Accommodating natural and sexual selection in butterfly wing pattern evolution.
Visual patterns in animals may serve different functions, such as attracting mates and deceiving predators. If a signal is used for multiple functions, the opportunity arises for conflict among the different functions, preventing optimization for any one visual signal. Here we investigate the hypothesis that spatial separation of different visual signal functions has occurred in Bicyclus butterflies. Using phylogenetic reconstructions of character evolution and comparisons of evolutionary rates, we found dorsal surface characters to evolve at higher rates than ventral characters. Dorsal characters also displayed sex-based differences in evolutionary rates more often than did ventral characters. Thus, dorsal characters corresponded to our predictions of mate signalling while ventral characters appear to play an important role in predator avoidance. Forewing characters also fit a model of mate signalling, and displayed higher rates of evolution than hindwing characters. Our results, as well as the behavioural and developmental data from previous studies of Bicyclus species, support the hypothesis that spatial separation of visual signal functions has occurred in Bicyclus butterflies. This study is the first to demonstrate, in a phylogenetic framework, that spatial separation of signals used for mate signalling and those used for predator avoidance is a viable strategy to accommodate multiple signal functions. This signalling strategy has important ramifications on the developmental evolution of wing pattern elements and diversification of butterfly species.


Infectious Cognition: Risk Perception Affects Socially Shared Retrieval-Induced Forgetting of Medical Information.
When speakers selectively retrieve previously learned information, listeners often concurrently, and covertly, retrieve their memories of that information. This concurrent retrieval typically enhances memory for mentioned information (the rehearsal effect) and impairs memory for unmentioned but related information (socially shared retrieval-induced forgetting, SSRIF), relative to memory for unmentioned and unrelated information. Building on research showing that anxiety leads to increased attention to threat-relevant information, we explored whether concurrent retrieval is facilitated in high-anxiety real-world contexts. Participants first learned category-exemplar facts about meningococcal disease. Following a manipulation of perceived risk of infection (low vs. high risk), they listened to a mock radio show in which some of the facts were selectively practiced. Final recall tests showed that the rehearsal effect was equivalent between the two risk conditions, but SSRIF was significantly larger in the high-risk than in the low-risk condition. Thus, the tendency to exaggerate consequences of news events was found to have deleterious consequences.


NMR and Fluorescence Spectroscopies Reveal the Preorganized Binding Site in Family 14 Carbohydrate-Binding Module from Human Chitotriosidase.
Carbohydrate-binding modules (CBM) play important roles in targeting and increasing the concentration of carbohydrate active enzymes on their substrates. Using NMR to get the solution structure of CBM14, we can gain insight into secondary structure elements and intramolecular interactions with our assigned nuclear overhauser effect peaks. This reveals that two conserved aromatic residues (Phe437 and Phe456) make up the hydrophobic core of the CBM. These residues are also responsible for connecting the two β-sheets together, by being part of β2 and β4, respectively, and together with disulfide bridges, they create CBM14's characteristic "hevein-like" fold. Most CBMs rely on aromatic residues for substrate binding; however, CBM14 contains just a single tryptophan (Trp465) that together with Asn466 enables substrate binding. Interestingly, an alanine mutation of a single residue (Leu454) located behind Trp465 renders the CBM incapable of binding. Fluorescence spectroscopy performed on this mutant reveals a significant blue shift, as well as a minor blue shift for its neighbor Val455. The reduction in steric hindrance causes the tryptophan to be buried into the hydrophobic core of the structure and therefore suggests a preorganized binding site for this CBM. Our results show that both Trp465 and Asn466 are affected when CBM14 interacts with both (GlcNAc)3 and β-chitin, that the binding interactions are weak, and that CBM14 displays a slightly higher affinity toward β-chitin.


Glycemic and insulinemic responses to multiple preexercise carbohydrate feedings.
This investigation was undertaken to determine whether consuming several small feedings of preexercise carbohydrate (CHO), rather than a single bolus, would affect blood glucose and insulin responses during rest and exercise. Eight trained cyclists ingested 22.5, 45, or 75 total g maltodextrin and dextrose dissolved in 473 ml of water or an equal volume of placebo (PL). Drinks were divided into four portions and consumed at 15-min intervals in the hour before a 120-min ride at 66% VO2max. Serum glucose values were elevated by the CHO feedings at rest and fell significantly below baseline and PL at 15 min of exercise. However, glucose concentrations were similar in each of the CHO trials. Insulin concentrations also increased rapidly during rest, then fell sharply at the onset of exercise. The findings demonstrate that CHO consumed within an hour before exercise, even when taken in several small feedings, can produce transient hypoglycemia near the onset of exercise. Additionally, the magnitude of the response appears to be unrelated to either the amount of CHO ingested or the insulin response.


A Comment on the Post-Finasteride Syndrome.
The post-Finasteride syndrome (PFS) has been claimed to occur in men who have taken oral finasteride to treat hair loss or benign prostatic hyperplasia. While the incidence of persistent sexual, mental, and physical side effects despite quitting finasteride is unknown, and the condition is not recognized by the scientific community, individuals who suffer from PFS do present with very distinctive and homogenous symptoms. The concept has emerged from reports of nondermatologists, neuroendocrinological research, case reports, and uncontrolled studies. These have been scrutinized by hair experts who found that persistent sexual side effects were only documented in low-quality studies with a strong bias selection and a significant nocebo effect. Others totally dispute the credibility of the PFS. In any case, the PFS is a problem that has to be dealt with. Low-quality studies neither confirm nor refute the condition as a valid nosologic entity. Therefore, it is as inappropriate to dismiss the condition, as it would be to demonize finasteride for the treatment of male pattern hair loss. Whether the PFS represents a nocebo reaction or a real drug adverse event is irrelevant, while the best way to alleviate the emotional distress related to hair loss is to effectively treat the condition causing the problem. It is not sufficient to only discuss the plausibility of the PFS. There is a need for practical recommendations to include such important issues as patient selection and risk assessment, appropriate patient information, how to react in case of drug-related adverse events, issues of fertility and malignancy, management of the PFS, and alternatives, specifically the use of topical finasteride. It is the aim of this commentary to provide the respective information.


Changes in incidence of diabetes in U.S. adults, 1997-2003.
The incidence of self-reported diagnosed diabetes may be increasing because of recent changes in the diagnostic criteria for diabetes, enhanced case detection, and a true increase in disease incidence. These factors may also be changing the characteristics of newly diagnosed cases. Therefore, we examined recent trends in the incidence of diagnosed diabetes, changes to the characteristics of incident cases, and factors associated with incidence. First, National Health Interview Survey data for 1997 to 2003 were used to examine 7-year trends in the incidence of diagnosed diabetes among U.S. adults aged 18 to 79 years. Second, among 1997-1998 and 2002-2003 incident cases, differences in sociodemographic characteristics, risk factors, and indicators of health status were examined. Lastly, multivariate-adjusted incidence from multiple logistic regression of 2001-2003 survey data were derived. From 1997 to 2003, the incidence of diagnosed diabetes increased 41% from 4.9 to 6.9 per 1,000 population (p <0.01). Incidence increased among men and women, non-Hispanic whites, persons with at least a high school education, nonsmokers, active and inactive persons, and among obese persons (p <0.05). Obesity was more prevalent (p <0.01) and physical limitation was less prevalent (p =0.03) in 2002-2003 versus 1997-1998 incident cases. Multivariate-adjusted incidence increased with age and BMI category, and decreased with education level (p <0.05). Obesity was a major factor in the recent increase of newly diagnosed diabetes. Lifestyle interventions that reduce or prevent the prevalence of obesity among persons at risk for diabetes are needed to halt the increasing incidence of diabetes.


Effects of exercising before breakfast on the health of T2DM patients-A randomized controlled trial.
This is the first study to examine whether training before breakfast in the overnight-fasted state is more effective in improving the health of patients with type 2 diabetes mellitus (T2DM) than after breakfast in the fed state. Thirty T2DM patients (60 ± 8 years, 33.7 ± 4.6 kg/m2 ) were randomly assigned to the F group (training in the overnight-fasted state (n = 15)) and to the C group (training in the fed state (control group, n = 15)). All patients completed an 8-week combined endurance/strength training program. Physical training significantly increased time to physical exhaustion during an endurance test (+10.4%), power output during strength tests (chest presses: +36.7% and seated rows: +37.8%), and fat-free mass (+1.7 kg). Body fat mass (-1.9 kg), glycated hemoglobin (HbA1c) values (absolute change: -0.3%), serum insulin values (-2.5 microU/mL), the homeostatic model assessment for insulin resistance (HOMA-IR) index (-1.1), and circulating triglyceride levels (-31 mg/dL) decreased significantly from pre- to post-training. The training had no effect on body mass index, serum fasting glucose, total cholesterol, low-density lipoprotein/high-density lipoprotein ratio or interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)α levels. Analyses of variance revealed no time × group interaction for any variable (P > .05). The training was effective in improving the health of T2DM patients. However, the preliminary study's data do not provide any evidence that the nutritional state (overnight-fasted or fed) in regular physical training plays a significant role for training-induced adaptations in T2DM patients. Full trials (using other training protocols as well) should be conducted to gain further knowledge about the relevance of pre-exercise breakfast ingestion.


Guidelines for the Management of Extremely Premature Deliveries: A Systematic Review.
Available data on survival rates and outcomes of extremely low gestational age (GA) infants (22-25 weeks' gestation) display wide variation by country. Whether similar variation is found in statements by national professional bodies is unknown. The objectives were to perform a systematic review of management from scientific and professional organizations for delivery room care of extremely low GA infants. We searched Embase, PubMed, and Google Scholar for management guidelines on perinatal care. Countries were included if rated by the United Nations Development Programme's Human Development Index as "very highly developed." The primary outcome was rating of recommendations from "comfort care" to "active care." Secondary outcomes were specifying country-specific survival and considering potential for 3 biases: limitations of GA assessment; bias from different definitions of stillbirths and live births; and bias from the use of different denominators to calculate survival. Of 47 highly developed countries, 34 guidelines from 23 countries and 4 international groups were identified. Of these, 3 did not state management recommendations. Of the remaining 31 guidelines, 21 (68%) supported comfort care at 22 weeks' gestation, and 20 (65%) supported active care at 25 weeks' gestation. Between 23 and 24 weeks' gestation, much greater variation was seen. Seventeen guidelines cited national survival rates. Few guidelines discussed potential biases: limitations in GA (n = 17); definition bias (n = 3); and denominator bias (n = 7). Although there is a wide variation in recommendations (especially between 23 and 24 weeks' GA), there is general agreement for comfort care at 22 weeks' GA and active care at 25 weeks' GA.


