Loss of a callose synthase results in salicylic acid-dependent disease resistance.
Plants attacked by pathogens rapidly deposit callose, a beta-1,3-glucan, at wound sites. Traditionally, this deposition is thought to reinforce the cell wall and is regarded as a defense response. Surprisingly, here we found that powdery mildew resistant 4 (pmr4), a mutant lacking pathogen-induced callose, became resistant to pathogens, rather than more susceptible. This resistance was due to mutation of a callose synthase, resulting in a loss of the induced callose response. Double-mutant analysis indicated that blocking the salicylic acid (SA) defense signaling pathway was sufficient to restore susceptibility to pmr4 mutants. Thus, callose or callose synthase negatively regulates the SA pathway.


External fixation of tibial fractures.
External fixation for definitive or initial management of tibial fractures has a long history, with pin-to-bar external fixation being the standard of care for definitive management. However, the use of this method has lessened because of the increased popularity of intramedullary nailing and drawbacks associated with external fixation. This method is still commonly used in the military environment and can be used for temporary stabilization of tibial fractures, especially in the setting of periarticular injuries. These fixators also may be useful for salvage of open and/or infected fractures that are unsuitable for internal fixation.


Action Recognition by an Attention-Aware Temporal Weighted Convolutional Neural Network.
Research in human action recognition has accelerated significantly since the introduction of powerful machine learning tools such as Convolutional Neural Networks (CNNs). However, effective and efficient methods for incorporation of temporal information into CNNs are still being actively explored in the recent literature. Motivated by the popular recurrent attention models in the research area of natural language processing, we propose the Attention-aware Temporal Weighted CNN (ATW CNN) for action recognition in videos, which embeds a visual attention model into a temporal weighted multi-stream CNN. This attention model is simply implemented as temporal weighting yet it effectively boosts the recognition performance of video representations. Besides, each stream in the proposed ATW CNN framework is capable of end-to-end training, with both network parameters and temporal weights optimized by stochastic gradient descent (SGD) with back-propagation. Our experimental results on the UCF-101 and HMDB-51 datasets showed that the proposed attention mechanism contributes substantially to the performance gains with the more discriminative snippets by focusing on more relevant video segments.


Criminal recidivism among justice-involved veterans following substance use disorder residential treatment.
Veterans in treatment for substance use disorders (SUD) often report past criminal offending. However, the rate of criminal recidivism in this population is unknown. Further, prior research in veterans has not examined personality factors as predictors of recidivism, despite the prominence of such factors in leading models of recidivism risk management. We examined these issues in a secondary data analysis of 197 military veterans with a history of criminal offending who were enrolled in an SUD residential treatment program. Participants were interviewed using several measurement instruments at treatment entry, one month into treatment, treatment discharge, and 12 months post-discharge. Most veterans (94%) had a history of multiple charges, and 53% had recent involvement in the criminal justice system at the time of treatment entry. In the 12 months post-discharge, 22% reported reoffending. In addition, 30% of patients who had been recently involved in the criminal justice system at treatment entry reoffended during follow-up. Higher friend relationship quality (OR = 2.32, 95% CI [1.03, 5.21]) at treatment entry and higher staff ratings of patients' relationship quality with other residents during treatment (OR = 2.76, 95% CI [1.40, 5.41]) predicted lower odds of recidivism post-discharge. After accounting for these factors, smaller reductions during treatment in the personality trait of Negative Emotionality predicted an increased risk for criminal recidivism post-discharge (OR = 1.13, 95% CI [1.01, 1.26]). Results support augmenting the curriculum of SUD programs for veterans with services aimed at reducing risk for criminal recidivism, with a focus on interventions that directly target patients' social support networks and tendencies towards negative emotionality.


Embarking with laparoscopic radical prostatectomy and dealing with the complications and collateral problems: A single-center experience.
The aim of the present study was to report our single-center initial experience in laparoscopic radical prostatectomy (LRP) with special emphasis on the complications and collateral problems and their management. A total of 48 patients (mean age 64 years) underwent LRP in our institution between August 2014 and July 2018. Two surgeons completed a fellowship training program for LRP before. Mentored operations started after the first 10 cases. The patients were divided in two groups of 30 (group I) and 18 (group II) patients. Demographic, preoperative, peroperative, and postoperative data were collected prospectively. Anesthesiology and nurses' team performances, as well as problems and their management, were reviewed. The demographic data for both groups (group I vs. group II) were similar. Estimated blood loss (695.5±139.23 vs. 398±339.39 mL) and intraoperative complication rates (36.66% vs. 5.55%) were significantly (p<0.05) higher in group I. Conversion to open surgery occurred in 7 (20%) patients in group I and in 1 (5.55%) patient in group II. Continence rates at 12 (83%) months were similar in both groups. Positive surgical margins were 8.33% for pT2 and 27.1% for pT3 stages. A validated fellowship program before starting LRP and performing the first cases under mentorship are helpful. The complication and conversion rates decrease after 30 cases in addition to the improved experience also with improved cooperation with the anesthesiologist and scrub nurse.


Transanal polypectomy using single incision laparoscopic instruments.
Transanal excision of rectal polyps with laparoscopic instrumentation and a single incision laparoscopic port is a novel technique that uses technology originally developed for abdominal procedures from the natural orifice of the rectum. Transanal endoscopic microsurgery (TEM) is a well established surgical approach for certain benign or early malignant lesions of the rectum, under specific indications. Our technique is a hybrid technique of transanal surgery, a reasonable method for polyp resection without the need of the sophisticated and expensive instrumentation of TEM which can be applied whenever endoscopic or conventional transanal surgical removal is not feasible.


Extractive concentrations and cellular-level distributions change radially from outer to inner heartwood in Scots pine.
The heartwood of many wood species is rich in extractives, which improve the wood material's resistance to biological attack. Their concentration is generally higher in outer than inner heartwood, but the exact radial changes in aging heartwood remain poorly characterized. This investigation studied these radial changes in detail in Scots pine (Pinus sylvestris L.), using radial sample sequences prepared from three different trees. Stilbene and resin acid contents were first measured from bulk samples, after which the extractive contents of individual heartwood annual rings were investigated using Raman spectroscopy and fluorescence microscopy. Raman imaging and fluorescence microscopy were also used to study the cellular-level distributions of extractives in different annual rings. Although there were substantial differences between the trees, the content and distribution of stilbenes seemed to follow a general radial trend. The results suggest that stilbenes are absorbed into heartwood tracheid cell walls from small stilbene-rich extractive deposits over several years and then eventually transform into non-extractable compounds in aging heartwood. Resin acids followed no consistent radial trends, but their content was strongly connected to the frequency of large extractive deposits in latewood tracheid lumens. The results highlight the variability of heartwood extractives: their content and distribution vary not only between trees but also between and even within the annual rings of a single tree. This high variability is likely to have important effects on the properties of heartwood and the utilization of heartwood timber.


Immune response in lymphocyte cultures stimulated by oral bacteria preparations.
Lymphocyte cultures were used as an in vitro experimental model to get a deeper insight into immune response to oral bacteria in periapical granulomas. Lymphocytes isolated from leucocyte concentrate were in lymphocyte cultures stimulated by antigen preparations of oral bacteria. Lymphocyte subsets that have developed in lymphocyte cultures after a week of stimulation were analysed by flow cytometry. A significant increase in expression of INF-gamma molecules in CD3+ cells stimulated by antigen preparations of oral streptococci was found, compared with negative control. On the other hand we observed a significant increase in expression of IL-4 in CD3+ cells stimulated by antigens of anaerobic bacteria, compared with negative control. Our results show that antigens of oral streptococci in in vitro lymphocyte cultures induce the differentiation of T helper cells into Th2 cells and that antigen preparations of anaerobic bacteria induce the differentiation of T helper cells into Th1 cells. Furthermore, an increased expression of HLA-DR molecules on CD8+ T cells stimulated by antigens of oral streptococci was found, compared with negative control.


A Review of Impact of Tobacco Use on Patients with Co-occurring Psychiatric Disorders.
Consumption of tobacco has been a worldwide problem over the past few decades due to the highly prevalent tobacco-attributable complications. Tobacco use has also been found to be more prevalent in patients with psychiatric disorders. Therefore, we conducted this review about the impact of tobacco use on co-occurring psychiatric disorders. Various facets of this interaction between tobacco use among those with co-occurring psychiatric disorders have been explored. It has been found that people with psychiatric disorders have a higher chance of currently smoking tobacco and lesser chance of cessation. Tobacco use and mental disorders continue to share a complex relationship that has been further evolving after the change in the pattern of tobacco use and also the advent of newer modalities of treatment. However, at the same time, it is believed that cessation of smoking may lead to improvement in the symptoms of mental illness.


Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review.
Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.


Health professionals' views on advance directives: a qualitative interdisciplinary study.
The aim of this study was to discover the views of health professionals in the Greater Glasgow area on advance directives, using semi-structured interviews and focus groups. The twelve participants interviewed included four hospital doctors, four general practitioners (GPs) and four nurses. The six focus groups comprised hospice nurses, GPs, consultant geriatricians, geriatricians in training grades and an interdisciplinary group. Participants were purposively selected to reflect a range of personal experiences with, and attitudes toward, the advance directive using key informants and a short questionnaire. Participants were asked to comment on a specially constructed sample advance directive. All research encounters were recorded, transcribed and analysed using accepted methods in qualitative research. The advance directive was seen as a means of promoting peace of mind in will makers, of allowing carers to honour the patients' wishes and of stimulating communication between all parties. Conversely the advance directive was seen as generating certain risks for the will maker--including those of coercion, misunderstanding, paradoxical overintervention and inadvertent undertreating. A core concern surrounded the issue of 'informedness' in will makers and the ethics of deciding for a future demented self.


