Examining the relationship between academic stress and motivation toward physical education within a semester: A two-wave study with Chinese secondary school students.
The present study aimed to investigate the relationship between academic stress and motivation toward physical education (PE) through a longitudinal design with cross-lagged panel analyses. A sample of 556 Chinese secondary school students participated in the research and completed Perceived Locus of Causality Scale and Educational Stress Scale for Adolescents at the beginning of the semester and 3 months later. The results demonstrated that academic stress factors were positively related to less self-determined motivations except that worry about grades was positively related to more self-determined motivations within each time point. In addition, we found that academic stress negatively predicted more self-determined motivations but positively predicted less self-determined motivations, whereas worry about grades negatively predicted amotivation 3 months later. Meanwhile, the influence of amotivation on despondency was also found. These results suggest that academic stress can obstruct students' participation in PE through an impact on self-determined motivation. Our findings also indicate that self-determined students in PE will seek academic achievement as well, which in turn improves students' academic status.


Growth hormone changes bone geometry and body composition in patients with juvenile idiopathic arthritis requiring glucocorticoid treatment: a controlled study using peripheral quantitative computed tomography.
Osteopenia and growth retardation have been described in children with chronic arthritis. GH has an impact on both. In the present controlled study, we used peripheral quantitative computed tomography to evaluate forearm bone mass, density, and geometry as well as forearm muscle and fat area in 17 patients with juvenile idiopathic arthritis (JIA) receiving treatment with GH for 3.8 +/- 1.1 yr compared with an untreated age- and sex-matched control group (n = 17). All patients had a mean age of 15.3 +/- 2.5 yr and a mean duration of illness of 8.2 +/- 4.4 yr. Height, weight, body mass index, bone parameters, and muscle area were significantly decreased in both groups compared with those in healthy age-matched children. Compared with untreated JIA patients, GH-treated JIA patients had significant higher bone mineral content as well as total cross-sectional area (CSA), cortical CSA, and muscle CSA. Fat CSA was lower in the GH-treated group. A significant difference between groups for height-corrected cortical and muscle areas was only seen in male patients. Cortical CSA relative to muscle CSA was not different between groups. These findings are compatible with an anabolic effect of GH on muscle and bone development.


Citrus aurantium as a thermogenic, weight-reduction replacement for ephedra: an overview.
Obesity is a serious health problem throughout the world. More than half of U.S. adults are overweight (61%) and more than a quarter (26%) of U.S. adults are obese. The inability of many individuals to keep their weight in check by diet and exercise has created a need for additional therapeutic means to combat obesity. Despite great effort, the pharmaceutical industry has not come up with the solution; because most weight-loss drugs to date have serious adverse effects to health and well-being. The theory that beta agonists, especially beta 3 agonists, can affect body weight and fat mass is well accepted. Ephedrine has proven time and time again that it is an effective weight loss agent through its ability to increase thermogenesis and quench appetite. However, the publicity concerning adverse reactions has led to its gradual withdrawal from use by many despite the perceived consequences of obesity. Many companies are now substituting Citrus aurantium for ephedra in their formulations. Citrus aurantium, an agent containing beta agonists, has been reported to aid in weight loss in two studies and increase thermogenesis, at least to some extent, in three studies. Colker et al. (1999) reported that in a double-blind, placebo-controlled, randomized study the subjects receiving a combination of Citrus aurantium, caffeine and St John's Wort, lost significant amounts of total body weight while on a strict diet and exercise. Those in the placebo and control groups who also were on the same restricted diet did not. However, intergroup analysis showed no statistical significance among the weight changes in the three groups. In contrast, the loss of fat mass in the test group was significantly greater compared to the placebo and control groups. Jones describes an open labeled study performed on 9 women. The subjects showed a mean of 0.94 kg lost during the first week when no product was given and 2.40 kg during the second week when a Citrus aurantium product was taken. Body weight losses were statistically greater during the second week compared to the first week. Since most clinicians would agree that the most weight loss should occur initially coinciding with a greater fluid loss during the first week, these differences are even more remarkable. Three studies reported increased metabolic rates when ingesting Citrus aurantium products, however, at least two of these studies were acute. At present, Citrus aurantium may be the best thermogenic substitute for ephedra. However, more studies are needed to establish this definitively.


Cataract and the use of statins: a case-control study.
In animal studies, statins have induced cataract formation. Because incident cataract is relatively uncommon, studies in humans have been unable to exclude a clinically important effect. To assess the risk of cataract associated with the use of statins, and whether it is increased by concurrent use of drugs that inhibit the cytochrome P450 system. Population-based case-control study. Patients were randomly sampled from the UK General Practice Research Database. The study included 15,479 people with cataract and 15,479 controls matched for age, sex, practice and observation period. The crude odds ratio (OR) for the association between any recorded exposure to statins and cataract was 1.41 (95%CI 1.21-1.65), but this reduced to 1.04 (95%CI 0.89-1.23, p=0.6) after adjustment for consultation rate. There was no evidence that the risk increased with higher doses or longer duration of statin use, or that the risk varied by individual statin. There was no evidence that the risk of cataract was increased by concurrent use of statins and drugs that inhibit the cytochrome P450 system. In the short- and medium-term, statins do not seem to be associated with an increased risk of cataract. The need to assess the effects of long-term statin exposure on the eye remains.


Evidence-based primary care treatment guidelines for skin infections in Europe: a comparative analysis.
In Europe, most antibiotics for human use are prescribed in primary care. Incorporating resistance data into treatment guidelines could improve appropriate prescribing, increase treatment effectiveness and control the development of resistance. This study reviews primary care treatment guidelines for bacterial skin infections across Europe and assesses to what extent they are based on antibiotic resistance data. Thirteen primary care treatment guidelines were obtained from eight countries across Europe. Both the treatment recommendations and the underlying evidence were assessed. The class and dose of recommended antibiotics were investigated and compared using the World Health Organisation's standardized volume of Defined Daily Dose. Furthermore, analysis investigated whether guidelines included references to scientific publications about antibiotic resistance data, and whether these were of national origin. Guidelines were included regarding common skin infections in primary care: Impetigo, Cellulitis, Erysipelas, Folliculitis and Furuncle. RESULTS showed a high agreement across Europe: all recommended antibiotics are of the beta-lactam class and mainly in the small spectrum. The advised treatment durations are consistent; the dosages, however, vary considerably, with the highest dosages recommended in Sweden. Seven guidelines (54%) did not include scientific references related to resistance. There may be a lack of relevant national data on resistance. This study highlights the need to collect more national resistance data (particularly regarding beta-lactams) to create stronger evidence-based treatment guidelines for skin infections in Europe.


The Other Side of Rapport: Data Collection Mode and Interviewer Gender Effects on Sexual Health Reporting in Ghana.
Accurate data on young people's sexual behaviour and sexual health practice is essential to inform effective interventions and policy. However, little empirical evidence exists to support methodological design decisions in projects assessing young people's sexual health, especially in African contexts. This short report uses original empirical data collected in Ghana in 2012 to assess the effects of data collection mode and interviewer gender on young people's reporting of sexual health and access to supportive sexual health resources. The findings indicate that the effect of data collection mode may vary by gender, and there is no indication of an interviewer gender effect for males in this study. Preliminary results suggest that building strong rapport with research participants in this context may lead to reduced sexual health data quality. These findings merit further investigation and have direct implications for the design of projects measuring sexual health and related variables in Ghana.


Mesenchymal stem cell-derived exosomes have altered microRNA profiles and induce osteogenic differentiation depending on the stage of differentiation.
Human mesenchymal stem cell (hMSC)-derived exosomes have shown regenerative effects, but their role in osteogenesis and the underlying mechanism are yet to be determined. In this study, we examined the time-course secretion of exosomes by hMSCs during the entire process of osteogenic differentiation. Exosomes derived from hMSCs in various stages of osteogenic differentiation committed homotypic cells to differentiate towards osteogenic lineage, but only exosomes from late stages of osteogenic differentiation induced extracellular matrix mineralisation. Exosomes from expansion and early and late stages of osteogenic differentiation were internalised by a subpopulation of hMSCs. MicroRNA profiling revealed a set of differentially expressed exosomal microRNAs from the late stage of osteogenic differentiation, which were osteogenesis related. Target prediction demonstrated that these microRNAs enriched pathways involved in regulation of osteogenic differentiation and general mechanisms how exosomes exert their functions, such as "Wnt signalling pathway" and "endocytosis". Taken together, the results show that MSCs secrete exosomes with different biological properties depending on differentiation stage of their parent cells. The exosomal cargo transferred from MSCs in the late stage of differentiation induces osteogenic differentiation and mineralisation. Moreover, it is suggested that the regulatory effect on osteogenesis by exosomes is at least partly exerted by exosomal microRNA.


The inotropic actions of N-acetylprocainamide: blockade and reversal by propranolol.
The inotropic actions of N-acetylprocainamide (NAPA) were studied in chloralose-urethane anesthetized dogs. Myocardial contractile force was measured with a Walton-Brodie strain gauge sutured to the right ventricle. A low-dose NAPA infusion (12 mg/kg i.v.) increased myocardial force by a maximum of 11.6 +/- 2.4% (mean +/- SEM), whereas a high dose of NAPA (60 mg/kg i.v.) increased myocardial force by 33.3 +/- 2.6% at the peak of the effect. The high-dose NAPA infusion also caused significant reductions in heart rate and blood pressure, while the low-dose NAPA infusion lacked significant chronotropic or hypotensive actions. Pretreatment with propranolol (0.5 mg/kg i.v. loading, followed by a 10 micrograms/kg/min infusion) did not block the positive inotropic actions of NAPA 12 mg/kg, but these actions were blocked in dogs pretreated with both propranolol and atropine (1 mg/kg). On the other hand, pretreatment with propranolol blocked and reversed the inotropic actions of NAPA 60 mg/kg, and potentiated its negative chronotropic effects. Thus, the positive inotropic actions of NAPA are indirect and more than one mechanism is involved; a component due to direct action related to the lengthening of cardiac repolarization is not discounted. At low doses, the increase in myocardial force seems related to NAPA's vagolytic properties, whereas at high doses the positive inotropic actions appear to be catecholamine-mediated. Furthermore, a negative inotropic action of high-dose NAPA is apparent after beta-adrenergic receptor blockade.