On using prototype reduction schemes and classifier fusion strategies to optimize kernel-based nonlinear subspace methods.
In Kernel-based Nonlinear Subspace (KNS) methods, the length of the projections onto the principal component directions in the feature space, is computed using a kernel matrix, K, whose dimension is equivalent to the number of sample data points. Clearly this is problematic, especially, for large data sets. In this paper, we solve this problem by subdividing the data into smaller subsets, and utilizing a Prototype Reduction Scheme (PRS) as a preprocessing module, to yield more refined representative prototypes. Thereafter, a Classifier Fusion Strategy (CFS) is invoked as a postprocessing module, to combine the individual KNS classification results to derive a consensus decision. Essentially, the PRS is used to yield computational advantage, and the CFS, in turn, is used to compensate for the decreased efficiency caused by the data set division. Our experimental results demonstrate that the proposed mechanism significantly reduces the prototype extraction time as well as the computation time without sacrificing the classification accuracy. The results especially demonstrate a significant computational advantage for large data sets within a parallel processing philosophy.


Genetic analysis of the low calcium response in Yersinia pestis mu d1(Ap lac) insertion mutants.
Yersinia pestis strain KIM requires plasmid pCD1 for expression of the low calcium response, plague virulence antigen V, and virulence. We constructed Mu d1(Ap lac) insertion mutants of this plasmid which were unable to express the low calcium response. The insertions mapped to a 17-kilobase region of the plasmid. By determining the orientation of the insertions and examining beta-galactosidase production from the Mu d1 lac genes, we determined that this region contains three units of transcription, one of which is transcribed in a direction opposite the direction of transcription of the other two. Transcription of at least two of these units was induced significantly at 37 degrees C compared with 26 degrees C. Ca2+ (2.5 mM) and ATP (18 mM) had no significant effect on the level of expression of the Mu d1 lac genes of these mutants. All insertions in the region strongly reduced production of the V antigen. Insertions from each unit of transcription also reduced virulence in mice.


Gambling in the Czech Republic.
To provide an overview of gambling and associated problems in the Czech Republic, including an overview of the historical context, legislation, prevalence, treatment and research base and agenda. A review of literature and relevant sources. The trajectory of gambling patterns in the territory of the Czech Republic in the 20th century reflected broad socio-political changes. Those included significant expansion between the wars, strict state control and bans on some gambling activities during the communist regime and finally dynamic development characterized by a boom in electronic gaming machines (EGMs) and increasing accessibility of gambling facilities after 1989, which aggravated gambling-related problems. Many municipalities have banned EGMs, which has created conflict in regulation at state and municipal levels. The draft gambling law prepared in 2014 aims to clarify the regulatory framework. Before 2012 there was only sporadic research interest in gambling, but in 2012 the first complex research on gaming and problem gambling in the Czech population took place. The estimated prevalence of problem gambling is currently 2% in the population aged 15-64 years. Preventive measures, counselling and treatment services for problem gamblers are limited. Weak and ineffective regulation of the gambling market in the Czech Republic during the past 20 years, despite the large growth in gambling, has led to inadequate prevention and response to problem gambling which has become a considerable public health, social and political issue.


Intermode light diffusion in multimode optical waveguides with rough surfaces.
A theoretical analysis of incoherent intermode light power diffusion in multimode dielectric waveguides with rough (corrugated) surfaces is presented. The correlation length a of the surface-profile variations is assumed to be sufficiently large (a less less than lambda/2pi) to permit light scattering into the outer space only from the modes close to the critical angles of propagation and yet sufficiently small (a less less than d, where d is the average width of the waveguide) to permit direct interaction between a given mode and a large number of neighboring ones. The cases of a one-dimensional (1D) slab waveguide and a two-dimensional cylindrical waveguide (optical fiber) are analyzed, and we find that in both cases the partial differential equations that govern the evolution of the angular light power profile propagating along the waveguide are 1D and of the diffusion type. However, whereas in the former case the effective conductivity coefficient proves to be linearly dependent on the transverse-mode wave number, in the latter one the linear dependence is for the effective diffusion coefficient. The theoretical predictions are in reasonable agreement with experimental results for the intermode power diffusion in multimode (700 x 700) optical fibers with etched surfaces. The characteristic length of dispersion of a narrow angular power profile evaluated from the correlation length and standard deviation of heights of the surface profile proved to be in good agreement with the experimentally observed changes in the output angular power profiles.


Differential Impact of Aging on Cardiovascular Risk in Women Military Service Members.
Background Atherosclerotic cardiovascular disease (ASCVD) is the third leading cause of death in women service members and veterans. This study assessed 10-year ASCVD risk in women service members and veterans using their own electronic health record data extracted from Veterans Affairs (VA) national Corporate Data Warehouse database. Methods and Results We retrospectively followed 69 574 VA women, aged 30 to 79 years, from 2007 to 2017. Of these, 52% were whites (n=36 172), 42% were blacks (n=29 232), and 6% were Hispanics (n=4171). Risk factors and ASCVD events (nonfatal myocardial infarction, nonfatal stroke, and cardiac deaths) were identified using diagnostic and procedural codes from electronic health records. Then, within the same construct of the current American College of Cardiology/American Heart Association 10-year ASCVD risk assessment models for women, coefficients for risks factors were recalculated using the VA national electronic health record data, stratified by race (hereafter, VA women model). Our study found a curvilinear association of aging with increased risk of 10-year ASCVD event in VA women starting at ages as young as 30 years across all race groups. The VA women model performance in predicting ASCVD events at 10 years was mixed-moderate in discrimination (C statistics, 0.61-0.64) but good in accuracy, as demonstrated by calibration plots approximating a 45° line. Conclusions The study finding, a curvilinear association of aging with increased ASCVD risk in VA women across all races, demonstrates the need for cardiovascular risk screening of younger VA women, aged <45 years.


A nationwide epidemiologic, clinical, genetic study of Usher syndrome in Japan.
Usher syndrome (USH) typically leads to deaf-blindness, requiring the provision of extensive education and rehabilitation services. Therefore, investigating the prevalence is crucial to requests for proper government support for USH patients. The aim was to perform a nationwide epidemiologic survey of USH in Japan to estimate the prevalence of USH and reveal the relative frequency and characteristics of the three USH subtypes. To estimate the number of USH patients visiting hospitals over a 1-year period, 1,628 hospitals were randomly selected from all Departments of Otorhinolaryngology and Ophthalmology in Japan. Subsequently, we collected data regarding the clinical characteristics of each patient treated and the results of genetic testing, if performed. We found that the prevalence of USH was at least 0.4 per 100,000 population. The frequency of clinical subtypes and causal genes for USH were consistent with previous reports. Also, we demonstrated the feasibility of genetic counseling for USH patients based on the results of genetic testing. USH is a rare disease, but requires social support due to the severity of symptoms. To minimize these issues, understanding the clinical characteristics and performing comprehensive genetic testing could allow early and accurate diagnosis as well as medical intervention.


Food color is in the eye of the beholder: the role of human trichromatic vision in food evaluation.
Non-human primates evaluate food quality based on brightness of red and green shades of color, with red signaling higher energy or greater protein content in fruits and leafs. Despite the strong association between food and other sensory modalities, humans, too, estimate critical food features, such as calorie content, from vision. Previous research primarily focused on the effects of color on taste/flavor identification and intensity judgments. However, whether evaluation of perceived calorie content and arousal in humans are biased by color has received comparatively less attention. In this study we showed that color content of food images predicts arousal and perceived calorie content reported when viewing food even when confounding variables were controlled for. Specifically, arousal positively co-varied with red-brightness, while green-brightness was negatively associated with arousal and perceived calorie content. This result holds for a large array of food comprising of natural food - where color likely predicts calorie content - and of transformed food where, instead, color is poorly diagnostic of energy content. Importantly, this pattern does not emerged with nonfood items. We conclude that in humans visual inspection of food is central to its evaluation and seems to partially engage the same basic system as non-human primates.


'We are all in the same boat': How societal discontent affects intention to help during the COVID-19 pandemic.
The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis. Consequently, many countries have adopted restrictive measures that caused a substantial change in society. Within this framework, it is reasonable to suppose that a sentiment of societal discontent, defined as generalized concern about the precarious state of society, has arisen. Literature shows that collectively experienced situations can motivate people to help each other. Since societal discontent is conceptualized as a collective phenomenon, we argue that it could influence intention to help others, particularly those who suffer from coronavirus. Thus, in the present study, we aimed (a) to explore the relationship between societal discontent and intention to help at the individual level and (b) to investigate a possible moderating effect of societal discontent at the country level on this relationship. To fulfil our purposes, we used data collected in 42 countries (N = 61,734) from the PsyCorona Survey, a cross-national longitudinal study. Results of multilevel analysis showed that, when societal discontent is experienced by the entire community, individuals dissatisfied with society are more prone to help others. Testing the model with longitudinal data (N = 3,817) confirmed our results. Implications for those findings are discussed in relation to crisis management. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.


Higher order SVD analysis for dynamic texture synthesis.
Videos representing flames, water, smoke, etc., are often defined as dynamic textures: "textures" because they are characterized by the redundant repetition of a pattern and "dynamic" because this repetition is also in time and not only in space. Dynamic textures have been modeled as linear dynamic systems by unfolding the video frames into column vectors and describing their trajectory as time evolves. After the projection of the vectors onto a lower dimensional space by a singular value decomposition (SVD), the trajectory is modeled using system identification techniques. Synthesis is obtained by driving the system with random noise. In this paper, we show that the standard SVD can be replaced by a higher order SVD (HOSVD), originally known as Tucker decomposition. HOSVD decomposes the dynamic texture as a multidimensional signal (tensor) without unfolding the video frames on column vectors. This is a more natural and flexible decomposition, since it permits us to perform dimension reduction in the spatial, temporal, and chromatic domain, while standard SVD allows for temporal reduction only. We show that for a comparable synthesis quality, the HOSVD approach requires, on average, five times less parameters than the standard SVD approach. The analysis part is more expensive, but the synthesis has the same cost as existing algorithms. Our technique is, thus, well suited to dynamic texture synthesis on devices limited by memory and computational power, such as PDAs or mobile phones.


