reliably facilitate an accurate diagnosis. We therefore aimed to determine the feasibility of a simple diagnostic test by analysing differentially expressed genes in the blood of patients diagnosed with CNP of the lower back and compared to healthy human controls. Refinement of microarray expression data was performed using correlation analysis with 3900 human 2-colour microarray experiments. Selected genes were analysed in the dorsal horn of Sprague-Dawley rats after L5 spinal nerve ligation (SNL), using qRT-PCR and ddPCR, to determine possible associations with pathophysiological mechanisms underpinning CNP and whether they represent translational biomarkers of CNP. We found that of the 15 potential biomarkers identified, tissue inhibitor of matrix metalloproteinase-1 (TIMP1) gene expression was upregulated in chronic neuropathic lower back pain (CNBP) (p = 0.0049) which positively correlated (R = 0.68, p = ≤0.05) with increased plasma TIMP1 levels in this group (p = 0.0433). Moreover, plasma TIMP1 was also significantly upregulated in CNBP than chronic inflammatory lower back pain (p = 0.0272). In the SNL model, upregulation of the Timp1 gene was also observed (p = 0.0058) alongside a strong trend for the upregulation of melanocortin 1 receptor (p = 0.0847). Our data therefore highlights several genes that warrant further investigation, and of these, TIMP1 shows the greatest potential as an accessible and translational CNP biomarker.


[Properties of bacteria of pathovars of Pseudomonas syringae affecting cereals].
Antigenic properties of Pseudomonas syringae pv. coronafaciens isolated from the oats have been studied for the first time, and serologic grouping of the strains of P. syringae pv. coronafaciens and P. syringae pv. atrofaciens has been carried out. It has been determined that the strains of P. syringae pv. coronafaciens, as to availability of specific antigenic complexes belong to two serological groups I and V, and thus they are differed from the strains of the pathovar atrofaciens which includes four serological groups of the strain isolated from wheat (II, IV, V, VI) and five serological groups of the strains, isolated from rye (I, II, IV, V, VI). It has been shown that the overwhelming majority of strains of P. syringae pv. coronafaciens isolated from the affected plants of the oats belong to serogroup V, while P. syringae pv. atrofaciens from the rye--to serogroup I. The strains of these bacteria, isolated as epiphytes, dominate in the other serological groups.


Recordings of consultations are beneficial in the transition from curative to palliative cancer care: a pilot-study in patients with oesophageal or head and neck cancer.
There is reluctance in providing incurable cancer patients with recordings of their consultation. In this pilot-study, we explored the feasibility and utility of providing consultation recordings when patients are told a new diagnosis of non-curable cancer, and the impact of the recordings on quality of life and the openness to discuss cancer-related issues in the family. Seventeen patients with a new diagnosis of incurable oesophageal or head and neck cancer were randomized to receive a CD (n = 10) or no CD (n = 7) of their consultation in which the diagnosis was told and the decision to provide only palliative care was discussed. Data were collected before consultation and 1 week and 1 month afterwards. After 1 month, patients allocated to the control group were offered to receiving the CD of their consultation as well. No major technical or procedural problems were encountered. Three-quarters of the patients appreciated receiving the CD, which was listened to by 8/10 patients and by 10/10 others in the CD group. After 1 month, two-thirds of the patients in the control group also asked to receive the CD. We found a trend towards a poorer quality of life but an improved openness to discuss cancer-related issues, in the CD group. The provision of a CD recording on the consultation in which the transition from a curative to a palliative care stage was communicated is feasible and was well-received by most cancer patients and their family. These findings require however verification in a study with a larger sample size.


Effect of Low Complement C4 on Clinical Characteristics of Patients with First-Episode Neuromyelitis Optica Spectrum Disorder.
To describe and compare the clinical features of patients with first-episode neuromyelitis optica spectrum disorder (NMOSD) in a normal complement C4 group and a low complement C4 group, and explore the mechanism by which low complement C4 affects the clinical features of patients with NMOSD. We retrospectively analyzed clinical data of 169 aquaporin-4 (AQP4) antibody positive patients with NMOSD from the First Affiliated Hospital of Zhengzhou University from December 2013 to March 2021. Prior to treatment, the blood was drawn for detection, and the patients underwent a 3.0 Tesla MRI examination. A low complement C4 level was defined as a serum complement C4 level <0.14 g/L. Depending on whether the complement C4 level was reduced, it was divided into the normal complement C4 group and low complement C4 group. The basic demographics, clinical manifestations, laboratory examinations, and imaging findings of the two groups were compared. Among the 169 AQP4 antibody positive patients, 54 were low-complement C4 patients and 115 were normal. There were no significant differences in the demographics, clinical manifestations, treatment options, or admission Expanded Disability Status Scale (EDSS) score between two groups (P > 0.05). The median of discharged EDSS was the same (4 vs 4), but the difference between the two was statistically significant (P = 0.019). Compared with the normal complement C4 group, the blood uric acid level (225 vs 179; P = 0.001) and the C3 level (1.06 vs 0.87, P = 0.000) of the low complement C4 group were significantly lower. The incidence of brainstem lesions in patients with low complement C4 was higher (53.7% vs 33%, P = 0.01). The treatment effect of the first-episode AQP4 antibody positive NMOSD low complement C4 group was poor, the blood-brain barrier was more severely damaged, and the disease changes were likely to involve the brainstem.


The effect of essential oils of sweet fennel and pignut on mortality and learning in africanized honeybees (Apis mellifera L.) (Hymenoptera: Apidae).
It was recently discovered that exposure to small concentrations of the essential oils of sweet fennel (Foeniculum vulgare Mill) or pignut [Hyptis suaveolens (L.) Poit] can be used to control aphids. What is not known is whether these oils also influence honeybee behavior. Experiments using both harnessed and free-flying foragers at concentrations used to control aphids showed that bees readily associated the odors with a reward, discriminated between them, and were not repelled. Honeybees, however, would not consume the oils when mixed with sucrose to create an unconditioned stimulus. An experiment in which harnessed bees consumed various concentrations showed that concentrations greater than 50% were detrimental. The experiments reported here provide further evidence supporting the use of conditioning techniques to evaluate the use of essential oils on honey bee behavior.