Low intensity extracorporeal shockwave therapy for erectile dysfunction: a study in an Indian population.
Erectile dysfunction (ED) has been shown to be associated with a number of physical conditions and affects not only physical but also psychosocial health. Currently oral, on-demand phosphodiesterase type 5 inhibitors (PDE5i) are preferred first line treatment. Though effective, these drugs have limitations and are associated with significant non-compliance, side effects and do not reverse the underlying pathology. Non-invasive low intensity shockwave therapy (LISWT) has been shown to significantly improve erectile function in men previously PDE5i dependent. We describe our experience and results with this therapy in an Indian population of men with ED. This study assessed the efficacy of low intensity extracorporeal shockwave therapy (LI-ESWT) on Indian men with organic ED who had previously responded to PDE5i. All the patients underwent a 1 month PDE5i washout period. Men were randomized to receive either 12 sessions of LI-ESWT (n = 95) or placebo/sham therapy (n = 40). Before the first treatment, erectile function and penile hemodynamics were assessed to substantiate a vascular etiology for the ED. Outcomes were assessed using Erection Hardness Score (EHS), International Index of Erectile Function-Erectile Function Domain (IIEF-EF domain) and Clinical Global Impression of Change (CGIC) scores at 1, 3, 6, 9 and 12 months post-treatment. We found a significant increase in the EHS and IIEF-EF Domain scores from visit 1 to follow up 5 (12 months) in the treated group compared to the placebo group. By 1 month after treatment there were highly significant differences between the LI-ESWT and placebo groups (p < 0.0001). Out of 60 men in the LI-ESWT group who completed the study, 47 (78%) men at FU1 and 43 (71%) at FU5 who were initially unable to achieve spontaneous erections hard enough for penetration (EHS ≤ 2) were able to do so (EHS ≥ 3) compared to none in the placebo group. The treatment was well tolerated and none of the men experienced treatment related discomfort or reported any adverse effects from the treatment. In this double-blind, placebo-controlled study, LI-ESWT demonstrated a positive long term clinical effect with improvement in erectile function of Indian men with vasculogenic ED who were prior responders to PDE5i therapy. The efficacy and tolerability of this treatment, coupled with its long term benefits and rehabilitative characteristics, make it an attractive new therapeutic option for men with vasculogenic erectile dysfunction.


Prevalence of Involuntary Environmental Cannabis and Tobacco Smoke Exposure in Multi-Unit Housing.
No research has examined the prevalence of involuntary cannabis exposure in the home within the context of multi-unit housing (MUH). The 2017 cycle of the Centre for Addiction and Mental Health Monitor population RDD survey included measures of environmental cannabis smoke (ECS) and environmental tobacco smoke (ETS) for Ontario, Canada. These ECS measures were defined for those who did not live in a detached dwelling self-reporting noticing any tobacco or cannabis smoke enter the home from a neighboring unit or from outside the building at least once in the past 6 months. Overall, 6.6% (95% CI: 4.5-9.5%) and 7.5% (9% CI: 5.4-10.4%) of the population reported being exposed to ETS and ECS in MUH respectively. Individuals exposed to ECS were single, had used cannabis in the past 12 months, and had lower household incomes. The prevalence of involuntary exposure to cannabis smoke is similar to exposure to tobacco smoke. Exposure correlates were primarily associated with characteristics of those who lived in MUH who tend to be members of more vulnerable populations.


The reliability and validity of a matrix to assess the completed reflective personal development plans of general practitioners.
We wished to determine whether assessors could make reliable and valid judgements about the quality of completed reflective personal development plans (PDPs) for the purpose of accrediting UK general practitioners (GPs) for a postgraduate education allowance using a marking matrix, and secondly, to plan a feasible model of PDP assessment in the context of forthcoming GP appraisal/revalidation that would overcome the main sources of error identified from this study. Within generalisability theory, a variance components analysis on PDP scores estimated reliability and the effect on them of varying, for example, the number of assessors. We investigated the construct validity of the matrix through its internal consistency and detection of differences in the quality of PDPs. For a single PDP and one assessor, 37.6% of the variance in scores was due to true differences in the quality of the PDP. Between 5 and 7 PDP assessors are needed to achieve summative reliability of greater than 0.8. While increasing the number of judges is important, reliability could also be improved by addressing assessor subjectivity. Construct validity was demonstrated, as the matrix distinguished between good, satisfactory and poor PDPs, and it had good internal consistency. PDP assessment has reasonable summative characteristics for the purpose of assessing GPs' reflective continuing professional development. If doctors could include their PDPs within their revalidation folders as evidence of their reflections on pursuing better clinical performance, we have described a reliable, valid and feasible method of external assessment.


[Study on the quantitative and qualitative of fungi colonizing soybeans (Glycine max L.)].
The aim of study was to analyse the qualitative and quantitative composition of fungi in soybeans on RBCA, YpSs, and DG18 culture media at 25, 37 and 45°C. The analysis included 15 samples of soybeans. The highest number of mould species (23) were isolated on RBCA at 25°C, followed by xerophilic species (20) on DG18 at 25°C, and mesophilic (13) and thermophilic species (4) on YpSs medium at 37° and 45°C, respectively. Ninety-five strains belonging to 40 species were isolated from soybean samples. The predominant species were Penicillium chrysogenum and Eurotium herbariorum. This study revealed new species of mycobiota not previously isolated from soybeans.


Impact of early haemodynamic goal-directed therapy in patients undergoing emergency surgery: an open prospective, randomised trial.
Haemodynamic goal-directed therapies (GDT) may improve outcome following elective major surgery. So far, few data exist regarding haemodynamic optimization during emergency surgery. In this randomized, controlled trial, 50 surgical patients with hypovolemic or septic conditions were enrolled and we compared two algorithms of GDTs based either on conventional parameters and pressure pulse variation (control group) or on cardiac index, global end-diastolic volume index and stroke volume variation as derived from the PiCCO monitoring system (optimized group). Postoperative outcome was estimated by a composite index including major complications and by the Sequential Organ Failure Assessment (SOFA) Score within the first 3 days after surgery (POD1, POD2 and POD3). Data from 43 patients were analyzed (control group, N = 23; optimized group, N = 20). Similar amounts of fluid were given in the two groups. Intraoperatively, dobutamine was given in 45 % optimized patients but in no control patients. Major complications occurred more frequently in the optimized group [19 (95 %) versus 10 (40 %) in the control group, P < 0.001]. Likewise, SOFA scores were higher in the optimized group on POD1 (10.2 ± 2.5 versus 6.6 ± 2.2 in the control group, P = 0.001), POD2 (8.4 ± 2.6 vs 5.0 ± 2.4 in the control group, P = 0.002) and POD 3 (5.2 ± 3.6 and 2.2 ± 1.3 in the control group, P = 0.01). There was no significant difference in hospital mortality (13 % in the control group and 25 % in the optimized group). Haemodynamic optimization based on volumetric and flow PiCCO-derived parameters was associated with a less favorable postoperative outcome compared with a conventional GDT protocol during emergency surgery.


Widespread bleaching in the One Tree Island lagoon (Southern Great Barrier Reef) during record-breaking temperatures in 2020.
The global marine environment has been impacted significantly by climate change. Ocean temperatures are rising, and the frequency, duration and intensity of marine heatwaves are increasing, particularly affecting coral reefs. Coral bleaching events are becoming more common, with less recovery time between events. Anomalous temperatures at the start of 2020 caused widespread bleaching across the Great Barrier Reef (GBR), extending to southern, previously less affected reefs such as One Tree Island. Here, nine video transects were conducted at One Tree Island, in the Capricorn Bunker Group, and analysed for community composition and diversity, and the extent of bleaching across taxa. Average live hard coral cover across the area was 11.62%, and almost half of this was identified as severely bleached. This bleaching event is concerning as it occurred in an area previously considered a potential refuge for corals and associated fauna from the risks of climate warming. Due to the global impacts of COVID-19 during 2020, this report provides one of potentially few monitoring efforts of coral bleaching.


Discourse and Strategic Use of the Military in France and Europe in the COVID-19 Crisis.
In March 2020, the French President called to war against the COVID-19 which was followed by the launch of a military operation called Operation Resilience. This use of martial rhetoric initiated an effective mobilisation consisting in logistical assistance to the health sector. While armies are increasingly used to deal with environmental disasters, aside from their traditional role, this paper postulates that the geography of the French and international military engagement can be used to analyse both the institutional strategy of crisis management and the message governments send to their population. Military involvement differs in terms of missions given and of the amount of troops mobilised. It first questions the use of the military in the name of national resilience in the political discourse and the way it displays a symbolic message to the population, before analysing the role of armies in the crisis through the spatiality of their interventions.


Cardiac remodeling in response to embryonic crude oil exposure involves unconventional NKX family members and innate immunity genes.
Cardiac remodeling results from both physiological and pathological stimuli. Compared with mammalian hearts, fish hearts show a broader array of remodeling changes in response to environmental influences, providing exceptional models for dissecting the molecular and cellular bases of cardiac remodeling. We recently characterized a form of pathological remodeling in juvenile pink salmon (Oncorhynchus gorbuscha) in response to crude oil exposure during embryonic cardiogenesis. In the absence of overt pathology (cardiomyocyte death or inflammatory infiltrate), cardiac ventricles in exposed fish showed altered shape, reduced thickness of compact myocardium and hypertrophic changes in spongy, trabeculated myocardium. Here, we used RNA sequencing to characterize molecular pathways underlying these defects. In juvenile ventricular cardiomyocytes, antecedent embryonic oil exposure led to dose-dependent upregulation of genes involved in innate immunity and two NKX homeobox transcription factors not previously associated with cardiomyocytes, nkx2.3 and nkx3.3 Absent from mammalian genomes, the latter is largely uncharacterized. In zebrafish embryos, nkx3.3 demonstrated a potent effect on cardiac morphogenesis, equivalent to that of nkx2.5, the primary transcription factor associated with ventricular cardiomyocyte identity. The role of nkx3.3 in heart growth is potentially linked to the unique regenerative capacity of fish and amphibians. Moreover, these findings support a cardiomyocyte-intrinsic role for innate immune response genes in pathological hypertrophy. This study demonstrates how an expanding mechanistic understanding of environmental pollution impacts - i.e. the chemical perturbation of biological systems - can ultimately yield new insights into fundamental biological processes.