Wall correction factors, Pwall, for parallel-plate ionization chambers.
The EGSnrc Monte Carlo user-code CSnrc is used to calculate wall correction factors, Pwall,, for parallel-plate ionization chambers in photon and electron beams. A set of Pwall values, computed at the reference depth in water, is presented for several commonly used parallel-plate chambers. These values differ from the standard assumption of unity used by dosimetry protocols by up to 1.7% for clinical electron beams. Calculations also show that Pwall is strongly dependent on the depth of measurement and can vary by as much as 6% for a 6 MeV beam in moving from a depth of dref to a depth of R50. In photon beams, where there is limited information available regarding Pwall for parallel-plate chambers, CSnrc calculations show Pwall values of up to 2.4% at the reference depth over a range of photon energies. The Pwall values for photon beams are in good agreement with previous estimates of the wall correction but have much lower statistical uncertainties and cover a wider range of photon beam energies.


The role of sex on stability and change of depression symptom subtypes over 20 years: a latent transition analysis.
Prospective studies investigating the long-term stability of depression symptom subtypes are rare. Moreover, sex has received little attention as a predictor. This study aimed to investigate the role of sex on stability and transition patterns of depressive symptom subtypes over 20 years. The data were drawn from three follow-ups (1988, 1999, and 2008) of the longitudinal Zurich Study. Latent transition analyses were fitted to the data of 322 subjects, using depressive symptoms from the face-to-face interviews. The stable classes were characterized by psychosocial correlates. Three subtypes were identified: 'severe atypical,' 'severe typical,' and 'moderate.' While stability of the severe atypical and moderate subtype was relatively high and increased over time (70-71; 45-90%), stability of the severe typical subtype was lower (45-48%). Females had a higher risk of being in the severe atypical subtype and exhibited more transitions, particularly with respect to the severe typical subtype. In contrast, males displayed more stable subtypes. The stable severe atypical subtype was associated with comorbid eating disorders as well as psychosis syndromes, whereas the stable severe typical subtype was associated only with psychosis syndromes. Our results provide first evidence for the notion that long-term stability and transition patterns differ by sex and depression subtypes. This finding has received too little attention in previous research and should be considered in treatments.


A hermeneutic analysis of delusion content from the casebooks of the Grahamstown Lunatic Asylum, 1890-1907.
This study sought to investigate the content of the delusions recorded in the casebooks of the Grahamstown Lunatic Asylum as a means to explore how the colonial context shaped or influenced psychopathology. To this end, the study aimed to (1) identify the sociopolitical events of the time period that were reflected in the delusion content presented by the patients and (2) pinpoint discernible patterns in the delusion content based on the race and gender of the patient. The study was delimited to the period of Dr T.D. Greenlees' tenure as medical superintendent, 1890-1907. The study sampled the casebook records of 400 patients. A qualitative analysis of the casebooks was followed by adopting a Gadamerian approach to hermeneutics. The analysis drew upon the clearly articulated method and step-by-step approach for Gadamerian hermeneutics outlined by Fleming, Gaidys and Robb. The sociocultural and political events of South Africa during the turn of the 20th century had a marked influence on the content of the patients' delusions. The South African War (1899-1902), the rinderpest epidemic of 1896-1898, diamond mining in Kimberley and the discovery of gold in the Witwatersrand were common features in the delusion content. Moreover, there is evidence of discernible patterns in the content of the delusions based on the race and gender of the patients. The study identified how the colonial context influenced the delusional content presented by the patients of the Grahamstown Lunatic Asylum. Of key significance is the fact that the study retrieved themes in the delusional content presented by black subjects that were silenced, omitted or censored from psychiatric texts published during colonialism.


Wireless magnetothermal deep brain stimulation.
Wireless deep brain stimulation of well-defined neuronal populations could facilitate the study of intact brain circuits and the treatment of neurological disorders. Here, we demonstrate minimally invasive and remote neural excitation through the activation of the heat-sensitive capsaicin receptor TRPV1 by magnetic nanoparticles. When exposed to alternating magnetic fields, the nanoparticles dissipate heat generated by hysteresis, triggering widespread and reversible firing of TRPV1(+) neurons. Wireless magnetothermal stimulation in the ventral tegmental area of mice evoked excitation in subpopulations of neurons in the targeted brain region and in structures receiving excitatory projections. The nanoparticles persisted in the brain for over a month, allowing for chronic stimulation without the need for implants and connectors.


RabGEF1 is a negative regulator of mast cell activation and skin inflammation.
Mast cell activation induced by aggregation of Fc epsilon RI receptors with immunoglobulin E and antigen is mediated through the activation of multiple protein kinase cascades. Here we report that the regulatory protein RabGEF1 bound to Ras and negatively regulated Ras activation and its 'downstream' effector pathways in Fc epsilon RI-dependent mast cell activation. RabGEF1-deficient mast cells showed enhanced degranulation and release of lipid mediators and cytokines in response to Fc epsilon RI aggregation. RabGEF1-deficient mice developed severe skin inflammation and had increased numbers of mast cells. Thus, RabGEF1 is a negative regulator of Fc epsilon RI-dependent mast cell activation, and a lack of RabGEF1 results in the development of skin inflammation in vivo.


Validation of a Dish-Based Semiquantitative Food Questionnaire in Rural Bangladesh.
A locally validated tool was needed to evaluate long-term dietary intake in rural Bangladesh. We assessed the validity of a 42-item dish-based semi-quantitative food frequency questionnaire (FFQ) using two 3-day food diaries (FDs). We selected a random subset of 47 families (190 participants) from a longitudinal arsenic biomonitoring study in Bangladesh to administer the FFQ. Two 3-day FDs were completed by the female head of the households and we used an adult male equivalent method to estimate the FD for the other participants. Food and nutrient intakes measured by FFQ and FD were compared using Pearson's and Spearman's correlation, paired t-test, percent difference, cross-classification, weighted Kappa, and Bland-Altman analysis. Results showed good validity for total energy intake (paired t-test, p < 0.05; percent difference <10%), with no presence of proportional bias (Bland-Altman correlation, p > 0.05). After energy-adjustment and de-attenuation for within-person variation, macronutrient intakes had excellent correlations ranging from 0.55 to 0.70. Validity for micronutrients was mixed. High intraclass correlation coefficients (ICCs) were found for most nutrients between the two seasons, except vitamin A. This dish-based FFQ provided adequate validity to assess and rank long-term dietary intake in rural Bangladesh for most food groups and nutrients, and should be useful for studying dietary-disease relationships.


Activation protein 1-dependent transcriptional activation of interleukin 2 gene by Ca2+/calmodulin kinase type IV/Gr.
The Ca2+/calmodulin-dependent protein kinase (CaMK) type IV/Gr is selectively expressed in T lymphocytes and is activated after signaling via the T cell antigen receptor (TCR), indicating that it mediates some of the Ca(2+)-dependent transcriptional events that follow TCR engagement. Here we show that CaMKIV/Gr induces the transcription factor activation protein 1 (AP-1) alone or in synergy with T cell mitogens and with the p21ras oncoprotein. CaMKIV/ Gr signaling is associated with transcriptional activation of c-fos but is independent of p21ras or calcineurin. AP-1 is an integral component of the nuclear factor of activated T cells (NFAT) transcriptional complex, which is required for interleukin 2 gene expression in T cells. We demonstrate that CaMKIV/Gr reconstitutes the capacity of the cytosolic component of NFAT to direct transcription from NFAT sites in non-T cells. These results reveal a central role for CaMKIV/Gr as a Ca(2+)-regulated activator of gene transcription in T lymphocytes.


Ultrasound methodology used to construct the fetal growth standards in the INTERGROWTH-21st Project.
A unified protocol is essential to ensure that fetal ultrasound measurements taken in multicentre research studies are accurate and reproducible. This paper describes the methodology used to take two-dimensional, ultrasound measurements in the longitudinal, fetal growth component of the INTERGROWTH-21(st) Project. These standardised methods should minimise the systematic errors associated with pooling data from different study sites. They represent a model for carrying out similar research studies in the future.


Complete Genome Sequence of the Marine Hydrocarbon Degrader Alcaligenes aquatilis QD168, Isolated from Crude Oil-Polluted Sediment of Quintero Bay, Central Chile.
Alcaligenes aquatilis strain QD168 (= CCUG 69566) is a marine hydrocarbon-degrading bacterium isolated from crude oil-polluted sediment from Quintero Bay, Central Chile. Here, we present the 4.32-Mb complete genome sequence of strain QD168, with 3,892 coding sequences, 58 tRNAs, and a 56.3% G+C content.