Characterisation of CYP2C8, CYP2C9 and CYP2C19 polymorphisms in a Ghanaian population.
Genetic influences on drug efficacy and tolerability are now widely known. Pharmacogenetics has thus become an expanding field with great potential for improving drug efficacy and reducing toxicity. Many pharmacologically-relevant polymorphisms do show variability among different populations. Knowledge of allelic frequency distribution within specified populations can be useful in explaining therapeutic failures, identifying potential risk groups for adverse drug reactions (ADRs) and optimising doses for therapeutic efficacy. We sought to determine the prevalence of clinically relevant Cytochrome P450 (CYP) 2C8, CYP2C9, and CYP2C19 variants in Ghanaians. We compared the data with other ethnic groups and further investigated intra country differences within the Ghanaian population to determine its value to pharmacogenetics studies. RFLP assays were used to genotype CYP2C8 (*2, *3, *4) variant alleles in 204 unrelated Ghanaians. CYP2C9*2 and CYP2C19 (*2 and *3) variants were determined by single-tube tetra-primer assays while CYP2C9 (*3, *4, *5 and *11) variants were assessed by direct sequencing. Allelic frequencies were obtained for CYP2C8*2 (17%), CYP2C8*3 (0%), CYP2C8*4 (0%), CYP2C9*2 (0%), CYP2C9*3 (0%), CYP2C9*4 (0%), CYP2C9*5 (0%), CYP2C9*11 (2%), CYP2C19*2 (6%) and CYP2C19*3 (0%). Allele frequency distributions for CYP2C8, CYP2C9 and CYP2C19 among the Ghanaian population are comparable to other African ethnic groups but significantly differ from Caucasian and Asian populations. Variant allele frequencies for CYP2C9 and CYP2C19 are reported for the first time among indigenous Ghanaian population.


100% orange juice consumption is associated with better diet quality, improved nutrient adequacy, decreased risk for obesity, and improved biomarkers of health in adults: National Health and Nutrition Examination Survey, 2003-2006.
Consumption of 100% orange juice (OJ) has been positively associated with nutrient adequacy and diet quality, with no increased risk of overweight/obesity in children; however, no one has examined these factors in adults. The purpose of this study was to examine the association of 100% OJ consumption with nutrient adequacy, diet quality, and risk factors for metabolic syndrome (MetS) in a nationally representative sample of adults. Data from adults 19+ years of age (n = 8,861) participating in the National Health and Nutrition Examination Survey 2003-2006 were used. The National Cancer Institute method was used to estimate the usual intake (UI) of 100% OJ consumption, selected nutrients, and food groups. Percentages of the population below the Estimated Average Requirement (EAR) or above the Adequate Intake (AI) were determined. Diet quality was measured by the Healthy Eating Index-2005 (HEI-2005). Covariate adjusted logistic regression was used to determine if consumers had a lower odds ratio of being overweight or obese or having risk factors of MetS or MetS. Usual per capita intake of 100% OJ was 50.3 ml/d. Among consumers (n = 2,310; 23.8%), UI was 210.0 ml/d. Compared to non-consumers, consumers had a higher (p < 0.05) percentage (% ± SE) of the population meeting the EAR for vitamin A (39.7 ± 2.5 vs 54.0 ± 1.2), vitamin C (0.0 ± 0.0 vs 59.0 ± 1.4), folate (5.8 ± 0.7 vs 15.1 ± 0.9), and magnesium (51.6 ± 1.6 vs 63.7 ± 1.2). Consumers were also more likely to be above the AI for potassium (4.1 ± 0.8 vs 1.8 ± 0.2). HEI-2005 was significantly (p < 0.05) higher in consumers (55.0 ± 0.4 vs 49.7 ± 0.3). Consumers also had higher intakes of total fruit, fruit juice, whole fruit, and whole grain. Consumers had a lower (p < 0.05) mean body mass index (27.6 ± 0.2 vs 28.5 ± 0.1), total cholesterol levels (197.6 ± 1.2 vs 200.8 ± 0.75 mg/dL), and low density lipoprotein-cholesterol levels (112.5 ± 1.4 vs 116.7 ± 0.93 mg/dL). Finally, compared to non-consumers of 100% OJ, consumers were 21% less likely to be obese and male consumers were 36% less likely to have MetS. The results suggest that moderate consumption of 100% OJ should be encouraged to help individuals meet the USDA daily recommendation for fruit intake and as a component of a healthy diet.


Prosthodontic implications of saliva and salivary gland dysfunction.
To provide a detailed overview of the fundamentals of saliva constituents and production. The review outlines the clinical manifestations as a consequence of salivary gland dysfunction and management strategies for patients with salivary gland dysfunction. Prosthodontic implications of saliva and salivary gland dysfunction are presented. English-language literature relating to saliva constituents, physiologic saliva production, clinical manifestations secondary to salivary gland dysfunction, salivary biomarkers, and management strategies were retrieved via electronic search. Relevant articles were summarized for this manuscript with a view toward providing pragmatic information. Saliva is produced by three pairs of major and minor salivary glands. The major salivary glands, namely, the parotid, submandibular, and sublingual glands, contribute approximately 90% of saliva production. Saliva contains serous and mucinous secretions produced by different types of cells within salivary glands. Parasympathetic and sympathetic fibers innervate the major salivary glands, and upon stimulation, the parasympathetic innervation increases serous secretions, while the sympathetic innervation increases protein secretion. Stimulated saliva is mainly derived from the parotid glands which are composed of serous acini, while unstimulated saliva is mainly derived from the submandibular glands which are composed of mixed seromucous acini. As major salivary glands contribute the most to salivary flow, local or systemic factors influencing those glands can disrupt saliva production resulting in clinically significant oral manifestations. This review provides a fundamental overview of saliva production. In addition, the review highlights the various clinical manifestations secondary to salivary gland dysfunction, explores salivary biomarkers for screening of systemic diseases, discusses management strategies for patients with salivary gland dysfunction, and outlines the prosthodontic implications of saliva and salivary gland dysfunction.


Relationship between resilience, social support as well as anxiety/depression of lung cancer patients: A cross-sectional observation study.
The mood of patients with lung carcinoma would be greatly influenced by the diagnosing and treating processes. This study was aimed to explore the effects of resilience between social assistance and anxiety/depression of patients with lung cancer, which may assist in clinical intervention. A cross-sectional pilot study was conducted on lung cancer patients at Xiangya Hospital of Central South University, China. A total of 289 patients aged 25-81 years were included in this study. Correlational analyses revealed that anxiety/depression was negatively associated with psychological resilience and each dimension of social assistance, including subjective support, objective support along with the supports utilization (P < 0.01). Furthermore, psychological resilience was positively related to subjective support (P < 0.01), support utilization (P < 0.01) along with objective support (P < 0.05). Mediational analyses showed that, on the one hand, resilience could partially mediate the relation between anxiety and subjective support and totally mediate the relationship between support utilization and anxiety. On the other hand, resilience could totally mediate the relation between depression and subjective support and partially mediate the relation between support utilization and depression. However, resilience did not play an intermediary role between anxiety/depression and objective support. Lower psychological anxiety and depression would be experienced by lung cancer patients with higher resilience and social support. The level of anxiety and depression would be indirectly affected by social support through the mediation of resilience.


Characterisation of a novel poly (ether ether ketone)/calcium sulphate composite for bone augmentation.
Calcium sulphate (CS) has been used in bone grafting since the 1800s. It has not replaced autograft as the gold standard, however, since its dissolution occurs rapidly in bodily fluids, meaning that the material cannot support long-term bone growth. Here, the polymer poly (ether ether ketone) (PEEK) was used to slow dissolution in in vitro physiological environments and augment the mechanical properties of the material. PEEK/CS specimens were fabricated by combining powders of PEEK and CS with water, resulting in a hardening paste. To enhance physical interactions between phases, cylindrical specimens were heat-treated to melt and fuse the PEEK. Following analysis of physical and chemical interactions by SEM and FT-IR respectively, dynamic ageing in PBS and compression testing was undertaken to measure how the PEEK influenced the mechanical properties of the final parts. Changes in structure and chemistry were determined using helium pycnometry, SEM and analysis of powder XRD patterns. Powders of PEEK and CS hemihydrate (CSH) (CaSO4.0.5H2O) were combined with PEEK at 0 wt%, 2.5 wt%, 20 wt%, 40 wt% and 80 wt% and at a P:L ratio of 0.85 g/mL. The subsequently hardened structures were heat-treated, which initiated the melting of PEEK and dehydration of CSD (CaSO4.2H2O) to the CS anhydrite (CSA) (CaSO4) phase, which changed colour and apparent volume. FT-IR and SEM analysis revealed heat treatment of PEEK/CS specimens facilitated both physical and chemical interactions between phases. Over a period of 21 days of ageing in PBS, the hydration of CS was determined by XRD and improved specimen longevity at all levels of PEEK wt% loading was measured compared with the control. Importantly, increasing PEEK wt% loading resulted in a marked increase in the mechanical properties of PEEK/CS specimens in terms of both compressive strength and modulus. Reinforcement of CS with PEEK significantly enhanced in vitro dissolution resistance, in addition to enhancing mechanical properties. This composite therefore has significant future potential as a bone graft replacement.


Disruption of genes encoding eIF4E binding proteins-1 and -2 does not alter basal or sepsis-induced changes in skeletal muscle protein synthesis in male or female mice.
Sepsis decreases skeletal muscle protein synthesis in part by impairing mTOR activity and the subsequent phosphorylation of 4E-BP1 and S6K1 thereby controlling translation initiation; however, the relative importance of changes in these two downstream substrates is unknown. The role of 4E-BP1 (and -BP2) in regulating muscle protein synthesis was assessed in wild-type (WT) and 4E-BP1/BP2 double knockout (DKO) male mice under basal conditions and in response to sepsis. At 12 months of age, body weight, lean body mass and energy expenditure did not differ between WT and DKO mice. Moreover, in vivo rates of protein synthesis in gastrocnemius, heart and liver did not differ between DKO and WT mice. Sepsis decreased skeletal muscle protein synthesis and S6K1 phosphorylation in WT and DKO male mice to a similar extent. Sepsis only decreased 4E-BP1 phosphorylation in WT mice as no 4E-BP1/BP2 protein was detected in muscle from DKO mice. Sepsis decreased the binding of eIF4G to eIF4E in WT mice; however, eIF4E•eIF4G binding was not altered in DKO mice under either basal or septic conditions. A comparable sepsis-induced increase in eIF4B phosphorylation was seen in both WT and DKO mice. eEF2 phosphorylation was similarly increased in muscle from WT septic mice and both control and septic DKO mice, compared to WT control values. The sepsis-induced increase in muscle MuRF1 and atrogin-1 (markers of proteolysis) as well as TNFα and IL-6 (inflammatory cytokines) mRNA was greater in DKO than WT mice. The sepsis-induced decrease in myocardial and hepatic protein synthesis did not differ between WT and DKO mice. These data suggest overall basal protein balance and synthesis is maintained in muscle of mice lacking both 4E-BP1/BP2 and that sepsis-induced changes in mTOR signaling may be mediated by a down-stream mechanism independent of 4E-BP1 phosphorylation and eIF4E•eIF4G binding.