Capsaicin pre- and post-treatment on rat monocrotaline pneumotoxicity.
Monocrotaline (MCT) produces respiratory dysfunction, pulmonary hypertension (PH), and right ventricular hypertrophy (RVH) in rats. Tachykinins, such as substance P (SP) and neurokinin A (NKA), may mediate these effects. The purpose of this study was to investigate the length of tachykinin depletion (via capsaicin treatment) is needed to prevent (or attenuate) PH and/or RVH. Six groups of rats were injected subcutaneously with saline (3 ml/kg); capsaicin followed by saline or MCT (60 mg/kg); or MCT followed 7, 11, or 14 days later by capsaicin. Capsaicin (cumulative dose, 500 mg/kg) was given over a period of 4-5 days. Respiratory function, pulmonary vascular parameters, lung tachykinin levels, and tracheal neutral endopeptidase (NEP) activity were measured 21 days after MCT or saline injection. Capsaicin significantly decreased lung levels of SP but not NKA. Both capsaicin pretreatment and posttreatment blocked the following MCT-induced alterations: increases in lung SP and airway constriction; decreases in tracheal NEP activity and dynamic respiratory compliance. Administration of capsaicin before or 7 days after MCT blocked MCT-induced PH and RVH. The above data suggest that the early tachykinin-mediated airway dysfunction requires only transient elevated tachykinins, while progression of late tachykinin-mediated effects (PH and RVH) requires elevated tachykinins for more than one week.


Renal targeting of kinase inhibitors.
Activation of proximal tubular cells by fibrotic and inflammatory mediators is an important hallmark of chronic kidney disease. We have developed a novel strategy to intervene in renal fibrosis, by means of locally delivered kinase inhibitors. Such compounds will display enhanced activity within tubular cells and reduced unwanted systemic effects. In our approach kinase inhibitors are linked to the renal carrier lysozyme using a platinum-based linker that binds drugs via a coordinative linkage. Many kinase inhibitors contain aromatic nitrogen atoms able to bind to this linker without the need of prior derivatization. The resulting drug-lysozyme conjugates are rapidly filtered in the glomerulus into the tubular lumen and subsequently reabsorbed via the endocytic pathway for clearance of low-molecular weight proteins. An important property of the formed conjugates is their in vivo stability and the sustained drug release profile within target cells. This review summarizes the state-of-the-art of drug targeting to the kidney. Furthermore, we will highlight recent results obtained with kinase inhibitor-lysozyme conjugates targeted to different kinases, i.e. the transforming growth factor (TGF)-beta-receptor kinase, p38 MAPkinase and Rho-associated kinase. Both in vitro and in vivo results demonstrated their efficient tubular uptake and beneficial therapeutic effects, superior to treatment with free kinase inhibitors. These proof-of-concept studies clearly indicate the feasibility of drug targeting for improving the renal specificity of kinase inhibitors.


Diagnosing attention-deficit hyperactivity disorder (ADHD) in children involved with child protection services: are current diagnostic guidelines acceptable for vulnerable populations?
Children involved with child protection services (CPS) are diagnosed and treated for attention-deficit hyperactivity disorder (ADHD) at higher rates than the general population. Children with maltreatment histories are much more likely to have other factors contributing to behavioural and attentional regulation difficulties that may overlap with or mimic ADHD-like symptoms, including language and learning problems, post-traumatic stress disorder, attachment difficulties, mood disorders and anxiety disorders. A higher number of children in the child welfare system are diagnosed with ADHD and provided with psychotropic medications under a group care setting compared with family-based, foster care and kinship care settings. However, children's behavioural trajectories change over time while in care. A reassessment in the approach to ADHD-like symptoms in children exposed to confirmed (or suspected) maltreatment (e.g. neglect, abuse) is required. Diagnosis should be conducted within a multidisciplinary team and practice guidelines regarding ADHD diagnostic and management practices for children in CPS care are warranted both in the USA and in Canada. Increased education for caregivers, teachers and child welfare staff on the effects of maltreatment and often perplexing relationship with ADHD-like symptoms and co-morbid disorders is also necessary. Increased partnerships are needed to ensure the mental well-being of children with child protection involvement.


Early versus late drain removal after standard pancreatic resections: results of a prospective randomized trial.
The role of surgically placed intra-abdominal drainages after pancreatic resections has not been clearly established. In particular, their effect on morbidity rates and the optimal timing for their removal remains controversial. A total of 114 eligible patients who underwent standard pancreatic resections and at low risk of postoperative pancreatic fistula according to our institutional protocol (amylase value in drains < or =5000 U/L on postoperative day [POD] 1) were randomized on POD 3 to receive either early (POD 3) or standard drain removal (POD 5 or beyond). The primary end point of the study was the incidence of pancreatic fistula. Secondary endpoints included abdominal complications, pulmonary complications, in-hospital stay, and perioperative mortality. Cost-analysis between the 2 groups was also made. Early drain removal was associated with a decreased rate of pancreatic fistula (P = 0.0001), abdominal complications (P = 0.002), and pulmonary complications (P = 0.007). Median in-hospital stay was shorter (P = 0.018), and hospital costs decreased (P = 0.02). Mortality was nil. A significant association with pancreatic fistula was found for timing of drain removal (P < 0.001), unintentional weight decrease before surgery (P = 0.022), type of pancreas texture (P = 0.015), serum amylase levels on POD 1 (P = 0.001), and albumin levels on POD 1 (P = 0.039). Multivariate analysis showed that timing of drain removal (P = 0.0003) and unintentional weight decrease before surgery (P = 0.02) were independent risk factors of pancreatic fistula. In patients at low risk of pancreatic fistula, intra-abdominal drains can be safely removed on POD 3 after standard pancreatic resections. A prolonged period of drain insertion is associated with a higher rate of postoperative complications with increased hospital stay and costs. The manuscript is a randomized trial, registered in the NLM database as NCT00931554.


[The use of antibiotics and chemotherapeutic agents during pregnancy].
Physicians engaged in all general and specialist fields of medicine may at times be confronted with the necessity of prescribing an antibiotic or chemotherapy for pregnant patients. This article gives ample advice on the therapy with antibiotics and chemotherapeutic agents during pregnancy.


Clinically enlarged lateral pelvic lymph nodes do not influence prognosis after neoadjuvant therapy and TME in stage III rectal cancer.
The significance of lateral pelvic lymph nodes (LPLN) in rectal cancer remains unclear. The purpose of this study was to determine the outcome of patients with LPLNs identified on pretherapy imaging who were treated with neoadjuvant therapy followed by proctectomy without LPLN dissection. Pretherapy imaging of patients with stage III rectal cancer was reviewed to determine perirectal and LPLN enlargement. Data were collected on preoperative therapy, operative resection, adjuvant therapy, and patient outcomes and were correlated to the presence or absence of preoperatively identified LPLNs (LPLN+ and LPLN-). Of the 53 patients identified who were treated between 2000 and 2005, 30 (57%) were LPLN+ on preoperative imaging. All patients received preoperative radiation therapy and total mesorectal excision. The local recurrence was 13%, and there was no difference related to LPLN status. A comparison of the overall and disease-free survival in patients with and without enlarged LPLNs revealed no difference. The LPLNs that were identified on pretherapy imaging do not affect the overall or disease-free survival after the neoadjuvant therapy and proctectomy in stage III rectal cancer. A lateral pelvic lymph node dissection does not appear to be justified in stage III patients with LPLNs on pretherapy imaging who receive neoadjuvant therapy.


Can 2-Pyridyl-1,2,3-triazole "Click" Ligands be Used to Develop Cu(I)/Cu(II) Molecular Switches?
Molecular switching processes are important in a range of areas including the development of molecular machines. While there are numerous organic switching systems available, there are far less examples that exploit inorganic materials. The most common inorganic switching system remains the copper(I)/copper(II) switch developed by Sauvage and co-workers over 20 years ago. Herein, we examine if bidentate 2-(1-benzyl-1H-1,2,3-triazol-4-yl)pyridine (pytri) and tridentate 2,6-bis[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]pyridine (tripy) moieties can be used to replace the more commonly exploited polypyridyl ligands 2,2'-bypyridine (bpy)/1,10-phenanthroline (phen) and 2,2';6',2″-terpyridine (terpy) in a copper(I)/(II) switching system. Two new ditopic ligands that feature bidentate (pytri, L1 or bpytri, L2) and tridentate tripy metal binding pockets were synthesized and used to generate a family of heteroleptic copper(I) and copper(II) 6,6'-dimesityl-2,2'-bipyridine (diMesbpy) complexes. Additionally, we synthesized a series of model copper(I) and copper(II) diMesbpy complexes. A combination of techniques including nuclear magnetic resonance (NMR) and UV-vis spectroscopies, high-resolution electrospray ionization mass spectrometry, and X-ray crystallography was used to examine the behavior of the compounds. It was found that L1 and L2 formed [(diMesbpy)Cu(L1 or L2)]2+ complexes where the copper(II) diMesbpy unit was coordinated exclusively in the tridenate tripy binding site. However, when the ligands (L1 and L2) were complexed with copper(I) diMesbpy units, a complex mixture was obtained. NMR and MS data indicated that a 1:1 stoichiometry of [Cu(diMesbpy)]+ and either L1 or L2 generated three complexes in solution, the dimetallic [(diMesbpy)2Cu2(L1 or L2)]2+ and the monometallic [(diMesbpy)Cu(L1 or L2)]+ isomers where the [Cu(diMesbpy)]+ unit is coordinated to either the bidentate or tridentate tripy binding sites of the ditopic ligands. The dimetallic [(diMesbpy)2Cu2(L1 or L2)](PF6)2 complexes were structurally characterized using X-ray crystallography. Both complexes feature a [Cu(diMesbpy)]+ coordinated to the bidentate (pytri or bpytri) pocket of the ditopic ligands (L1 or L2), as expected. They also feature a second [Cu(diMesbpy)]+ coordinated to the nominally tridentate tripy binding site in a four-coordinate hypodentate κ2-fashion. Competition experiments with model complexes showed that the binding strength of the bidentate pytri is similar to that of the κ2-tripy ligand, leading to the lack of selectivity. The results suggest that the pytri/tripy and bpytri/tripy ligand pairs cannot be used as replacements for the more common bpy/phen-terpy partners due to the lack of selectivity in the copper(I) state.