Knowledge, attitudes and practices regarding HIV/AIDS among senior secondary school students in Fako Division, South West Region, Cameroon.
Knowledge, attitudes and practices (KAPs) regarding HIV/AIDS is one of the corner stones in the fight against the disease. Youths are most vulnerable to infection because they engage in risky practices due to a lack of adequate information. Thus, evaluating their KAPs will help in designing appropriate prevention strategies. This study was aimed at assessing the KAPs of senior secondary school students in Fako Division, Cameroon, on HIV/AIDS. This was a cross-sectional study carried out on 464 students aged 13-25 years, selected by systematic quota random sampling from some secondary schools in Fako, from April to June 2014, to evaluate their KAPs regarding HIV/AIDS. Participants were drawn from one secondary school in each of the four health districts in Fako. Pre-tested questionnaires were administered to the students to obtain information about their KAPs on HIV/AIDS. Data were analyzed using SPSS version 20.0. All respondents were aware of HIV/AIDS. Sources of information varied, the most common being sex education in school. The majority of participants demonstrated an adequate understanding of HIV transmission and prevention. However, misconceptions about routes of transmission were observed in 3.4 to 23.3 % of respondents. Risky behaviors were found among participants as about 60 % practice safe sex and 40 % reported not to. Up to 196 (42.2 %) respondents had a history of sexual intercourse of which 108 (56.25 %) had used a condom during their last three sexual encounters. About half of the respondents had negative views about HIV infected people. Students with medium (34.3 %) and high (62.1 %) levels of knowledge were more likely to display positive attitudes Although statistically not significant, we found that as knowledge increased the ability of respondents to report safer sex decreased (95 % CI, P = 0.922). Students had a satisfactory level of knowledge on HIV/AIDS prevention. Those with adequate knowledge were more likely to display positive attitudes towards PLHIV. Having adequate knowledge did not imply engaging in safe practices. This study none-the-less highlighted some misconceptions about HIV transmission, intolerant and discriminatory attitudes towards PLHIV, and risky sexual practices among study participants which can be corrected by reinforcing sex education curriculum as sex education in school was their main source of information on HIV/AIDS.


Current Therapy of Drugs in Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS), commonly termed as motor neuron disease (MND) in UK, is a chronically lethal disorder among the neurodegenerative diseases, meanwhile. ALS is basically irreversible and progressive deterioration of upper and lower motor neurons in the motor cortex, brain stem and medulla spinalis. Riluzole, used for the treatment of ALS, was demonstrated to slightly delay the initiation of respiratory dysfunction and extend the median survival of patients by a few months. In this study, the key biochemical defects were discussed, such as: mutant Cu/Zn superoxide dismutase, mitochondrial protectants, and anti-excitotoxic/ anti-oxidative / antiinflammatory/ anti-apoptotic agents, so the related drug candidates that have been studied in ALS models would possibly be further used in ALS patients.


Paternal loss (pal): a meiotic mutant in Drosophila melanogaster causing loss of paternal chromosomes.
The effects of a male-specific meiotic mutant, paternal los (pal), in D. melanogaster have been examined genetically. The results indicate the following: (1) When homozygous in males, pal can cause loss, but not nondisjunction, of any chromosome pair. The pal-induced chromosome loss produces exceptional progeny that apparently failed to receive one, or more, paternal chromosomes and, in addition, mosaic progeny during whose early mitotic divisions one or more paternal chromosomes were lost. (2) Only paternally derived chromosomes are lost. (3) Mitotic chromosome loss can occur in homozygous pal+progeny of pal males. (4) Chromosomes differ in their susceptibility to pal-induced loss. The site responsible for the insensitivity vs. sensitivity of the X chromosome to pal mapped to the basal region of the X chromosome at, or near, the centromere. From these results, it is suggested that pal+acts in male gonia to specify a product that is a component of, or interacts with, the centromeric region of chromosomes and is necessary for the normal segregation of paternal chromosomes. In the presence of pal, defective chromosomes are produced and these chromosomes tend to get lost during the early cleavage divisions of the zygote. (5) The loss of heterologous chromosome pairs is not independent; there are more cases of simultaneous loss of two chromosomes than expected from independence. Moreover, an examination of cases of simultaneous somatic loss of two heterologs reveals an asymmetry in the early mitotic divisions of the zygote such that when two heterologs are lost at a somatic cleavage division, almost invariably one daughter nucleus fails to get either, and the other daughter nucleus receives its normal chromosome complement. It is suggested that this asymmetry is not a property of pal but is rather a normal process that is being revealed by the mutant. (6) The somatic loss of chromosomes in the progeny of pal males allows the construction of fate maps of the blastoderm. Similar fate maps are obtained using data from gynandromorphs and from marked Y chromosome (nonsexually dimorphic) mosaics.


Quantitation of cerebral blood volume by 99mTc-DTPA-HSA SPECT.
The characteristics of technetium-99m diethylenetriaminepentaacetic acid human serum albumin (99mTc-DTPA-HSA) as an agent for quantitation of cerebral blood volume (CBV) were examined. The radioactivity after decay correction as a percentage of the activity at 10 minutes was 84.3 +/- 1.3% at 120 minutes after the injection of 99mTc-DTPA-HSA. Radioactivity was found exclusively in plasma, with little in blood cells. The blood retention of 99mTc-DTPA-HSA is sufficient, and its use in the quantitation of CBV omits the need for centrifugation of the blood sample. CBV quantified using the tracer and a SPECT system with a single-head rotating gamma camera was 4.09 +/- 0.60 ml/100 g brain, similar to values reported previously. Two serial SPECT scans provided similar images, and the CBV values determined by the two scans were closely correlated (p < 0.001). The high reproducibility suggests that the method may be used to monitor the cerebrovascular response to drugs. It was concluded that 99mTc-DTPA-HSA has useful properties for quantitative CBV measurement and that quantitation of CBV by 99mTc-DTPA-HSA SPECT is feasible using a system with a single-head rotating gamma camera.


Retrospective study of the relative frequency of feline hepatobiliary disease in New Zealand based on 10 years of hepatic biopsy samples.
To retrospectively determine the relative frequency of feline hepatobiliary diseases from biopsy specimens submitted to a single laboratory across a 10-year period and to establish whether age, sex or breed associations exist. Histopathological data from 154 liver biopsies of New Zealand cats sampled between 2008 and 2018 were analysed. The samples were allocated to primary, secondary and tertiary disease categories using criteria established by the World Small Animal Veterinary Association. Breed associations were derived using ORs and 95% CIs. Gender and age associations were also evaluated. The most frequently diagnosed hepatobiliary diseases were lymphocytic cholangitis (20 per cent), hepatitis (16.9 per cent), reversible hepatocellular injury (16.4 per cent), neutrophilic cholangitis (9.7 per cent), haematopoietic neoplasia (9.7 per cent), hepatocellular neoplasia (5.6 per cent) and cholangiocellular neoplasia (4.1 per cent). Burmese cats were found to be at significantly increased risk of both biliary and parenchymal diseases and Birman cats to be at significantly increased risk of parenchymal disease. Domestic longhair cats were at significantly increased risk of hepatobiliary neoplasia. Birman cats were at significantly increased risk of hepatitis while domestic shorthair cats were at significantly decreased risk of neutrophilic cholangitis, reversible hepatocellular injury and hepatitis. This study is the first retrospective examination of the relative frequency of hepatobiliary disease in biopsy specimens from New Zealand cats. Some breeds were associated with specific histopathology.


Grader Variability and the Importance of Reference Standards for Evaluating Machine Learning Models for Diabetic Retinopathy.
Use adjudication to quantify errors in diabetic retinopathy (DR) grading based on individual graders and majority decision, and to train an improved automated algorithm for DR grading. Retrospective analysis. Retinal fundus images from DR screening programs. Images were each graded by the algorithm, U.S. board-certified ophthalmologists, and retinal specialists. The adjudicated consensus of the retinal specialists served as the reference standard. For agreement between different graders as well as between the graders and the algorithm, we measured the (quadratic-weighted) kappa score. To compare the performance of different forms of manual grading and the algorithm for various DR severity cutoffs (e.g., mild or worse DR, moderate or worse DR), we measured area under the curve (AUC), sensitivity, and specificity. Of the 193 discrepancies between adjudication by retinal specialists and majority decision of ophthalmologists, the most common were missing microaneurysm (MAs) (36%), artifacts (20%), and misclassified hemorrhages (16%). Relative to the reference standard, the kappa for individual retinal specialists, ophthalmologists, and algorithm ranged from 0.82 to 0.91, 0.80 to 0.84, and 0.84, respectively. For moderate or worse DR, the majority decision of ophthalmologists had a sensitivity of 0.838 and specificity of 0.981. The algorithm had a sensitivity of 0.971, specificity of 0.923, and AUC of 0.986. For mild or worse DR, the algorithm had a sensitivity of 0.970, specificity of 0.917, and AUC of 0.986. By using a small number of adjudicated consensus grades as a tuning dataset and higher-resolution images as input, the algorithm improved in AUC from 0.934 to 0.986 for moderate or worse DR. Adjudication reduces the errors in DR grading. A small set of adjudicated DR grades allows substantial improvements in algorithm performance. The resulting algorithm's performance was on par with that of individual U.S. Board-Certified ophthalmologists and retinal specialists.


The timing of infarction pain in patients with acute myocardial infarction after previous revascularization.
Circadian variation of onset of acute myocardial infarction (AMI) has been noted in many studies, but there are no data about subgroups of patients with previous coronary artery bypass grafting (CABG). Because of abnormalities in the circadian rhythm of autonomic tone after surgery, it was very interesting to analyze the circadian patterns in the onset of symptoms of AMI in various subgroups of 1784 patients with previous CABG. As in the other studies, a peak occurred in the morning hours with 26.3% of the patients, but there was a second nearly equal, but higher, peak (26.4%) in the evening hours. The subgroups with specific clinical characteristics exhibited different patterns that determined these peaks in all populations. In patients older than 70 years of age, in both sexes, in smokers, diabetics, in patients with hypertension, in those undergoing beta-blocker therapy, and in patients without previous angina, two nearly equal peaks were observed, with higher evening peaks, except in those patients with hypertension and without angina. Only one peak in the evening hours was observed in a subgroup of patients with previous congestive heart failure (CHF) and non-STEMI. The subgroup of patients with previous angina and previous AMI exhibited no discernible peaks. The distribution of time of onset within the four intervals was not uniform, and the difference was statistically significant only for patients undergoing beta-blocker therapy at time of onset (p = 0.0013), nonsmokers (p = 0.0283), and patients with non-STEMI (p = 0.0412). It is well known that patients with AMI have a dominant morning peak of circadian variation of onset. However, analyzing a different subgroup of patients with AMI after previous CABG, it was found that some subgroups had two peaks of onset, but a higher evening peak (patients older than 70 years of age, smokers, diabetics, and a group of patients who were taking beta-blocker therapy). This subgroup of patients, together with the subgroups of patients with a dominant evening peak (patients with CHF and those with non-STEMI) and with patients with no peak (patients with previous angina and previous AMI), probably appear to modify characteristic circadian variation of infarction onset, expressing a higher evening peak, respectively to the previous CABG, with adverse consequences for central nervous system functioning.