Stacked-blade, single-cut, ulnar-shortening osteotomy.
The authors reviewed a 10-year consecutive series of ulnar-shortening osteotomies using a freehand, single oblique cut with 2 or 3 stacked saw blades. Twenty-one patients (23 wrists) with chronic ulnar impaction syndrome (mean age, 45 years; range, 16 to 73 years) demonstrated an average preoperative ulnar variance of +2.1 mm (range, 0.0 to 4.0 mm). An oblique osteotomy was performed in the distal one-third of the ulnar diaphysis at an estimated 45° or 60° angle, relative to the ulnar axis, and was fixed with a 7-hole, 2.7- or 3.5-mm dynamic compression plate placed dorsally. Using a previously described formula, the authors estimated ulnar shortening on the basis of intraoperative measurement of kerf width and osteotomy angle as 3.3 mm (range, 2.3 to 4.7 mm). The actual measured average radiographic change in ulnar variance (preoperative to postoperative) was 2.8 mm (average 18% variance from intraoperative estimate). Final ulnar variance averaged -0.6 mm (range, -2.0 to 1.0 mm). Radiographic union occurred in all 23 (100%) osteotomies. Ten (43%) wrists required hardware removal for pain; 2 additional patients were symptomatic but declined removal. Ulnar-sided wrist pain was relieved in 22 wrists. This technique is simple, effective, and inexpensive. It can also be translated for use in shortening osteotomies for other long bones, although larger or smaller saw blades may be necessary for larger or smaller bones to achieve the desired amount of shortening. The authors' results also show it to be reasonably predictable, although the intraoperative use of a sterile goniometer for cut placement is recommended.


Pseudogymnoascus destructans: evidence of virulent skin invasion for bats under natural conditions, Europe.
While Pseudogymnoascus destructans has been responsible for mass bat mortalities from white-nose syndrome (WNS) in North America, its virulence in Europe has been questioned. To shed the light on the issue of host-pathogen interaction between European bats and P. destructans, we examined seventeen bats emerging from the fungus-positive underground hibernacula in the Czech Republic during early spring 2013. Dual wing-membrane biopsies were taken from Barbastella barbastellus (1), Myotis daubentonii (1), Myotis emarginatus (1), Myotis myotis (11), Myotis nattereri (1) and Plecotus auritus (2) for standard histopathology and transmission electron microscopy. Non-lethal collection of suspected WNS lesions was guided by trans-illumination of the wing membranes with ultraviolet light. All bats selected for the present study were PCR-positive for P. destructans and showed microscopic findings consistent with the histopathological criteria for WNS diagnosis. Ultramicroscopy revealed oedema of the connective tissue and derangement of the fibroblasts and elastic fibres associated with skin invasion by P. destructans. Extensive fungal infection induced a marked inflammatory infiltration by neutrophils at the interface between the damaged part of the wing membrane replaced by the fungus and membrane tissue not yet invaded by the pathogen. There was no sign of keratinolytic activity in the stratum corneum. Here, we show that lesions pathognomonic for WNS are common in European bats and may also include overwhelming full-thickness fungal growth through the wing membrane equal in severity to reports from North America. Inter-continental differences in the outcome of WNS in bats in terms of morbidity/mortality may therefore not be due to differences in the pathogen itself.


Identification of a chymotrypsin-like proteinase in human mast cells.
An antiserum was produced against a chymotryptic proteinase purified from human skin. The antiserum did not cross-react with human leukocyte cathepsin G and elastase, rat mast cell proteinase I, and human skin tryptase. Indirect immunofluorescent staining of frozen skin sections to localize the proteinase showed cytoplasmic staining of cells scattered about the papillary dermis and around blood vessels and appendages. Restaining these sections with toluidine blue revealed that the fluorescently stained cells contained metachromatically staining granules, the major distinguishing feature of mast cells. A similar correlation was found in lung tissue. Ultrastructural studies employing the ferritin bridge technique to immunologically identify the proteinase additionally localized the proteinase to mast cell granules. Biochemical and immunochemical characterization of chymotryptic activity solubilized from isolated human lung mast cells identified a chymotryptic proteinase that may be identical to the skin chymotryptic proteinase. These studies establish that human skin mast cells contain a chymotrypsin-like proteinase that is a granule constituent and provide evidence that indicates a comparable proteinase is also present in lung mast cells.


Evaluating a Combined Method of UV and Washing for Sanitizing Blueberries, Tomatoes, Strawberries, Baby Spinach, and Lettuce.
We assessed a fresh produce decontamination system using a combined method of UV and washing (water-assisted UV [WUV]) in different scales. The system used tap water to wash fresh produce while exposing it to UV light. First, the reduction of Salmonella in tap water under UV treatment (1 to 1,740 mJ/cm2) was determined. Increasing the UV dose significantly (P < 0.05) increased the Salmonella reduction in wash water, and UV intensity of more than 2 mW/cm2 could reduce Salmonella in tap water to below 1 CFU/mL given enough processing time (more than 1 min; UV dose of 120 mJ/cm2). Then, the decontamination effectiveness of a small WUV system was tested on blueberries (50 g). Blueberries were spot or dip inoculated with a Salmonella cocktail and treated by the small WUV system (200 mL of water). In general, WUV treatments achieved significantly better Salmonella inactivation than tap water wash; tap water wash (10 min) and 2 mW/cm2 WUV treatment (with a UV dose of 1,200 mJ/cm2) reduced populations of spot-inoculated Salmonella on blueberries by 2.44 and 5.45 log, respectively. Compared with spot-inoculated Salmonella on blueberries, dip-inoculated Salmonella was more difficult to be inactivated by WUV treatments. Then, the decontamination effectiveness of WUV treatments was tested on blueberries (170 g), tomatoes (290 g), strawberries (170 g), baby spinach (60 g), and lettuce (60 g) using a larger WUV system. In general, 10 min of 29 mW/cm2 WUV treatment (a high UV dose of 17,400 mJ/cm2) resulted in significantly better Salmonella inactivation than tap water wash (for 10 min) regardless the inoculation method, agreeing with the results of the small-scale study. For both spot- and dip-inoculated lettuce, no significant difference (P > 0.05) in Salmonella inactivation by WUV treatments was observed when the quantity of lettuce increased from 50 to 100 g.