Repeated nasopharyngeal lavage predicts freedom from silent carriage of Streptococcus equi after a strangles outbreak.
The value of repeated nasopharyngeal lavage (NPL) to detect silent carriers of Streptococcus equi has not been investigated. Determine if results of serial testing for S. equi by NPL predicts subsequent true carrier status as determined by both NPL and guttural pouch lavage. An outbreak of strangles with 100% morbidity in 41 mature Icelandic horses was followed prospectively to investigate development of silent carriers. All were initially positive to S. equi on NPL. The farm was closed to horse movement during the entire study. Prospective observational study. Testing for S. equi was performed by NPL at weeks 18, 28, 29, and 30 postindex case and subsequently at week 45 by both NPL and guttural pouch lavage. Carrier status at week 45 was compared to results obtained at weeks 18, 28, 29, and 30. Descriptive statistics were calculated. Comparisons were made using Fisher's exact test or the Freeman-Halton extension with a P < .05 level of significance. Of 24 noncarriers at week 45, only 4 horses were negative on all 3 consecutive weekly NPL samples at weeks 28 to 30. However, 10 of the 11 horses with at least 3 negative NPL obtained from weeks 18, 28, 29, and 30 were S. equi-free at week 45 (P = .03). Repeated NPL on at least 3 separate occasions can assist in predicting S. equi carrier-free status in horses after recovery from a strangles outbreak.


Estimated Healthcare Costs of Melanoma in Australia Over 3 Years Post-Diagnosis.
Skin cancer exerts a large and growing burden on health systems. With new pharmacotherapies for metastatic melanoma now available, a contemporary understanding of the cost burden of melanoma control is warranted. To comprehensively assess the healthcare costs of malignant melanoma diagnosis and treatment in Australia, over 3 years after diagnosis. We developed a decision-analytic model and micro-costing method to estimate the mean cost per patient for melanoma, incorporating all diagnostic and treatment modalities used in Australia (2017 AU$). By using the de-identified 10% sample of Medicare Benefits Scheme, we analysed health service use and supplemented our analyses with published estimates. We took a health system cost perspective, and addressed input uncertainty with sensitivity analyses. The mean annual cost per patient for melanoma stage 0/I/II was AU$1681 (US$1175) rising to AU$37,729 (US$26,365) for stage III resectable, and AU$115,109 (US$80,440) for stage III unresectable/IV. Three-year costs for stage III unresectable/IV were AU$187,720. Nationally, the annual estimated cost for treatment of all new cases of in situ and invasive melanomas was AU$201 million (95% CI: AU$187 to AU$216 million). When we included treatments for presumptive melanoma later found to be benign lesions, the estimated annual cost burden reached AU$272 million. With rapidly rising treatment costs, there is a need to consider a comprehensive melanoma control strategy that includes primary prevention of skin cancers and cost-effective sun protection initiatives.


[Reproducibility of data in a study of the risk factors for insulin-dependent diabetes mellitus].
The reliability of information about mothers' and fathers' education, weight and height at birth, history of diarrhoea, duration of exclusive breast feeding and age of introduction of cows' milk products, selected from a structured questionnaire used in home interviewers was examined in a sample of 38 cases and 38 controls from a study related to the risk factors of insulin-dependent diabetes mellitus. The repetition of the questions was done by telephone. The agreement between the answers of both interviewers was verified using the kappa statistic (categorical variables) and the intra-class correlation coefficient (quantitative variables). The results enable one to conclude that the information is reproducible.


Selection of broiler chickens for a high and low incidence of tibial dyschondroplasia with observations on spondylolisthesis and twisted legs (perosis).
Radiography was used to select normal birds and affected with tibial dyschondroplasia from a commercial stock of broiler chickens. Birds were selected for three generations and mated like to like in an attempt to establish low and high incidence strains. Incidence of tibial dyschondroplasia in the low incidence strain was reduced to negligible levels while it was increased in the high incidence strain. Incidence of the defect in the high incidence strain could be influenced by diet. Observations during the selection program on the incidence of spondylolisthesis and twisted legs in birds younger than eight weeks of age indicated that these other skeletal defects were unrelated to tibial dyschondroplasia.


Effect of three-year consumption of erythritol, xylitol and sorbitol candies on various plaque and salivary caries-related variables.
The objective of the present paper is to report results from oral biologic studies carried out in connection with a caries study. Samples of whole-mouth saliva and dental plaque were collected from initially 7- to 8-year-old subjects who participated in a 3-year school-based programme investigating the effect of the consumption of polyol-containing candies on caries rates. The subjects were randomized in three cohorts, consumed erythritol, xylitol, or sorbitol candies. The daily polyol consumption from the candies was approximately 7.5 g. A significant reduction in dental plaque weight from baseline (p<0.05) occurred in the erythritol group during almost all intervention years while no changes were found in xylitol and sorbitol groups. Usage of polyol candies had no significant or consistent effect on the levels of plaque protein, glucose, glycerol, or calcium, determined yearly in connection with caries examinations. After three years, the plaque of erythritol-receiving subjects contained significantly (p<0.05) lower levels of acetic acid and propionic acid than that of subjects receiving xylitol or sorbitol. Lactic acid levels partly followed the same pattern. The consumption of erythritol was generally associated with significantly (p<0.05) lower counts of salivary and plaque mutans streptococci compared with the other groups. There was no change in salivary Lactobacillus levels. Three-year consumption of erythritol-containing candies by initially 7- to 8-year old children was associated with reduced plaque growth, lower levels of plaque acetic acid and propionic acid, and reduced oral counts of mutans streptococci compared with the consumption of xylitol or sorbitol candies.


Predicting successful long-term weight loss from short-term weight-loss outcomes: new insights from a dynamic energy balance model (the POUNDS Lost study).
Currently, early weight-loss predictions of long-term weight-loss success rely on fixed percent-weight-loss thresholds. The objective was to develop thresholds during the first 3 mo of intervention that include the influence of age, sex, baseline weight, percent weight loss, and deviations from expected weight to predict whether a participant is likely to lose 5% or more body weight by year 1. Data consisting of month 1, 2, 3, and 12 treatment weights were obtained from the 2-y Preventing Obesity Using Novel Dietary Strategies (POUNDS Lost) intervention. Logistic regression models that included covariates of age, height, sex, baseline weight, target energy intake, percent weight loss, and deviation of actual weight from expected were developed for months 1, 2, and 3 that predicted the probability of losing <5% of body weight in 1 y. Receiver operating characteristic (ROC) curves, area under the curve (AUC), and thresholds were calculated for each model. The AUC statistic quantified the ROC curve's capacity to classify participants likely to lose <5% of their body weight at the end of 1 y. The models yielding the highest AUC were retained as optimal. For comparison with current practice, ROC curves relying solely on percent weight loss were also calculated. Optimal models for months 1, 2, and 3 yielded ROC curves with AUCs of 0.68 (95% CI: 0.63, 0.74), 0.75 (95% CI: 0.71, 0.81), and 0.79 (95% CI: 0.74, 0.84), respectively. Percent weight loss alone was not better at identifying true positives than random chance (AUC ≤0.50). The newly derived models provide a personalized prediction of long-term success from early weight-loss variables. The predictions improve on existing fixed percent-weight-loss thresholds. Future research is needed to explore model application for informing treatment approaches during early intervention.


Antigen-specific T(h)1 cells as direct effectors of Propionibacterium acnes-primed lipopolysaccharide-induced hepatic injury.
T(h)1 cells are cytotoxic effector cells that utilize Fas ligand (FasL) and tumor necrosis factor. The physiological roles of cytotoxic T(h)1 cells are considered to be immunoregulation by eliminating autoreactive lymphocytes or hyper-activated foreign antigen-specific lymphocytes. Their pathological roles, however, remain to be clarified. To investigate whether T(h)1 cells can destroy organs, we generated a Propionibacterium acnes-specific T(h)1 clone from C57BL/6 mice and tested whether the clone could serve as an effector in a P. acnes-primed lipopolysaccharide (LPS)-induced hepatic injury system, one of the septic shock models. B6SMN:C3H-FasL(gld) (B6-gld) mice, which were deficient in functional FasL, were resistant to P. acnes/LPS-induced hepatic shock. The T(h)1 clone rendered B6-gld mice sensitive to the hepatic shock after the i.v. transfer. The hepatic injury in the clone-transferred B6-gld mice, which was evaluated by both biochemical and histological examination, was inhibited by an anti-FasL mAb that we developed. These results suggested that bacterial antigen-specific T(h)1 cells like this clone can participate in organ destruction in vivo as one of the cytotoxic effectors and play a critical role in endotoxin-induced hepatic injury.


[Peritoneal dialysis at a regional hospital in Norway].
In 2006, an expert group appointed by the Norwegian Social and Health Directory recommended that the proportion of patients on peritoneal dialysis should increase from 15 % to about 30 %. We wanted to investigate if treatment in our hospital was in compliance with that recommendation. The patient material consisted of the total number of patients on dialysis and anonymised data collected for patients treated with peritoneal dialysis at Innlandet Hospital Trust, Lillehammer in the period 1.01.2004-31.12.2008. For patients in peritoneal dialysis we assessed patient dynamics, length of hospital stay, incidence of peritonitis, need for assistance and organisation of peritoneal dialysis activity. Dialysis treatment was given to 176 patients, 62 (35 %) of whom were treated by peritoneal dialysis for at least 30 days (mean treatment time 16.2 months). 17 patients were switched from hemodialysis to peritoneal dialysis and nine patients from peritoneal dialysis to hemodialysis. Patients older than 70 years stayed in hospital 6 days longer than those younger than 70 years. 27 (44 %) of the patients acquired peritonitis in the study period and 18 (29 %) patients needed help to exchange the dialysis bag. The proportion of patients treated with peritoneal dialysis in our hospital has reached the recommended level. The reason may be that all eligible patients are offered peritoneal dialysis and that the treatment chain is well organised.