Neostigmine treatment protocols applied in acute colonic pseudo-obstruction disease: A retrospective comparative study.
When conservative methods fail, neostigmine is recommended in the pharmacological treatment of acute colonic pseudo-obstruction (ACPO). The objective of this study was to analyze the response of patients to different neostigmine protocols. Patients diagnosed with ACPO in the intensive care unit between January 2015 and September 2017 were retrospectively studied. Either of the two neostigmine protocols, the bolus dose (BD) or continuous infusion (CI), was applied to the ACPO patients who were unresponsive to conservative treatments, and the results were analyzed. In 79 of 122 (64%) patients, the resolution of symptoms was observed with conservative treatments. Of 43 patients who did not respond to conservative treatments, 20 were applied neostigmine as BD, and 23 were applied by CI. A total of 55% of patients in the BD group and 60.9% patients in the CI group responded to neostigmine therapy after the first dose. The group-specific protocols were reapplied in patients unresponsive to the first dose. A total of 25% in the BD group and 8.7% in the CI group responded to the second dose treatment. As a result, 80% of patients from the BD group and 69.6% from the CI group responded to neostigmine therapy. Although an overall response rate was higher in the BD group, there was no significant difference between groups (P=0.322). Colonic complications were observed in 2 patients, 1 from each group. There were no major side effects requiring treatment cessation. The safety and effectiveness of both neostigmine protocols applied to ACPO patients were similar. Clinical and radiological responses were obtained without serious side effects with CI.


Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis.
Epithelial-mesenchymal feedback signaling is the key to diverse organogenetic processes such as limb bud development and branching morphogenesis in kidney and lung rudiments. This study establishes that the BMP antagonist gremlin (Grem1) is essential to initiate these epithelial-mesenchymal signaling interactions during limb and metanephric kidney organogenesis. A Grem1 null mutation in the mouse generated by gene targeting causes neonatal lethality because of the lack of kidneys and lung septation defects. In early limb buds, mesenchymal Grem1 is required to establish a functional apical ectodermal ridge and the epithelial-mesenchymal feedback signaling that propagates the sonic hedgehog morphogen. Furthermore, Grem1-mediated BMP antagonism is essential to induce metanephric kidney development as initiation of ureter growth, branching and establishment of RET/GDNF feedback signaling are disrupted in Grem1-deficient embryos. As a consequence, the metanephric mesenchyme is eliminated by apoptosis, in the same way as the core mesenchymal cells of the limb bud.


Removal of anionic surfactants from wastewater using a constructed wetland.
Removal of anionic surfactants from municipal wastewater using a constructed wetland with a horizontal subsurface flow was studied in 2007 and 2008. Extraction spectrophotometry with methylene blue served to determine the analyte concentrations in individual samples. The anionic surfactant-removal efficiency depended on actual conditions, mostly the treated water flow intensity, its temperature, and a redox-potential gradient in the longitudinal profile of the wetland bed. It increased with decreasing inflow and increasing temperature. The average efficiency was 83.7% in 2007 and 81.7% in 2008; however, values higher than 85% were often determined during the summer period. On the other hand, the efficiencies were usually lower than 80% in winter, especially in periods with intensive precipitation and inflows. The average concentration of anionic surfactants in water taken at the outflow was lower than 0.65 mg/l (expressed as sodium dodecyl sulfate). The most significant fraction of anionic surfactants (almost 50%) was degraded at the beginning (1 m from the inflow zone) of the wetland bed. The rhizosphere aeration via the vegetation roots strongly supported the anionic-surfactant removal.


Developmental patterns of plasma and pituitary growth hormone (GH) in the female rat.
Circulating GH levels measured by RIA in developing female rats were elevated between day 5 and 12. Titers declined by day 15, reaching a nadir at day 20 and by day 25 they began to increase again. During the pubertal period (days 32-38), plasma GH was elevated in the anestrous phase, reaching peak values in the afternoon of the early proestrous phase. Levels were also elevated the day of the first preovulatory discharge of gonadotropins, showing peak values in the afternoon of that day. Thereafter, plasma GH declined, reaching a nadir in the morning of diestrus 1 (day 2 after vaginal opening) and remained slightly more elevated during the afternoon of that day and throughout diestrus 2. Plasma GH levels at this time were similar to those of adult diestrus females. Pituitary GH concentration was low between days 5 and 15 and increased markedly thereafter, reaching adult concentrations by day 25. Body weight increased linearly between day 5 and 25. At this time, the slope of the curve of body weight gain increased significantly. Although the majority of animals revealed open vaginae only after they had reached a body weight of 100 g, a critical weight for vaginal opening could not be established. The pronounced changes in circulating GH levels which preceded by several days the surge in gonadotropin release that normally accompanies the onset of puberty in the rat suggest that GH may play a physiological role in the control of the pubertal process in this species.


Weight increase in patients with dementia, and alteration in meal routines and meal environment after integrity promoting care.
To follow weight changes in patients with moderate and severe dementia and analyse how these changes related to biological and psychological parameters after staff education and support in integrity promoting care. A further aim was to describe meal environment and routines relative to the intervention. Weight loss in patients with dementia and in particular Alzheimer's disease is common. The aetiology appears multifactorial with the meal environment and a decreased independence while eating among the factors. Over a three-month intervention period, an integrity-promoting care training programme was conducted with the staff of a long-term ward. Alzheimer's disease patients, 18 from an intervention ward and 15 from a control ward were included and possible effects were evaluated. Weighing was conducted at the start and after completion of the intervention. Weight changes were analysed in relation to psychological and biochemical parameters. In addition, the staff wrote diaries about, for example changes made in the environment and in their work. The most prominent difference observed was weight increases in 13 of 18 patients compared with two of 15 patients in the control ward. No weight changes were related to the type of dementia. The individual weight changes correlated significantly to changes in the intellectual functions. Relationships between weight change, increased motor function and increased appetite were non-significant. There was no significant relationship between weight changes and changes in biochemical parameters. According to the staff, increased contact with the patients and a more pleasant atmosphere resulted when the meal environment and routines were changed. Weight gain in patients with moderate and severe dementia was achieved by adjusting the meal environment to the individual's needs. Staff education was profitable, as increased competence seemed to promote individually adapted feeding situations. Ensuring good meal situations need to be given high priority.


Further expanding versatility of surface-enhanced Raman spectroscopy: from non-traditional SERS-active to SERS-inactive substrates and single shell-isolated nanoparticle.
After surface-enhanced Raman spectroscopy (SERS) was initiated over four decades ago, its practical application seems to be far behind the fundamental research that has made tremendous progress. SERS as a highly sensitive technique has not been widely adopted by the materials science and surface science communities or in the market of analytical instruments. In this discussion, we first classify the previous approaches along this direction over the past four decades and divide them into three strategies. Based on our recent theoretical and experimental approaches, we discuss in more detail the third strategy related to shell-isolated nanostructures. It can significantly expand the SERS study on nontraditional SERS-active (i.e. weakly SERS-active) materials (e.g. Pt, Ni, Fe, etc.) and even SERS-inactive materials (e.g. Si and Al2O3). We then focus on a single shell-isolated nanoparticle and how to controllably locate the strong electromagnetic field just at the probe surface of various materials. The use of side illumination at a high incident angle and/or nanocubes can further enhance the Raman signal by one to two orders of magnitude, which could be helpful for quantitative studies for surface science, heterogeneous catalysis, and soft matter science.


Improved centerline tree detection of diseased peripheral arteries with a cascading algorithm for vascular segmentation.
Vascular segmentation plays an important role in the assessment of peripheral arterial disease. The segmentation is very challenging especially for arteries with severe stenosis or complete occlusion. We present a cascading algorithm for vascular centerline tree detection specializing in detecting centerlines in diseased peripheral arteries. It takes a three-dimensional computed tomography angiography (CTA) volume and returns a vascular centerline tree, which can be used for accelerating and facilitating the vascular segmentation. The algorithm consists of four levels, two of which detect healthy arteries of varying sizes and two that specialize in different types of vascular pathology: severe calcification and occlusion. We perform four main steps at each level: appropriate parameters for each level are selected automatically, a set of centrally located voxels is detected, these voxels are connected together based on the connection criteria, and the resulting centerline tree is corrected from spurious branches. The proposed method was tested on 25 CTA scans of the lower limbs, achieving an average overlap rate of 89% and an average detection rate of 82%. The average execution time using four CPU cores was 70 s, and the technique was successful also in detecting very distal artery branches, e.g., in the foot.


The effect of school bag design and load on spinal posture during stair use by children.
Thirteen male children ascending and descending stairs with loads that equalled 0%, 10%, 15% and 20% of their body weight were the subject of our research: the boys were wearing an asymmetrical single-strap athletic bag or a symmetrical double-strap backpack during our experiments with them. The maximum spinal tilt to the loading side and to the support side, and the range of spinal motions, were obtained by using a motion analysis system. Our results showed that symmetry of spinal posture was observed both when they ascended staircase with all loads and descended in a backpack. When carrying an athletic bag with 15% and 20% of their body weight while ascending the staircase, the lateral spinal tilt to the supporting side was significantly increased. We concluded that a symmetrical backpack with a load not exceeding 20% or an asymmetrical single-strap athletic bag with a load not exceeding 10% should be recommended for school children in order to promote safer staircase use. STATEMENT OF RELEVANCE: Children carrying heavy school bags may develop spinal problems. This study suggested that when they are using stairs, a symmetrical backpack with a load within 20% body weight is acceptable for them. When they are carrying an asymmetrical single-strap athletic bag, the bag's weight should not exceed 10% of the body weight in order to avoid excessive spinal tilt.


Diagnosis, prevention and treatment of urinary tract infections in older people.
Urinary tract infections (UTIs) are common in older people, with the prevalence increasing with age in both sexes. UTI is a frequent reason for emergency admission to hospital. There are many conditions that contribute to older people being more at risk of UTI and the main preventive strategy is to avoid the use of indwelling urethral catheters. Where an indwelling catheter is inserted its continued use should be regularly reviewed and the catheter removed, especially if the reason for insertion is incontinence and the person becomes additionally incontinent of faeces. Diagnosis of UTI can be complex because older people do not always exhibit the signs and symptoms commonly associated with UTI. Diagnosis can be further complicated by a person's inability to provide a comprehensive history and by difficulties obtaining an uncontaminated, 'clean catch' urine specimen. Antibiotic therapy should not be used routinely for people with asymptomatic bacteriuria and, where antibiotics are required, healthcare professionals should follow local prescribing guidelines.


Breath pentane as a potential biomarker for survival in hepatic ischemia and reperfusion injury--a pilot study.
Exhaled pentane, which is produced as a consequence of reactive oxygen species-mediated lipid peroxidation, is a marker of oxidative stress. Propofol is widely used as a hypnotic agent in intensive care units and the operating room. Moreover, this agent has been reported to inhibit lipid peroxidation by directly scavenging reactive oxygen species. In this study, using a porcine liver ischemia-reperfusion injury model, we have evaluated the hypothesis that high concentrations of breath pentane are related to adverse outcome and that propofol could reduce breath pentane and improve liver injury and outcome in swine in this situation. Twenty male swine were assigned to two groups: propofol (n = 10) and chloral hydrate groups (n = 10). Hepatic ischemia was induced by occluding the portal inflow vessels. Ischemia lasted for 30 min, followed by reperfusion for 360 min. Exhaled and blood pentane concentrations in the chloral hydrate group markedly increased 1 min after reperfusion and then decreased to baseline. Breath and blood pentane concentrations in the propofol group increased 1 min after reperfusion but were significantly lower than in the chloral hydrate group. A negative correlation was found between breath pentane levels and survival in the chloral hydrate group. The median overall survival was 251 min after reperfusion (range 150-360 min) in the chloral hydrate group. All of the swine were alive in the propofol group. Monitoring of exhaled pentane may be useful for evaluating the severity of hepatic ischemia-reperfusion injury and aid in predicting the outcome; propofol may improve the outcome in this situation.


[The COVID-19 emergency management in Nephrology: a cross-sectional survey on the procedures management to deal with the pandemic].
From mid-March 2020, the pandemic caused by COVID 19 has placed health facilities in front of the need to implement a rapid and profound reorganization. However, many hospitals have not had time to organize a rapid and effective response, both for the speed of spread of the virus, and for the lack of previous experience with a pandemic of this magnitude. With the aim of assessing the knowledge and adoption of the procedures and recommendations disseminated by hospitals during the COVID-19 pandemic, in the dialysis and hemodialysis services of Italian centers, a cross-sectional survey was designed by the Society of Nurses in Nephrology (SIAN). The online survey was conducted among nurses who work in the Italian services of dialysis and hemodialysis during the first and second waves. The online survey was completed by 150 nurses. Although hospitals have set up protocols and procedures for patient management during the COVID-19 pandemic, among participants not all were aware of it. With regard to the training of personnel in the use of personal protective equipment, 18.6% declared that they have not received it. The majority implemented specific precautions for patient management, awareness and information.


Attitudes Toward Medications and the Relationship to Outcomes in Patients with Schizophrenia.
The determinants of attitudes toward medication (ATM) are not well elucidated. In particular, literature remains equivocal regarding the influence of cognition, adverse events, and psychiatric symptomatology. This study evaluated relationships between those outcomes in schizophrenia and ATM. This is a retrospective analysis of data collected during the Texas Medication Algorithm Project (TMAP, n=307 with schizophrenia-related diagnoses), in outpatient clinics at baseline and every 3 months for ≥1 year (for cognition: 3rd and 9th month only). The Drug Attitude Inventory (DAI-30) measured ATM, and independent variables were: cognition (Trail Making Test [TMT], Verbal Fluency Test, Hopkins Verbal Learning Test), adverse events (Systematic Assessment for Treatment-Emergent Adverse Events, Barnes Akathisia Rating Scale), psychiatric symptomatology (Brief Psychiatric Rating Scale, Scale for Assessment of Negative Symptoms [SANS]), and medication adherence (Medication Compliance Scale). Analyses included binary logistic regression (cognition, psychiatric symptoms) and chi-square (adverse events, adherence) for baseline comparisons, and linear regression (cognition) or ANOVA (adverse events, adherence) for changes over time. Mean DAI-30 scores did not change over 12 months. Odds of positive ATM increased with higher TMT Part B scores (p=0.03) and lower SANS scores (p=0.02). Worsening of general psychopathology (p<0.001), positive symptoms (p<0.001), and negative symptoms (p=0.007) correlated with negative changes in DAI-30 scores. Relationships between cognition, negative symptoms, and ATM warrant further investigation. Studies evaluating therapies for cognitive deficits and negative symptoms should consider including ATM measures as endpoints. Patterns and inconsistencies in findings across studies raise questions about whether some factors thought to influence ATM have nonlinear relationships.


Prediction of non-recovery from ventilator-demanding acute respiratory failure, ARDS and death using lung damage biomarkers: data from a 1200-patient critical care randomized trial.
It is unclear whether biomarkers of alveolar damage (surfactant protein D, SPD) or conductive airway damage (club cell secretory protein 16, CC16) measured early after intensive care admittance are associated with one-month clinical respiratory prognosis. If patients who do not recover respiratory function within one month can be identified early, future experimental lung interventions can be aimed toward this high-risk group. We aimed to determine, in a heterogenous critically ill population, whether baseline profound alveolar damage or conductive airway damage has clinical respiratory impact one month after intensive care admittance. Biobank study of biomarkers of alveolar and conductive airway damage in intensive care patients was conducted. This was a sub-study of 758 intubated patients from a 1200-patient randomized trial. We split the cohort into a "learning cohort" and "validating cohort" based on geographical criteria: northern sites (learning) and southern sites (validating). Baseline SPD above the 85th percentile in the "learning cohort" predicted low chance of successful weaning from ventilator within 28 days (adjusted hazard ratio 0.6 [95% CI 0.4-0.9], p = 0.005); this was confirmed in the validating cohort. CC16 did not predict the endpoint. The absolute risk of not being successfully weaned within the first month was 48/106 (45.3%) vs. 175/652 (26.8%), p < 0.0001 (high SPD vs. low SPD). The chance of being "alive and without ventilator ≥20 days within the first month" was lower among patients with high SPD (adjusted OR 0.2 [95% CI 0.2-0.4], p < 0.0001), confirmed in the validating cohort, and the risk of ARDS was higher among patients with high SPD (adjusted OR 3.4 [95% CI 1.0-11.4], p = 0.04)-also confirmed in the validating cohort. Early profound alveolar damage in intubated patients can be identified by SPD blood measurement at intensive care admission, and high SPD level is a strong independent predictor that the patient suffers from ARDS and will not recover independent respiratory function within one month. This knowledge can be used to improve diagnostic and prognostic models and to identify the patients who most likely will benefit from experimental interventions aiming to preserve alveolar tissue and therefore respiratory function. Trial registration This is a sub-study to the Procalcitonin And Survival Study (PASS), Clinicaltrials.gov ID: NCT00271752, first registered January 1, 2006.


Effect of Toxoplasma gondii upon neophobic behaviour in wild brown rats, Rattus norvegicus.
The effect of Toxoplasma gondii on neophobic behaviour (the avoidance of novel stimuli) was assessed in four groups of wild rats with naturally occurring Toxoplasma infection. Two groups were placed in individual cages and tested in a series of experiments which examined the effect of Toxoplasma on the rat's reaction to 3 food-related novel stimuli (odour, food-container, food). A trappability study was performed on the other two groups to test whether Toxoplasma had an effect on probability of capture. The results show that low neophobia was significantly associated with positive Toxoplasma titres in 3 out of 4 groups. We suggest that differences between infected and uninfected wild rats arise from pathological changes caused by Toxoplasma cysts in the brains of infected rats. Such behavioural changes may be selectively advantageous for the parasite as they may render Toxoplasma-infected rats more susceptible to predation by domestic cats (the definitive host of Toxoplasma) and, as a side-effect, more susceptible to trapping and poisoning during post control programmes.


Antibiotic-Resistant Escherichia coli and Class 1 Integrons in Humans, Domestic Animals, and Wild Primates in Rural Uganda.
Antibiotic resistance is a global concern, although it has been studied most extensively in developed countries. We studied Escherichia coli and class 1 integrons in western Uganda by analyzing 1,685 isolates from people, domestic animals, and wild nonhuman primates near two national parks. Overall, 499 isolates (29.6%) were resistant to at least one of 11 antibiotics tested. The frequency of resistance reached 20.3% of isolates for trimethoprim-sulfamethoxazole but was nearly zero for the less commonly available antibiotics ciprofloxacin (0.4%), gentamicin (0.2%), and ceftiofur (0.1%). The frequency of resistance was 57.4% in isolates from people, 19.5% in isolates from domestic animals, and 16.3% in isolates from wild nonhuman primates. Isolates of livestock and primate origin displayed multidrug resistance patterns identical to those of human-origin isolates. The percentage of resistant isolates in people was higher near Kibale National Park (64.3%) than near Bwindi Impenetrable National Park (34.6%), perhaps reflecting local socioeconomic or ecological conditions. Across antibiotics, resistance correlated negatively with the local price of the antibiotic, with the most expensive antibiotics (nalidixic acid and ciprofloxacin) showing near-zero resistance. Among phenotypically resistant isolates, 33.2% harbored class 1 integrons containing 11 common resistance genes arranged into nine distinct gene cassettes, five of which were present in isolates from multiple host species. Overall, these results show that phenotypic resistance and class 1 integrons are distributed broadly among E. coli isolates from different host species in this region, where local socioeconomic and ecological conditions may facilitate widespread diffusion of bacteria or resistance-conferring genetic elements.IMPORTANCE Antibiotic resistance is a global problem. This study, conducted in rural western Uganda, describes antibiotic resistance patterns in Escherichia coli bacteria near two forested national parks. Resistance was present not only in people, but also in their livestock and in nearby wild nonhuman primates. Multidrug resistance and class 1 integrons containing genes that confer resistance were common and were similar in people and animals. The percentage of resistant isolates decreased with increasing local price of the antibiotic. Antibiotic resistance in this setting likely reflects environmental diffusion of bacteria or their genes, perhaps facilitated by local ecological and socioeconomic conditions.