Immunonutrition before esophagectomy: Impact on immune surveillance mechanisms.
Preoperative oral immunonutrition was demonstrated to improve immune response and to decrease the infection rate in patients with cancer. This study aimed to assess how immunonutrition could influence the immune cell response in the mucosal microenvironment of esophageal adenocarcinoma. Therefore, A prospective cohort of consecutive patients undergoing esophagectomy for esophageal adenocarcinoma was enrolled. A subgroup of them was given preoperative oral immunonutrition with Oral Impact® and was compared to those who received no preoperative supplementation. Mucosal samples from healthy esophagus were obtained at esophagectomy. Histology, immunohistochemistry, gene expression analysis, and cytofluorimetry were performed. Markers of activation of antigen-presenting cells (CD80, CD86, and HLA-I), innate immunity (TLR4 and MyD88), and cytotoxic lymphocyte infiltration and activation (CD8, CD38, CD69, and CD107) were measured. In all, 50 patients received preoperative Oral Impact® and 129 patients received no nutritional support. CD80, CD86, MyD88, and CD69 messenger RNA expression was significantly increased in patients receiving immunonutrition compared to controls. In the subgroup of patients with stages I-II cancer, the rate of epithelial cells expressing CD80 and HLA-ABC was significantly higher in those receiving immunonutrition compared to controls as well as CD8+ CD28+ cell rate. Immunonutrition administration before surgery was significantly associated to increased degranulating CD8 and natural killer cells (CD107+) infiltrating the healthy esophageal mucosa. All the comparisons were adjusted for cancer stage and preoperative therapy. In conclusion, in healthy esophageal mucosa of patients undergoing esophagectomy, a 5-day course of immunonutrition enhances expression of antigen-presenting cells activity and increased CD8+ T cell activation and degranulating activity. Further studies are warranted to understand the clinical implication in terms of cancer recurrence.


Modified Functional Superficial Parotidectomy With Ligation of the Major Branch of the Parotid Duct Extending to the Superficial Lobe.
A functional superficial parotidectomy can maintain salivary function by preserving the Stensen duct. However, this technique still brings the possibility of salivary leakage, because major branches of the parotid duct from the resected site do not get ligated. To reduce this complication, this study introduces a modified technique with major branch ligation. From December 2008 to February 2015, 14 patients who underwent superficial parotidectomy were divided into 2 groups. Group A was treated with the modified functional superficial parotidectomy involving the major branch between the superficial lobe and parotid duct. Group B was treated with the conventional superficial parotidectomy without involving the major branch of the parotid duct. The clinical complications, period of Hemovac usage, and surgical duration were noted in each group. Two of 8 patients in group A had a major branch from Stensen duct that was ligated, and there was no evidence of salivary leakage or sialocele in any of the patients of group A, whereas group B contained 2 cases of salivary leakage, one of which became sialocele. Group A had a significantly longer Hemovac maintenance period than group B (P < 0.05), and the duration of surgery was also significantly different between the 2 groups (P < 0.05). Because a solitary major branch of the main parotid duct occasionally extends toward the superficial lobe, our modified technique-functional superficial parotidectomy with ligation of the major branch toward the superficial lobe-is a useful option for treatment of a benign parotid mass in such cases.


Management of bone disease in cystinosis: Statement from an international conference.
Cystinosis is an autosomal recessive storage disease due to impaired transport of cystine out of lysosomes. Since the accumulation of intracellular cystine affects all organs and tissues, the management of cystinosis requires a specialized multidisciplinary team consisting of pediatricians, nephrologists, nutritionists, ophthalmologists, endocrinologists, neurologists' geneticists, and orthopedic surgeons. Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome. Virtually all individuals with classical, nephropathic cystinosis suffer from cystinosis metabolic bone disease (CMBD), related to the renal Fanconi syndrome in infancy and progressive chronic kidney disease (CKD) later in life. Manifestations of CMBD include hypophosphatemic rickets in infancy, and renal osteodystrophy associated with CKD resulting in bone deformities, osteomalacia, osteoporosis, fractures, and short stature. Assessment of CMBD involves monitoring growth, leg deformities, blood levels of phosphate, electrolytes, bicarbonate, calcium, and alkaline phosphatase, periodically obtaining bone radiographs, determining levels of critical hormones and vitamins, such as thyroid hormone, parathyroid hormone, 25(OH) vitamin D, and testosterone in males, and surveillance for nonrenal complications of cystinosis such as myopathy. Treatment includes replacement of urinary losses, cystine depletion with oral cysteamine, vitamin D, hormone replacement, physical therapy, and corrective orthopedic surgery. The recommendations in this article came from an expert meeting on CMBD that took place in Salzburg, Austria, in December 2016.


Ergogenic effects of caffeine are mediated by myokines.
Exercise has long been known to effectively improve and enhance skeletal muscle function and performance. The favorable effects of exercise on remote organs other than skeletal muscle are well known, but the underlying mechanism has remained elusive. Recent studies have indicated that skeletal muscle not only enables body movement, but also contributes to body homeostasis and the systemic stress response via the expression and/or secretion of cytokines (so-called myokines). Not only the induction of muscle contraction itself, but also changes in intracellular calcium concentration ([Ca2+]i) have been suggested to be involved in myokine production and secretion. Caffeine is widely known as a Ca2+ ionophore, which improves skeletal muscle function and exercise performance (i.e., an "ergogenic aid"). Interestingly, some studies reported that caffeine or an increase in [Ca2+]i enhances the expression and/or secretion of myokines. In this review, we discuss the association between caffeine as an ergogenic aid and myokine regulation.


Loss of caveolin-3-dependent regulation of ICa in rat ventricular myocytes in heart failure.
β2-Adrenoceptors and L-type Ca2+ current ( ICa) redistribute from the t-tubules to the surface membrane of ventricular myocytes from failing hearts. The present study investigated the role of changes in caveolin-3 and PKA signaling, both of which have previously been implicated in this redistribution. ICa was recorded using the whole cell patch-clamp technique from ventricular myocytes isolated from the hearts of rats that had undergone either coronary artery ligation (CAL) or equivalent sham operation 18 wk earlier. ICa distribution between the surface and t-tubule membranes was determined using formamide-induced detubulation (DT). In sham myocytes, β2-adrenoceptor stimulation increased ICa in intact but not DT myocytes; however, forskolin (to increase cAMP directly) and H-89 (to inhibit PKA) increased and decreased, respectively, ICa at both the surface and t-tubule membranes. C3SD peptide (which decreases binding to caveolin-3) inhibited ICa in intact but not DT myocytes but had no effect in the presence of H-89. In contrast, in CAL myocytes, β2-adrenoceptor stimulation increased ICa in both intact and DT myocytes, but C3SD had no effect on ICa; forskolin and H-89 had similar effects as in sham myocytes. These data show the redistribution of β2 -adrenoceptor activity and ICa in CAL myocytes and suggest constitutive stimulation of ICa by PKA in sham myocytes via concurrent caveolin-3-dependent (at the t-tubules) and caveolin-3-independent mechanisms, with the former being lost in CAL myocytes. NEW & NOTEWORTHY In ventricular myocytes from normal hearts, regulation of the L-type Ca2+ current by β2-adrenoceptors and the constitutive regulation by caveolin-3 is localized to the t-tubules. In heart failure, the regulation of L-type Ca2+ current by β2-adrenoceptors is redistributed to the surface membrane, and the constitutive regulation by caveolin-3 is lost.


Reproductive toxicology of environmental toxicants: emerging issues and concerns.
Environmental toxicants comprise a number of man-made organic chemicals which may resist metabolism or their metabolites may persist in the environment and accumulate in the food chain. Some of these persistent chemicals are carried over long distances via the atmospheric transport and can have biological effects in fish, wildlife and humans. In this review the relationship between structure of these chemicals, their mode of action and their possible roles in adverse developmental and reproductive processes in humans will be discussed. The focus will be on model polychlorinated biphenyls and dioxins, organochlorines, phthalates, a constituent of cigarette smoke (benzo-a-pyrene), synthetic polymers (polybrominated diphenyl ethers and polyfluorinated compounds), and a fungicide (vinclozolin).


Type 2 Transglutaminase, mitochondria and Huntington's disease: menage a trois.
Mitochondria produce the bulk of cellular energy and work as decisional "hubs" for cellular responses by integrating different input signals. The determinant in the physiopathology of mammals, they attract major attention, nowadays, for their contribution to brain degeneration. How they can withstand or succumb to insults leading to neuronal death is an object of great attention increasing the need for a better understanding of the interplay between inner and outer mitochondrial pathways residing in the cytosol. Of the latter, those dictating protein metabolism and therefore influencing the quality function and control of the organelle are of our most immediate interest and here we describe the Transglutaminase type 2 (TG2) contribution to mitochondrial function, dysfunction and neurodegeneration. Besides reviewing the latest evidences we share also the novel ones on the IF1 pathway depicting a molecular conduit governing mitochondrial turnover and homeostasis relevant to envisaging preventive and therapeutic strategies to respectively predict and counteract deficiencies associated with deregulated mitochondrial function in neuropathology.