Effect of a vibration exposure on muscular performance and body balance. Randomized cross-over study.
This randomized cross-over study was designed to investigate the effects of a 4-min vibration bout on muscle performance and body balance in young, healthy subjects. Sixteen volunteers (eight men, eight women, age 24-33 years) underwent both the 4-min vibration- and sham-interventions in a randomized order on different days. Six performance tests (stability platform, grip strength, isometric extension strength of lower extremities, tandem-walk, vertical jump and shuttle run) were performed 10 min before (baseline), and 2 and 60 min after the intervention. The effect of vibration on the surface electromyography (EMG) of soleus, gastrocnemius and vastus lateralis muscles was also investigated. The vibration-loading, based on a tilting platform, induced a transient (significant at the 2-min test) 2.5% net benefit in the jump height (P = 0.019), 3.2% benefit in the isometric extension strength of lower extremities (P=0.020) and 15.7% improvement in the body balance (P = 0.049). In the other 2-min or in the 60-min tests, there were no statistically significant differences between the vibration- and sham-interventions. Decreased mean power frequency in EMG of all muscles during the vibration indicated evolving muscle fatigue, while the root mean square voltage of EMG signal increased in calf muscles. We have shown in this study that a single bout of whole body vibration transiently improves muscle performance of lower extremities and body balance in young healthy adults.


Outcome after corticoamygdalohippocampectomy in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis without preoperative ictal recording.
We report on the surgical outcome obtained in patients with refractory temporal lobe epilepsy with mesial temporal sclerosis (MTS) who were evaluated preoperatively without ictal recording and were submitted to corticoamygdalohippocampectomy. Two hundred twelve patients with refractory temporal lobe epilepsy were evaluated by means of clinical history, neurological examination, interictal electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychological testing. MRI disclosed unilateral MTS in all patients. All patients were submitted to corticoamygdalohippocampectomy at the side determined by MRI. Interictal EEG showed unilateral temporal lobe spiking in 176 patients; in 36 patients, bilateral discharges were found. Mean follow-up time was 2.7 years. One hundred ninety-four patients (92%) were classified as Engel's class I. Eighteen patients (8%) were rated as Engel's class II. Thirty-two out of 36 patients, in whom bilateral discharges were found, were in Engel's class I. Sixty percent of the patients had an improvement in memory function related to the nonoperated temporal lobe. Fifty-nine percent of the patients had a 10-point increase in general IQ postoperatively. Verbal memory decline was noted in three patients. Pathological examination showed MTS in all patients. It is possible to adequately select good surgical candidates for temporal lobe resection using MRI and interictal EEG alone. In patients with MRI-defined MTS, we should expect a 90% postoperative remission rate. Cognitive decline was very rarely seen in this patient population. The finding of MTS on MRI is the single most important prognostic factor for good outcome after temporal lobe surgery.


Left hippocampus sparing whole brain radiotherapy (WBRT): A planning study.
Unilateral sparing of the dominant (left) hippocampus during whole brain radiotherapy (WBRT) could mitigate cognitive decline, especially verbal memory, similar to the widely investigated bilateral hippocampus avoidance (HA-WBRT). The aim of this planning study is dosimetrical comparison of HA-WBRT with only left hippocampus sparing (LHA-WBRT) plans. HA-WBRT plans for 10 patients were prepared in accordance with RTOG 0933 trial and served as baseline for comparisons with several LHA-WBRT plans prepared with an effort: 1) to maintain the same left hippocampus dosimetry ("BEST PTV") and 2) to maintain same dosimetry in planning target volume as in HA-WBRT ("BEST LH"). All HA-WBRT plans met RTOG 0933 protocol criteria with a mean Conformity index 1.09 and mean Homogeneity index (HI) 0.21. Mean right and left hippocampal D100% was 7.8 Gy and 8.5 Gy and mean Dmax 14.0 Gy and 13.8 Gy, respectively. "BEST PTV" plans reduced HI by 31.2% (P=0.005) which is mirrored by lower PTV_D2% (-0.8 Gy, P=0.005) and higher PTV_D98% (+1.3 Gy, P=0.005) as well as decreased optic pathway's Dmax by 1 Gy. In "BEST LH", mean D100% and Dmax for the left hippocampus were significantly reduced by 11.2% (P=0.005) and 10.9% (P=0.005) respectively. LHA-WBRT could improve target coverage and/or further decrease in dose to spared hippocampus. Future clinical trials must confirm whether statistically significant reduction in left hippocampal dose is also clinically significant.


Jamming by shear.
A broad class of disordered materials including foams, glassy molecular systems, colloids and granular materials can form jammed states. A jammed system can resist small stresses without deforming irreversibly, whereas unjammed systems flow under any applied stresses. The broad applicability of the Liu-Nagel jamming concept has attracted intensive theoretical and modelling interest but has prompted less experimental effort. In the Liu-Nagel framework, jammed states of athermal systems exist only above a certain critical density. Although numerical simulations for particles that do not experience friction broadly support this idea, the nature of the jamming transition for frictional grains is less clear. Here we show that jamming of frictional, disk-shaped grains can be induced by the application of shear stress at densities lower than the critical value, at which isotropic (shear-free) jamming occurs. These jammed states have a much richer phenomenology than the isotropic jammed states: for small applied shear stresses, the states are fragile, with a strong force network that percolates only in one direction. A minimum shear stress is needed to create robust, shear-jammed states with a strong force network percolating in all directions. The transitions from unjammed to fragile states and from fragile to shear-jammed states are controlled by the fraction of force-bearing grains. The fractions at which these transitions occur are statistically independent of the density. Jammed states with densities lower than the critical value have an anisotropic fabric (contact network). The minimum anisotropy of shear-jammed states vanishes as the density approaches the critical value from below, in a manner reminiscent of an order-disorder transition.


PTEN regulates Mdm2 expression through the P1 promoter.
MDM2 is an oncoprotein that controls tumorigenesis through both p53-dependent and -independent mechanisms. Mdm2 mRNA level is transcriptionally regulated by p53 in response to stress such as DNA damage, and its protein level and subcellular localization are post-translationally modulated by the AKT serine/threonine kinase. Previous studies showed that PTEN, a dual specificity phosphatase that antagonizes phosphatidylinositol 3-kinase/AKT signaling, is capable of blocking MDM2 nuclear translocation and destabilizing the MDM2 protein. Results from our current study demonstrate an additional role for PTEN in regulating MDM2 functions; PTEN modulates Mdm2 transcription and isoform selection by negatively regulating its P1 promoter. In Pten-null cell lines and prostate cancer tissues, Mdm2 P1 promoter activity is up-regulated, resulting in increased L-Mdm2 expression and enhanced p90(MDM2) isoform production. Furthermore, PTEN controls Mdm2 P1 promoter activity through its lipid phosphatase activity, independent of p53. Thus, our results provide a novel mechanism for PTEN in controlling MDM2 oncoprotein functions.


Selective excision of AZTMP by drug-resistant human immunodeficiency virus reverse transcriptase.
Two distinct mechanisms can be envisioned for resistance of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) to nucleoside analogs: one in which the mutations interfere with the ability of HIV-1 RT to incorporate the analog, and the other in which the mutations enhance the excision of the analog after it has been incorporated. It has been clear for some time that there are mutations that selectively interfere with the incorporation of nucleoside analogs; however, it has only recently been proposed that zidovudine (AZT) resistance can involve the excision of the nucleoside analog after it has been incorporated into viral DNA. Although this proposal resolves some important issues, it leaves some questions unanswered. In particular, how do the AZT resistance mutations enhance excision, and what mechanism(s) causes the excision reaction to be relatively specific for AZT? We have used both structural and biochemical data to develop a model. In this model, several of the mutations associated with AZT resistance act primarily to enhance the binding of ATP, which is the most likely pyrophosphate donor in the in vivo excision reaction. The AZT resistance mutations serve to increase the affinity of RT for ATP so that, at physiological ATP concentrations, excision is reasonably efficient. So far as we can determine, the specificity of the excision reaction for an AZT-terminated primer is not due to the mutations that confer resistance, but depends instead on the structure of the region around the HIV-1 RT polymerase active site and on its interactions with the azido group of AZT. Steric constraints involving the azido group cause the end of an AZT 5'-monophosphate-terminated primer to preferentially reside at the nucleotide binding site, which favors excision.


Vitamin D in the prevention and treatment of coronary heart disease.
The pathogenesis of coronary heart disease is of multifactorial origin. Probably, not all risk factors are satisfactorily understood. This article outlines beneficial vitamin D effects on cardiac function and the vasculature. In addition, human data associating serum vitamin D metabolite levels or oral vitamin D dosages or both with coronary heart disease outcome parameters are reviewed. There is accumulating evidence that the vitamin D hormone calcitriol exerts important physiological effects in cardiomyocytes, vascular smooth muscle cells, and the vascular endothelium. Low levels of the calcitriol precursor 25-hydoxyvitamin D are associated with myocardial infarction, congestive heart failure, and calcific aortic stenosis. Deficient calcitriol concentrations probably contribute to the massive vascular calcification seen in chronic kidney disease. In patients with end-stage renal disease and end-stage heart failure, very low-circulating calcitriol levels or nonuse of active vitamin D or both are independently associated with high mortality rates. Despite these exciting data, it is still too early to recommend exact dosages for the prevention or therapy of coronary heart disease. Prospective, randomized controlled trials with different amounts of vitamin D and probably with its active form calcitriol are needed to determine whether vitamin D can prevent coronary heart disease events and mortality.