"The part of me that you bring out": ideal similarity and the Michelangelo phenomenon.
This work examines the Michelangelo phenomenon, an interpersonal model of the means by which people move closer to (vs. further from) their ideal selves. The authors propose that partner similarity--similarity to the ideal self, in particular--plays an important role in this process. Across 4 studies employing diverse designs and measurement techniques, they observed consistent evidence that when partners possess key elements of one another's ideal selves, each person affirms the other by eliciting important aspects of the other's ideals, each person moves closer to his or her ideal self, and couple well-being is enhanced. Partner similarity to the actual self also accounts for unique variance in key elements of this model. The associations of ideal similarity and actual similarity with couple well-being are fully attributable to the Michelangelo process, to partner affirmation and target movement toward the ideal self. The authors also performed auxiliary analyses to rule out several alternative interpretations of these findings.


Pre-participation physical evaluation.
The pre-participation physical evaluation is an integral part of any sports or activity program. There are many alternative methods for completing this evaluation, using varying degrees of frequency and thoroughness. A practical approach to the pre-participation physical evaluation is presented for use in an office as well as in a mass-screening situation.


Very long chain fatty acids activate NADPH oxidase in human dermal fibroblasts.
Very long chain fatty acids (VLCFAs) are exclusively oxidized in peroxisomes and their levels are significantly increased in tissues of patients with peroxisomal disorders. Although the biochemical indicators of peroxisomal dysfunction, such as elevated VLCFAs, are well known, the mechanisms of pathogenesis of peroxisomal diseases are unclear. In this study we have examined the effect of VLCFAs on NADPH oxidase (NOX), a complex enzyme system responsible for the production of superoxide anions, in order to understand the oxidative stress-mediated mechanisms involved in pathology of peroxisomal disorders. Varying concentrations (2.5 to 10 microg ml(-1)) of VLCFAs, lignoceric acid and cerotic acid, significantly (p < 0.001) increased the enzymic activity of NOX in cultures of human dermal fibroblasts. VLCFAs did not affect the expression of gp91phox or p22phox whereas the mRNA and protein levels of p47phox were significantly (two or three-fold) increased following treatment of fibroblasts with lignoceric acid or cerotic acid. VLCFAs also caused a significant (p < 0.01) increase in lipid peroxidation in dermal fibroblasts which could be markedly reversed by treatment with apocyanin (10 mM) or superoxide dismutase (SOD, 25 U ml(-1)). With these results, we report for the first time that VLCFAs enhance NOX activity and superoxide anion-mediated lipid peroxidation in cultured dermal fibroblasts. This study proposes a mechanism that may be taking place in vivo during peroxisomal dysfunction and that leads to oxidative stress-mediated pathogenesis.


Naturally derived honeycomb-like N,S-codoped hierarchical porous carbon with MS2 (M = Co, Ni) decoration for high-performance Li-S battery.
Even though lithium-sulfur batteries have appealing advantages including a high theoretical capacity and energy density, their commercial implementation has been seriously hindered by some notorious reasons, particularly the severe shuttling effect, the insulating nature of sulfur, the large volumetric variation during cycling and the sluggish redox reaction kinetics. To tackle these issues, a biomass (ginkgo-nut) derived N,S-codoped porous carbon (GC) with an interconnected honeycomb-like hierarchical structure is synthesized by a templated carbonization method, followed by hydrothermal growth of transition metal sulfide MS2 (M = Co, Ni) nanocrystals, giving rise to a hybrid 3D electrocatalyst. The unique structure constructed by N,S-codoping can expose more active sites and polar surfaces to physically confine and chemically adsorb polysulfides. Meanwhile, the embedded MS2 polyhedral-like nanoparticles further enhance the interaction with polysulfides and improve conversion and redox kinetics of polysulfides. Remarkably, with 80 wt% sulfur loading (∼2.5 mg cm-2), GC-CoS2 exhibits a reversible capacity of 988.8 mA h g-1 after 500 cycles at 0.1 C and an excellent capacity of 610.3 mA h g-1 after 1000 cycles at 2 C, outperforming bare GC and GC-NiS2. Compared with the electrochemical performances of the representative reported biomass-derived sulfur host for Li-S batteries, evidently, both the discharge capacity and cycling stability of our GC-CoS2 sample are superior. Density functional theory (DFT) calculation results suggest that CoS2 exhibits a higher binding energy towards lithium polysulfides and a lower energy barrier for Li+ diffusion on the surface compared to the NiS2 counterpart, suggesting that CoS2 is a better choice for lithium-sulfur batteries than NiS2. This work provides a new avenue to rationally design a carbonaceous catalyst host for high-performance lithium-sulfur batteries.


Evolutionary conservation of species' roles in food webs.
Studies of ecological networks (the web of interactions between species in a community) demonstrate an intricate link between a community's structure and its long-term viability. It remains unclear, however, how much a community's persistence depends on the identities of the species present, or how much the role played by each species varies as a function of the community in which it is found. We measured species' roles by studying how species are embedded within the overall network and the subsequent dynamic implications. Using data from 32 empirical food webs, we find that species' roles and dynamic importance are inherent species attributes and can be extrapolated across communities on the basis of taxonomic classification alone. Our results illustrate the variability of roles across species and communities and the relative importance of distinct species groups when attempting to conserve ecological communities.


Receptive-field properties of transcallosal visual cortical neurons in the normal and reeler mouse.
The receptive-field properties of neurons in the striate visual cortex of normal and reeler mutant mice were studied with single-unit recording methods in order to determine whether the connections underlying these properties are altered by the developmental abnormality in neuronal position that characterizes reeler neocortex. Neurons with a projection through the corpus callosum were selected for study because they form a physiologically identifiable class of visual cortical neurons with a characteristic distribution of receptive-field properties that can be compared for normal and reeler cortex. Transcallosal cortical neurons in area 17 near its border with area 18a were identified by antidromic stimulation delivered through bipolar electrodes in the contralateral cortex. A computer controlled the visual stimuli, data acquisition, and analysis. Transcallosal neurons were principally found in layers II-III and V in the normal cortex and in a broand band deep in the reeler cortex. These populations had similar distributions of antidromic latencies, indicating that the neurons sampled from normal and reeler cortex were taken from populations with similar axonal diameters and soma sizes. The receptive-field properties of 46 units in 22 normal mice and 28 units in 11 reeler mice were characterized. Transcallosal neurons in both normal and reeler cortex were usually binocularly responsive and dominated by input from the contralateral eye. They exhibited either nonoriented (31 and 48%, respectively) or oriented (69 and 52%) receptive fields. Tuning 10 stimulus velocity was broad, with peak velocity sensitivities ranging from 1 to 1,000 degrees/s. Directional selectivity was present in 41% of normal units ad 32% of reeler units. There was no significant difference between normal and reeler cortex in the distribution of these properties. Transcallosal neurons were also examined for the presence of an inhibitory surround by comparing their responses to moving or stationary stimuli of varying sizes. Of the tested neurons, most (11/17 in normal cortex, 6/9 in reeler) showed evidence of a decrease in response to large moving stimuli. A large proportion (16/20) of normal neurons tested with stationary flashing stimuli had some degree of surround inhibition whereas significantly fewer (5/17) neurons in reeler cortex had this property. Thus, transcallosal neurons in reeler cortex less frequently had an inhibitory surround demonstrable with stationary flashing stimuli, but this difference between normal and reeler was not apparent with a moving stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)


Basic research in HIV vaccinology is hampered by reductionist thinking.
This review describes the structure-based reverse vaccinology approach aimed at developing vaccine immunogens capable of inducing antibodies that broadly neutralize HIV-1. Some basic principles of protein immunochemistry are reviewed and the implications of the extensive polyspecificity of antibodies for vaccine development are underlined. Although it is natural for investigators to want to know the cause of an effective immunological intervention, the classic notion of causality is shown to have little explanatory value for a system as complex as the immune system, where any observed effect always results from many interactions between a large number of components. Causal explanations are reductive because a single factor is singled out for attention and given undue explanatory weight on its own. Other examples of the negative impact of reductionist thinking on HIV vaccine development are discussed. These include (1) the failure to distinguish between the chemical nature of antigenicity and the biological nature of immunogenicity, (2) the belief that when an HIV-1 epitope is reconstructed by rational design to better fit a neutralizing monoclonal antibody (nMab), this will produce an immunogen able to elicit Abs with the same neutralizing capacity as the Ab used as template for designing the antigen, and (3) the belief that protection against infection can be analyzed at the level of individual molecular interactions although it has meaning only at the level of an entire organism. The numerous unsuccessful strategies that have been used to design HIV-1 vaccine immunogens are described and it is suggested that the convergence of so many negative experimental results justifies the conclusion that reverse vaccinology is unlikely to lead to the development of a preventive HIV-1 vaccine. Immune correlates of protection in vaccines have not yet been identified because this will become feasible only retrospectively once an effective vaccine exists. The finding that extensive antibody affinity maturation is needed to obtain mature anti-HIV-1 Abs endowed with a broad neutralizing capacity explains why antigens designed to fit matured Mabs are not effective vaccine immunogens since these are administered to naive recipients who possess only B-cell receptors corresponding to the germline version of the matured Abs.


Clinical Complexity in Women Veterans: A Systematic Review of the Recent Evidence on Mental Health and Physical Health Comorbidities.
A recent evidence map focused on women veterans underscored the limited number of articles published on mental health comorbid with physical health conditions in this population. The quality of this small body of research has yet to be evaluated. The aim of this systematic review was to evaluate and synthesize research published between 2008 and 2015 and identified in the Women Veterans' Health Research Evidence Map as related to mental and physical health comorbidities among women veterans. Following PRISMA guidelines, 23 published studies were identified and 21 were included in the review. In general, significant associations between several mental health conditions (e.g., depression, posttraumatic stress disorder, substance use disorders) and physical health disorders (e.g., cardiovascular disease, diabetes, gastrointestinal disorders, hypertension, obesity, pain, and urinary symptoms) and health behaviors (e.g., preventative care and treatment adherence) were noted. The majority of studies were rated as low risk of bias, with selection and detection bias most frequently observed across studies. Additionally, gaps in the recent literature were observed, including the need for further investigation of the role of medical conditions in complicating mental health symptoms and care provision. Results underscore the importance of healthcare providers attending to women veterans' mental and physical health simultaneously and irrespective of setting. Further, while the Department of Veterans Affairs continues to make sizable gains in its focus on women veterans' health, continued research on several health domains is needed to ensure adequate understanding of the health needs of women veterans.


Loss of long-term non-progressor and HIV controller status over time in the French Hospital Database on HIV - ANRS CO4.
We studied the frequency and risk factors for loss of long-term non-progressor (LTNP) and HIV controller (HIC) status among patients identified as such in 2005 in the French Hospital Database on HIV (FHDH-ANRS CO4). We selected patients who were treatment-naïve and asymptomatic in 2005 (baseline). Those with ≥8 years of known HIV infection and a CD4 cell nadir ≥500/mm3 were classified as LTNP and those with ≥10 years of known HIV infection and 90% of plasma viral load (VL) values ≤500 copies/ml in the absence of cART as HIC. cART initiation without loss of status and death from non AIDS-defining causes were considered as competing events. After 5 years of follow-up, 33% (95%CI; 27-42) of 171 LTNP patients and 17% (95%CI; 10-30) of 72 HIC patients had lost their status. In multivariable analyses, loss of LTNP status was associated with lower baseline CD4 cell counts and CD4/CD8 ratios. Only VL was significantly associated with loss of HIC status after adjustment for the baseline CD4 cell count, the CD4/CD8 ratio, and concomitant LTNP status. The hazard ratio for loss of HIC status was 5.5 (95%CI, 1.5-20.1) for baseline VL 50-500 vs ≤50 cp/mL, after adjustment for the baseline CD4 cell count. One-third of LTNP and one-fifth of HIC patients lost their status after 5 years of follow-up, raising questions as to the possible benefits and timing of ART initiation in these populations.


The impact of cleft type on early vocal development in babies with cleft palate.
The purpose of the present investigation was to examine the impact of cleft type on early sound development in children with cleft palate (with or without cleft lip). The participants included 53 babies with unrepaired cleft palate aged 8 to 10 months. Thirty-five babies had cleft lip and palate (CLP) and 18 had cleft palate only (CPO). Spontaneous vocalizations of the CLP and CPO groups were compared to determine whether differences were evident in canonical babbling, size of consonant inventory as well as place and manner of consonant production, and frequency of vocalization. Student's t tests revealed no significant differences between the groups in canonical babbling, size of consonant inventory, place and manner of consonant production, or frequency of vocalization. However, there was a trend for babies in the CPO group to produce fewer compensatory stop consonants and more anterior place features. In addition, a larger percentage of children in the CPO group had entered the canonical babbling stage at the time of this study. In general, the findings of this study suggested that cleft type does not appear to play a significant role in early consonant development for babies with cleft palate. Additional study using a larger CPO group is recommended to further investigate the trend toward better performance noted in this group.


'An extra fight I didn't ask for': A qualitative survey exploring the impact of calories on menus for people with experience of eating disorders.
The UK government made it mandatory for large restaurants and cafes in England to display calorie labels on menus. Existing evidence identifies minimal potential for benefit, but significant potential for harm to those with eating disorders. To date, only one published study has directly explored the impact of this legislation on those with eating disorders. This study explores the impact of calorie labelling on menus on adults with experience of eating disorders in England. A qualitative online survey was designed and distributed, and 399 adults with current or past experience/s of eating disorders completed the survey. Reflexive thematic analysis was used, informed by a critical realist approach. Six themes were developed: (1) impacts on relationships, (2) exclusion and increased isolation, (3) restricted freedom, (4) dis/embodiment, (5) anger and frustration at the perpetuation of diet culture and (6) we are all responsible for ourselves. Most participants felt calorie labels on menus is detrimental to their eating disorder and/or recovery. People are navigating multiple opposing cultural narratives around health, bodies and eating disorder recovery that can put additional barriers in place to developing a relationship with food and body that they would like. Calorie labelling on menus is likely to adversely impact those with eating disorders. Menus with calories should be available separately but should not be the first or only one provided. People with experience of eating disorders should be directly involved in the development of public health legislation and policy that is likely to affect them.


Active retrotransposons are a common feature of grass genomes.
A large fraction of the genomes of grasses, members of the family Graminae, is composed of retrotransposons. These elements resemble animal retroviruses in their structure and possess a life cycle similar to theirs that includes transcription, translation, and integration of daughter copies. We have investigated if retrotransposons are generally transcribed in the grasses and other plants, and whether the various families of elements are translationally and integrationally active in multiple grass species. A systematic search of 7.8 x 10(5) publicly available expressed sequence tags from plants revealed widespread retrotransposon transcripts at a frequency of one in 1,000. Monocot retrotransposons found relatively more expressed sequence tags from non-source species than did those of dicots. Antibodies were raised to the capsid protein, GAG, of BARE-1, a transcribed and translated copia-like retrotransposon of barley (Hordeum vulgare). These detected immunoreactive proteins of sizes identical to those of the BARE-1 GAG and polyprotein, respectively, in other species of the tribe Triticeae as well as in oats (Avena sativa) and rice (Oryza sativa). Retrotransposon-based markers showed integrational polymorphisms for BARE-1 in different subfamilies of the Graminae. The results suggest that grasses share families of transcriptionally, translationally, and integrationally active retrotransposons, enabling a comparative and integrative approach to understanding the life cycle of retrotransposons and their impact on the genome.


Electrochemically deposited bimetallic SERS substrate for trace sensing of antibiotics.
Electrochemically deposited bimetallic copper-gold nanoparticles on indium tin oxide (Cu-AuNPs on ITO) glass are demonstrated to be a sensitive and reproducible surface-enhanced Raman scattering (SERS) platform. An optimal signal enhancement with reasonably good degree of homogeneity was obtained by tuning the deposition parameters of the electrochemical setup. For Raman active analytes such as malachite green (MG) and rhodamine 6G (R6G), the developed SERS platform yields a limit of detection (LOD) of 0.75 nM. The usability of the proposed SERS platform has been realized through detection of two important antibiotics namely sulfamethoxazole (SFZ) and tetracycline hydrochloride (TCH) commonly used in egg farms. Furthermore, a machine learning (ML)-based model coupled with a dimensionality reduction technique-principal component analysis (PCA)-has been implemented to classify the targeted analytes in egg samples.


Differential molecular profiles and associated functionalities characterize connective tissue grafts obtained at different locations and depths in the human palate.
The present study aimed to assess the molecular profiles of subepithelial connective tissue grafts (CTGs) obtained at different locations and depths in the human palate. Sixty-four CTGs belonging to anterior deep (AD), anterior superficial (AS), posterior deep (PD), and posterior superficial (PS) groups were subjected to RNA-Sequencing and their transcriptomes were analyzed computationally. Functional correlations characterizing the CTG groups were validated by cell biological experiments using primary human palatal fibroblasts (HPFs) extracted from the CTGs. A clearly more pronounced location-dependent than depth-dependent difference between the grafts, with a minimal number of genes (4) showing no dependence on the location, was revealed. Epithelial, endothelial, and monocytic cell migration was strongly (P < 0.001) potentiated by AD- and PS-HPFs. Moreover, significantly increased expression of genes encoding C-C and C-X-C motif chemokine ligands as well as significantly (P < 0.01) activated p38 signaling suggested immunomodulatory phenotype for AD- and PS-HPFs. Increased growth factor gene expression and significantly activated (P < 0.001) Erk and Akt signaling in HPFs originating from A-CTGs implied their involvement in cell survival, proliferation, and motility. Prominent collagen-rich expression profile contributing to high mechanical stability, increased osteogenesis-related gene expression, and strongly activated (P < 0.001) Smad1/5/8 signaling characterized HPFs originating from P-CTGs. The present data indicate that in humans, differences between palatal CTGs harvested from different locations and depths appear to be location- rather than depth-dependent. Our findings provide the basis for future personalization of the therapeutic strategy by selecting an optimal graft type depending on the clinical indications.


Detection of West Nile virus genome and specific antibodies in Iranian encephalitis patients.
West Nile virus (WNV) is a mosquito-borne flavivirus which circulates in birds, horses and humans. An estimated 80% of WNV infections are asymptomatic. Fewer than 1% of infected persons develop neuroinvasive disease, which typically presents as encephalitis, meningitis, or acute flaccid paralysis. This study was conducted from January 2008 to June 2009 in Isfahan, Iran. Patients attending the emergency department with fever and loss of consciousness were consecutively included. Cerebrospinal fluids (CSF) were initially analysed through bacteriology and biochemistry examinations, resulting in those with evidence of meningitis being excluded. Patients' CSF and serum were diagnosed by serological and molecular assays. A total of 632 patients with fever and loss of consciousness were tested by CSF analyses. Samples of the remaining patients (39·4%) were referred for WNV investigation. Three (1·2%) of the patients were positive for both serum and CSF by RT-PCR, and six (2·4%) were positive only for IgG antibodies. History of insect bite, and blood transfusion and transplantation were risk factors for being positive by RT-PCR (P=0·048) and being IgG positive (P=0·024), respectively. The results of this study showed that the prevalence of West Nile fever is low in patients with encephalitis.


Methotrexate dosage as a source of bias in biological trials in rheumatoid arthritis: a systematic review.
To evaluate if optimal dose of either oral or injectable regimens of methotrexate (MTX) of 25 mg/week was used in the comparator arms of studies comparing biologic drugs with MTX in rheumatoid arthritis (RA). A systematic literature search was carried out in MEDLINE, EMBASE and the Cochrane Library databases for randomised controlled trials comparing biologics with MTX in RA. A systematic review was performed among studies that met predefined criteria focusing on assessment of dose of MTX used in the comparator arm. Study authors were contacted when necessary. Study quality was assessed. A total of 3276 references were identified and 13 trials were included. We obtained maximal dose and regimen for all. The maximal dose of MTX used in the comparator arm of the trials was no more than 20 mg/week in any trial and for all but one trial, MTX was given orally and not by injection. The trial that used an injectable form reached a maximum of 15 mg/week. A suboptimal dose of MTX was used in biological clinical trials performed in RA, particularly regarding route of administration. This may have biased findings in favour of biological agents.


Enhancing exposure therapy for anxiety disorders with glucocorticoids: from basic mechanisms of emotional learning to clinical applications.
Current neurophysiological and psychological accounts view exposure therapy as the clinical analog of extinction learning that results in persistent modifications of the fear memory involved in the pathogenesis, symptomatology, and maintenance of anxiety disorders. Evidence from studies in animals and humans indicate that glucocorticoids have the potential to facilitate the processes that underlie extinction learning during exposure therapy. Particularly, glucocorticoids can restrict retrieval of previous aversive learning episodes and enhance consolidation of memory traces relating to non-fearful responding in feared situations. Thus, glucocorticoid treatment especially in combination with exposure therapy might be a promising approach to optimize treatment of anxiety disorders. This review examines the processes involved in aversive conditioning, fear learning and fear extinction, and how glucocorticoids might enhance restructuring of fear memories during therapy.


Opportunities to improve asthma and COPD prevention and care: insights from the patient journey obtained through focus groups.
The healthcare experiences of patients hold valuable insights for improving the quality of services related to their well-being. We therefore invited and explored the perspectives of patients living with asthma and chronic obstructive pulmonary disease (COPD) on their interaction with the systems supporting health, in order to identify opportunities to improve services to prevent, treat and manage these conditions. Two virtual focus groups were held in August 2021, one for adult asthma and one for COPD, to learn of patients' experiences receiving care for these conditions in the Vancouver Coastal Health (VCH) region of British Columbia. Participants were recruited through online postings or their clinician. We discussed the care pathway for each condition and invited participants to share their experiences of the past 5 years, specifically their reflections on the process, including feelings, points of praise and frustration, and opportunities for improvement in this context. Composite patient journey maps were developed for each condition to reflect the experiences shared. Audio recordings of the focus groups were transcribed and used in qualitative data analysis. Thematic analysis revealed the following as possible areas for improvement: low public awareness of asthma and COPD and associated risk factors, non-standardised diagnosis pathways that delay diagnosis, and inconsistency in delivering valued aspects of care such as supports for self-management, trust-inspiring acute care, empowering patient communication and timely access to care. We successfully used focus groups to generate composite journey maps of the experiences of patients living with asthma (n=8) and COPD (n=9) to identify features that these patients consider important for improving the healthcare system for asthma and COPD in VCH. Health professionals, decision makers and patient advocates in VCH and beyond can consider these insights when evaluating, and planning changes to, current practices and policies in service delivery.


Regulation of neurogenesis and neuronal differentiation in primary and immortalized cells from mouse olfactory epithelium.
We have developed an in vitro system for studying molecular events regulating neurogenesis in the mouse olfactory epithelium (OE). Our observations suggest that two types of neuronal precursor may be involved: (1) a transiently existing, immediate neuronal precursor (INP), which generates two postmitotic daughter neurons; and (2) a neuroepithelial stem cell, which may be the basal cell (or some subclass of basal cell) of the OE, and is presumed to be the progenitor of the INP. Using antibody markers that distinguish basal cells and postmitotic receptor neurons in vitro and in vivo, we have shown that neurogenesis occurs early on in OE cultures, but then ceases because INPs divide only once to generate postmitotic neurons and no new INPs are produced by basal cells. To determine whether the basal cell-to-INP transition, or proliferation and neuronal differentiation of the INP, are regulated by crucial growth factors or cellular interactions, we are testing various polypeptide growth factors and extracellular matrix proteins for their effects on OE neurogenesis in vitro. We have also generated immortalized OE cell lines by using retroviruses to transduce oncogenes into cultured OE cells. One such cell line (derived from a primary OE basal cell culture) develops branching processes when transplanted into neonatal mouse brain--a condition in which cells from freshly isolated OE can undergo apparent morphological differentiation into neurons.


An epidemiological study on alcohol/drugs related fatal traffic crash cases of deceased drivers in Hong Kong between 1996 and 2000.
This study is designed to evaluate the correlation between fatal vehicle crashes (FVC) and consumption of alcohol and/or drugs among drivers. Between 1996 and 2000 in Hong Kong, a total of 197 FVC cases of deceased drivers were investigated. The blood and/or urine samples of the victims were examined for the presence of alcohol and drugs. The 197 cases were then classified into two groups: single-vehicle crashes (SVC) and multiple-vehicle crashes (MVC). Out of the 106 cases for the latter group, alcohol and/or drugs were detected in 22 cases (21%) while the remaining 84 cases (79%) were regarded as no significant finding. As for the 91 cases in SVC group, 51 cases (56%) were positive for alcohol and/or drugs. The findings indicate that a driver consuming alcohol and/or drugs has a higher risk of being involved in a FVC. The most frequently detected drugs for SVC group (11 cases) were: 46% central nervous system (CNS) stimulants (including designer drugs like MDMA); 36% cannabis; 18% benzodiazepines and 9% ketamine. The detected drug for the only case in the MVC group was a CNS stimulant. The number of cases with ketamine, methamphetamine and MDMA detected has increased in recent years as these party drugs have gained popularity in Hong Kong.


[The structured summary: a tool for reader and author].
To determine and to compare the information contained in structured abstracts in original articles in Annals of Internal Medicine (AIM), British Medical Journal (BMJ), New England Journal of Medicine (NEJM) and of abstracts that have been published in Nederlands Tijdschrift voor Geneeskunde (NTvG). Editorial office NTvG. Descriptive. Critical reading of 15 original articles of AIM (5), BMJ (5) and NEJM (5) in 5 consecutive issues starting from 1 March 1990 and all original articles of 6 consecutive issues of NTvG starting from 7 april 1990. According to the criteria of the 'ad hoc working group for critical appraisal of the medical literature' the amount of information in all foreign abstracts and 10 selected abstracts of NTvG were determined. The authors made structured abstracts of all read articles of NTvG. Structured abstracts of AIM, BMJ and NEJM are clear and detailed. However information about key sociodemographic features of patients, their selection and the way of statistical analysis of the results was often missing. In NTvG articles essential information was lacking with respect to objective, design, setting of the study, sociodemographic features of patients, and patients and methods. Structured abstracts of articles in NTvG take more space: an average of 266 instead of 164 words. Structured abstracts take more space but are more informative. Authors of original articles in NTvG are advised to prepare structured abstracts. Editors and peer reviewers should ascertain that no essential information is lacking.


Cost-effective treatment of depression with selective serotonin reuptake inhibitors.
To compare factors that influence cost of antidepressant therapy between older tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) and among drugs in the SSRI class. Literature review. Pharmacoeconomic data from the primary care and managed care settings demonstrate that the higher acquisition cost of the SSRIs is offset by reduced medical utilization because of a lower incidence of treatment-related adverse events, drug switching, and dosage adjustments than among patients taking TCAs. Analysis of pharmacy claims data suggests that drug acquisition costs, use of concomitant medications, incidence of dose titration, frequency of multitablet therapy (dose stratification), and duration of therapy are the key factors in determining the cost of SSRI therapy. Among the established SSRIs, drug acquisition costs are lowest for paroxetine and sertraline. Costs for concomitant medications may vary by healthcare plan. Recent reports indicate that paroxetine is associated with a low incidence of dose titration. Paroxetine and sertraline are available in extended dosage forms to reduce the need for multitablet therapy. Duration of therapy with all SSRIs is typically shorter than recommended. Antidepressant therapy with SSRIs has been shown to be more cost effective than treatment with TCAs when overall healthcare utilization and expenses are considered.


Hexokinase levels in discrete regions of rat brain: evaluation by quantitative immunofluorescence using interactive laser cytometry and comparison with basal rates of glucose utilization.
Relative levels of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 126.96.36.199) have been determined in 16 discrete regions of adult rat brain by a quantitative immunofluorescence method. The distribution of immunofluorescence in brain sections was determined by interactive laser cytometry and related to hexokinase content by comparison with standard sections containing known amounts of the enzyme. In many of these regions, referred to here as group I regions, hexokinase content was correlated with previously reported basal rates of glucose utilization. However, several regions (group II regions) in which hexokinase content exceeded that expected from basal rates of glucose utilization were also detected. Compared with the corresponding regions from albino rat brain, higher hexokinase levels were found in the dorsal and ventral lateral geniculate (group I regions) of pigmented Norway rats, a result reflecting previously reported increased glucose utilization by these regions in pigmented rats. There was no difference in hexokinase levels in the superior colliculus, a group II structure, from albino and pigmented rats, a finding implying that a reported increase in rate of glucose utilization in the superior colliculus of pigmented rats is effected without an increase in hexokinase content. It is suggested that group II regions may be adapted to sustain increases in rates of glucose utilization that are, relative to basal rates, considerably greater than those experienced by group I regions.


Elimination of Mother-to-Child Transmission of Hepatitis B Virus in Gulf Cooperation Council Countries: Current Status and Future Prospects.
The WHO member states endorsed the goal to eliminate mother-to-child transmission (EMTCT) of hepatitis B virus (HBV) by 2030, which requires achievement of ≥ 90% coverage with timely hepatitis B birth dose (HepB-BD), three doses of the hepatitis B vaccine (HepB3), and a hepatitis B surface antigen (HBsAg) seroprevalence ≤ 0.1% in children. We assessed the progress made to achieve EMTCT of HBV in Gulf Cooperation Council (GCC) countries. Data was extracted from National Viral Hepatitis Strategic Frameworks and WHO hepatitis B vaccination coverage estimates during 2018-2022 for all GCC countries. We also reviewed the literature to summarize the prevalence of HBsAg in children. During 2018-2022, coverage with timely HepB-BD and HepB3 was > 90% in all countries. All newborns irrespective of whether parents are nationals or immigrants/expatriates receive HepB-BD and other routine immunization vaccines. Prevalence of HBsAg among children was available in three of six GCC countries; it ranged from 0% in Qatar and Saudi Arabia to 0.4% in Oman. Five countries reported screening pregnant women for HBsAg, and three provided antiviral treatment of those eligible, and hepatitis B immunoglobulin to exposed newborns. In conclusion, all GCC countries achieved hepatitis B vaccination targets and countries with available data have either achieved or are close to achieving EMTCT of HBV. Remaining countries need to implement hepatitis B serosurveys to track progress to EMTCT of HBV.


Primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1: Impact of genotype and surgical approach on long-term postoperative outcomes.
Protein-truncating germline pathogenic variants in the N- and C-terminal exons (2, 9, and 10) of the MEN1 gene may be associated with aggressive pancreatic neuroendocrine tumors. However, the impact of these variants on parathyroid disease is poorly understood. We sought to investigate the effects of genotype and surgical approach on clinical phenotype and postoperative outcomes in patients with multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism. We identified patients with MEN1 evaluated at our institution from 1985 to 2020 and stratified them by genotype, (truncating variants in exons 2, 9, or 10, or other variants), and index surgical approach, (less-than-subtotal parathyroidectomy [<SPTX], SPTX, or total parathyroidectomy). We analyzed baseline characteristics, persistent/recurrent disease rates, and incidence of postoperative hypoparathyroidism. Of the 209 patients we identified, primary hyperparathyroidism was diagnosed in 194 (93%) and at a younger median age in those with truncating exon 2, 9, or 10 variants compared with other variants (27 years vs 31 years; P = .006). Median disease-free survival was significantly worse in patients who underwent <SPTX (60 months) than those who underwent <SPTX (152 months; P = .0005) or total parathyroidectomy (210 months; P = .04). Patients with truncating exon 2, 9, or 10 variants who underwent <SPTX had significantly shorter median disease-free survival than those with other variants (30 vs 84 months; P = .007). Prolonged hypoparathyroidism rates after final surgery were highest after total parathyroidectomy (40%), followed by <SPTX (9%) and SPTX (7%). The MEN1 genotype may affect the age of onset of primary hyperparathyroidism and the time to recurrence after surgery. <SPTX at index operation should be performed with caution, especially in patients with truncating MEN1 variants in exons 2, 9, or 10, as the higher risk of recurrence is not offset by a decreased incidence of permanent hypoparathyroidism compared to upfront SPTX.


Effects of feeding intensity during the dry period. 2. Metabolic and hormonal responses.
The metabolic response to different feeding levels during the dry period was studied in 24 multiparous dairy cows of the Swedish Red and White breed. The cows represented two lines, selected for high or low milk fat percentage, at the same amount of energy produced in milk. The cows were fed one of three different amounts of the same total mixed diet during the dry period, starting 8 wk prior to the expected parturition. The rations provided 71, 106, or 177 MJ metabolizable energy per day. After parturition the cows were offered another total mixed diet ad libitum for the first 12 wk of lactation. Glucose challenges were performed 3 wk prior to and 3 wk after parturition. Prepartum the glucose clearance rate was related to feeding level. Insulin response to the glucose challenge was reduced during the postpartum period, compared to the prepartum period. During about 6 wk prepartum, the insulin level in plasma was related to feeding level. At the sampling 3 wk prior to parturition the plasma level of leptin also was related to the feeding level. After parturition both leptin and insulin were reduced. In early lactation plasma leptin concentration was not related to adiposity as reflected by body condition scoring. It was suggested that lactation as such affected the leptin concentration in plasma.