Optimization of Statin-Loaded Delivery Nanoparticles for Treating Chronic Liver Diseases by Targeting Liver Sinusoidal Endothelial Cells.
In this study, we developed functionalized polymeric micelles (FPMs) loaded with simvastatin (FPM-Sim) as a drug delivery system to target liver sinusoidal endothelial cells (LSECs) for preserving liver function in chronic liver disease (CLD). Polymeric micelles (PMs) were functionalized by coupling peptide ligands of LSEC membrane receptors CD32b, CD36 and ITGB3. Functionalization was confirmed via spectroscopy and electron microscopy. In vitro and in vivo FPM-Sim internalization was assessed by means of flow cytometry in LSECs, hepatocytes, Kupffer and hepatic stellate cells from healthy rats. Maximum tolerated dose assays were performed in healthy mice and efficacy studies of FPM-Sim were carried out in bile duct ligation (BDL) and thioacetamide (TAA) induction rat models of cirrhosis. Functionalization with the three peptide ligands resulted in stable formulations with a greater degree of in vivo internalization in LSECs than non-functionalized PMs. Administration of FPM-Sim in BDL rats reduced toxicity relative to free simvastatin, albeit with a moderate portal-pressure-lowering effect. In a less severe model of TAA-induced cirrhosis, treatment with FPM-CD32b-Sim nanoparticles for two weeks significantly decreased portal pressure, which was associated with a reduction in liver fibrosis, lower collagen expression as well as the stimulation of nitric oxide synthesis. In conclusion, CD32b-FPM stands out as a good nanotransporter for drug delivery, targeting LSECs, key inducers of liver injury.


Systemic inequities and depressive symptomology in Hispanic mothers: A path analysis model.
Hispanic mothers are one of the largest groups to give birth. They also experience high rates of morbidity and mortality; however, there is limited data related to their health inequities. The purpose of this study was to evaluate systemic inequities associated with discrimination using the Reproductive Justice Framework to observe factors that influenced depressive symptomology in Hispanic women. A path analysis was conducted to evaluate systemic inequities that influenced postpartum depression using the public database, Listening to Mothers III (LMIII). The sub-sample consisted of n = 406 Hispanic mothers. Data was initially collected between the years 2011 and 2013. Hispanic mothers were more likely to experience occurrences of perceived discrimination while seeking perinatal healthcare. These occurrences of discrimination led to lower trust in their healthcare providers, lower satisfaction with care, more instances of unwanted medical procedures, the need to feel to hold back comments about their health which ultimately resulted in higher rates of self-reported postpartum depression. The model fit indices supported the model's plausibility (χ2 /df ratio = 3.16, Comparative Fit Index = 0.91, Root Mean Square Error of Approximation = 0.06). This data supported our hypothesis that the pathway of discriminatory barriers Hispanic mothers experience during pregnancy influence postpartum depression.


Selection and estimation for mixed graphical models.
We consider the problem of estimating the parameters in a pairwise graphical model in which the distribution of each node, conditioned on the others, may have a different exponential family form. We identify restrictions on the parameter space required for the existence of a well-defined joint density, and establish the consistency of the neighbourhood selection approach for graph reconstruction in high dimensions when the true underlying graph is sparse. Motivated by our theoretical results, we investigate the selection of edges between nodes whose conditional distributions take different parametric forms, and show that efficiency can be gained if edge estimates obtained from the regressions of particular nodes are used to reconstruct the graph. These results are illustrated with examples of Gaussian, Bernoulli, Poisson and exponential distributions. Our theoretical findings are corroborated by evidence from simulation studies.


Comparison of Published Estimates of the National Prevalence of Iron, Vitamin A, and Zinc Deficiency and Sources of Inconsistencies.
Micronutrient deficiencies result in a broad range of adverse health and functional consequences, but the true prevalence of specific deficiencies remains uncertain because limited information is available from nationally representative surveys using recommended biomarkers. The present review compares various reported national deficiency prevalence estimates for nutrients and years where the estimates overlap for individual countries that conducted nationally representative surveys and explores possible reasons for any discrepancies discovered. Nationally representative micronutrient status surveys that were conducted since 2000 among preschool-aged children or women of reproductive age and included assessment of iron, vitamin A, or zinc status based on recognized biomarkers were considered eligible for inclusion, along with any modeled deficiency prevalence estimates for these same countries and years. There was considerable variation across different published prevalence estimates, with larger inconsistencies when the prevalence estimate was based on proxies, such as hemoglobin for iron deficiency and dietary zinc availability for zinc deficiency. Numerous additional methodological issues affected the prevalence estimates, such as which biomarker and what cutoff was used to define deficiency, whether the biomarker was adjusted for inflammation, and what adjustment method was used. For some country-years, the various approaches resulted in fairly consistent prevalence estimates. For other country-years, however, the results differed markedly and changed the conclusions regarding the existence and severity of the micronutrient deficiency as a public health concern. In conclusion, to determine micronutrient status, we consider the assessment of one of the recommended biomarkers in a population representative survey as the best available information. If indicated, results should be adjusted for inflammation and generally acceptable cutoffs should be applied to facilitate comparisons, although individual countries may also apply nationally defined cutoffs to determine when and where to intervene. Global consensus is needed on best practices for presenting survey results and defining the prevalence of deficiency.


Building partnerships to address the HIV epidemic.
Batam is one of the islands comprising the Riau Province in Indonesia, and is closest to Singapore. It is a popular destination of many Singaporeans. Surveillance reports among commercial sex workers conducted in Batam showed the prevalence rate of human immunodeficiency virus (HIV) is 16.2 percent. At the end of 2006, the total number of HIV-infected Singaporeans was 3,060, the majority being infected via heterosexual transmission. The aim of the Indonesian government is to rapidly scale up HIV treatment to those needing it. One of the factors critical to the rapid scale-up is healthcare worker training. An intersectoral collaboration addressing the issue of HIV care and treatment with a hospital in Batam was created. The first activity of the collaboration was a two-day HIV training course conducted in February 2007. The aim of the course was to provide a basic understanding of HIV, as well as knowledge on common opportunistic infections that may present to a general hospital or clinical setting. 34 doctors from 23 institutions in Batam and three doctors from two hospitals in the Riau Islands attended the two-day HIV training course. The participants found the training very useful and highly relevant. This first HIV training provided a foundation to build on further HIV education. It is our belief that through the HIV training programme, there will be more awareness of HIV among the various medical institutions in Batam. As the HIV epidemic knows no borders, working with neighbouring countries is one strategy that deserves attention.


Neurologic manifestations of human immunodeficiency virus infection in children.
This report describes the neurologic manifestations of 36 children with human immunodeficiency virus (HIV) infection. In this cohort, in 16 of 21 children with acquired immunodeficiency syndrome (AIDS), three of 12 children with AIDS-related complex, and one of three asymptomatic seropositive children, a progressive encephalopathy developed. Neurologic signs were often detected early but tended to worsen coincident with progression of the immunodeficiency. The presence of progressive encephalopathy correlated with the absence of serum neutralizing antibodies to HIV and with a poor, usually fatal, outcome. The incubation period from initial HIV infection in the perinatal period to the onset of progressive encephalopathy varied from 2 months to 5 years. Intrablood-brain barrier synthesis of HIV-specific antibodies was demonstrated in eight of 14 children with AIDS and AIDS-related complex, indicating active brain infection with HIV. In three cases this was unassociated with progressive neurologic signs. Unique neuropathologic findings in children who died with HIV infection further suggest that the progressive encephalopathy is the result of primary and persistent infection of the brain with this retrovirus. These findings broaden the spectrum of HIV infection in children and have important implications for the development of antiviral therapy.


Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment.
Autism spectrum disorder (ASD) is characterized by impaired social interactions and repetitive patterns of behavior. Symptoms appear in early life and persist throughout adulthood. Early social stimulation can help reverse some of the symptoms, but the biological mechanisms of these therapies are unknown. By analyzing the effects of early social stimulation on ASD-related behavior in the mouse, we aimed to identify brain structures that contribute to these behaviors. We injected pregnant mice with 600-mg/kg valproic acid (VPA) or saline (SAL) at gestational day 12.5 and evaluated the effect of weaning their offspring in cages containing only VPA animals, only SAL animals, or mixed. We analyzed juvenile play at PD21 and performed a battery of behavioral tests in adulthood. We then used preclinical PET imaging for an unbiased analysis of the whole brain of these mice and studied the function of the piriform cortex by c-Fos immunoreactivity and HPLC. Compared to control animals, VPA-exposed animals play less as juveniles and exhibit a lower frequency of social interaction in adulthood when reared with other VPA mice. In addition, these animals were less likely to investigate social odors in the habituation/dishabituation olfactory test. However, when VPA animals were weaned with control animals, these behavioral alterations were not observed. Interestingly, repetitive behaviors and depression-related behaviors were not affected by social enrichment. We also found that VPA animals present high levels of glucose metabolism bilaterally in the piriform cortex (Pir), a region known to be involved in social behaviors. Moreover, we found alterations in the somatosensory, motor, and insular cortices. Remarkably, these effects were mostly reversed after social stimulation. To evaluate if changes in glucose metabolism in the Pir correlated with changes in neuronal activity, we measured c-Fos immunoreactivity in the Pir and found it increased in animals prenatally exposed to VPA. We further found increased dopamine turnover in the Pir. Both alterations were largely reversed by social enrichment. We show that early social enrichment can specifically rescue social deficits in a mouse model of ASD. Our results identified the Pir as a structure affected by VPA-exposure and social enrichment, suggesting that it could be a key component of the social brain circuitry.


Bile acids induce IL-1α and drive NLRP3 inflammasome-independent production of IL-1β in murine dendritic cells.
Bile acids are amphipathic molecules that are synthesized from cholesterol in the liver and facilitate intestinal absorption of lipids and nutrients. They are released into the small intestine upon ingestion of a meal where intestinal bacteria can modify primary into secondary bile acids. Bile acids are cytotoxic at high concentrations and have been associated with inflammatory diseases such as liver inflammation and Barrett's Oesophagus. Although bile acids induce pro-inflammatory signalling, their role in inducing innate immune cytokines and inflammation has not been fully explored to date. Here we demonstrate that the bile acids, deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) induce IL-1α and IL-1β secretion in vitro in primed bone marrow derived dendritic cells (BMDCs). The secretion of IL-1β was found not to require expression of NLRP3, ASC or caspase-1 activity; we can't rule out all inflammasomes. Furthermore, DCA and CDCA were shown to induce the recruitment of neutrophils and monocytes to the site of injection an intraperitoneal model of inflammation. This study further underlines a mechanistic role for bile acids in the pathogenesis of inflammatory diseases through stimulating the production of pro-inflammatory cytokines and recruitment of innate immune cells.