Expression of subunits of the metalloendopeptidase meprin in renal cortex in experimental hydronephrosis.
Meprin A is a metalloendopeptidase in the proximal tubular epithelium of rodents that is capable of hydrolyzing a great variety of peptides and proteins. The aim of the present investigation was to investigate effects of ureteral ligation on the expression of meprin subunits. Ureteral ligation resulted in marked decreases in the expression of both alpha- and beta-meprin subunits within 12 h of ureteral obstruction. Even greater downregulation of expression of meprin alpha- and beta-mRNA was noted at 24, 48, and 96 h after ureteral ligation. The greatest decrease in meprin mRNA expression in obstructed kidneys over contralateral unobstructed control kidneys (CUK) occurred at 24 h postunilateral ureteral obstruction (post-UUO) for the meprin alpha-subunit (20-fold decrease compared with controls) and at 48 h for the meprin beta-subunit (90-fold decrease). On immunolabeling, the intensity for the two meprin subunits at the corticomedullary junction was dramatically decreased at 24 to 96 h after ureteral ligation in contrast to the CUK specimens. Results of in situ hybridization indicated that the CUK specimens expressed meprin beta-mRNA at the corticomedullary junction, whereas the obstructed kidneys exhibited a decrease in mRNA signal for meprin beta-subunit. There was a steady increase in the interstitial macrophage number in UUO rat kidneys over the 96 h of evaluation post-UUO. ED-1-positive macrophages were observed almost exclusively in the peritubular cortical interstitial space in a ringlike pattern with a preponderance of macrophage clusters around glomeruli. Unexpectedly, after reversal of UUO, the interstitial macrophage number remained higher than controls, despite the demonstrable decompression of the renal pelvis and caliceal system. In summary, this investigation demonstrates downregulation of meprin alpha and beta within hours of UUO and indicates a novel tubular response to ureteral obstruction.


Selective smoothing of the generative topographic mapping.
Generative topographic mapping is a nonlinear latent variable model introduced by Bishop et al. as a probabilistic reformulation of self-organizing maps. The complexity of this model is mostly determined by the number and form of basis functions generating the nonlinear mapping from latent space to data space, but it can be further controlled by adding a regularization term to increase the stiffness of the mapping and avoid data over-fitting. In this paper, we improve the map smoothing by introducing multiple regularization terms, one associated with each of the basis functions. A similar technique to that of automatic relevance determination, our selective map smoothing locally controls the stiffness of the mapping depending on length scales of the underlying manifold, while optimizing the effective number of active basis functions.


The language capability of Neanderthal man.
Considerable publicity has been given a recent article by Lieberman and Crelin ('71) which argues that Neanderthal man lacked the physical features necessary for speech. This present paper presents statistics on some modern men with normal speech who show physical features in common with Neanderthal man. The brain of Neanderthal man was as large as, or larger than, that of modern man. The brain reflected by endocranial cast of the La Chapelle-aux-Saints skull resembles that of modern man in an area important for speech and therapy suggests Neanderthal man had the neural development necessary for language.


Structural Capacitance in Protein Evolution and Human Diseases.
Canonical mechanisms of protein evolution include the duplication and diversification of pre-existing folds through genetic alterations that include point mutations, insertions, deletions, and copy number amplifications, as well as post-translational modifications that modify processes such as folding efficiency and cellular localization. Following a survey of the human mutation database, we have identified an additional mechanism that we term "structural capacitance," which results in the de novo generation of microstructure in previously disordered regions. We suggest that the potential for structural capacitance confers select proteins with the capacity to evolve over rapid timescales, facilitating saltatory evolution as opposed to gradualistic canonical Darwinian mechanisms. Our results implicate the elements of protein microstructure generated by this distinct mechanism in the pathogenesis of a wide variety of human diseases. The benefits of rapidly furnishing the potential for evolutionary change conferred by structural capacitance are consequently counterbalanced by this accompanying risk. The phenomenon of structural capacitance has implications ranging from the ancestral diversification of protein folds to the engineering of synthetic proteins with enhanced evolvability.


Assessment of SNP-SNP interactions by using square contingency table analysis.
The evolution of SNP-SNP interactions has become an interesting field in genetic epidemiology. Most of the studies, aimed to analyze the relationship between genetic factors and disease of interest, are focused on single SNP associations. However, for quantitative traits, influenced by the interplay of environmental and more than one genetic factors, interaction between the multi factors should be taken into consideration. In this study, symmetry models for square contingency tables are applied to the cross-classified SNP-SNP interactions data. Results from a genome-wide association analysis of blood pressure are used as a prior evidence for the interacted SNPs.


Mechanical Strength of the Proximal Tibia Following Total Knee Arthroplasty: A Cadaveric Study of Resection Depth and Bone Density.
Tibial component failure has been a problem in total knee arthroplasty, it is still undetermined how tibial resection depth affects the strength to support a tibial component. This study examined the relationship between the resection depth and the bone density and the mechanical strength to support the tibial component. Eight matched pairs of fresh, frozen cadaver lower legs were imaged with computed tomography to assess the bone density. A right tibia was resected at minimum resection level and a left tibia was resected at deep resection level. After the tibial component was implanted with cement on each tibia, it was loaded on a materials testing load frame to measure the stiffness and the load to failure. The average bone density at the minimum resection level of the tibia was significantly higher than at deep level (p=0.0003). The average stiffness and load to failure of the proximal tibia were 1105 N/mm (range 889 to 1303 N/mm) and 5626 N (range 3360 to 9098 N). There was no statistical correlation between tibial resection depth and the axial stiffness (p=0.4107) or the load to failure (p=0.1487). Although the bone density at a minimum resection level was higher than that at a deep level, the strength to support the tibial component was not statistically higher at a minimum cutting level than at a deeper cutting level proportionally. Surgeons may not need to minimize a proximal tibial bone resection to maintain a stronger support for a tibial component.


Effect of colcemid on the centriole cycle in Chinese hamster ovary cells.
The structural changes in the centrioles in Chinese hamster ovary cells were monitored by electron microscopy of whole mount preparations to investigate the effects of colcemid on the events in the centriole cycle. The population of mitotic cells increased with time of incubation with colcemid, but the arrest at mitosis by this drug was soon overcome, resulting in the formation of nuclei and a change in the shape of the cells again spreading over the substrate. The maximal mitotic index was reached every 25 h in the presence of either 0.10 or 0.91 micrograms/ml of colcemid. During this time, cells became multinucleated, increased greatly in size, and accumulated 8 to 10-nm filamentous bundles in the cytoplasm instead of microtubules, almost all of which had been depolymerized after exposure to colcemid. In the cells that were continuously treated with colcemid, a pair of centrioles became disoriented and each subsequently produced a daughter centriole. However, these daughter centrioles elongated to only half their full length; many unusual figures in the centriolar pairs resulted from their proceeding normally to the phases for disorientation and nucleation for centrioles in the next cycle. Although the rate of centriole elongation and the frequency of formation of the daughter centrioles were decreased by increasing the concentration of colcemid, the disorientation of the centrioles was not disturbed by this drug. The inhibitory effect of colcemid on centriolar nucleation and elongation was found to be totally reversible; the formation and elongation of new daughter centrioles occurred again just after removal of the drug. Prolonged treatment of cells with colcemid caused ultrastructural changes in the centrioles, such as the outgrowth of microtubules from the wall of centriolar triplets or the formation of unusual bundles of microtubules around the centrioles.


Effects of interdisciplinary team review on the use of antipsychotic agents with severely and profoundly mentally retarded persons.
Prescriptions of antipsychotic agents for 28 mentally retarded residents of a public institution were recorded over a 6-month interval with traditional medical reviews followed by a 6-month interval with interdisciplinary reviews in which specific recipient behaviors were considered. Substantial and sustained decreases in prescribed antipsychotic agents were observed during the latter interval. Analysis of injury reports for all residents in the environment (N = 63) indicated that these decreases did not significantly increase major injuries on the unit. Results supported an interdisciplinary approach with behavioral monitoring when making decisions related to managing behavior with antipsychotic agents.


Health literacy: emerging evidence and applications in kidney disease care.
Health literacy represents the communication among patients, their social networks, providers, and health systems to promote patients' understanding and engagement in their care. This is particularly relevant in kidney disease, in which the complexity of the medical condition and the extent of the health-care team require strategies to overcome health-literacy-related barriers. Limited literacy is common in patients with all stages of kidney disease and is associated with important outcomes, including reduced knowledge, less adherence, hospitalization, and death. A growing understanding and characterization of the health system, or organizational health literacy, may further our understanding of this dynamic relationship. Although various valid methods exist, assessment of health literacy within individuals or systematically within care settings has not been routinely performed. This may be in part due to the limited research in kidney-specific strategies to address limited health literacy. Future research to understand the mechanisms of health literacy will permit targeted, efficient interventions to bridge gaps and improve outcomes even in patients with complex kidney disease.


A multimodal 3D neuro-microphysiological system with neurite-trapping microelectrodes.
Three-dimensional cell technologies as pre-clinical models are emerging tools for mimicking the structural and functional complexity of the nervous system. The accurate exploration of phenotypes in engineered 3D neuronal cultures, however, demands morphological, molecular and especially functional measurements. Particularly crucial is measurement of electrical activity of individual neurons with millisecond resolution. Current techniques rely on customized electrophysiological recording set-ups, characterized by limited throughput and poor integration with other readout modalities. Here we describe a novel approach, using multiwell glass microfluidic microelectrode arrays, allowing non-invasive electrical recording from engineered 3D neuronal cultures. We demonstrate parallelized studies with reference compounds, calcium imaging and optogenetic stimulation. Additionally, we show how microplate compatibility allows automated handling and high-content analysis of human induced pluripotent stem cell-derived neurons. This microphysiological platform opens up new avenues for high-throughput studies on the functional, morphological and molecular details of neurological diseases and their potential treatment by therapeutic compounds.


Convergence of biofilm successional trajectories initiated during contrasting seasons.
Biofilm communities play a major role in explaining the temporal variation of biogeochemical conditions in freshwater ecosystems, and yet we know little about how these complex microbial communities change over time (aka succession), and from different initial conditions, in comparison to other stream communities. This has resulted in limited knowledge on how biofilm community structure and microbial colonization vary over relevant time scales to become mature biofilms capable of significant alteration of the freshwater environment in which they live. Here, we monitored successional trajectories of biofilm communities from summer and winter in a headwater stream and evaluated their structural state over time by DNA high-throughput sequencing. Significant differences in biofilm composition were observed when microbial colonization started in the summer vs. winter seasons, with higher percentage of algae (Bacillariophyta) and Bacteroidetes in winter-initiated samples but higher abundance of Proteobacteria (e.g., Rhizobiales, Rhodobacterales, Sphingomonadales, and Burkholderiales), Actinobacteria, and Chloroflexi in summer-initiated samples. Interestingly, results showed that despite seasonal effects on early biofilm succession, biofilm community structures converged after 70 days, suggesting the existence of a stable, mature community in the stream that is independent of the environmental conditions during biofilm colonization. Overall, our results show that algae are important in the early development of biofilm communities during winter, while heterotrophic bacteria play a more critical role during summer colonization and development of biofilms.