Hot Carrier Generation and Extraction of Plasmonic Alloy Nanoparticles.
The conversion of light to electrical and chemical energy has the potential to provide meaningful advances to many aspects of daily life, including the production of energy, water purification, and optical sensing. Recently, plasmonic nanoparticles (PNPs) have been increasingly used in artificial photosynthesis (e.g., water splitting) devices in order to extend the visible light utilization of semiconductors to light energies below their band gap. These nanoparticles absorb light and produce hot electrons and holes that can drive artificial photosynthesis reactions. For n-type semiconductor photoanodes decorated with PNPs, hot charge carriers are separated by a process called hot electron injection (HEI), where hot electrons with sufficient energy are transferred to the conduction band of the semiconductor. An important parameter that affects the HEI efficiency is the nanoparticle composition, since the hot electron energy is sensitive to the electronic band structure of the metal. Alloy PNPs are of particular importance for semiconductor/PNPs composites, because by changing the alloy composition their absorption spectra can be tuned to accurately extend the light absorption of the semiconductor. This work experimentally compares the HEI efficiency from Ag, Au, and Ag/Au alloy nanoparticles to TiO2 photoanodes for the photoproduction of hydrogen. Alloy PNPs not only exhibit tunable absorption but can also improve the stability and electronic and catalytic properties of the pure metal PNPs. In this work, we find that the Ag/Au alloy PNPs extend the stability of Ag in water to larger applied potentials while, at the same time, increasing the interband threshold energy of Au. This increasing of the interband energy of Au suppresses the visible-light-induced interband excitations, favoring intraband excitations that result in higher hot electron energies and HEI efficiencies.


Efficacy and tolerability of a new formulation of artesunate-mefloquine for the treatment of uncomplicated malaria in adult in Senegal: open randomized trial.
Prompt treatment of malaria attacks with arteminisin-based combination therapy (ACT) is an essential tool for malaria control. A new co-blister tablet of artesunate-mefloquine (AM) with 25 mg/kg mefloquine has been developed for the management of uncomplicated malaria attacks. This non-inferiority randomized trial, was conducted to evaluate the efficacy and safety of the new formulation of AM in comparison to artemether-lumefantrine (AL) for the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in Senegal. The study was carried out from September to December 2010 in two health centres in Senegal. The study end points included (i) PCR corrected adequate clinical and parasitological response (ACPR) at day 28, (ii) ACPR at days 42 and 63, (iii) parasites and fever clearance time, (iv) incidence of adverse events and patients biological profile at day 7 using the WHO 2003 protocol for anti-malarial drug evaluation. Overall, 310 patients were randomized to receive either AM (n = 157) or AL (n = 153). PCR corrected ACPR at day 28 was at 95.5% in the AM arm while that in the AL arm was at 96.7% (p = 0.83). Therapeutic efficacy was at 98.5% in the AM arm versus 98.2% in the AL group at day 42 (p = 1). At day 63, ACPR in the AM and AL arms was at 98.2% and 97.7%, respectively (p = 0.32). The two treatments were well tolerated with similar biological profile at day 7. However, dizziness was more frequent in the AM arm. Artesunate-mefloquine (25 mg/Kg mefloquine) is efficacious and well-tolerated for the treatment of uncomplicated P. falciparum malaria in adult patients.


Comparison of the conformational stability of the molten globule and native states of horse cytochrome c. Effects of acetylation, heat, urea and guanidine-hydrochloride.
The molten globule state has been assumed to be a major intermediate of protein folding. We compared the stability of the native and acidic molten globule states of horse ferricytochrome c against heat, urea and guanidine hydrochloride (Gdn-HCl) using the intact species and species modified by various degrees of acetylation of the lysyl epsilon-amino groups. After acetylation, the amino groups cannot protonate at acidic pH. Thermal and urea-induced unfolding transitions measured by far-UV circular dichroism and differential scanning calorimetry showed that, whereas acetylation stabilizes the molten globule state at pH 2, it destabilizes the native state at pH 7, suggesting a difference in their mechanisms of conformational stability. On the other hand, the effects of Gdn-Hcl were remarkable. Contrary to what was expected from the thermal and urea-induced unfolding transitions, the Gdn-HCl-induced unfolding transition of the native state at pH 7 was insensitive to the extent of acetylation. At pH 2, Gdn-HCl at low concentrations stabilized the molten globule state and, at high concentrations, destabilized it. Consideration of the difference in the effects of Gdn-HCl from those of urea or heat indicated that, whereas the net positive charge repulsion destabilizes the molten globule state at pH 2, the local negative charge repulsion produced by acetylation of amino groups, and not the net charge, critically destabilizes the native state at pH 7. These results predict that, because of its ionic nature, Gdn-HCl will produce substantially different effects on the conformational states of some proteins compared with those of urea.


uhrf1 and dnmt1 Loss Induces an Immune Response in Zebrafish Livers Due to Viral Mimicry by Transposable Elements.
Activation of transposable elements (TEs) can cause cellular damage. Cytoplasmic nucleic acid sensing pathways evolved to detect pathogens, but can also serve to cull cells with inappropriate TE activation as TEs can be viral mimetics. Epigenetic silencing of TEs is mediated in part by DNA methylation, but it is not clear if TE activation or the immune system contribute to the cellular damage caused by loss of DNA methylation. Here, we provide mechanistic insight into the observation of an activated interferon response in the liver of zebrafish larvae with deletion in critical components of the DNA methylation machinery, uhrf1 and dnmt1. We focus on dissecting the relationship between DNA methylation, TE activation and induction of an immune response through cytoplasmic DNA and double stranded RNA sensing pathways and identify tnfa as a mediator of cell death in the liver of these mutants. Integrated RNAseq and methylome analysis identified LTR transposons as the most upregulated in these mutants and also the most methylated in control larvae, indicating a direct role of DNA methylation in suppressing this TE subclass. RNAseq analysis from these same samples revealed expression signatures of a type-I interferon response and of tnfa activation, mimicking the pattern of gene expression in virally infected cells. CRISPR/Cas9 mediated depletion of the cellular antiviral sensors sting and mavs reduced expression of interferon response genes and tnfa depletion dramatically reduced cell death in uhrf1 mutant livers. This suggests that the antiviral response induced by DNA hypomethylation and TE activation in the liver is mediated by the signaling pathways activated by both cytoplasmic double stranded RNA and DNA and that tnfa mediates cell death as a potential mechanism to eliminate these damaged cells.


The reliability of short-term measurement of heart rate variability during spontaneous breathing in people with chronic obstructive pulmonary disease.
Reduced heart rate variability (HRV), a marker of autonomic system dysfunction, has been reported in patients with chronic obstructive pulmonary disease (COPD). Yet, limited data exists on the reliability of HRV measurement in this population. Here we investigated the reliability of short-term HRV measurement performed during spontaneous breathing in patients with COPD. Thirteen individuals (8 males) with moderate-to-severe COPD (FEV1 46±16% predicted; FEV1/FVC 49±13) underwent standard time and frequency domain HRV measurements derived from 5-minute electrocardiograms collected on two separate days using a SphygmoCor device. Absolute and relative reliability was assessed by a number of coefficients including within-subject random variation, systematic change in the mean, and retest correlations. Within-subject coefficients of variation (CV) ranged from 4.3% to 193.4%. The intraclass correlation coefficients (ICCs) ranged from 0.72 to 0.93 for parameters related to overall HRV, and from 0.57 to 0.59 for those related to parasympathetic tone in both time and frequency domains. Mean heart rate was the only parameter that showed excellent absolute and relative reliability (CV=4.3%, ICC=0.93). The HRV measurements showed overall moderate-to-substantial reliability during spontaneous breathing in COPD population. Our findings support the use of HRV parameters for diagnosis and cardiac risk assessment, but only mean heart rate can be used reliably for monitoring changes in autonomic status following rehabilitation intervention in this population.


Fluoroscopy-free Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for controlling life threatening postpartum hemorrhage.
Severe postpartum hemorrhage occurs in 1/1000 women giving birth. This condition is often dramatic and may be life threatening. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has in recent years been introduced as a novel treatment for hemorrhagic shock. We present a series of fluoroscopy-free REBOA for controlling life threatening postpartum hemorrhage. In 2008 an 'aortic occlusion kit' was assembled and used in three Norwegian university hospitals. The on-call interventional radiologist (IR) was to be contacted with a response time < 30 minutes in case of life threatening PPH. Demographics and characteristics were noted from the medical records. This retrospective study includes 36 patients treated with fluoroscopy-free REBOA for controlling severe postpartum hemorrhage in the years 2008-2015. The REBOA success rate was 100% and no patients died from REBOA related complications. Uterine artery embolization was performed in 17 (47%) patients and a hysterectomy in 16 (44%) patients. A short (11cm) introducer length was strongly associated with iliac artery thrombus formation (ρ = 0.50, P = 0.002). In addition, there was a strong negative correlation between uterine artery embolization and hysterectomy (ρ = -0.50, P = 0.002). Our Norwegian experience indicates the clinical safety and feasibility of REBOA in life threatening PPH. Also, REBOA can be used in an emergency situation without the use of fluoroscopy with a high degree of technical success. It is important that safety implementation of REBOA is established, especially through limited aortic balloon occlusion time and a thorough balloon deflation regime.


What physicians want to learn about sickness certification: analyses of questionnaire data from 4019 physicians.
Sickness absence is a problem in many Western countries. Physicians have an essential role in sickness certification of patients, which is often recommended in health care but may have side effects. Despite the potentially harming impact of sickness absence, physicians have very limited training in insurance medicine, and there is little research on sickness certification practices. Our aim was to ascertain what knowledge and skills physicians in different clinical settings feel they need in order to improve their competence in sickness certification. The data for analysis were collected in 2004 in Stockholm and Ostergötland Counties, Sweden, by use of a comprehensive questionnaire about sickness certification issues, which was sent to 7,665 physicians aged <or= 64 years. The response rate was 71% (n = 5455). Analyses of association and factor analysis were applied to the various aspects of competence to establish a skills index and a knowledge index, which were used to compare the results for physicians in different clinical settings. Most physicians stated they needed more knowledge and skills in handling sickness certification, e.g. regarding how to assess work capacity (44%) and optimal length and degree of sickness absence (50%), and information about aspects of the social insurance system (43-63%). Few (20%) reported needing to know more about issuing sickness certificates. The index scores varied substantially between different clinical settings, and this disparity remained after adjustment for sex, years in practice, workplace policy, and support from management. Scores on the skills index were significantly higher for physicians in primary care than for those working in other areas. A majority of physicians in most types of clinics/practices, not only primary care, indicated the need for more knowledge and skills in handling sickness certification cases. Increased knowledge and skills are needed in order to protect both the health and equity of patients. However, few physicians stated that they needed more skills in filling out sickness certificates, which contradicts previous findings about such documents being of poor quality and suggests that factors other than mere knowledge and skills are involved.


Amyloid-beta levels are significantly reduced and spatial memory defects are rescued in a novel neuroserpin-deficient Alzheimer's disease transgenic mouse model.
Amyloid-beta (Aβ) plaques are a hallmark of Alzheimer's disease. Several proteases including plasmin are thought to promote proteolytic cleavage and clearance of Aβ from brain. The activity of both plasmin and tissue plasminogen activator are reduced in Alzheimer's disease brain, while the tissue plasminogen activator inhibitor neuroserpin is up-regulated. Here, the relationship of tissue plasminogen activator and neuroserpin to Aβ levels is explored in mouse models. Aβ(1-42) peptide injected into the frontal cortex of tissue plasminogen activator knockout mice is slow to disappear compared to wildtype mice, whereas neuroserpin knockout mice show a rapid clearance of Aβ(1-42). The relationship of neuroserpin and tissue plasminogen activator to Aβ plaque formation was studied further by knocking-out neuroserpin in the human amyloid precursor protein-J20 transgenic mouse. Compared to the J20-transgenic mouse, the neuroserpin-deficient J20-transgenic mice have a dramatic reduction of Aβ peptides, fewer and smaller plaques, and more active tissue plasminogen activator associated with plaques. Furthermore, neuroserpin-deficient J20-transgenic mice have near normal performances in the Morris water maze, in contrast to the spatial memory defects seen in J20-transgenic mice. These results support the concept that neuroserpin inhibition of tissue plasminogen activator plays an important role both in the accumulation of brain amyloid plaques and loss of cognitive abilities.


Phosphorylation of Nephrin Triggers Ca2+ Signaling by Recruitment and Activation of Phospholipase C-{gamma}1.
A specialized intercellular junction between podocytes, known as the slit diaphragm (SD), forms the essential structural frame-work for glomerular filtration in the kidney. In addition, mounting evidence demonstrates that the SD also plays a crucial role as a signaling platform in physiological and pathological states. Nephrin, the major component of the SD, is tyrosine-phosphorylated by a Src family tyrosine kinase, Fyn, in developing or injured podocytes, recruiting Nck to Nephrin via its Src homology 2 domain to regulate dynamic actin remodeling. Dysregulated Ca(2+) homeostasis has also been implicated in podocyte damage, but the mechanism of how podocytes respond to injury is largely unknown. Here we have identified phospholipase C-gamma1 (PLC-gamma1) as a novel phospho-Nephrin-binding protein. When HEK293T cells expressing a chimeric protein consisting of CD8 and Nephrin cytoplasmic domain (CD) were treated with anti-CD8 and anti-mouse antibodies, clustering of Nephrin and phosphorylation of Nephrin-CD were induced. Upon this clustering, PLC-gamma1 was bound to phosphorylated Nephrin Tyr-1204, which induced translocation of PLC-gamma1 from cytoplasm to the CD8/Nephrin cluster on the plasma membrane. The recruitment of PLC-gamma1 to Nephrin activated PLC-gamma1, as detected by phosphorylation of PLC-gamma1 Tyr-783 and increase in inositol 1,4,5-trisphosphate level. We also found that Nephrin Tyr-1204 phosphorylation triggers the Ca(2+) response in a PLC-gamma1-dependent fashion. Furthermore, PLC-gamma1 is significantly phosphorylated in injured podocytes in vivo. Given the profound effect of PLC-gamma in diverse cellular functions, regulation of the Ca(2+) signaling by Nephrin may be important in modulating the glomerular filtration barrier function.


Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells.
Harmine, a β-carboline alkaloid from Peganum harmala, has multiple anti-tumor activities, especially for its folk therapy for digestive system neoplasm. However, the underlying mechanism of harmine on gastric cancer remains unclear. To illuminate the potential anti-tumor activity and mechanism of harmine against gastric cancer cells. The anti-proliferative activity of harmine in vitro was evaluated by MTT assay. The autophagic activity induced by harmine was assessed using GFP-LC3 transfection. FITC/PI double staining was applied for the apoptosis inspection. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. The potential mechanisms for proteins level in autophagy and apoptosis were analyzed by Western blot. Harmine exhibited potent effects on both autophagy and apoptosis. Treatment with harmine could enhance dots of GFP-LC3 in cells. Meanwhile, the process had connection with Beclin-1, LC3-II, and p62 by the inhibition of Akt/mTOR/p70S6K signaling. However, high concentration of harmine led to apoptosis characterized by the propidium/Annexin V-positive cell pollution, cell shrunk and the collapse of mitochondrial membrane potential. The regulation of Bcl-2, Bax and the gathering of cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 9 contributed to the induction of apoptosis. In addition, 10μM LY294002 (a specific inhibitor of PI3K/Akt) combination with 40μM harmine significantly increased the cytotoxicity to the gastric cancer cells and up-regulated both the apoptosis-related protein (cleaved-PARP, cleaved-caspase-3) and autophagy-related protein (Beclin-1, LC3-II, and p62). Adding the inhibitor of autophagy, 3-MA or BafA1, increased the viability of harmine-exposured gastric cancer cells, which confirmed the role of autophagy played in the gastric cancer cell death induced by harmine. Harmine might be a potent inducer of apoptosis and autophagy, which offered evidences to therapy of harmine in gastric carcinoma in the folk medicine.


Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis.
Creatine monohydrate (CrM) supplementation during resistance exercise training results in a greater increase in strength and fat-free mass than placebo. Whether this is solely due to an increase in intracellular water or whether there may be alterations in protein turnover is not clear at this point. We examined the effects of CrM supplementation on indexes of protein metabolism in young healthy men (n = 13) and women (n = 14). Subjects were randomly allocated to CrM (20 g/day for 5 days followed by 5 g/day for 3-4 days) or placebo (glucose polymers) and tested before and after the supplementation period under rigorous dietary and exercise controls. Muscle phosphocreatine, creatine, and total creatine were measured before and after supplementation. A primed-continuous intravenous infusion of L-[1-(13)C]leucine and mass spectrometry were used to measure mixed-muscle protein fractional synthetic rate and indexes of whole body leucine metabolism (nonoxidative leucine disposal), leucine oxidation, and plasma leucine rate of appearance. CrM supplementation increased muscle total creatine (+13.1%, P < 0.05) with a trend toward an increase in phosphocreatine (+8.8%, P = 0.09). CrM supplementation did not increase muscle fractional synthetic rate but reduced leucine oxidation (-19.6%) and plasma leucine rate of appearance (-7.5%, P < 0.05) in men, but not in women. CrM did not increase total body mass or fat-free mass. We conclude that short-term CrM supplementation may have anticatabolic actions in some proteins (in men), but CrM does not increase whole body or mixed-muscle protein synthesis.


Reconciliation of the carbon budget in the ocean's twilight zone.
Photosynthesis in the surface ocean produces approximately 100 gigatonnes of organic carbon per year, of which 5 to 15 per cent is exported to the deep ocean. The rate at which the sinking carbon is converted into carbon dioxide by heterotrophic organisms at depth is important in controlling oceanic carbon storage. It remains uncertain, however, to what extent surface ocean carbon supply meets the demand of water-column biota; the discrepancy between known carbon sources and sinks is as much as two orders of magnitude. Here we present field measurements, respiration rate estimates and a steady-state model that allow us to balance carbon sources and sinks to within observational uncertainties at the Porcupine Abyssal Plain site in the eastern North Atlantic Ocean. We find that prokaryotes are responsible for 70 to 92 per cent of the estimated remineralization in the twilight zone (depths of 50 to 1,000 metres) despite the fact that much of the organic carbon is exported in the form of large, fast-sinking particles accessible to larger zooplankton. We suggest that this occurs because zooplankton fragment and ingest half of the fast-sinking particles, of which more than 30 per cent may be released as suspended and slowly sinking matter, stimulating the deep-ocean microbial loop. The synergy between microbes and zooplankton in the twilight zone is important to our understanding of the processes controlling the oceanic carbon sink.


Topical fluorouracil. II. Postoperative administration in an animal model of glaucoma filtering surgery.
Unilateral posterior lip sclerectomies were performed in ten owl monkeys. Five milligrams of fluorouracil was injected subconjunctivally in each operated eye immediately after surgery. Three drops (approximately 2.4 mg/drop) of fluorouracil were instilled ten minutes apart in each operated eye twice daily on postoperative days 1 through 7 and once daily on postoperative days 8 through 15, 17, 19, and 21. One monkey died on the seventh postoperative day; its death could not be attributed to systemic fluorouracil toxicity. All of the operated eyes had filtering blebs after the full course of fluorouracil, but seven also had corneal epithelial defects. By the seventh postoperative week, two of the operated eyes manifested moderately severe corneal opacification. Ten weeks postoperatively, the electroretinographic a- and b-wave amplitudes averaged 17% and 12% less, respectively, in the seven operated eyes without clinically significant corneal opacification than in the unoperated fellow eyes. Only two eyes had blebs after the 12th postoperative week. Histopathologic examination was performed on five eyes, of which only two revealed patent sclerostomies. Although topical fluorouracil appears to delay bleb scarring, the corneal findings suggest that it may be more toxic than subconjunctival fluorouracil.