Sleep and its regulation in zebrafish.
The function of sleep remains a central enigma of modern biology, in spite of the obvious importance of sleep for normal physiology and cognition. The zebrafish has emerged as a promising new model for studying sleep, its changes with age, and the impact of sleep alterations on cognitive function. Recent studies of this diurnal vertebrate have provided new insights into the dual role of the pineal hormone melatonin and its receptors, regulating sleep in diurnal vertebrates through both homeostatic and circadian mechanisms. Research in zebrafish has also revealed interactions between melatonin and the hypocretin/orexin system, another important sleep-wake modulator. Future investigations should benefit from the conservation in zebrafish of mechanisms that regulate normal sleep, our extensive knowledge of their molecular biology, the availability of multiple transgenic and mutant phenotypes, and the feasibility of applying sensitive in vivo imaging techniques to record sleep-related neuronal activity in these optically transparent subjects. The established sensitivity of zebrafish to many pharmacological hypnotics should also contribute to the development of new, safe and effective sleep medications.


The relationship between isometric force-time curve characteristics and club head speed in recreational golfers.
The primary purpose of the present investigation was to examine the relationships between club head speed, isometric midthigh pull performance, and vertical jump performance in a cohort of recreational golfers. Twelve recreational golfers (age, 20.4 ± 1.0 years; weight, 77.0 ± 9.8 kg; height, 177.8 ± 6.3 cm; body fat, 17.1 ± 7.6%; handicap, 14.5 ± 7.3; experience, 8.9 ± 3.6 years) completed 3 testing sessions: (a) familiarization session and body composition measurements; (b) measurement of force-time curves in the isometric midthigh pull, countermovement, and static vertical jump (SJ); and (c) measurement of club head speed. During sessions 1 and 2, subjects performed 5 countermovement jumps, 5 SJ, and 2 isometric midthigh pulls. Isometric peak force was measured at 30, 50, 90, 100, 200, and 250 milliseconds. Rate of force development was measured among 0-30, 0-50, 0-90, 0-100, 0-200, and 0-250 milliseconds. Peak rate of force development was determined as the highest value in a 10-millisecond sampling windows. During session 3, subjects performed 10 maximal golf swings with a driver to measure club head speed; peak and average club head speed were analyzed across the 10 swings. Golf handicap was moderately correlated with average (r = -0.52, p = 0.04) and maximal club head speed (r = -0.45, p = 0.07). Force at 150 milliseconds during the isomeric midthigh pull test was moderately correlated with average (r = 0.46, p = 0.07) and maximal club head speed (r = 0.47, p = 0.06). Moderate correlations were also found between the rate of force development from 0 to 150 milliseconds and average (r = 0.38, p = 0.11) and maximal club head speed (r = 0.36, p = 0.12). The present findings suggest that the ability to exhibit high ground reaction forces in time frames <200 milliseconds are related to high club head speeds.


Measuring compensation in neurodegeneration using MRI.
Despite signs of cortical and subcortical loss, patients with prodromal and early-stage neurodegenerative disease are able to perform at a level comparable to the normal population. It is presumed that the onset of compensatory processes, that is changes in brain activation within a function-specific network or in the recruitment of a region outside of the task-network, underlies this maintenance of normal performance. However, in most studies to date, increased brain activity is not correlated with indices of both disease and performance and what appears to be compensation could simply be a symptom of neurodegeneration. MRI studies have explored compensation in neurodegenerative disease, claiming that compensation is evident across a number of disorders, including Alzheimer's and Parkinson's disease, but generally always in early stages; after this point, compensation is generally no longer able to operate under the severe burden of disease. However, none of these studies explicitly adopted a particular model of compensation. Thus, we also discuss our recent attempts to operationalize compensation for empirical testing. There is clear evidence of compensatory processes in the early stages of neurodegenerative disease. However, for a more complete understanding, this requires more explicit empirical modelling.


Prenatal nicotine exposure enhances the trigeminocardiac reflex via serotonin receptor facilitation in brainstem pathways.
In this study we used a rat model for prenatal nicotine exposure to test whether clinically relevant concentrations of brain nicotine and cotinine are passed from dams exposed to nicotine to her pups, whether this changes the trigeminocardiac reflex (TCR), and whether serotonergic function in the TCR brainstem circuitry is altered. Pregnant Sprague-Dawley dams were exposed to 6 mg·kg(-1)·day(-1) of nicotine via osmotic minipumps for the duration of pregnancy. Following birth dams and pups were killed, blood was collected, and brain nicotine and cotinine levels were measured. A separate group of prenatal nicotine-exposed pups was used for electrophysiological recordings. A horizontal brainstem slice was obtained by carefully preserving the trigeminal nerve with fluorescent identification of cardiac vagal neurons (CVNs) in the nucleus ambiguus. Stimulation of the trigeminal nerve evoked excitatory postsynaptic current in CVNs. Our data demonstrate that prenatal nicotine exposure significantly exaggerates both the TCR-evoked changes in heart rate in conscious unrestrained pups, and the excitatory neurotransmission to CVNs upon trigeminal afferent nerve stimulation within this brainstem reflex circuit. Application of the 5-HT1A receptor antagonist WAY 100635 (100 μM) and 5-HT2A/C receptor antagonist ketanserin (10 μM)significantly decreased neurotransmission, indicating an increased facilitation of 5-HT function in prenatal nicotine-exposed animals. Prenatal nicotine exposure enhances activation of 5-HT receptors and exaggerates the trigeminocardiac reflex.


The Effect of Substrate on Water Quality in Ornamental Fish Tanks.
Almost all home aquaria contain substrate, either as intentional enrichment or for aesthetic purposes. For fishes, benefits of structural enrichment have been well considered, particularly in research and aquaculture settings. However, our understanding of the impacts of tank substrate as enrichment is limited. While substrate can induce foraging in some species, a major drawback is the potential of substrate to harbour elevated levels of waste and pathogenic bacteria. Here, we considered whether substrate as a form of environmental enrichment significantly altered water quality and bacterial presence in home aquaria. Water quality (temperature, oxygen, pH, TAN, unionised ammonia, nitrate, Ca2+, Na+, Mg2+ and K+) and bacterial presence (Pseudomonas spp.) were measured over two seven-week periods in stand-alone, tropical, freshwater tanks that simulated home aquaria. The following four enrichment conditions were considered: bare tanks, plastic plants, gravel substrate or sand substrate. The addition of both gravel and sand resulted in increased pH, concentrations of total ammonia nitrogen and nitrate. Substrate was also associated with a greater Pseudomonas presence. Decreased pH alongside an increased concentration of ions were also observed depending on the time of year. In conclusion, enrichment type affected the water quality of home aquaria, with further research needed on the role of the tank biome in fish welfare.


Cell-detaching activity mediated by an enzyme(s) obtained from human leukocyte granules.
Granule proteins have been isolated from human peripheral blood leukocytes and their effects on intact tissue culture cells have been determined. Three hours after the addition of the mixture of granule hydrolases, both HeLa cells and human newborn fibroblasts were detached from one another and from their growth surface, but they seemed to remain viable, since cell-bound -51Cr was retained. Further studies with HeLa cells indicated that after as long as 24 hours in the presence of these enzymes the cells remained viable as judged by several independent criteria. The enzyme activity responsible for cell detachment was subject to inhibition by various protease inhibitors. Its molecular size, as determined by gel filtration, was approximately 20,000 daltons. In addition, the naturally occurring serum inhibitor of this enzyme activity was characterized as either alpha(1)-antitrypsin or another protein with similar properties.


[A case of asymptomatic Brugada syndrome with type 1 ECG pattern and cardiac arrest: an evaluation of the prognostic value of electrophysiologic study].
Brugada syndrome is characterized by ST-segment elevation in the leads V1-3 of electrocardiography (ECG) in the absence of a structural heart disease. A 26-year old male patient was admitted with sudden cardiac arrest. Cardiopulmonary resuscitation was successful and he was referred to the reanimation unit due to unconsciousness. A year before, he was diagnosed as having Brugada syndrome with type 1 ECG pattern at another center, at which time electrophysiologic study (EPS) was not performed due to lack of symptoms and a family history of sudden cardiac death. In addition, family screening revealed two asymptomatic brothers having Brugada syndrome with type 1 ECG pattern. Medical follow-up was recommended to one of them. The other sibling underwent EPS at a different center where ventricular fibrillation was induced. An implantable cardioverter defibrillator (ICD) was recommended, but the patient refused. A further analysis of the family made at our center showed type 2 ECG changes in the father and in one of the cousins. Due to the development of persistent brain injury and an expected survival of less than a year, an ICD was not considered in the patient. The prognostic value of EPS is still controversial in asymptomatic patients with type 1 Brugada syndrome, without a family history of sudden cardiac death.


Characterization of human liver alpha-D-mannosidase purified by affinity chromatography.
Human liver acidic alpha-D-mannosidase was purified 1400-fold by a relatively short procedure incorporating chromatography on concanavalin A-Sepharose and affinity chromatography on Sepharose 4B-epsilon-aminohexanoylmannosylamine. In contrast with the acidic enzymic activity the neutral alpha-mannosidase did not bind to the concanavalin A-Sepharose so the two types of alpha-mannosidase could be separated at an early stage in the purification. The only significant glycosidase contaminant after affinity chromatography on the mannosylamine ligand was alpha-L-fucosidase, which was selectively removed by affinity chromatography on the corresponding fucosylamine ligand. The final preparation was free of other glycosidase activities. The pI of the purified enzyme was increased from 6.0 to 6.45 on treatment with neuraminidase. Although the pI and the mol.wt. (220 000) suggested that alpha-mannosidase A had been purified selectively, ion-exchange chromatography on DEAE-cellulose indicated that the preparation consisted predominantly of alpha-mannosidase B. This discrepancy is discussed in relation to the basis of the multiple forms of human alpha-mannosidase. The purified enzyme completely removed the alpha-linked non-reducing terminal mannose from a trisaccharide isolated from the urine of a patient with mannosidosis. A comparison of the activity of the pure enzyme towards the natural substrate and synthetic substrates suggests that the same enzymic activity is responsible for hydrolysing all the substrates. These results validate the use of synthetic substrates for determining the mannosidosis genotype. They are also further evidence that mannosidosis is a lysosomal storage disease resulting from a deficiency of acidic alpha-mannosidase.


Comparative bactericidal activities of blood serum and plasma serum.
Rabbit and human plasma can be prepared without resort to anticoagulants by employing low temperatures and non-wetting surfaces. Serum formed after clotting of rabbit plasma devoid of cells and platelets manifests essentially no bactericidal activity on Bacillus subtilis, Bacillus megaterium, and a strain of Staphylococcus aureus. In contrast, rabbit blood serum exhibits this activity to a high degree. Rabbit plasma rich in platelets gives rise to a serum with capacity to kill these Gram-positive microbes equal to that of serum prepared from whole blood. This heat-stable antibacterial agent is efficiently formed or released when platelets are present during the coagulation of plasma, but not on incubation of platelets in heparinized or citrated plasma or in saline. Leucocytes and red cells appear to play no significant role in its production. Rabbit blood serum and plasma serum have similar heat-labile lethal effects on enteric bacilli. Human serum, whether from blood or plasma, manifests much less bactericidal activity on Bacillus subtilis than does rabbit blood serum. These findings serve to emphasize the fact that substances formed or released during coagulation of whole blood may impart to the serum activities not present in circulating plasma.


Declining effect of latitude on melanoma mortality rates in the United States. A preliminary study.
The gradient of mortality from melanoma of the skin with latitude among US whites was estimated from the slopes of semilogarithmic models fitted to the state-specific mortality rates and the latitudes of the states' capital cities. The upward gradient of mortality from north to south for malignant melanoma of the skin has been decreasing since 1950-1959, when data first became available, through 1960-1969, 1970-1979, and 1988-1992. By the early years of the 21st century, rates of melanoma mortality in the contiguous United States are expected to be unaffected by latitude. For the country as a whole, melanoma mortality rates have been rising for many years. This rise has become progressively slower, such that national rates have been projected to stabilize in the near future. While increasing geographic mobility has probably played a role in reducing the latitude effect, melanoma mortality rates may have reached levels at which increased exposure of US whites to sunlight has little incremental effect.


Bcl-2 regulates store-operated Ca2+ entry to modulate ER stress-induced apoptosis.
Ca2+ plays a significant role in linking the induction of apoptosis. The key anti-apoptotic protein, Bcl-2, has been reported to regulate the movement of Ca2+ across the ER membrane, but the exact effect of Bcl-2 on Ca2+ levels remains controversial. Store-operated Ca2+ entry (SOCE), a major mode of Ca2+ uptake in non-excitable cells, is activated by depletion of Ca2+ in the ER. Depletion of Ca2+ in the ER causes translocation of the SOC channel activator, STIM1, to the plasma membrane. Thereafter, STIM1 binds to Orai1 or/and TRPC1 channels, forcing them to open and thereby allow Ca2+ entry. In addition, several anti-cancer drugs have been reported to induce apoptosis of cancer cells via the SOCE pathway. However, the detailed mechanism underlying the regulation of SOCE by Bcl-2 is not well understood. In this study, a three-amino acid mutation within the Bcl-2 BH1 domain was generated to verify the role of Bcl-2 in Ca2+ handling during ER stress. The subcellular localization of the Bcl-2 mutant (mt) is similar to that in the wild-type Bcl-2 (WT) in the ER and mitochondria. We found that mt enhanced thapsigargin and tunicamycin-induced apoptosis through ER stress-mediated apoptosis but not through the death receptor- and mitochondria-dependent apoptosis, while WT prevented thapsigargin- and tunicamycin-induced apoptosis. In addition, mt depleted Ca2+ in the ER lumen and also increased the expression of SOCE-related molecules. Therefore, a massive Ca2+ influx via SOCE contributed to caspase activation and apoptosis. Furthermore, inhibiting SOCE or chelating either extracellular or intracellular Ca2+ inhibited mt-mediated apoptosis. In brief, our results explored the critical role of Bcl-2 in Ca2+ homeostasis and the modulation of ER stress.


Genetic analysis of the role of proteolysis in the activation of latent myostatin.
Myostatin is a secreted protein that normally acts to limit skeletal muscle growth. As a result, there is considerable interest in developing agents capable of blocking myostatin activity, as such agents could have widespread applications for the treatment of muscle degenerative and wasting conditions. Myostatin normally exists in an inactive state in which the mature C-terminal portion of the molecule is bound non-covalently to its N-terminal propeptide. We previously showed that this latent complex can be activated in vitro by cleavage of the propeptide with members of the bone morphogenetic protein-1/tolloid (BMP-1/TLD) family of metalloproteases. Here, I show that mice engineered to carry a germline point mutation rendering the propeptide protease-resistant exhibit increases in muscle mass approaching those seen in mice completely lacking myostatin. Mice homozygous for the point mutation have increased muscling even though their circulating levels of myostatin protein are dramatically increased, consistent with an inability of myostatin to be activated from its latent state. Furthermore, I show that a loss-of-function mutation in Tll2, which encodes one member of this protease family, has a small, but significant, effect on muscle mass, implying that its function is likely redundant with those of other family members. These findings provide genetic support for the hypothesis that proteolytic cleavage of the propeptide by BMP-1/TLD proteases plays a critical role in the activation of latent myostatin in vivo and suggest that targeting the activities of these proteases may be an effective therapeutic strategy for enhancing muscle growth in clinical settings of muscle loss and degeneration.


IL-9(+) IL-10(+) T cells link immediate allergic response to late phase reaction.
The mechanism underlying late-phase allergic reactions (LPR) remains incompletely understood. This study aimed to investigate the role of a newly described subset of T cells, interleukin (IL)-9(+) IL-10(+) T cells, in the pathogenesis of LPR. Using a T helper type 2 (Th2) inflammatory mouse model, we examined the frequency of IL-9(+) IL-10(+) T cells in the jejunum by immunohistochemistry. The LPR in the jejunum was observed afterwards. The cytokine profile of IL-9(+) IL-10(+) T cells was characterized and the major cytokine that plays the critical role in the initiation of LPR was investigated. Abundant IL-9(+) IL-10(+) T cells as well as inflammatory cell extravasation in the jejunal sections were observed in sensitized mice 48 h after specific antigen challenge. IL-9(+) IL-10(+) T cells expressed high levels of macrophage inflammatory protein 1 (MIP1) that could be enhanced by T cell receptor activation. MIP1 facilitated macrophage extravasation in local tissue. Macrophage-derived MIP2 contributed to neutrophil infiltration in the intestine in LPR. Pretreatment with anti-MIP antibody inhibited the LPR in the intestine. IL-9(+) IL-10(+) T cells play an important role in LPR. This subset of T cells has the potential to be a novel therapeutic target in the treatment of LPR and LPR-related inflammation.


Characterization of the CI repressor protein encoded by the temperate lactococcal phage TP901-1.
The gene regulatory mechanism determining the developmental pathway of the temperate bacteriophage TP901-1 is regulated by two phage-encoded proteins, CI and MOR. Functional domains of the CI repressor were investigated by introducing linkers of 15 bp at various positions in cI and by limited proteolysis of purified CI protein. We show that insertions of five amino acids at positions in the N-terminal half of CI resulted in mutant proteins that could no longer repress transcription from the lytic promoter, P(L). We confirmed that the N-terminal domain of CI contains the DNA binding site, and we showed that this part of the protein is tightly folded, whereas the central part and the C-terminal part of CI seem to contain more flexible structures. Furthermore, insertions at several different positions in the central part of the CI protein reduced the cooperative binding of CI to the operator sites and possibly altered the interaction with MOR.


Covalent Inhibition of Ubc13 Affects Ubiquitin Signaling and Reveals Active Site Elements Important for Targeting.
Ubc13 is an E2 ubiquitin conjugating enzyme that functions in nuclear DNA damage signaling and cytoplasmic NF-κB signaling. Here, we present the structures of complexes of Ubc13 with two inhibitors, NSC697923 and BAY 11-7082, which inhibit DNA damage and NF-κB signaling in human cells. NSC697923 and BAY 11-7082 both inhibit Ubc13 by covalent adduct formation through a Michael addition at the Ubc13 active site cysteine. The resulting adducts of both compounds exploit a binding groove unique to Ubc13. We developed a Ubc13 mutant which resists NSC697923 inhibition and, using this mutant, we show that the inhibition of cellular DNA damage and NF-κB signaling by NSC697923 is largely due to specific Ubc13 inhibition. We propose that unique structural features near the Ubc13 active site could provide a basis for the rational development and design of specific Ubc13 inhibitors.


[Use of troponin analysis in Norwegian hospitals].
A highly sensitive troponin T analysis became available in Norway in 2009. The Norwegian Society of Medical Biochemistry believed that a national strategy for implementation of the analysis would ensure a more coherent practice for diagnosing acute myocardial infarction (AMI). 70 laboratories were requested to identify (in a questionnaire) the type of assay used, routines for reporting results of analyses, internal quality control programmes (IQA) and local cut-off values for making the diagnosis AMI. 62 laboratories responded and 57 of these analyzed troponins; 60 % used troponin T and 40 % troponin I. 82 % of laboratories were familiar with the decision limit used for diagnosing AMI at their hospital; 43 % of troponin T laboratories used the cut-off recommended by the Norwegian Society of Cardiology (0.03 microg/l) to diagnose AMI. For the two most used troponin I methods (16 laboratories) eight different cut-off values were reported. 24 % (troponin T) and 35 % (troponin I) of laboratories performed IQA at a concentration similar or lower than the local decision limit used when diagnosing AMI. 73 % (troponin T) and 54 % (troponin I) of laboratories used the lower limit of quantification as the lower cut-off value for reportable results. In Norwegian hospitals, users of the same methods for analysis of troponin have different routines for interpreting, IQA and reporting of results. Patient diagnoses may therefore vary according to the hospital used. The Norwegian Society of Medical Biochemistry has developed recommendations for implementation of troponin analyses in Norwegian laboratories.


Chiral superconductors.
Chiral superconductivity is a striking quantum phenomenon in which an unconventional superconductor spontaneously develops an angular momentum and lowers its free energy by eliminating nodes in the gap. It is a topologically non-trivial state and, as such, exhibits distinctive topological modes at surfaces and defects. In this paper we discuss the current theory and experimental results on chiral superconductors, focusing on two of the best-studied systems, Sr2RuO4, which is thought to be a chiral triplet p-wave superconductor, and UPt3, which has two low-temperature superconducting phases (in zero magnetic field), the lower of which is believed to be chiral triplet f-wave. Other systems that may exhibit chiral superconductivity are also discussed. Key signatures of chiral superconductivity are surface currents and chiral Majorana modes, Majorana states in vortex cores, and the possibility of half-flux quantum vortices in the case of triplet pairing. Experimental evidence for chiral superconductivity from μSR, NMR, strain, polar Kerr effect and Josephson tunneling experiments are discussed.


Systemic prophylactic antibiotics: need the 'cost' be so high?
To assess compliance with accepted principles, the use of prophylaxis with systemic antibiotics in selected specialty procedures was examined. The operations reviewed were aortofemoral bypass, pulmonary resections, open-hip procedures, and head-neck cancer procedures that involve the oropharyngeal cavity. Of all patients, 74% received antibiotics preoperatively and 79% received prophylaxis with antibiotics longer than 24 hours postoperatively. Evaluated against the criteria of preoperative initiation and limited postoperative administration (less than 24 hours) only 10% of the patients received appropriate prophylaxis. A 3% incidence of drug-associated complications was identified; each patient with complications had received antibiotics for a prolonged time postoperatively. Reduction in the length of postoperative prophylaxis with systemic antibiotics will reduce (1) the number of drug-associated complications, (2) selection pressures on the hospital microbial population, and (3) needless expense in hospitalized patients.


Treatment With Treprostinil and Metformin Normalizes Hyperglycemia and Improves Cardiac Function in Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction.
Pulmonary hypertension (PH) due to left heart disease (group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide; however, at present, there is no proven effective therapy available for its treatment. PH-HFpEF is associated with insulin resistance and features of metabolic syndrome. The stable prostacyclin analog, treprostinil, is an effective and widely used Food and Drug Administration-approved drug for the treatment of pulmonary arterial hypertension. While the effect of treprostinil on metabolic syndrome is unknown, a recent study suggests that the prostacyclin analog beraprost can improve glucose intolerance and insulin sensitivity. We sought to evaluate the effectiveness of treprostinil in the treatment of metabolic syndrome-associated PH-HFpEF. Approach and Results: Treprostinil treatment was given to mice with mild metabolic syndrome-associated PH-HFpEF induced by high-fat diet and to SU5416/obese ZSF1 rats, a model created by the treatment of rats with a more profound metabolic syndrome due to double leptin receptor defect (obese ZSF1) with a vascular endothelial growth factor receptor blocker SU5416. In high-fat diet-exposed mice, chronic treatment with treprostinil reduced hyperglycemia and pulmonary hypertension. In SU5416/Obese ZSF1 rats, treprostinil improved hyperglycemia with similar efficacy to that of metformin (a first-line drug for type 2 diabetes mellitus); the glucose-lowering effect of treprostinil was further potentiated by the combined treatment with metformin. Early treatment with treprostinil in SU5416/Obese ZSF1 rats lowered pulmonary pressures, and a late treatment with treprostinil together with metformin improved pulmonary artery acceleration time to ejection time ratio and tricuspid annular plane systolic excursion with AMPK (AMP-activated protein kinase) activation in skeletal muscle and the right ventricle. Our data suggest a potential use of treprostinil as an early treatment for mild metabolic syndrome-associated PH-HFpEF and that combined treatment with treprostinil and metformin may improve hyperglycemia and cardiac function in a more severe disease.


Dimethylsphingosine regulates intracellular pH and Ca(2+) in human monocytes.
Dimethylsphingosine (DMS) was first reported as an inhibitor of protein kinase C and later has been used as a specific inhibitor of sphingosine kinase. Furthermore, its anti-cancer effect has become a basis for development of chemotherapy. Nevertheless, its anti-neoplastic mechanism has poorly been understood. In the present study, we observed that DMS increased intracellular pH and Ca(2+) concentration in U937 human monocytes. To further characterize these DMS-induced actions, we employed structurally-related sphingolipids and specific pharmacological tools such as inhibitors of protein kinase C and Na(+)/H(+) exchanger and found that the two responses of DMS were mimicked by four stereoisomers of sphingosine and two isomers to dihydrosphingosine, but not with sphingosine 1-phosphate, sphingosyl-phosphorylcholine, and C2-ceramide. Furthermore, DMS-induced pH increase was independent of Na(+)/H(+) exchanger activity. We also characterized the interrelationship between DMS-induced pH increase and DMS-induced Ca(2+) increase. Since DMS is considered to be a good anti-cancer candidate, our characterization of DMS actions provides useful information for development of DMS chemotherapy.


Dental practice closure during the first wave of COVID-19 and associated professional, practice and structural determinants: a multi-country survey.
The coronavirus outbreak (COVID-19) in China has influenced every aspect of life worldwide. Given the unique characteristics of the dental setting, the risk of cross-infection between dental practitioners and patients is high in the absence of adequate protective measures, and dentists may develop severe anxiety in relation to the current pandemic. The limited provision of services and widespread closure of dental practices have raised concerns among dental professionals about the financial impact. The present study assessed the frequency of dental practice closure during the pandemic's first wave in several countries and whether closures and their associated factors differ between the private and non-private sectors. An electronic cross-sectional survey questionnaire was sent to dentists in several countries, from April to May 2020. The survey assessed professional, practice related and country-level structural factors elucidating the reason for practice closure. Multilevel logistic regression was used to assess the association between practice closure and these factors, and differences were evaluated by sector type. Dentists from 29 countries (n = 3243) participated in this study. Most of the participants (75.9%) reported practice closure with significantly higher percentage in the private sector than the non-private sector. Greater pandemic-related fears were associated with a significantly higher likelihood of practice closure in the private (odds ratio [OR] = 1.54, 95% confidence interval [CI] 1.24, 1.92) and non-private (OR = 1.38, 95% CI 1.04, 1.82) sectors. Dentists in non-private rural areas (OR = 0.58, 95% CI 0.42, 0.81), and those in hospitals (overall OR = 0.60, 95% CI 0.36, 0.99) reported a low likelihood of closure. A high likelihood of closure was reported by dentists in the academia (OR = 2.13, 95% CI 1.23, 3.71). More hospital beds at the country-level were associated with a lower likelihood of closure in the non-private sector (OR = 0.65, 95% CI 0.46, 0.91). Private- sector dentists in high- income countries (HICs) reported fewer closures than those in non-HICs (OR = 0.55, 95% CI 0.15, 1.93). Most dentists reported practice closure because of COVID-19, and greater impacts were reported in the private sector than in the non-private sector. Closure was associated with professional, practice, and country-levels factors.


Impact of Intensity of Continuous Renal Replacement Therapy on Duration of Ventilation in Critically Ill Patients: A Secondary Analysis of the RENAL Trial.
More intensive renal replacement therapy (RRT) has been associated with prolonged mechanical ventilation (MV). However, such finding may be dependent on RRT modality. We hypothesized that, when using continuous renal replacement therapy (CRRT), RRT intensity would not be associated with prolonged MV. In a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement trial comparing different CRRT intensities, we applied Fine-Gray competing risk analysis with time to successful extubation within 28 days as primary outcome. We studied 531 patients in the higher intensity and 551 in the lower intensity group. Higher intensity patients had more hypophosphatemia (66.7 vs. 58.1%; p = 0.004) and more days with hypophosphatemia (2.2 ± 2.8 vs. 1.6 ± 2.2; p < 0.001). There was no difference in the number of patients extubated within 28 days (60.1% vs. 62.4%; adjusted subdistribution hazard ratio [SHR], 0.95 [95% CI, 0.86 to 1.06]) or time to extubation (8 [5-16] vs. 8 [5-15] days; adjusted median difference, 0.65 [95% CI, -0.41 to 1.70]). Among patients from the upper tertile of days with hypophosphatemia, higher intensity CRRT was associated with a lower chance of successful extubation within 28 days (SHR, 0.67 [95% CI, 0.55 to 0.82]; p for heterogeneity = 0.013). In the RENAL trial, higher intensity CRRT was not associated with delayed extubation. However, it was associated with a greater rate of hypophosphatemia and more days with hypophosphatemia was associated with a lower chance of successful extubation.


Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian mother.
In developed countries, vitamin B12 (cobalamin) deficiency usually occurs in children, exclusively breastfed ones whose mothers are vegetarian, causing low body stores of vitamin B12. The haematologic manifestation of vitamin B12 deficiency is pernicious anaemia. It is a megaloblastic anaemia with high mean corpuscular volume and typical morphological features, such as hyperlobulation of the nuclei of the granulocytes. In advanced cases, neutropaenia and thrombocytopaenia can occur, simulating aplastic anaemia or leukaemia. In addition to haematological symptoms, infants may experience weakness, fatigue, failure to thrive, and irritability. Other common findings include pallor, glossitis, vomiting, diarrhoea, and icterus. Neurological symptoms may affect the central nervous system and, in severe cases, rarely cause brain atrophy. Here, we report an interesting case, a 12-month old infant, who was admitted with neurological symptoms and diagnosed with vitamin B12 deficiency.


Quality of life and exercise in renal disease.
Many publications describe the advantages of physical exercise in improving quality of life. The aim of this study was to highlight the need for physical activity when patients commence haemodialysis. A correlation was found between muscular deterioration and the years on haemodialysis and it was accentuated in men. From our study we recommend adequate physical activity at the beginning of, and during the lifetime of haemodialysis to enhance the physical and psychological well being of patients.


Impact of an irreversibly adsorbed layer on local viscosity of nanoconfined polymer melts.
We report the origin of the effect of nanoscale confinement on the local viscosity of entangled polystyrene (PS) films at temperatures far above the glass transition temperature. By using marker x-ray photon correlation spectroscopy with gold nanoparticles embedded in the PS films prepared on solid substrates, we have determined the local viscosity as a function of the distance from the polymer-substrate interface. The results show the impact of a very thin adsorbed layer (~7 nm in thickness) even without specific interactions of the polymer with the substrate, overcoming the effect of a surface mobile layer at the air-polymer interface and thereby resulting in a significant increase in the local viscosity as approaching the substrate interface.


Generalized anxiety disorder and online intelligence: a phenomenological account of why worrying is unhelpful.
Worrying is the central feature of generalized anxiety disorder (GAD). Many people worry from time to time, but in GAD the worrying is prolonged and difficult to control. Worrying is a specific way of coping with perceived threats and feared situations. Meanwhile, it is not considered to be a helpful coping strategy, and the phenomenological account developed in this paper aims to show why. It builds on several phenomenological notions and in particular on Michael Wheeler's application of these notions to artificial intelligence and the cognitive sciences. Wheeler emphasizes the value of 'online intelligence' as contrasted to 'offline intelligence'. I discuss and apply these concepts with respect to worrying as it occurs in GAD, suggesting that GAD patients overrate the value of detached contemplation (offline intelligence), while underrating their embodied-embedded adaptive skills (online intelligence). I argue that this phenomenological account does not only help explaining why worrying is used as a coping strategy, but also why cognitive behavioral therapy is successful in treating GAD.


Nutritional status among elderly: A community-based cross-sectional study.
Malnutrition in the elderly is a significant public health problem and has serious implications on the overall health of the elderly. There are very few community-based studies on malnutrition among the elderly, especially in India. The objective was to find out the prevalence of malnutrition and its associated risk factors among the elderly in urbanized villages of Delhi. A cross-sectional study was conducted during November 2015 to April 2017 in two urbanized villages of East Delhi among 353 elderly (>60 years) individuals. A semi-structured interview schedule was used to record the sociodemographic and relevant personal details of the elderly. To determine the prevalence of malnutrition, Mini Nutritional Assessment scale was used. Statistical analysis included simple descriptive analysis and tests of significance such as Chi-square test. Multivariable logistic regression was used to identify the predictors of malnutrition. The prevalence of possible malnutrition was found to be 49.3%. On bivariate analysis, age, gender, education status, marital and residential status, per capita income, financial dependency, and family size were found to be associated with malnutrition (P < 0.05). Age >70 years, being tenant, and financial dependency were observed to be significant predictors of possible malnutrition in multiple logistic regression. Malnutrition needs to be identified at an early stage using appropriate tools so that proper interventions can be directed to those who need it to ensure healthy aging. Social and economic parameters are linked with the occurrence of malnutrition among the elderly and must be considered in the development of preventive strategies.


Amniocentesis rate and the detection of Down syndrome and other chromosomal anomalies in Israel.
We investigated the contribution of different screening criteria to the prenatal detection of Down syndrome (DS) as well as other chromosomal anomalies in the Jewish population in Israel during 1990 and 1992. There was a significant decrease (P < 0.03) in the incidence of DS live-births during 1992 (40:78 442) compared with 1990 (69:73 751) which paralleled a marked increase in total prenatal testing and in DS cases detected prenatally. Private laboratories, which perform amniocenteses mostly for women with a low risk of DS and without genetic counselling, had a significantly lower detection rate (1:917) compared with that of the genetic institutes, which following genetic counselling test both women > or = 37 years of age (1:91) and women younger than 37 years (1:113). The detection of chromosomal anomalies other than DS was less affected by the reason for amniocentesis. Amniocentesis indicated by maternal serum marker screening of women younger than 37 years identified a greater number of chromosomal anomalies other than DS than amniocentesis based on age (> or = 37 years) alone (111:9604 versus 94:9810; P < 0.06). Prenatal detection of DS is most effective when the indication for amniocentesis follows genetic counselling. The increasing use of maternal serum marker screening leads to a significant improvement in the positive detection rate of chromosomal anomalies other than DS in young women.


Devaluation of low-quality food during early experience by sheep.
A ruminant's early experience with low-quality food (LQF) is expected to increase its acceptance and preference in adulthood. Contrarily, we found that experienced sheep (ES) exposed to mature oat hay early in life ate less of this LQF than inexperienced sheep (IS). A possibility is that ES might have devaluated the LQF through continuous comparisons against high-quality food (HQF) supplements (sunflower meal and ground corn) that were simultaneously available during early experience. In this study, we tested the devaluation hypothesis with a successive negative contrast (SNC) procedure. In a consummatory SNC procedure, 'shift' subjects are unexpectedly changed from HQF to LQF, and their consumption is then compared against the consumption of 'unshift' subjects that receive LQF all throughout the SNC procedure. The magnitude of the difference in consumption between preshift and postshift is regarded as a measure of the degree to which both foods (HQF and LQF) are perceived to differ hedonically. When sheep from our previous study were 300 days old, both ES and IS were randomly assigned to either shift (ES-S and IS-S) or unshift conditions (ES-U and IS-U; n = 6 in each group). Groups ES-S and IS-S were fed HQF (alfalfa hay) during the preshift phase, and then suddenly changed to LQF (oat hay) in the postshift phase. Groups ES-U and IS-U (controls) were fed only LQF throughout the SNC procedure. Subjects in ES-S showed a significantly lower intake of LQF than those in ES-U in the first postshift session (i.e. they showed an SNC effect), which was not observed in IS. These results agree with ES subjects having devalued LQF during early experience. We discuss the possibility that high levels of nutrient supplementation can result in devaluation of LQF (i.e. decrease in preference and acceptance), whereas restricted levels of supplementation may promote a positive experience with LQF.


Advancing the science of microbial symbiosis to support invasive species management: a case study on Phragmites in the Great Lakes.
A growing body of literature supports microbial symbiosis as a foundational principle for the competitive success of invasive plant species. Further exploration of the relationships between invasive species and their associated microbiomes, as well as the interactions with the microbiomes of native species, can lead to key new insights into invasive success and potentially new and effective control approaches. In this manuscript, we review microbial relationships with plants, outline steps necessary to develop invasive species control strategies that are based on those relationships, and use the invasive plant species Phragmites australis (common reed) as an example of how development of microbial-based control strategies can be enhanced using a collective impact approach. The proposed science agenda, developed by the Collaborative for Microbial Symbiosis and Phragmites Management, contains a foundation of sequential steps and mutually-reinforcing tasks to guide the development of microbial-based control strategies for Phragmites and other invasive species. Just as the science of plant-microbial symbiosis can be transferred for use in other invasive species, so too can the model of collective impact be applied to other avenues of research and management.


Effect of Community-Initiated Kangaroo Mother Care on Fecal Biomarkers of Gut Function in Low Birth Weight Infants in North India: A Randomized Clinical Trial.
This individually randomized trial was conducted to estimate the effect of promoting community-initiated Kangaroo Mother Care (ciKMC) in low birth weight (LBW) infants on gut inflammation and permeability. Participants included 200 stable LBW infants (weighing 1,500-2,250 g) in North India enrolled between May and October 2017. The ciKMC intervention included promotion and support of continuous skin-to-skin contact and exclusive breastfeeding through home visits. The mothers in the intervention arm were supported to practice ciKMC until 28 days after birth, i.e., the neonatal period, or till the baby wriggled out of KMC position, if earlier. Infant stool specimens were collected during the first week of birth, and within 1 week after end of the neonatal period. Concentrations of fecal neopterin (nmol/L), myeloperoxidase (ng/mL), and alpha-1-antitrypsin (μg/mL) were determined using ELISA, and composite enteric enteropathy (EE) score at the end of the neonatal period was calculated by principal component analysis. We did not find any substantial difference in means between the ciKMC and control arm infants in the log-transformed values of neopterin (0.03; 95% CI -0.15 to 0.21), myeloperoxidase (0.28; 95% CI -0.05 to 0.61) and alpha-1-antitrypsin (0.02; 95% CI -0.30 to 0.34). The mean (SD) composite EE score was 13.6 (7.5) in the ciKMC and 12.4 (8.3) in the control arm infants, and the adjusted difference in means was, 0.4 (95% CI -1.8 to 2.7). Our findings suggest that the promotion of ciKMC did not affect gut inflammation and permeability in our target population of LBW infants in North India.


Solidago, orthosiphon, birch and cranberry extracts can decrease microbial colonization and biofilm development in indwelling urinary catheter: a microbiologic and ultrastructural pilot study.
Plants extracts are used in urology to manage urinary tract infections. We aimed to evaluate the efficacy of a preparation with solidago, orthosiphon, birch and cranberry extracts (CISTIMEV PLUS(®)) in reducing microbial colonization and biofilm development in patients with indwelling urinary catheters. All consecutive outpatients attending our department between January and June 2010 for the substitution of indwelling catheters were considered for this single-blinded, randomized and controlled pilot study to test superiority of the preventative management (CISTIMEV PLUS(®), 1 tablet daily for 30 days) in respect to no treatment. A sample size of 10-40 participants per group was considered adequate. All patients underwent urine culture the same day of the catheter substitution and were then randomized into test group (n = 48) and control group (n = 35). Ultrastructural analysis was also performed. After 30 days, the catheter was replaced and the analysis repeated. The primary outcome was the rate of positive urinary culture at the end of the entire study period. Ten patients abandoned the study. At 30 days, according to per-protocol analysis, the groups statistically differed regarding the rate of positive urine cultures: test group 10/43 and control group 16/30 (p = 0.013) (-30.1 % [95 % CI -51.94 to -8.21]). The most common isolated bacteria were Escherichia coli and Enterococcus faecalis. The use of solidago, orthosiphon, birch and cranberry extracts resulted in a significant reduction of microbial colonization in patients with indwelling urinary catheters. Larger clinical trials are needed to demonstrate that the effects here reported are sufficient to reduce symptomatic catheter-associated urinary tract infections.