Muscle protein synthesis in the streptozotocin-diabetic rat. A possible role for corticosterone in the insensitivity to insulin infusion in vivo.
The effect of insulin infusion in vivo on muscle protein synthesis was investigated in rats. In 10-days-streptozotocin-diabetic rats infused in vivo with amino acids and glucose, the rate of protein synthesis per unit of RNA (RNA activity) was markedly decreased. Pre-treatment with large doses of insulin at 17 and 1 h before the infusion fully restored RNA activity to normal. Infusion of insulin for 6 h with amino acids and glucose did not restore RNA activity to normal in the diabetic rats. However, in diabetic-adrenalectomized rats similar infusions of insulin fully restored RNA activity to normal. Measurements of plasma corticosterone concentrations indicated a 50% increase in the diabetic rats. Since pre-treatment with corticosterone suppressed the stimulatory effect of insulin infusion on RNA activity in adrenalectomized rats, and since corticosterone treatment for 6 days suppressed RNA activity even though insulin concentrations were elevated, it is suggested that increased concentrations of corticosterone are responsible for the lag in response to insulin in the diabetic rat. This means that the catabolic effects of glucocorticoids must be also considered together with the catabolic effect of insulin lack in diabetes.


Matrix metalloproteinase-9 deficiency protects mice from severe influenza A viral infection.
Matrix metalloproteinase-9 (MMP-9) cleaves various proteins to regulate inflammatory and injury responses. However, MMP-9's activities during influenza A viral (IAV) infections are incompletely understood. Herein, plasma MMP-9 levels were increased in patients with pandemic H1N1 and seasonal IAV infections. MMP-9 lung levels were increased and localized to airway epithelial cells and leukocytes in H1N1-infected WT murine lungs. H1N1-infected Mmp-9-/- mice had lower mortality rates, reduced weight loss, lower lung viral titers, and reduced lung injury, along with lower E-cadherin shedding in bronchoalveolar lavage fluid (BALF) samples than WT mice. H1N1-infected Mmp-9-/- mice had an altered immune response to IAV with lower BALF PMN and macrophage counts, higher Th1-like CD4+ and CD8+ T cell subsets, lower T regulatory cell counts, reduced lung type I interferon levels, and higher lung interferon-γ levels. Mmp-9 bone marrow-chimera studies revealed that Mmp-9 deficiency in lung parenchymal cells protected mice from IAV-induced mortality. H1N1-infected Mmp-9-/- lung epithelial cells had lower viral titers than H1N1-infected WT cells in vitro. Thus, H1N1-infected Mmp-9-/- mice are protected from IAV-induced lung disease due to a more effective adaptive immune response to IAV and reduced epithelial barrier injury due partly to reduced E-cadherin shedding. Thus, we believe that MMP-9 is a novel therapeutic target for IAV infections.


Intravenous therapy in older patients.
Intravenous therapy is available in a variety of settings and for patients of all ages. Therefore, it is essential that nurses have the clinical knowledge and technical expertise to carry out this procedure and care for patients, particularly those who are vulnerable, such as older people. This article provides an overview of the anatomy and physiology of the skin and veins. Considerations for improving venous access, selection and insertion of a peripheral cannula, and recognition, prevention and management of complications in older people are discussed. Alternative routes for the administration of fluids and medications are also explored.


IL-21 in Homeostasis of Resident Memory and Exhausted CD8 T Cells during Persistent Infection.
CD4 T cells guide the development of CD8 T cells into memory by elaborating mitogenic and differentiation factors and by licensing professional antigen-presenting cells. CD4 T cells also act to stave off CD8 T cell dysfunction during repetitive antigen stimulation in persistent infection and cancer by mitigating generation of exhausted T cells (TEX). CD4 T cell help is also required for establishing and maintaining tissue-resident memory T cells (TRM), the nonrecirculating memory T cell subset parked in nonlymphoid tissues to provide frontline defense against reinvading pathogens. Interleukin (IL)-21 is the signature cytokine secreted by follicular helper CD4 T cells (TFH) to drive B cell expansion and differentiation in germinal centers to mount high-affinity, isotype class-switched antibodies. In several infection models, IL-21 has been identified as the CD4 T help needed for formation and survival of TRM and TEX. In this review, we will explore the different memory subsets of CD8 T cells in persistent infections, the metabolic profiles associated with each, and evidence documenting the importance of CD4 T cell-derived IL-21 in regulating CD8 TRM and TEX development, homeostasis, and function.


Comparison of detection sensitivity of immuno- and genotoxicological effects of subacute cypermethrin and permethrin exposure in rats.
Immuno- and genotoxicological effects of a 28-day oral treatment by equitoxic (1/10, 1/25, 1/50 LD50) doses of cypermethrin (55.4, 22.2, and 11.1 mg/kg) and permethrin (125.7, 50.3, and 12.6 mg/kg) were compared on male Wistar rats. Humoral and cell-mediated immunity were investigated by PFC assay and delayed type hypersensitivity (DTH) reaction (footpad swelling assay), and the genotoxic effects were studied by structural and numerical chromosome aberrations in bone marrow cells. The experimental system also involved certain general toxicological (body weight gain, organ weights) and haematological [white blood cell (WBC), red blood cell (RBC), haematocrit (Ht) and cell content of the femoral bone marrow] investigations. Among the immune function assays, only DTH reaction decreased at the two higher cypermethrin (CY) doses. These doses also increased the number of numerical chromosome aberrations of the bone marrow cells but did not change the number of structural aberrations. All CY doses decreased the mean cell volume (MCV) of RBCs and the Ht value. The two higher doses also reduced the WBC count in the peripheral blood. Permethrin (PE), in the applied dose range, had no effect on the examined immune function parameters, but all three doses increased the number of numerical chromosome aberrations. A dose-dependent increase in the liver weight, decreased MCV value, and elevated cell content of the femoral bone marrow were also observed. Under these experimental conditions, examination of chromosome aberrations proved to be less sensitive in detection of exposure by cypermethrin than applied immune function assays did. Permethrin, on the contrary, increased the number of numeric aberrations at all dose levels but had no effect on the immune function parameters examined.


[Molecular mechanisms behind the immunological reaction against gluten in patients with celiac disease].
Coeliac disease is a complex inflammatory disorder of the small intestine, induced by dietary gluten in genetically susceptible individuals. Recently, the nature of gluten-derived peptides recognized by gut-derived T cells from patients has been elucidated. It has further been established that the binding of such peptides to HLA-DQ2 and DQ8 molecules is enhanced following the modification of the peptides by the ubiquitous enzyme tissue transglutaminase. This knowledge has allowed the establishment of a molecular basis for the well-known association between coeliac disease and the expression of these HLA-molecules. This article summarizes the latest progress in coeliac disease molecular biology.


Formula-Feeding of HIV-Exposed Uninfected African Children Is Associated with Faster Growth in Length during the First 6 Months of Life in the Kesho Bora Study.
Background: Early feeding patterns may affect the growth of HIV-exposed children and thus their subsequent health and cognition.Objective: We assessed the association of infant feeding (IF) mode with length-for-age z score (LAZ) and stunting from age 2 d to 18 mo in HIV-exposed African children within a controlled randomized trial, which evaluated triple antiretrovirals initiated during pregnancy and continued for 6 mo postpartum to prevent HIV transmission.Methods: HIV-infected pregnant women with CD4+ counts of 200-500 cells/mm3 from Burkina Faso, Kenya, and South Africa were advised to exclusively breastfeed for up to 6 mo or to formula-feed from birth. Factors associated with LAZ were investigated in all uninfected children by using mixed-effects linear models; those associated with stunting (LAZ <-2) at 6 or 12 mo were assessed in multiple logistic regression after exclusion of children stunted at age 2 d. Independent variables were IF mode: formula feeding (FF), exclusive breastfeeding (EBF) <3 mo, or EBF ≥3 mo (reference); sex; trial arm; maternal characteristics; and site.Results: Among 728 children, FF was associated with a greater increase in LAZ from 2 d to 6 mo (+0.07 z score/mo, P < 0.001). Between 6 and 18 mo, FF and EBF <3 mo were both associated with greater mean LAZ than was EBF ≥3 mo (+0.52 z scores and +0.43 z scores, respectively, P < 0.001). Among children not stunted at 2 d, FF was independently associated with a reduced risk of stunting at 6 mo (OR: 0.24; 95% CI: 0.07, 0.81; P = 0.021), whereas EBF <3 mo was not (OR: 0.49; 95% CI: 0.22, 1.10; P = 0.09).Conclusions: In this observational study of HIV-exposed uninfected infants, growth in length in the first 6 mo of life was faster in formula-fed infants than in exclusively breastfed infants. The plausibility of residual confounding and reverse causality is discussed. This trial was registered at www.controlled-trials.com as ISRCTN71468401.


The Role of Prevolitional Processes in Video Game Playing: A Test of the Model of Goal-Directed Behavior and the Extended Model of Goal-Directed Behavior.
The aim of the current study is to investigate the relationship between prevolitional processes and video game playing. Models of attitude, the model of goal-directed behavior (MGB) and the extended model of goal-directed behavior (EMGB) are tested with structural equation models to analyze the process that leads to video game playing. More specifically, the roles of affective, motivational, habitual processes in video game playing and the goal underlying video game playing are examined. The participants were 210 video game players who completed measures of Attitude, Subjective Norms, Perceived Behavioral Control, Behavioral Desire, Anticipated Emotions, Intention to Play, intensity of actual and past video game playing (Playing Behavior and Past Playing Behavior) and Goal Desire. The results showed that the initial MGB did not achieve a satisfactory fit and thus, a revised model with more acceptable fit was proposed. It was found that anticipated emotions and attitude are significant predictors of desire to play; desire to play, perceived behavioral control, subjective norms and attitude are significant predictors of intention to play and intention is a significant predictor of playing behavior (actual playing time). Moreover, past playing is a stronger significant predictor of behavior itself than of prevolitional processes in video game playing. Goal desire within the EMGB is a significant predictor of desire to play and the relationship of goal to playing behavior is indirect. Nevertheless, goal desire has an important role in the prevolitional processes of video game playing. In the discussion, potential explanations are further explored.


Late pulmonary toxicity after treatment for Hodgkin's disease.
The combination of mediastinal radiotherapy (RT) with chemotherapy (CT) including bleomycin is associated with an increased risk of pulmonary toxicity. The aim of the present investigation was to evaluate late pulmonary effects of RT plus CT consisting of the ABVD regimen in patients suffering from early stage Hodgkin's disease. For this purpose pulmonary function was serially evaluated before, at the end and at least 1 year after therapy in 32 patients (median age 28 years) with Hodgkin's disease stages IA,B-IIA. Treatment consisted of four cycles of ABVD chemotherapy followed by mediastinal irradiation at the median dose of 36 Gy (range 30.6-43.2). At the end of treatment, resting mean pulmonary function tests showed a significant decline of forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25-75%, (FEF25-75%), total lung capacity (TLC), vital capacity (VC) and carbon monoxide diffusing capacity (DLCO). The decline of TLC, VC and DLCO, indicative of a pulmonary defect of restrictive type, persisted 1 year from the end of therapy. Only seven patients developed symptoms of cough and mild shortness of breath with effort. These data confirm that RT combined with short term ABVD result in pulmonary dysfunction that does not seem to have clinical significance.


Clinical efficacy of three assays for cardiac troponin I for risk stratification in acute coronary syndromes: a Thrombolysis In Myocardial Infarction (TIMI) 11B Substudy.
Significant analytic variability exists between the multiple assays for cardiac troponin I (cTnI) approved for clinical use. Until adequate cTnI standardization is possible, an evidence-based approach evaluating each assay at specific thresholds appears warranted. We examined the efficacy of three cTnI assays for predicting death, myocardial infarction (MI), or the composite of death, MI, or urgent revascularization at 43 days among patients with non-ST-elevation acute coronary syndromes enrolled in the Thrombolysis In Myocardial Infarction (TIMI) 11B study. Six hundred eighty-one patients with serum samples obtained at baseline and/or 12-24 h had cTnI determined using all three assays. Baseline cTnI was > or = 0.1 microg/L for 368, 395, and 418 patients with the Bayer Immuno 1(TM), ACS:180, and Dimension RxL assays, respectively. Correlation coefficients for the RxL with the ACS:180 and Bayer Immuno 1 results were 0.89 (P = 0.0001) and 0.87 (P = 0.0001), with a coefficient of 0.92 (P = 0.0001) for the ACS:180 and Bayer Immuno 1 assays. Patients with cTnI > or = 0.1 microg/L were at increased risk fo death or MI by 43 days (relative risk, 2.2-3.0; P <0.0006), regardless of the assay used. This prognostic capacity persisted among those with creatine kinase MB isoenzyme concentrations within the reference interval. Moreover, cTnI was the strongest multivariate predictor of death, MI, or urgent revascularization with adjusted odds ratios of 2.1-2.9 (P <0. 0006). This study demonstrates the prognostic efficacy of three independently developed cTnI assays at a threshold of 0.1 microg/L for the prediction of adverse clinical outcomes among patients with non-ST-elevation acute coronary syndromes.


The construction of Chasma Boreale on Mars.
The polar layered deposits of Mars contain the planet's largest known reservoir of water ice and the prospect of revealing a detailed Martian palaeoclimate record, but the mechanisms responsible for the formation of the dominant features of the north polar layered deposits (NPLD) are unclear, despite decades of debate. Stratigraphic analyses of the exposed portions of Chasma Boreale-a large canyon 500 km long, up to 100 km wide, and nearly 2 km deep-have led most researchers to favour an erosional process for its formation following initial NPLD accumulation. Candidate mechanisms include the catastrophic outburst of water, protracted basal melting, erosional undercutting, aeolian downcutting and a combination of these processes. Here we use new data from the Mars Reconnaissance Orbiter to show that Chasma Boreale is instead a long-lived, complex feature resulting primarily from non-uniform accumulation of the NPLD. The initial valley that later became Chasma Boreale was matched by a second, equally large valley that was completely filled in by subsequent deposition, leaving no evidence on the surface to indicate its former presence. We further demonstrate that topography existing before the NPLD began accumulating influenced successive episodes of deposition and erosion, resulting in most of the present-day topography. Long-term and large-scale patterns of mass balance achieved through sedimentary processes, rather than catastrophic events, ice flow or highly focused erosion, have produced the largest geomorphic anomaly in the north polar ice of Mars.


Phosphatidylcholine-specific phospholipase C and sphingomyelinase activities in bacteria of the Bacillus cereus group.
Bacillus anthracis is nonhemolytic, even though it is closely related to the highly hemolytic Bacillus cereus. Hemolysis by B. cereus results largely from the action of phosphatidylcholine-specific phospholipase C (PC-PLC) and sphingomyelinase (SPH), encoded by the plc and sph genes, respectively. In B. cereus, these genes are organized in an operon regulated by the global regulator PlcR. B. anthracis contains a highly similar cereolysin operon, but it is transcriptionally silent because the B. anthracis PlcR is truncated at the C terminus. Here we report the cloning, expression, purification, and enzymatic characterization of PC-PLC and SPH from B. cereus and B. anthracis. We also investigated the effects of expressing PlcR on the expression of plc and sph. In B. cereus, PlcR was found to be a positive regulator of plc but a negative regulator of sph. Replacement of the B. cereus plcR gene by its truncated orthologue from B. anthracis eliminated the activities of both PC-PLC and SPH, whereas introduction into B. anthracis of the B. cereus plcR gene with its own promoter did not activate cereolysin expression. Hemolytic activity was detected in B. anthracis strains containing the B. cereus plcR gene on a multicopy plasmid under control of the strong B. anthracis protective antigen gene promoter or in a strain carrying a multicopy plasmid containing the entire B. cereus plc-sph operon. Slight hemolysis and PC-PLC activation were found when PlcR-producing B. anthracis strains were grown under anaerobic-plus-CO(2) or especially under aerobic-plus-CO(2) conditions. Unmodified parental B. anthracis strains did not demonstrate obvious hemolysis under the same conditions.


Zeolitic imidazolate framework-8/polyaniline nanocomposite-based electrochemical sensor for sensitive detection of imidaclothiz.
Imidaclothiz (IMZ) is a class of neonicotinoid insecticide which can pose potential threat to human health and be frequently detected in water and foods. Herein, a zeolitic imidazolate framework-8/polyaniline (ZIF-8/PANI) nanocomposite has been modified on the surface of glassy carbon electrode (GCE) for the electrochemical determination of IMZ, and the electrochemical detection performance of the modified electrode was investigated by cyclic voltammetry (CV) and square wave voltammetry (SWV). With the large surface area of ZIF-8 and great electric conductivity of PANI, the ZIF-8/PANI-modified electrode showed a high catalytic performance towards IMZ reduction in PBS. Under the optimized conditions, the linear range was from 1.0 × 10-7 to 1.0 × 10-5 mol/L and the limit of detection was as low as 2.5 × 10-8 mol/L (S/N = 3). In addition, the developed sensor displayed high reproducibility, excellent stability, and applicability in real vegetable sample analysis, indicating that the proposed method offered an alternative approach for IMZ residues analysis.


The Sternum-Nipple Distance is Double the Nipple-Inframammary Fold Distance in Macromastia.
Reduction mammaplasty is one of the most commonly performed plastic surgery operations. For a majority of techniques, the most common long-term complication is pseudoptosis. It has previously been proposed that upper breast suspensory ligaments (SL) are weaker than lower breast SL. We tested this hypothesis through anthropometry of the proxies for upper and lower SL strength: the sternal notch-nipple (SN-N) distance and the nipple-inframammary fold (N-IMF) distance, respectively. An institutional review board-approved retrospective review of patients undergoing reduction mammoplasty in an academic faculty practice between 2008 and 2015 was conducted. Patient demographics included age, race, and body mass index (BMI); patient comorbidities included smoking status, diabetes, and hypertension. Breast anthropometric measurements included SN-N and N-IMF. Sternal notch-nipple was used as the primary metric of the upper SL strength, whereas N-IMF was used as the primary metric of the lower SL strength. Intraoperative details included reduction technique and resection mass. Postoperative complications were recorded, including nipple areola complex necrosis and hematoma. Linear regression analysis was performed with the primary endpoint of the relationship between SN-N and N-IMF distance in macromastia. Data from 208 patients, totaling 400 individual breast measurements, were collected. The mean SN-N length was 35.1 cm, mean N-IMF length was 16.0 cm, and mean resection weight was 1094 g. Linear regression found that N-IMF distance could be predicted as 45% of the SN-N distance (N-IMF = 0.454 * SN-N). This was a strong relationship, demonstrated by univariate analysis of SN-N and N-IMF (R, 0.624; P < 0.001). A Wise pattern was used in 89.9% of cases; an inferior pedicle was used in 83.7% of cases. Nipple areola complex necrosis occurred in 15 breasts (3.75%). Sternal notch-nipple (R, 0.127; P = 0.011) and N-IMF (R, 0.119; P = 0.017) were both predictive of nipple areola complex necrosis (Table 4). In our series, the N-IMF distance increased 0.45 cm for every 1 cm increase in the SN-N distance. This relationship strengthens our primary hypothesis that the lower pole ligaments stretch at a significantly slower rate than the upper pole ligaments. Taking this into consideration, we suggest that surgeons seeking to minimize pseudoptosis rates should favor techniques that minimally disrupt the lower SL.


Acute lipotoxicity regulates severity of biliary acute pancreatitis without affecting its initiation.
Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O-positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate-induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction.