Analytes and Metabolites Associated with Muscle Quality in Young, Healthy Adults.
Identification of mechanisms that underlie lower extremity muscle quality (leg press one repetition maximum/total lean mass; LP/Lean) may be important for individuals interested in optimizing fitness and sport performance. The purpose of the current study was to provide observational insight into mechanisms that may underlie muscle quality by characterizing the association between 286 mass spectrometry metabolites and 17 chemistry screen analytes with LP/Lean in young, healthy adults (N = 77 (49 women and 28 men); mean age, 24.4 ± 4.2 yr; BMI, 23.5 ± 2.6 kg·m). Principal components analysis (PCA) was used to reduce the 286 metabolites into 73 metabolite-containing PCA factors. Sex-adjusted linear regression was used to examine the association between PCA factors and chemistry screen analytes with LP/Lean. Q values were computed to account for multiple comparison testing. Stepwise linear regression and leave-one-out cross validation were used to identify a predictor set representative of LP/Lean and to assess internal validity, respectively. Metabolites or analytes related to dietary protein intake (albumin, branched-chain amino acids (BCAA)) and excitation-contraction coupling (calcium and magnesium) were positively associated, whereas metabolites related to gut bacterial metabolism (cinnamoylglycine, hydrocinnamate, hippurate, indolepropionate) and peroxisome proliferator-activated receptor-alpha (PPAR-α) (methylglutarylcarnitine and cinnamoylglycine) activation were negatively associated with LP/Lean. Use of leave-one-out cross validation identified magnesium, sex, and the PCA factors containing BCAAs and methionine and methylglutarylcarnitine to be present in more than 90% of the stepwise regression models, thereby explaining 26.7% of the variance (adjusted R) inherent in muscle quality. Collectively, these data suggest that mechanisms related to dietary protein intake, excitation-contraction coupling, gut microbial metabolism, and PPAR-α activation may underlie lower extremity muscle quality in young, healthy adults.


Performance status and smoking status are independent favorable prognostic factors for survival in non-small cell lung cancer: a comprehensive analysis of 26,957 patients with NSCLC.
Performance status (PS) is an important factor in determining survival outcome in non-small cell lung cancer (NSCLC) but is generally confounded by stage, age, gender, and smoking status. We investigated the prognostic significance of PS taking into account these important factors. Retrospective analysis of registry database of the National Hospital Study Group for Lung Cancer (NHSGLC) between 1990 and 2005. Univariate analysis was performed using Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards model to identify independent prognostic factors. A total of 26,957 patients with NSCLC were analyzed of which 12,613 patients (46.8%) had World Health Organization (WHO) PS = 0, 8,137 patients were never smokers (30.2%), and most of them were females (72.7%). The majority of PS = 0 patients presented with stage I disease (56.9%). Patients with PS = 0 constituted the group with the highest proportion of never smokers (36.7%). There was a significant difference in the median overall survival (OS) between patients with PS = 0 and PS = 1 (51.5 months versus 15.4 months, respectively; p < 0.0001) and among patients with various PS within individual American Joint Committee on Cancer stage (all p values <0.0001). Never smokers had significantly improved median OS than ever smokers (30.0 months versus 19.0 months, respectively; p < 0.0001). Multivariate analysis demonstrated good PS, never smoker (versus ever smoker; hazard ratio = 0.935, 95% confidence interval: 0.884-0.990; p = 0.0205), early stage, female gender, squamous cell carcinoma histology, and treatment were all as independent favorable prognostic factors. PS and smoking status are independent prognostic factors for OS in NSCLC.


Clinical and laboratory phenotypes associated with the aspirin-like defect: a study in 17 unrelated families.
Aspirin-like defect (ALD) is a rare, mostly autosomal dominant inherited dysfunction of the intraplatelet arachidonic acid (AA) pathway leading to impaired thromboxane A2 signalling. We aimed to establish diagnostic criteria for ALD diagnosis and present clinical and laboratory phenotypes of 52 individuals from 17 unrelated families. Platelet in vitro function was determined on the basis of platelet aggregation response (PAR) to AA, adenosine diphosphate, collagen and ristocetin as well as PFA-100 closure times (CT). Using impaired PAR to AA (< or =10%) as the mandatory diagnostic criterion, ALD could be confirmed in 17 patients. Subsequently, family members were investigated and among 35 individuals an additional 13 ALD patients as well as 4 individuals with mild ALD (PAR to AA: 19-32%) were identified. At least one bleeding symptom was reported by 25 (74%) ALD patients and prolonged CT was detected in 24 (71%) of the cases, both significantly correlated with impaired PAR to AA (P = 0.001 and P = 0.002, respectively). An estimated 0.6% prevalence was determined for ALD in our paediatric patients with suspected coagulation disorders. Due to the mild bleeding symptoms, ALD is probably underdiagnosed. If ALD is suspected, PAR to AA is suitable for the identification of individuals at risk of increased haemorrhage.


Extending a rehabilitation pathway to include multiple providers: outcomes and pitfalls.
Patients commonly experience a complete new set of caregivers as they progress from acute to subacute care settings. As a result, managing continuity of care, patient satisfaction, and cost containment across the rehabilitation continuum becomes impossible. In addition, accountability for overall outcomes is fragmented, and patients often feel abandoned by their primary caretakers. To eliminate these problems, a rehabilitation liaison nurse followed patients from the acute to subacute setting. A mutually beneficial partnership evolved between the facilities. Continuity of care improved, transdisciplinary teams shared resources, the subacute length of stays decreased significantly, and patients gained a sense of support throughout the continuum of care. This article describes the development of an extended pathway, clinical implications for rehabilitation of joint replacement patients, some unexpected outcomes, and the role of a rehabilitation liaison nurse.


TrwC-mediated site-specific recombination is controlled by host factors altering local DNA topology.
R388 conjugative relaxase TrwC acts as a site-specific recombinase, promoting recombination between two cognate oriTs on double-stranded DNA substrates. The relaxosome component TrwA is also required for efficient recombination. In this work we present data on the in vivo control of this reaction by host proteins that affect local DNA topology. In the absence of TrwA, binding of integration host factor (IHF) to the oriT keeps the recombination levels low, probably by keeping the relaxosome complex, formed at recombination locus 1, in a "closed" conformation. In an IHF-deficient (IHF-) background, the formation of a transcript elongation complex at this locus still hampers recombination. A mutation abating the promoter sequence at locus 1, or repression of transcription by exposure to rifampin, lifts the inhibition imposed on recombination in an IHF- background. We also observe an increase in conjugation efficiency under these conditions. Relieving the inhibition imposed by these host factors allows efficient levels of recombination between short oriT loci in the absence of TrwA. The presence of TrwA counteracts these inhibitory effects. TrwA would then activate both recombination and conjugation by switching the conformation of the relaxosome to an "open" form that exposes single-stranded DNA at the nic site, promoting the initial TrwC nicking reaction.


Cardiac arrest - has the time of MRI come?
Three recent articles have shown the potential use of magnetic resonance imaging for the evaluation of comatose survivors of cardiac arrest. While this technique appears promising, significant additional work is required before it can be routinely used in a clinical setting.


Beneficial Root-Associated Microbiome during Drought and Flooding Stress in Plants.
Crop productivity is seriously threatened by the rise in the frequency and severity of drought and flood events around the world. Reduced drought and flooding stress in vulnerable species and ecosystems depends on our ability to comprehend how drought and flooding affect plant physiology and plant-associated microbes. Involvement of both abscisic acid ABA-dependent and ABA-independent pathways has been noted during drought. Hypoxic conditions impede hydraulic conductance, nutrient uptake and plant growth and development, as well as root aerobic respiration. The root microbiome, which works with the roots during drought and flood, is made up of plant growth-promoting rhizosphere, endophytes and mycorrhizas. A large number of phytohormones, primarily auxins, cytokinin and ethylene, as well as enzymes like 1-Aminocyclopropane-1-Carboxylate deaminase (ACC deaminase) and metabolites like exopolysaccharides are produced by rhizospheric microbes. These phytohormones, enzymes and metabolites have role in the induction of systemic drought tolerance in plants. Under hypoxia, anaerobic microbes with the potential to harm the plant due to their pathogenic behavior or soil denitrification ability are more likely to be present in the rhizosphere and roots. This review concentrates on the primary mechanisms of plant-microbe interactions under drought and flood stress as well as the importance of flood and drought-tolerant microbes in maintaining and increasing crop plant productivity under stress.


Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: role of cytochrome c oxidase.
Far red and near infrared (NIR) light promotes wound healing, but the mechanism is poorly understood. Our previous studies using 670 nm light-emitting diode (LED) arrays suggest that cytochrome c oxidase, a photoacceptor in the NIR range, plays an important role in therapeutic photobiomodulation. If this is true, then an irreversible inhibitor of cytochrome c oxidase, potassium cyanide (KCN), should compete with LED and reduce its beneficial effects. This hypothesis was tested on primary cultured neurons. LED treatment partially restored enzyme activity blocked by 10-100 microm KCN. It significantly reduced neuronal cell death induced by 300 microm KCN from 83.6 to 43.5%. However, at 1-100 mm KCN, the protective effects of LED decreased, and neuronal deaths increased. LED significantly restored neuronal ATP content only at 10 microm KCN but not at higher concentrations of KCN tested. Pretreatment with LED enhanced efficacy of LED during exposure to 10 or 100 microm KCN but did not restore enzyme activity to control levels. In contrast, LED was able to completely reverse the detrimental effect of tetrodotoxin, which only indirectly down-regulated enzyme levels. Among the wavelengths tested (670, 728, 770, 830, and 880 nm), the most effective ones (830 nm, 670 nm) paralleled the NIR absorption spectrum of oxidized cytochrome c oxidase, whereas the least effective wavelength, 728 nm, did not. The results are consistent with our hypothesis that the mechanism of photobiomodulation involves the up-regulation of cytochrome c oxidase, leading to increased energy metabolism in neurons functionally inactivated by toxins.


Male germ cell gene expression.
Formation of the male gamete occurs in sequential mitotic, meiotic, and postmeiotic phases. Many germ cell-specific transcripts are produced during this process. Their expression is developmentally regulated and stage specific. Some of these transcripts are product of genes that are male germ cell-specific homologs of genes expressed in somatic cells, while some are expressed from unique genes unlike any others in the genome. Others are alternate transcripts derived from the same gene as transcripts in somatic cells but differing from them in size and/or overall sequence. They are generated during gene expression by using promoters and transcription factors that activate transcription at different start sites upstream or downstream of the usual site, by incorporation of alternate exons, by germ cell-specific splicing events, and by using alternate initiation sites for polyadenylation. Male germ cell development consists of an assortment of unique processes, including meiosis, genetic recombination, haploid gene expression, formation of the acrosome and flagellum, and remodeling and condensation of the chromatin. These processes are intricate, highly ordered, and require novel gene products and a precise and well-coordinated program of gene expression to occur. The regulation of gene expression in male germ cells occurs at three levels: intrinsic, interactive, and extrinsic. A highly conserved genetic program "intrinsic" to germ cells determines the sequence of events that underlies germ cell development. This has been underscored by recent studies showing that meiosis involves many genes that have been conserved during evolution from yeast to man. During meiosis and other processes unique to germ cells, the intrinsic program determines which genes are utilized and when they are expressed. In the postmeiotic phase, it coordinates the expression of genes whose products are responsible for constructing the sperm. The process of spermatogenesis occurs in overlapping waves, with cohorts of germ cells developing in synchrony. The intrinsic program operating within a particular germ cell requires information from and provides information to neighboring cells to achieve this coordination. Sertoli cells are crucial for this "interactive" process as well as for providing essential support for germ cell proliferation and progression through the phases of development. The interactive level of regulation is dependent on "extrinsic" influences, primarily testosterone and follicle-stimulating hormone (FSH). Studies during the last 4 years have established that FSH is not essential for germ cell development but instead serves an important supportive role for this process. While testosterone is essential for maintenance of spermatogenesis, it acts on Sertoli cells and peritubular cells and has indirect effects on germ cells. The extrinsic and interactive processes are extremely important for establishing and maintaining an optimum environment within which gametogenesis occurs. Nevertheless, an intrinsic evolutionarily conserved genetic program regulates male germ cell gene expression and development.


Training Networks of Local Health Departments: A Regional Assessment.
The public health system faces major challenges in 2020, including an aging workforce, reductions in funding, and 2 simultaneous major threats to public health-the coronavirus pandemic and racial injustice. To effectively harness promising new technologies and address these and other public health challenges ahead, public health professionals must be trained on evidence-based practices for protecting and improving public health. This project sought to understand the network of health departments and organizations that provide training in order to inform strategic efforts to fill training gaps and improve access to training for local health departments (LHDs), thereby strengthening the public health system. We conducted a Web-based survey of 501 LHDs in the 6 states constituting Region V of the Department of Health & Human Services. The survey focused on the training relationship between LHDs and state and national organizations that provide public health training, allowing for a social network analysis. We used data visualization and descriptive statistics to examine the network. Of 290 participating health departments (58% response rate), 248 had monthly or more frequent contact with at least 1 organization for the purpose of training. Altogether, the 248 LHDs were connected to 47 state-level organizations and 10 national-level organizations. In 5 of 6 states, more LHDs were connected to the state health department for training than to any other organization type. Universities, national nonprofits, and national membership organizations provided training to the fewest LHDs. Local health department characteristics did not have a clear relationship with its number of training connections. State health departments may benefit from the support of universities, national nonprofits, and national membership organizations by partnering to offer training or by recommending training from these organizations to LHDs. Additional qualitative information from local and state health departments would be useful to determine the best strategies for universities, national nonprofits, and national membership organizations to participate in training local practitioners to improve LHD capacity.


Assessing oncological productivity. is one method sufficient?
This work analyses the distribution of oncological papers published in 1995 by authors from the European Union (EU) in any journal of all the Subject Categories of the Science Citation Index compiled by ISI (Institute for Scientific Information, Philadelphia, USA) and is based on the country of origin of all of the contributors. The study compares the results with those of a previous study dealing with publications in journals of the ISI Oncology Category based on the country of origin of the corresponding author. The aim of the study was to compare two different methods used to evaluate research productivity in order to understand the extent to which the results are influenced by the methodology adopted. Data on the number of published papers for each country, ratio between the number of occurrences of papers and country population and gross domestic product (GDP), and mean Impact Factors (IF ) were compared. While findings on the number of published papers (United Kingdom (UK), Germany and France ranking best), source country population (Sweden, Denmark and the Netherlands ranking best) and gross domestic product (Sweden, Finland and the Netherlands ranking best) showed no important changes, the mean IF value result was, for some countries, very different from the previous study. In particular, while Germany, Belgium, Portugal and France fared well, Norway, Sweden, Austria and Spain showed poorer results. Some hypotheses are advanced, and care in the scientometric interpretation of data is urged. An analysis of the journals in which EU authors published their articles was also carried out and the main SCI categories to which the journals belong are reported. As was expected, many categories other than oncology were represented (biochemistry, haematology, pathology, etc.).


[RuCl2(p-cymene)]2-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated ketones under ligand-free and neutral conditions.
A simple and efficient Ru-catalyzed conjugate addition reaction of arylboronic acids to α,β-unsaturated ketones under neutral conditions without any additional ligands has been developed. This Ru(II)-catalytic system both fulfilled the inhibition of the β-hydride elimination in the catalytic cycle and minimized the protonolysis of arylboronic acids.


Differing effects of ethanol on in vitro stimulated pancreatic enzyme secretion in ethanol-fed and control rats.
The single most important risk factor for chronic and acute pancreatitis is the abuse of ethanol, which, theoretically, could affect the pancreas by interacting either with some of its cell receptors or with any of its intracellular signal transduction mechanisms. Therefore, we determined in isolated pancreatic acini from 3 month ethanol-fed rats and controls the dose-response effects of secretagogues on enzyme secretion, both in the presence and absence of ethanol in the incubation medium. In ethanol-fed rats, pancreatic amylase activity was decreased by 40%, compared to controls (with identical carbohydrates intakes), whereas lipase and trypsinogen activities were unaffected. With no ethanol in the incubation medium, basal enzyme releases and enzyme dose-response curves to CCK-8, VIP, secretin, bombesin, and bethanechol were essentially unchanged in ethanol-fed rats compared to controls. In contrast, with 0.1 M ethanol present in the medium, enzyme responses to VIP, secretin, and CCK-8 were inhibited and that to CCK-8 also shifted to the right in ethanol-fed rats compared to controls. Hence, if rechallenged to ethanol, acini from ethanol-fed rats show inhibited secretions, in response to two secretagogues acting through the release of cyclic AMP, and an inhibited and right-shifted secretory response to CCK.


Investigation of dynamic solution interactions between NET-1 and UNC-5B by multi-wavelength analytical ultracentrifugation.
NET-1 is a key chemotropic ligand that signals commissural axon migration and change in direction. NET-1 and its receptor UNC-5B switch axon growth cones from attraction to repulsion. The biophysical properties of the NET-1 + UNC-5B complex have been poorly characterized. Using multi-wavelength-AUC by adding a fluorophore to UNC-5B, we were able to separate the UNC-5B sedimentation from NET-1. Using both multi-wavelength- and single-wavelength AUC, we investigated NET-1 and UNC-5B hydrodynamic parameters and complex formation. The sedimentation velocity experiments show that NET-1 exists in a monomer-dimer equilibrium. A close study of the association shows that NET-1 forms a pH-sensitive dimer that interacts in an anti-parallel orientation. UNC-5B can form equimolar NET-1 + UNC-5B heterocomplexes with both monomeric and dimeric NET-1.


[Treatment of thoracoabdominal aortic diseases through hybrid operation].
To review the experience with the hybrid operations for patients with thoracoabdominal aortic diseases, as well as to evaluate and discuss the outcomes. Between June 2008 and September 2011, 11 patients (9 male and 2 female, mean age 52 years) were treated by hybrid operation. Hybrid operation includes debranching of the visceral arteries, followed by endovascular repair of the diseases (include aneurysmal disease, aortic dissection, or Takayasu's arteritis). All the operations were successful. The mean operating time was 8.5 hours for patients done in one stage and 8.1 hours for the first stage of patient related in two stages. The endovascular stage took on average 2.0 hours. Overall mortality rate was 1/11 and morbidity was 4/11. No aneurysm-related death occurred. Two patients developed endoleak. Permanent paraplegia and renal failure rate was 0. Mean follow-up was 13.5 months. Hybrid operation is a mini invasive and safe method for thoracoabdominal aortic diseases with acceptable morbidity and mortality.


Physical activity behavior after total hip arthroplasty (THA): a prediction based on patient characteristics.
To determine to what extent aspects of patient characteristics (age, gender, family status, education and comorbidity) are predictive for the level of physical activity of persons with a total hip arthroplasty (THA). A cross-sectional study including 372 patients. Demographics, comorbidity and physical activity behavior were assessed by means of a questionnaire and from medical records. Linear regression analysis was used to determine to what extent patient characteristics are predictive of level of physical activity. Binary logistic regression modeling was used to determine the extent to which patient characteristics are predictive in meeting international guidelines on health-enhancing physical activity. Age, education and family status significantly predict level of physical activity (R(2)=0.19). Only gender significantly predicts meeting international guidelines on health-enhancing physical activity (OR=2.06, 95% CI 1.20-3.54). Patients at risk can be identified by means of patient characteristics. Increasing age, lower education and living alone are associated with a physically inactive lifestyle. Health care workers involved in the treatment of THA patients should lay an emphasis on the beneficial aspects of physical activity.


[Clinical efficacy of cis-diamminedichloroplatinum [II] and 5-fluorouracil (UFT) in advanced cancer of the alimentary tract].
A clinical study of the combination of cis-diamminedichloroplatinum [II] (CDDP) and 5-fluorouracil derivatives was conducted in advanced cancer of the alimentary tract. The regimen consisted of CDDP 50 mg/body/day (day 1-2, continuous infusion), 5-fluorouracil 500-750 mg/body/day (day 2-7, continuous infusion) and UFT 400 mg/day (day 8-28) on 1-3 courses. Thirty patients could be evaluated. The response rate was 25% (2/8) in cases of esophageal cancer, 31% (4/13) in gastric cancer and 33% (3/9) in colorectal cancer, with an overall response rate of 30% (9/30). A comparatively higher response rate was obtained in lymph node metastases (46%) and liver metastases (50%). Anorexia, nausea/vomiting and leukocytopenia were frequently observed, but almost all were well tolerated and recovered except two cases with severe leukocytopenia and nephrotoxicity. Based on these results, this combination chemotherapy seems to be useful for advanced cancer of the alimentary tract.


Insights into caregivers' perspectives on abuse of older persons: a qualitative exploratory study in southwest Nigeria.
Elder abuse perpetration by caregivers is well documented, particularly from the perspectives of older persons who are victims of abuse. However, few studies in Nigeria have examined the caregivers' viewpoints. This study explored the perception about the perpetration of elder abuse perpetration among adults aged 18-59 in Nigeria. Using a qualitative descriptive approach, this study generated data through four in-depth interviews (IDIs) and eight focus group discussions (FGDs). All IDIs and FGDs were audiorecorded, transcribed coded and analysed thematically with Atlas ti. Rural and urban communities in Oyo State, southwest Nigeria. 73 purposively selected adults who had provided care for or lived near an older person in southwestern Nigeria. Types of elder abuse identified were verbal (grumbling, insulting, snapping and shouting at older persons), physical (shoving and beating an older person) and neglect (refusing to render assistance, cook or carry out chores for an older person). Participants believed relatives of older persons were unlikely to perpetrate abuse compared with neighbours and paid caregivers. They, however, felt that people whose parents had maltreated them during childhood could perpetrate abuse especially neglect of their older parents. Identified possible provocation for abuse included an unkempt physical appearance, poor attitude or offensive behaviour in the older person. Participants further opined that lack of communal unity or mutual respect, loss of moral ideals and religious values and erosion of cultural values could also provide an environment where elder abuse can thrive. Interventions for community-level prevention of elder abuse can leverage on the identified moral and religious values, relationship and cultural factors for successful deployment.


Saturation transfer difference NMR for fragment screening.
Fragment screening by saturation transfer difference nuclear magnetic resonance (STD-NMR) is a robust method for identifying small molecule binders and is well suited to a broad set of biological targets. STD-NMR is exquisitely sensitive for detecting weakly binding compounds (a common characteristic of fragments), which is a crucial step in finding promising compounds for a fragment-based drug discovery campaign. This protocol describes the development of a library suitable for STD-NMR fragment screening, as well as preparation of protein samples, optimization of experimental conditions, and procedures for data collection and analysis.


L-Lactide Ring-Opening Polymerization with Tris(acetylacetonate)Titanium(IV) for Renewable Material.
A new Ti-type of catalyst for L-lactide polymerization was synthesized by reaction of titanium(IV) isopropoxide (TTIP) with acetylacetone (AA). Moreover, PLA was prepared by the bulk ring-opening polymerization using synthesized Ti catalyst. Polymerization behaviors were examined depending on monomer/catalyst molar ratio, polymerization temperature and time. The structure of synthesized catalysts was verified with FT-IR and 1H NMR and the properties of poly(L-lactide) (PLLA) were examined by GPC, DSC and FT-IR. There existed about 30 minutes of induction time at the monomer/catalyst molar ratio of 300. The molecular weight (MW) increased as monomer/catalyst molar ratio increased. The MW increased almost linearly as polymerization progressed. Increasing polymerization temperature increased the molecular weight of PLLA as well as monomer/catalyst molar ratio. The melting point (T(m)) of polymers was in the range of 142 to 167 degrees C. Lower T(m) was expected to be resulted from relatively lower molecular weight.


Role of Cdk1 in the p53-independent abrogation of the postmitotic checkpoint by human papillomavirus E6.
Specific types of human papillomavirus (HPV) are strongly associated with the development of cervical carcinoma. The HPV E6 oncoprotein from HPV degrades p53 and abrogates cell cycle checkpoints. Nonetheless, functional p53 has been observed in cervical cancer. We have previously identified a p53-independent function of E6 in attenuating the postmitotic G1-like checkpoint that can lead to polyploidy, an early event during cervical carcinogenesis that predisposes cells to aneuploidy. How E6 promotes cell cycle progression in the presence of p53 and its target, p21, remains a mystery. In this study, we examined the expression of cell cycle-related genes in cells expressing wild-type E6 and the mutant that is defective in p53 degradation but competent in abrogating the postmitotic checkpoint. Our results demonstrated an increase in the steady-state levels of G1- and G2-related cyclins/Cdks in E6-expressing keratinocytes. Interestingly, only Cdk1 remained active in E6 mutant-expressing cells while bypassing the postmitotic checkpoint. Furthermore, the downregulation of Cdk1 impaired the ability of both wild-type and mutant E6 to induce polyploidy. Our study thus demonstrated an important role for Cdk1, which binds p21 with lower affinity than Cdk2, in abrogating the postmitotic checkpoint in E6-expressing cells. We further show that E2F1 is important for E6 to upregulate Cdk1. Moreover, reduced nuclear p21 localization was observed in the E6 mutant-expressing cells. These findings shed light on the mechanisms by which HPV induces genomic instability and hold promise for the identification of drug targets. HPV infection is strongly associated with the development of cervical carcinoma. HPV encodes an E6 oncoprotein that degrades the tumor suppressor p53 and abrogates cell cycle checkpoints. Nonetheless, functional p53 has been observed in cervical cancer. We have recently demonstrated a p53-independent abrogation of the postmitotic checkpoint by HPV E6 that induces polyploidy. However, the mechanism is not known. In this study, we provide evidence that Cdk1 plays an important role in this process. Previously, Cdk2 was thought to be essential for the G1/S transition, while Cdk1 only compensated its function in the absence of Cdk2. Our studies have demonstrated a novel role of Cdk1 at the postmitotic G1-like checkpoint in the presence of Cdk2. These findings shed light on the mechanisms by which HPV induces genomic instability and hold promise for the identification of drug targets.


An overview of statistical planning to address subgroups in confirmatory clinical trials.
The effects of treatments within demographic and clinical subgroups of patients are of major interest in most confirmatory clinical trials. Potential factors for defining subgroups include gender, age, disease severity, and geographic region. A major statistical issue for the interpretation of treatment comparisons for subgroups is whether the role of a subgroup is inferential, supportive, or exploratory through respectively corresponding to a primary, key secondary, or hypothesis-generating assessment. This article discusses statistical planning to control type 1 error for the multiple comparisons that correspond to the scope of prespecified inferential subgroups, and it provides some suggestions for addressing the type 2 error that can pertain to prespecified supportive subgroups. Treatment comparisons for exploratory subgroups without a priori specification should always have a very cautious interpretation that accounts for how random variation can influence their pattern of results, although the suggested methods for supportive subgroups can be helpful in this light.


Effect of intragastric and intraperitoneal immunisation with attenuated and wild-type LACK-expressing Listeria monocytogenes on control of murine Leishmania major infection.
Stable chromosomal constructs of attenuated DeltaactA and wild-type Listeria monocytogenes expressing the Leishmania major protein LACK were tested as live vaccine vectors in the Th2-orientated chronic L. major murine infection model. These vectors, either by intraperitoneal (i.p.) or intragastric (i.g.) route, were able to induce a strong CD4 Th1 immune response that was correlated with slower parasite growth in the infected footpad. Significant protection against L. major infection was observed in BALB/c mice, ranging from delay in the lesion onset to full protection in 80% of the challenged animals, depending on the size of the parasite inoculum challenge. The i.g. route gave clinically higher protection level than the i.p. route. Both bacterial vectors were as efficient, suggesting that the extent of in vivo bacterial dissemination and multiplication did not seem to be a key parameter for induction of an efficient protective immune response.


Anticancer activity of Sasa borealis leaf extract-mediated gold nanoparticles.
Advancements in metal nanoparticle synthesis using plant extracts and their anticancer activity have received significant attention in recent years. The green approach for the synthesis of gold nanoparticles (AuNPs) using leaf extract of Sasa borealis is reported in this study. Synthesis of AuNPs was performed at 50 °C, and nanoparticle formation was observed after 20 min incubation. AuNPs formation was confirmed by the UV-visible spectrum peak at 542 nm. The synthesized AuNPs were oval, spherical with sizes around 10-30 nm observed using the transmission electron microscope. Energy dispersive X-ray analysis was utilized for the detection of elemental compound. The face centered cubic structure was confirmed by X-ray diffraction pattern. The reduction of tetrachloroauric acid into AuNPs by the phytochemical compounds of S. borealis extract was determined by Fourier transform infrared spectroscopy and the presence of biomolecules was studied by GC-MS. The synthesized AuNPs was tested for toxic effect on HEK293 cells and anticancer activity on AGS cells by WST-1® assay. Condensation or fragmentation is a characteristics of apoptosis, which was confirmed by 4,6-diamidino-2-pheynylindole dihydrochoride (DAPI) staining. The S. borealis-mediated AuNPs have good activity as an anticancer agent and it will be beneficial in cancer therapeutics.


Human serum lyses Trypanosoma brucei by triggering uncontrolled swelling of the parasite lysosome.
Trypanosoma brucei brucei infects a wide range of mammals, but is unable to infect humans because this subspecies is lysed by normal human serum (NHS). The phenotype of cellular lysis is debated. For some authors the lysosome undergoes osmotic swelling due to massive influx of chloride ions from the cytoplasmic compartment, but others describe multiple small cytoplasmic vacuoles and general swelling of the cellular body. Using population-level imaging of live immobilized trypanosomes throughout the lysis process, we report that specific swelling of the lysosome is a genuine and major characteristic of NHS-mediated lysis and that this phenotype is independent of the strain of trypanosomes and of NHS aging or damaging. Thus, irrespective of experimental conditions NHS reproducibly induced the swelling of the parasite lysosome.


A televised entertainment-education drama to promote positive discussion about organ donation.
This article investigates pathways between the exposure to an entertainment-education (E-E) television drama called Three Rivers and positive discussion of organ donation among viewers of the drama in the United States. A cross-sectional survey was conducted using an online advertising for a period of one week. Survey participants included 1325 adults living in the United States, who had viewed the first episode of Three Rivers on television. Data were collected on recall of events in the storyline, perceived entertainment value, perceived accuracy of the presented health information, rejection of organ donation myths and positive discussion of organ donation and the storyline. Covariates were registration for organ donation, membership to the donation or transplant community and demographic variables. Results show that viewers with high recall of the storyline were more likely to reject myths about organ donation and engage in pro-donation discussions with others. Perceived entertainment value and perceived accuracy acted as mediators in such relationships. The insertion of accurate health information in television drama may be effective in promoting positive discussions about organ donation and myth rejection. Recall of events from the televised E-E drama Three Rivers, entertainment value and accuracy perception were associated with positive discussion.


Green 'heart' for new community hospital.
Replacing a healthcare facility first opened in 1908 as a 20-bed cottage hospital, the recently opened 'new' Finchley Memorial Hospital in north-west London was designed by architects, Murphy Philipps, 'to be at the heart of a health campus', surrounded by green space for use by both the hospital itself, and the local community. The 28 million pounds hospital, which has achieved a BREAAM Excellent rating - with an annual energy target of just 35 GJ/100 m3 set by SHINE, the Department of Health-backed learning network for sustainable healthcare buildings - has also featured as one of only 20 projects in the RIBA Health Buildings Exhibition. HEJ editor, Jonathan Baillie, met with lead architect, Marc Levinson, to find out more about the key elements, and the thinking, that went into the design.


Detection and quantitation of urinary 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid, a metabolite of tetrahydrocannabinol, by capillary gas chromatography and electron impact mass fragmentography.
A procedure for detection and quantitation of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid, a major metabolite of delta-9-tetrahydrocannabinol in urine, has been described. Since the metabolite is present in both conjugated and unconjugated forms, hydrolysis of urine was carried out to increase the sensitivity of detection. The acidic metabolite was isolated by strongly basic anion exchange resin, and subsequently derivatized to methyl 1-dehydroxy-1-methoxy-11-nor-delta-9-tetrahydrocannabinol-9-carbox ylate (1a) by methyliodide in the presence of tetramethylammonium hydroxide. The derivatized product was separated in a capillary column gas chromatograph, and finally detected by a mass spectrometer under electron impact mode. Confirmation of the product was carried out by monitoring three ions that represent the major portions of the molecule and comparing their relative abundances to that of a standard. Quantitation was based on 5'-2H3-11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid as internal standard. Excellent linearity was obtained over the range of 2 to 1000 ng/mL. The overall yield of extraction using the anion exchange resin was 50 to 60%. This extraction process is rapid and suitable for a large number of sample analyses. The methylated product (1a) is stable for at least 72 hr at room temperature.


Ano-Genital Warts and HIV Status- A Clinical Study.
Ano-Genital Warts (AGW) like other Sexually Transmitted Diseases (STD) is associated with Human Immunodeficiency Virus (HIV) infection. This study of AGW was done in HIV positive and HIV negative patients. To study the risk factors and clinical presentations of ano-genital warts in HIV positive and negative patients. A comparative, cross-sectional, descriptive study of 25 HIV positive and 25 HIV negative (n=50) AGW patients between 15-60 years of both sex was conducted in Dr. D. Y. Patil Hospital and Research Centre from July 2014 to July 2016. Significant association of HIV positivity (p<0.05) was observed between age group of 15-30 years and HIV negative status (p<0.05) in age group of 31-45 years. HIV positive status significantly higher in patients with self-admitted multiple sexual partners (p<0.01), homosexuality (p<0.05) and presentation with anal warts (p<0.01). HIV negative status correlated significantly with single sexual partner admission (p<0.01) and hetero-sexuality (p<0.05). Gender did not show significant association with number of sexual partners or HIV positivity. Extra-genital or only genital warts had no association with HIV status. Co-STDs though more in number in ser-positive group, did not show any significant association with HIV positivity (p>0.05). No patient presented with changes of malignancy. Four were adolescents below 19 years. Two patients had atypical presentations of giant condylomata i.e., Buschke-Lowenstein Tumour (BLT). HIV positivity was significantly associated with the risk factors of age below 30 years, homo sexuality and multiple sexual partners. Anal warts were significantly common in HIV positive patients. Four adolescents with AGW underline the need for high risk behaviour counselling. No patient had malignant ano-genital warts. Follow up of these patients with Human Papilloma Virus (HPV) sub-typing is necessary.


Clinical characteristics in non-insulin-dependent diabetic patients with long duration in Japan--relation to risk factors for vascular complications.
In this study, we evaluated the control state of body weight, blood pressure, and blood glucose during the recent 10 years in 82 patients of non-insulin-dependent diabetes mellitus (NIDDM) who had long duration of diabetes for 20-25 years without ischemic heart disease (IHD) and diabetic nephropathy (Neph). The patients without either IHD or Neph showed significantly lower incidences of obese (11 vs. 40%, p < 0.05), hypertensive (0 vs. 20%, p < 0.05) and poor glycemic control state (7 vs. 27%, p < 0.05) for 10 years than the patients with IHD alone, and showed significantly lower incidences of hypertensive (0 vs. 20%, p < 0.05) and poor glycemic control state (7 vs. 33%, p < 0.01) than the patients with Neph alone. The control state of body weight was similar between the patients without either IHD or Neph and with Neph alone. In addition, the patients without either IHD or Neph showed significantly lower incidences of obese (11 vs. 56%, p < 0.01) and hypertensive control state (0 vs. 40%, p < 0.01) for 10 years than the patients with both IHD and Neph. The control state of blood glucose was similar between the two groups. These results suggest that for long survival of NIDDM patients without development or progression of IHD and Neph, non-obese and non-hypertensive state as well as good glycemic control should be maintained for long time.


Impact of immunosuppression without steroids on rejection and hepatitis C virus evolution after liver transplantation: results of a prospective randomized study.
The purpose of this study was to evaluate the influence of a steroid-free immunosuppression on hepatitis C virus (HCV) recurrence. A total of 198 liver transplantation (LT) patients were randomized to receive immunosuppression with basiliximab and cyclosporine, either with prednisone (steroid [St] group) or without prednisone (no steroids [NoSt] group). The group of 89 HCV-infected patients was followed up with protocol biopsies for 2 years after LT. This group of HCV patients are the patients evaluated in the present study. The rejection rate was 19% (St: 21% versus NoSt: 17%; P = 0.67). Patients in the St group had a slightly higher rate of bacterial infections (59% versus 38%; P = 0.05). Almost all patients had histological HCV-recurrence (St: 39/40 (97%) versus NoSt: 40/41 (97%); P = 1). The percentage of accumulated biopsies with grade 4 portal inflammation at 6 months, 1 year, and 2 years were, 23%, 49%, and 49% in the NoSt group, compared to 33%, 55%, and 69% in the St group, respectively (P = 0.04 at 2 years). The percentage of accumulated biopsies with grade 3 or 4 fibrosis at 6 months, 1 year, and 2 years were 0%, 8%, and 22% in the NoSt group, compared to 8%, 19%, and 31% in the St group, respectively. Immunosuppression without steroids in HCV patients is safe, reduces bacterial infections and metabolic complications, and improves histological short-term evolution of HCV recurrence.


Adolescents' and adults' experiences of being surveyed about violence and abuse: a systematic review of harms, benefits, and regrets.
The neuroscience and psychological literatures suggest that talking about previous violence and abuse may not only be beneficial, as previously believed, but may also be associated with risks. Thus, studies on such topics introduce ethical questions regarding the risk-benefit ratio of sensitive research. We performed a systematic review of participants' experiences related to sensitive research and compared consequent harms, benefits, and regrets among victims and nonvictims of abuse. Thirty studies were included (4 adolescent and 26 adult studies). In adolescent studies, 3% to 37% of participants (median: 6%) reported harms, but none of these studies measured benefits or regrets. Among adults, 4% to 50% (median: 25%) reported harms, 23% to 100% (median: 92%) reported benefits, and 1% to 6% (median: 2%) reported regrets. Our results suggest that the risk-benefit ratio related to sensitive research is not unfavorable, but there are gaps in the evidence among adolescents.


An endo-(1 lead to 6) -beta-D-glucanase from Mucor hiemalis.
An endo-(1 lead to 6)-beta-D-glucanase (EC 3.2.1), isolated from the culture filtrate of Mucor hiemalis, was purified by ammonium sulphate fractionation and gel filtration. The homogeneity of the enzyme was confirmed by disc electrophoresis. The enzyme had a wide range of temperature and pH stability, high substrate specificity, and an action pattern of the endo-type.


Evaluation of a library of loxP variants with a wide range of recombination efficiencies by Cre.
Sparse labeling of individual cells is an important approach in neuroscience and many other fields of research. Various methods have been developed to sparsely label only a small population of cells; however, there is no simple and reproducible strategy for managing the probability of sparse labeling at desired levels. Here, we aimed to develop a novel methodology based on the Cre-lox system to regulate sparseness at desired levels, and we purely analyzed cleavage efficiencies of loxP mutants by Cre. We hypothesized that mutations in the loxP sequence reduce the recognition efficiency by Cre, which enables the regulation of the sparseness level of gene expression. In this research, we mutagenized the loxP sequence and analyzed a library of loxP variants. We evaluated more than 1000 mutant loxP sequences, including mutants with reduced excision efficiencies by Cre ranging from 0.51% to 59%. This result suggests that these mutant loxP sequences can be useful in regulating the sparseness of genetic labeling at desired levels.


Effect of procaterol on the isolated airway smooth muscle and the release of anaphylactic chemical mediators from the isolated lung fragments.
The effects of an orally active and selective beta 2-stimulant, procaterol (OPC-2009) on the isolated pulmonary smooth muscle and the release of chemical mediators from the passively sensitized lung fragments were studied and compared with those of isoprenaline (isoproterenol) and salbutamol. Procaterol potently relaxed the isolated guinea pig trachea and lung parenchyma in a concentration-dependent fashion. The drug at a similar range of concentrations antagonized the contraction of the isolated guinea pig trachea and lung parenchyma or human bronchus induced by leukotriene (LT) D4. Salbutamol and isoprenaline also showed similar effects to those of procaterol on the above experiments, but the potencies were consistently weaker than that of procaterol. The release of either histamine or LTs from the passively sensitized human lung fragments was markedly and dose-dependently inhibited by both the 5 min and 15 h treatment with procaterol (10(-10)-10(-7) mol/l) before antigen challenge. Isoprenaline and salbutamol in 5 min treatment experiments showed similar potency as and less potency than procaterol, respectively, on the release of these mediators, but the inhibition potencies of these drugs, particularly isoprenaline, were remarkably reduced by 15 h treatment. From these results, procaterol, besides the existing use as a bronchodilator, is expected to be a potentially prophylactic drug for allergic asthma because of the strong inhibition of the anaphylactic mediator release.


Microfluidics-based single-step preparation of injection-ready polymeric nanosystems for medical imaging and drug delivery.
Translation of therapeutic polymeric nanosystems to patients and industry requires simplified, reproducible and scalable methods for assembly and loading. A single-step in-line process based on nanocoprecipitation of oxazoline-siloxane block copolymers in flow-focusing poly(dimethylsiloxane) microfluidics was designed to manufacture injection-ready nanosystems. Nanosystem characteristics could be controlled by copolymer concentration, block length and chemistry, microchannel geometry, flow rate, aqueous/organic flow rate ratio and payload concentration. The well-tolerated nanosystems exhibited differential cell binding and payload delivery and could confer sensitivity to photodynamic therapy to HeLa cancer cells. Such injection-ready nanosystems carrying drugs, diagnostic or functional materials may facilitate translation to clinical application.


Changes in adenylyl cyclase activity in human endometrium during the menstrual cycle and in human decidua during pregnancy.
Adenylyl cyclase activity was studied in human endometrium during the menstrual cycle and in human decidua during pregnancy. Higher adenylyl cyclase activity was found in the endometrium than in the myometrium, corpus luteum or Fallopian tubes. In the endometrium, the basal and stimulated activities were highest in the fundus and decreased slightly from the fundus to the isthmus. Prostaglandin-stimulated adenylyl cyclase activity increased gradually from the proliferative phase to the secretory phase, and then quickly reached its highest value in the late secretory phase. Catecholamine-stimulated adenylyl cyclase activity reached a peak in the late proliferative phase and decreased significantly thereafter. Forskolin-stimulated activity was significantly higher throughout the secretory phase than in the proliferative phase. In the decidua, prostaglandin-, catecholamine- and forskolin-stimulated adenylyl cyclase activities in late pregnancy were significantly lower than those in early pregnancy. Our results demonstrate dramatic alterations in adenylyl cyclase activity in human endometrium during the menstrual cycle and in human decidua during pregnancy.


[Analysis of broad-sense heritability and genetic correlation of production and content of glycyrrhizin of annual Glycyrrhiza uralensis].
To estimate the broad-sense heritability of the production of Glycyrrhiza uralensis and the content of glycyrrhizin as well as the genetic relationship of various growth indexes and biomass indexes, and provide the scientific basis for establishment of high quality licorice cultivate technology system. The randomized method was used to assign the provenance trial, the content of glycyrrhizin was determined by HPLC, and the method of classic genetics was applied to estimate the broad-sense heritability and genetic correlation coefficient. The content of glycyrrhizin is influenced by the growth environment and gene, but the growth environment is the dominant factor. The estimated result of single sites about broad-sense heritability (h2) showed that the production of G. uralensis (W(u)) and the content of glycyrrhizin was controlled by gene which the broad-sense heritability was 0.663 2, 0.751 1 respectively, they had some potential on genetic modification. The results of genetic analysis correlation showed that the plant height and the stem diameter was positive (P < 0.01) correlated significantly with the production (W(u)) either on phenotype or on genetic, it suggests that the plant height and the stem diameter could be the index above ground to assessment the production of the G. uralensis. The content of glycyrrhizin had a positive correlation with the number of lateral root (P < 0.05), but it had a negative correlation with the plant height, stem diameter, diameter of root top (D(r)), the total biomass (W(t)) and the biomass underground (W(u)) on inheritance. It is suggested that it was difficult to achieve both high content and high yield simultaneously in the genetic improvement, so we should have a deeply thought about the specific improvement target when making the reformed scheme.


Alteration of circadian rhythm during epileptogenesis: implications for the suprachiasmatic nucleus circuits.
It is important to realize that characterization of the circadian rhythm patterns of seizure occurrence can implicate in diagnosis and treatment of selected types of epilepsy. Evidence suggests a role for the suprachiasmatic nucleus (SCN) circuits in overall circadian rhythm and seizure susceptibility both in animals and humans. Thus, we conclude that SCN circuits may exert modifying effects on circadian rhythmicity and neuronal excitability during epileptogenesis. SCN circuits will be studied in our brain centre and collaborating centres to explore further the interaction between the circadian rhythm and epileptic seizures. More and thorough research is warranted to provide insight into epileptic seizures with circadian disruption comorbidities such as disorders of cardiovascular parameters and core body temperature circadian rhythms.


Individual recognition and odor in rat-like hamsters: behavioral responses and chemical properties.
Individual recognition has been studied across a number of taxa and modalities; however, few attempts have been made to combine chemical and biological approaches and arrive at a more complete understanding of the use of secretions as signals. We combined behavioral habituation experiments with gas chromatography-mass spectrometry of glandular secretions from the left and right flank gland and midventral gland of the rat-like hamster, Tscheskia triton. We found that females became habituated to one scent and then could discriminate individuals via another scent source from the same individual only when familiar with the scent donor. However, this prior social interaction was not required for females to discriminate different individuals in single-stimulus habituation-dishabituation tests. Chemical analyses revealed a similarity in volatile compounds between the left and right flank gland and midventral gland scents. It appears that individually distinctive cues are integratively coded by a combination of both flank gland and midventral gland secretions, instead of a single scent, albeit animals show different preferences to the novel scent. Our results suggest that odors from the flank and midventral glands may provide information related to individuality and aid individual recognition in this species and confirm that prior interaction between individuals is a prerequisite for rat-like hamsters to form multi-odor memory of a particular conspecific.


Mechanistic Insights on ATP's Role as a Hydrotrope.
Hydrotropes are the small amphiphilic molecules which help in solubilizing hydrophobic entities in an aqueous medium. Recent experimental investigation has provided convincing evidence that adenosine triphosphate (ATP), besides being the energy currency of cell, also can act as a hydrotrope to inhibit the formation of protein condensates. In this work, we have designed computer simulations of prototypical macromolecules in aqueous ATP solution to dissect the molecular mechanism underlying ATP's newly discovered role as a hydrotrope. The simulation demonstrates that ATP can unfold a single chain of hydrophobic macromolecule as well as can disrupt the aggregation process of a hydrophobic assembly. Moreover, the introduction of charges in the macromolecule is found to reinforce ATP's disaggregation effects in a synergistic fashion, a behavior reminiscent of recent experimental observation of pronounced hydrotropic action of ATP in intrinsically disordered proteins. Molecular analysis indicates that this newfound ability of ATP is ingrained in its propensity of preferential binding to the polymer surface, which gets fortified in the presence of charges. The investigation also renders evidence that the key to the ATP's superior hydrotropic role over chemical hydrotropes (sodium xylene sulfonate, NaXS) may lie in its inherent self-aggregation propensity. Overall, via employing a bottom-up approach, the current investigation provides fresh mechanistic insights into the dual solubilizing and denaturing abilities of ATP.


Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA): safety and efficacy of low-dose prostacyclin administration and blood pressure target in addition to standard therapy, as compared to standard therapy alone, in post-cardiac arrest syndrome patients: study protocol for a randomized controlled trial.
Morbidity and mortality following initial survival of cardiac arrest remain high despite great efforts to improve resuscitation techniques and post-resuscitation care, in part due to the ischemia-reperfusion injury secondary to the restoration of the blood circulation. Patients resuscitated from cardiac arrest display evidence of endothelial injury and coagulopathy (hypocoagulability, hyperfibrinolysis), which in associated with poor outcome. Recent randomized controlled trials have revealed that treatment with infusion of prostacyclin reduces endothelial damage after major surgery and AMI. Thus, a study is pertinent to investigate if prostacyclin infusion as a therapeutic intervention reduces endothelial damage without compromising, or even improving, the hemostatic competence in resuscitated cardiac arrest patients. Post-cardiac arrest patients frequently have a need for vasopressor therapy (catecholamines) to achieve the guideline-supported blood pressure goals. To evaluate a possible catecholamine interaction with the primary endpoints of this study, included patients will be randomized into two different blood pressure goals within guideline-recommended targets. A randomized, placebo-controlled, double-blind investigator-initiated pilot trial in 40 out-of-hospital-cardiac-arrest (OHCA) patients will be conducted. Patients will be randomly assigned to either the active treatment group (48 hours of active study drug (iloprost, 1 ng/kg/min) or to the control group [placebo (saline) infusion]. Target mean blood pressure levels will be allocated 1:1 to 65 mmHg or approximately 75 mmHg, which gives four different permutations, namely: (i) iloprost/65 mHg, (ii) iloprost/75 mmHg, (iii) placebo/65 mmHg, and (iv) placebo/75 mmHg. All randomized patients will be treated in accordance with state-of-the art therapy including targeted temperature management. The primary endpoint of this study is change in biomarkers indicative of endothelial activation and damage, [soluble thrombomodulin (sTM), sE-selectin, syndecan-1, soluble vascular endothelial growth factor (sVEGF), nucleosomes] and sympathoadrenal over activation (epinephrine/norepinephrine) from baseline to 48 hours post-randomization. The secondary endpoints of this trial will include: (1) the hemostatic profile [change in functional hemostatic blood test (thrombelastography (TEG) and whole blood platelet aggregometry (multiplate)) blood cell and endothelial cell-derived microparticles]; (2) feasibility of blood pressure target intervention (target 90 %); (3) interaction of primary endpoints and blood pressure target; (4) levels of neuron-specific enolase at 48 hours post-inclusion according to blood pressure targets. The ENDO-RCA study is a pilot study trial that investigates safety and efficacy of low-dose infusion of prostacyclin administration as compared to standard therapy in post-cardiac arrest syndrome patients. Trial registration at ClinicalTrials.gov (identifier NCT02685618 ) on 18 February 2016.


Technition: When Tools Come Out of the Closet.
People are ambivalently enthusiastic and anxious about how far technology can go. Therefore, understanding the neurocognitive bases of the human technical mind should be a major topic of the cognitive sciences. Surprisingly, however, scientists are not interested in this topic or address it only marginally in other mainstream domains (e.g., motor control, action observation, social cognition). In fact, this lack of interest may hinder our understanding of the necessary neurocognitive skills underlying our appetence for transforming our physical environment. Here, we develop the thesis that our technical mind originates in perhaps uniquely human neurocognitive skills, namely, technical-reasoning skills involving the area PF within the left inferior parietal lobe. This thesis creates an epistemological rupture with the state of the art that justifies the emergence of a new field in the cognitive sciences (i.e., technition) dedicated to the intelligence hidden behind tools and other forms of technologies, including constructions.


Role of Helicobacter pylori in the pathogenesis of gastritis, peptic ulcer and gastric cancer.
Helicobacter pylori is the major causal factor in chronic gastritis. Its acquisition leads to a chronic, usually lifelong, inflammation of the gastric mucosa, which may gradually progress to atrophy (with intestinal metaplasia) in a significant proportion of infected individuals. This progression is probably multifactorial, being influenced by genetic or environmental factors in addition to H. pylori infection. The pathogenesis of peptic ulcer and gastric cancer is closely associated with H. pylori gastritis and its subsequent atrophic sequelae (atrophic gastritis). H. pylori-induced gastritis is an important risk factor in the multifactorial aetiology of these diseases. It causes a cascade of reactions that damage the gastric mucosa and epithelium in various ways. The specific mechanisms involved are largely unknown. Some are probably bacterium-related reactions, which are influenced by various virulence factors, and others are consequences of the mucosal inflammation and atrophy. The risk of peptic ulcer and gastric cancer in patients with H. pylori gastritis can be summarized as follows: i) the risk of both peptic ulcer and gastric cancer is low in individuals with a normal stomach; ii) the risk of peptic ulcer is approximately ten times higher and the risk of gastric cancer approximately twice as high in patients with non-atrophic H. pylori-positive gastritis as in those with a normal stomach; iii) these risks are further increased (twofold to threefold) when there is antral atrophy; whereas iv) in the presence of corpus atrophy the risk of gastric cancer remains high, but that of peptic ulcer decreases gradually to zero with increasing severity of corpus atrophy.


Prenatal diagnosis of abdominal cystic hygroma.
We present a case of fetal abdominal cystic hygroma that presented at 19 weeks of gestation. Ultrasonographic evaluation of the fetus revealed soft tissue enlargement of the left leg and a retroperitoneal mass in the left pelvis and abdomen. This represents the first reported case of prenatal diagnosis of abdominal cystic hygroma.


Seven years of cranioplasty in a regional neurosurgical centre.
In recent years craniectomy has been widely used in the management of traumatic brain injury and ischaemic stroke. The objective of this study was to evaluate the indications, techniques and outcomes for patients undergoing cranioplasty over a recent 7-year period in a geographically distinct population. An observational study was performed retrospectively, with review of case records from 2004 to 2011. Demographic, clinical and outcome data were collected, and complications were classified as major and minor. A multi-variant analysis was performed to identify patient and management factors that influenced outcome. Data were collected on a total of 87 cranioplasty patients with a median age of 42 and a mean follow-up time of 3 years and 10 months. The main indications for craniectomy were trauma (46%), infection (19%) intracranial haemorrhage (15%), tumour (13%) and ischaemic stroke (6%). Eight percent of patients had a synchronous craniectomy and cranioplasty, 14% had cranioplasty within 3 months of craniectomy, 21% within 3-6 months, 35% within 6-12 months, 14% over 1 year and 8% over 2 years later. The most frequently implanted cranioplasty material was titanium (53%), followed by autologous bone (26%) and acrylic (15%). Administration of prophylactic antibiotics was recorded in 97% of cases. Major complications occurred in 20% of patients, including 2 deaths (2%), 5 extradural haemorrhages (6%) and 9 infections (10%). A further 10% of cases experienced minor or cosmetic complications. Cranioplasty is often considered as a low-risk procedure following craniectomy. In our cohort, a 20% risk of major complications, including death, was identified. These findings contribute to the literature, emphasising that cranioplasty is a high-risk procedure. Whilst compelling reasons may guide the undertaking of craniectomy, it is essential that consideration is given to the significant subsequent risks of cranioplasty.


Intellectual and Developmental Disabilities Research Centers: A Multidisciplinary Approach to Understand the Pathogenesis of Methyl-CpG Binding Protein 2-related Disorders.
Disruptions in the gene encoding methyl-CpG binding protein 2 (MECP2) underlie complex neurodevelopmental disorders including Rett Syndrome (RTT), MECP2 duplication disorder, intellectual disabilities, and autism. Significant progress has been made on the molecular and cellular basis of MECP2-related disorders providing a new framework for understanding how altered epigenetic landscape can derail the formation and refinement of neuronal circuits in early postnatal life and proper neurological function. This review will summarize selected major findings from the past years and particularly highlight the integrated and multidisciplinary work done at eight NIH-funded Intellectual and Developmental Disabilities Research Centers (IDDRC) across the US. Finally, we will outline a path forward with identification of reliable biomarkers and outcome measures, longitudinal preclinical and clinical studies, reproducibility of results across centers as a synergistic effort to decode and treat the pathogenesis of the complex MeCP2 disorders.


Prediction of virus-host infectious association by supervised learning methods.
The study of virus-host infectious association is important for understanding the functions and dynamics of microbial communities. Both cellular and fractionated viral metagenomic data generate a large number of viral contigs with missing host information. Although relative simple methods based on the similarity between the word frequency vectors of viruses and bacterial hosts have been developed to study virus-host associations, the problem is significantly understudied. We hypothesize that machine learning methods based on word frequencies can be efficiently used to study virus-host infectious associations. We investigate four different representations of word frequencies of viral sequences including the relative word frequency and three normalized word frequencies by subtracting the number of expected from the observed word counts. We also study five machine learning methods including logistic regression, support vector machine, random forest, Gaussian naive Bayes and Bernoulli naive Bayes for separating infectious from non-infectious viruses for nine bacterial host genera with at least 45 infecting viruses. Area under the receiver operating characteristic curve (AUC) is used to compare the performance of different machine learning method and feature combinations. We then evaluate the performance of the best method for the identification of the hosts of contigs in metagenomic studies. We also develop a maximum likelihood method to estimate the fraction of true infectious viruses for a given host in viral tagging experiments. Based on nine bacterial host genera with at least 45 infectious viruses, we show that random forest together with the relative word frequency vector performs the best in identifying viruses infecting particular hosts. For all the nine host genera, the AUC is over 0.85 and for five of them, the AUC is higher than 0.98 when the word size is 6 indicating the high accuracy of using machine learning approaches for identifying viruses infecting particular hosts. We also show that our method can predict the hosts of viral contigs of length at least 1kbps in metagenomic studies with high accuracy. The random forest together with word frequency vector outperforms current available methods based on Manhattan and [Formula: see text] dissimilarity measures. Based on word frequencies, we estimate that about 95% of the identified T4-like viruses in viral tagging experiment infect Synechococcus, while only about 29% of the identified non-T4-like viruses and 30% of the contigs in the study potentially infect Synechococcus. The random forest machine learning method together with the relative word frequencies as features of viruses can be used to predict viruses and viral contigs for specific bacterial hosts. The maximum likelihood approach can be used to estimate the fraction of true infectious associated viruses in viral tagging experiments.


[Milk and dairy products for human nutrition: contribution of technology].
The complex composition of milk has led to the development of innovative technological processes such as membrane separation. The dairy industry is now able to offer consumers safe classical products (liquid milk, raw-milk cheeses) with little or no heat treatment. Indeed, heat treatment undermines the organoleptic qualities and bioactivity of many molecules found in milk. New technologies, and especially membrane microfiltration, have allowed researchers to identify two groups of milk proteins in terms of their human absorption kinetics: slow micellar casein and fast whey proteins. The highly purified products thus obtained are used for infant foods and slimming aids, and as functional ingredients. The same technologies have been applied to colostrum, yielding a sterile "serocolostrum" containing biologically active immunoglobulins, growth factors, and polypeptides. Combined with other separation techniques, membrane technologies should soon allow the separation and purification of minor milk proteins described as having essential roles in bone calcium uptake and vitamin transport, for example. The use of enzymatic membrane reactors has led to the identification of several bioactive peptides, such as--kappa-caseinomacropeptide, which induces CCK (cholecystokinin) secretion and thus regulates food intake and lipid assimilation,--alpha(S1) CN (91-100), a compound with benzodiazepine activity,-- kappaCN (106-116), which has anti-thrombotic activity by inhibiting blood platelet binding to fibrinogen, and--alpha(S) and beta casein phosphopeptides, which are thought to increase iron and calcium absorption.


Effect of inhaled heparin on lung function and coagulation in healthy volunteers.
The aim of the present study was to investigate the safety of increasing doses of a well-defined lower respiratory tract (LRT) dose of inhaled heparin with regard to pulmonary function and coagulation. Ten volunteers inhaled heparin from Sidestream jet nebulizers loaded with 100,000, 200,000, 300,000 or 400,000 International Units (IU) of heparin. Lung function, antifactor (anti)-Xa, activated partial thromboplastin time (APTT), tissue factor pathway inhibitor (TFPI), whole blood clotting time, platelets, von Willebrand factor, and C-reactive protein were determined before and 1, 3, 6, and 24 h after inhalation. The highest LRT dose was 32,000 IU heparin. Inhaled heparin did not affect pulmonary function. The area under the curve of the anti-Xa activity increased with increasing doses of heparin (p=0.005), but remained unchanged for all other variables. Peak anti-Xa activity was 0.113 IU x mL(-1) 6 h after inhalation of 400,000 IU heparin. When compared to baseline values: anti-Xa increased after 200,000 (p=0.03), 300,000 (p=0.004), and 400,000 IU (p=0.002) heparin; APTT increased to a maximum of 1.03 6 h after inhalation of 400,000 IU heparin (p=0.05); TFPI increased after 100,000 (p=0.01), 200,000 (p=0.01), 300,000 (p=0.006) and 400,000 IU (p<0.001). Inhaled heparin delivery of 32,000 International Units to the lower respiratory tract can safely be inhaled for clinical or research purposes.


Vitamin B6 intake and plasma pyridoxal phosphate concentrations in the first 2 weeks of life.
Plasma pyridoxal phosphate concentrations were measured in 178 hospitalised neonates. A reference interval for neonates less than 7 day old, of 25 to 78 nmol/l has been established. Vitamin B6 intakes did not correlate well with plasma pyridoxal concentrations despite 26 neonates receiving less than the Recommended Allowance (0.3 mg/d) and 19 receiving amounts below which convulsions have been associated (0.1 mg/d). Ten percent of those infants fed breast milk had plasma pyridoxal phosphate levels below the reference interval compared with only 4% of those fed milk formulae. Breast milk from mothers with babies less than 14 days old had a total vitamin B6 contents reference interval of 5 to 40 micrograms/l. Twenty percent of breast milk samples had virtually no vitamin B6 detected.


Cystic duct anastomosis can be a viable option for biliary reconstruction in case of multiple ducts in right lobe living-donor liver transplantation.
Multiple ducts in right lobe living-donor liver transplant (LDLT) pose a technical challenge in biliary reconstruction. In the absence of separate recipient hepatic ducts for duct-to-duct anastomoses and certain demerits of hepaticojejunostomy, duct to duct anastomoses with the recipient cystic duct might be a possible solution. A total of 329 recipients of LDLT who underwent two or more separate biliary anastomoses at our centre between January 2014 and November 2019 were studied retrospectively. Records of demographic data, donor and graft characteristics, operative details, postoperative biochemical parameters, and biliary complications were analysed. Of 329 recipients, 236 patients (71.7%) underwent purely duct-to-duct (DD group) anastomoses, 38 patients (11.5%) underwent at least one anastomosis with the cystic duct (CD group), and 55 patients (16.7%) underwent at least one hepaticojejunostomy (HJ group). At one year, biliary complication rates of these three groups were 20.3%, 26.3%, and 20.0%, respectively (p = 0.68). Postoperative intensive care unit and overall hospital stay were similar among the three groups. Grades IIIa, IIIb, IV, and V Clavien-Dindo complications were identical. One-year patient survival and graft survival were also similar among the three groups. Biliary outcomes using the cystic duct may have acceptable outcomes. Similar postoperative results as other means of biliary reconstruction could be anticipated with the cystic duct anastomoses in case of multiple ducts in the graft.


Phylogeny and biogeography of South Chinese brown frogs (Ranidae, Anura).
Few studies have explored the role of Cenozoic tectonic evolution in shaping the patterns and processes of extant animal distributions in and around East Asia. In this study, we selected South Chinese brown frogs as a model to examine the phylogenetic and biogeographical consequences of Miocene tectonic events within South China and its margins. We used mitochondrial and nuclear molecular data to reconstruct phylogenetic interrelationships among Chinese brown frogs using Bayesian and maximum likelihood analyses. The phylogeny results show that there are four main clades of Chinese brown frogs. Excepting the three commonly known Chinese brown frog species groups, R. maoershanensis forms an independent clade nearest to the R. japonica group. Phylogeny and P-distance analyses confirmed R. maoershanensis as a valid species. Among South Chinese brown frogs, there are four subclades associated with four geographical areas: (I) R. maoershanensis; (II) R. japonica; (III) R. chaochiaoensis; and (IV) other species of the R. longicrus species group. Divergence times, estimated using mitochondrial sequences, place the vicariance events among the four subclades in the middle to late Miocene epoch. Our results suggest that (1) South Chinese brown frogs originated due to a vicariance event separating them from the R. chensinensis species group at the time of the Geological movement (~18 million years ago, Ma) in southern Tibet and the Himalayan region; (2) the separation and speciation of R. maoershanensis from the R. japonica group occurred due to the dry climate at approximately 16 Ma; (3) South Chinese brown frogs migrated from South China to Japan at the time (~10.8 Ma) that the global sea-level fell and the East China Sea Shelf Basin was swamp facies, when a land gallery may have formed across the sea to connect the two areas; and (4) R. chaochiaoensis separated from other species of the R. longicrus species group during the uplift of the Tibetan Plateau at approximately 9.5 Ma.


Homozygous null variant in CRADD, encoding an adaptor protein that mediates apoptosis, is associated with lissencephaly.
Lissencephaly is a severe malformation of cortical development, most often attributed to abnormalities in neuronal migration. It is associated with a severe prognosis including developmental delay, intellectual disability, and seizures. Lissencephaly can be reliably diagnosed during late gestation by neurosonography or fetal magnetic resonance imaging (MRI). We report two sibling male fetuses who were diagnosed with delayed cortical sulcation highly suggestive of lissencephaly during late pregnancy. After receiving genetic counseling, the parents elected to terminate the pregnancies based on the neuroradiological findings and the associated severe prognosis. Whole exome sequencing (WES) of an affected fetus, and subsequent Sanger sequencing of the second fetus, revealed a homozygous frameshift variant in CRADD, which encodes an adaptor protein that interacts with PIDD and caspase-2 to initiate apoptosis. Biallelic variants in this gene have been recently reported to cause "thin" lissencephaly and intellectual disability. Interestingly, the allegedly healthy father was also found to be homozygous for the variant, prompting evaluation by brain MRI which revealed hypogyration. This study underscores the phenotypic variability of pathogenic variants in CRADD and the challenges of prenatal genetic counseling.


Endovascular treatment of a mycotic aneurysm in an immunocompromised child with acute leukemia-case report and review of the literature.
Mycotic aneurysms are dilatations of an artery, a rare but severe complication arising from infectious obliteration of the vessel wall. Thoracic aneurysms often present with unspecific symptoms and multiple diagnostic and therapeutic challenges. In an advanced state, they have an increased risk of perforation and a high mortality rate. The surgical therapeutic approach has a high perioperative complication rate. In this study, we report a case of a thoracic mycotic aortic aneurysm in an immunocompromised pediatric patient caused by Klebsiella pneumoniae bacteremia. A combination of prompt antibacterial treatment and minimally invasive stent implantation showed a good outcome, avoiding possible severe surgical problems.


Zebrafish dead end possesses ATPase activity that is required for primordial germ cell development.
Zebrafish dead end (dnd) mRNA is specifically expressed in primordial germ cells (PGCs) and is required for PGC migration and survival. Previous studies have shown that zebrafish Dnd functions by protecting the 3'UTRs of nanos1 and TDRD7 from miR-430b-mediated RNA deadenylation. In this work, we demonstrate that zebrafish Dnd protein possesses Mg(2+)-dependent ATPase activity that is required for PGC formation. Michaelis-Menten analysis revealed that the ATPase has a k(cat) of 0.632 +/- 0.036/min under optimal conditions, and mapping studies using Dnd truncates showed that ATPase resides in the last 91 aa of the Dnd C terminus. Internal deletion and point mutagenesis analysis of this region were used to identify key amino acids required for ATPase activity. Rescue experiments conducted by injecting mRNAs encoding the Dnd ATPase mutants into embryos in which the endogenous dnd expression was inhibited demonstrated that the ATPase activity is required for normal zebrafish PGC survival. Real-time PCR analysis showed that the expression of PGC markers nanos1 and TDRD7 but not vasa were down-regulated when dnd mutant proteins lacking ATPase were expressed in the rescued embryos, indicating that the Dnd ATPase is involved in protecting nanos1 and TDRD7 transcripts.


[On effectiveness of management of processes of health promotion and health preservation].
The article considers issues of effectiveness of management of human health in conditions of innovative development of society. The study was carried out to investigate functional condition of health of students in dynamics as compared with health indices of other population groups, to develop health promotion ideology and motivation for implementation of health culture and health preservation. The sampling consisted of 800 healthy volunteers out of various regions of Russia aged 17-60 years (males - 50%, females - 50%) having active social life-style and without chronic pathologies. The Martine-Kushelevskii test was applied for examination. The data was analyzed using technique of single-factor analysis of variance. It is established that number of individuals with health condition and estimated as "good" reliably decreased in the group of 17-20 years up to 13%, in the group of 21-30 years up to 6.7%, in the group of 31-49 years up to 3.3%, in the group of 41-50 years up to 3.3% during 6 years of observation. The number of volunteers with estimate "satisfactory" has a trend to decreasing in all groups. In the group 17-20 years' number of examinees with satisfactory values is significantly lower than in other age groups. The study data permits to conclude that it is necessary to introduce the passport of health reflecting both medical indices and individual algorithm of health. This algorithm will be a multifactorial indicator of stress resistance and capacity to adaptation.


[Tendency, features and cultural background of modern medicine in China].
The new tendency and features of development of medicine in modern China is discussed on the social and cultural background, which bears a dual character of both advancement and backwardness. By analysing the features of modern Chinese civilization, it is emphasized that modern China's medicine was developed on an extremely complex social and cultural background. It was not only restricted within the cultural framework but also governed by the intrinsic rule of medicine itself. This paper also mentions the five features and three tendencies of medicine based on historical facts, which reflects definitely the objective rules of modern Chinese medicine. It is these rules that links premodern and modern medicine. The work of contemporary China is in line with these rules.


Ovarian influence on pulmonary carcinogenesis by hydrazine sulfate in BALB/c/Cb/Se mice.
Daily administration of hydrazine sulfate, 1.13 mg/mouse for 150 doses, to BALB/c/Cb/Se female mice in various hormonal states varied the incidence and the average number of pulmonary tumors per tumor-bearing mouse as follows: in intact virgins, 90.0% and 3; in breeders, 100% and 14; in gonadectomized mice, 60.0% and 5. Histologically, in intact virgins, 3.3% were carcinomas and 96.6% were adenomas; in breeders, 47.2% were carcinomas and 52.7% were adenomas; in gonadectomized mice, 4% were carcinomas and 96% were adenomas. Many pulmonary carcinomas induced in breeders infiltrated the thoracic wall and the mediastinal organs and metastasized to the adrenal glands and myocardium. The greater biologic and morphologic malignancy of the induced tumors observed in breeders, as compared to those in intact virgin and gonadectomized mice, was associated with an increased ovarian hormone production.


Conformational analysis of peptides and glycopeptides derived from the consensus sequence for β-O-glucosylation.
Cys-Xxx-Ser-Xxx-Pro-Cys (Xxx= any amino acid but Pro) is the most common sequence present in naturally occurring peptides and proteins glycosylated with β-O-glucose (β-O-Glc). Taking into account the lack of studies concerning the spatial disposition of this sequence, we have synthesized and analyzed, in aqueous solution, the conformational behavior of peptides and a glycopeptide derived from the particular fragment Cys-Ala-Ser-Ser-Pro-Cys. This sequence is found in the crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor. Our studies, based on the use of NOESY experiments in combination with molecular dynamics (MD) simulations, indicate that for this particular fragment, initially characterized by a type I β-turn motif, the glycosylation with β-O-Glc forces the peptide backbone into an extended conformation. This conformation is stabilized by the presence of both hydrogen bonds and water pockets between the peptide and the sugar moieties.


Diet-controlled blood levels of oltipraz in healthy male subjects.
The bioavailability of the new antischistosomal agent, oltipraz, was examined under three different dietary conditions in seven healthy males. Oltipraz tablets (500 mg) were administered in single doses (25 mg/kg) under fasting conditions, with a low fat meal (less than 5% fat) and a high fat meal (24% fat). The extent and rate of oltipraz bioavailability were significantly increased by concurrent administration of the drug with food, as demonstrated by the increase in the plasma peak concentration, the area under the plasma concentration vs. time curve and the absorption rate constant. The plasma peak concentration was also reached earlier. Oltipraz plasma concentrations, following its administration under fasting conditions, were almost negligible. The likely mechanisms underlining oltipraz-food interaction are discussed.


Comparison of preferences of healthcare professionals and MS patients for attributes of disease-modifying drugs: A best-worst scaling.
The choice between disease-modifying drugs (DMDs) for the treatment of multiple sclerosis (MS) becomes more often a shared decision between the patient and the neurologist and MS nurse. This study aimed to assess which DMD attributes are most important for the healthcare professionals in selecting a DMD for a patient. Subsequently, within this perspective, the neurologists' and nurses' perspectives were compared. Lastly, the healthcare professionals' perspective was compared with the patients' perspective to detect any differences that may need attention in the communication about DMDs. A best-worst scaling (BWS) was conducted among 27 neurologists and 33 MS nurses treating patients with MS to determine the importance of 27 DMD attributes. These attributes were identified through three focus groups with MS patients in a previous study (N=19). Relative importance scores (RISs) were estimated for each attribute. Multivariable linear regression analyses were used to compare the different perspectives. According to the neurologists and nurses, safety of the DMD was the most important DMD attribute in the treatment decision, closely followed by effect on disability progression, quality of life and relapse rate. Patients with MS agreed with the importance of the last three attributes, but valued safety significantly lower (b=-2.59, P<.001). This study suggests that, overall, neurologists and nurses regard the same DMD attributes as important as MS patients with the notable exception of safety. This study provides valuable information for the development of interventions to support shared decision making and highlights which attributes of DMDs may need additional attention.


The role of ulnar nerve transposition in ulnar nerve repair: a cadaver study.
Ulnar nerve transposition at the elbow is recommended to diminish nerve gaps during neurorrhaphy. We undertook a cadaver study to determine the gap distance that can be overcome by subcutaneous transposition at the elbow, evaluating lacerations 2.0 cm distal to the medial epicondyle and 2.0 cm proximal to the wrist crease. With a 100-g load on each nerve stump, gaps that could be overcome were measured before and after transposition in different elbow and wrist positions. For the distal forearm lacerations, wrist position significantly affected nerve gap, while transposition and elbow position did not. Nerve gap was significantly reduced by approximately 11 mm with wrist flexion from 0 degrees to 45 degrees. For proximal forearm lacerations, gap distance was significantly affected by transposition and was dependent to a greater extent on the interaction between transposition and elbow position, with wrist position having no effect. A clinically relevant scenario for the proximal laceration compared the pretransposition gap with the elbow and wrist at neutral with the posttransposition gap with the elbow and wrist flexed. Posttransposition gap reduction, with elbow and wrist flexion at 45 degrees, was approximately 9 mm and was not significant. To span a gap near the elbow, we estimate that more than 45 degrees of elbow flexion is required.


Multigenerational memory in bacterial size control.
Cells maintain a stable size as they grow and divide. Inspired by the available experimental data, most proposed models for size homeostasis assume size-control mechanisms that act on a timescale of one generation. Such mechanisms lead to short-lived autocorrelations in size fluctuations that decay within less than two generations. However, recent evidence from comparing sister lineages suggests that correlations in size fluctuations can persist for many generations. Here we develop a minimal model that explains these seemingly contradictory results. Our model proposes that different environments result in different control parameters, leading to distinct inheritance patterns. Multigenerational memory is revealed in constant environments but obscured when averaging over many different environments. Inferring the parameters of our model from Escherichia coli size data in microfluidic experiments, we recapitulate the observed statistics. Our paper elucidates the impact of the environment on cell homeostasis and growth and division dynamics.


Our experience with incisive neuroleptic drugs in child psychiatry.
The authors report their own experiences of treatment with incisive neuroleptic drugs in child psychiatry (haloperidol, pimozide, penfluridol, sulpiride). An attention was paid to side effects of the treatment, especially to a possible side effect of cardiovascular character, namely that pimozide might block Ca channels. The authors made a control check of ECG and report the findings. The results of the treatment of various disorders (tic disorders, psychosis, obsessive- compulsive diseases, autism) are very good. The authors never came across the picture of serious side effects e.g. of tardive dyskinesis.


Selection-based learning in bird song development.
Bird song is a model system for study of the neurobiology, development, and functions of learned vocal communication signals. Research on avian song learning has been dominated by an instructive model of learning--the sensorimotor model. Developmental plasticity is assumed to be based on the incorporation of novel material into the song repertoire. Experimental evidence now indicates an alternative form of plasticity operating in harmony with sensorimotor learning, based on principles of selection, rather than instruction. Song dialects, a common consequence of vocal learning, can be achieved by overproduction of previously memorized songs and selective attrition of those that fail to match the dialect of interacting males. These distinct processes of learning have important implications for study of the neural substrates underlying song production and perception and for efforts to interpret patterns of geographic variation in song.


Natural selection on Erysimum mediohispanicum flower shape: insights into the evolution of zygomorphy.
Paleontological and phylogenetic studies have shown that floral zygomorphy (bilateral symmetry) has evolved independently in several plant groups from actinomorphic (radially symmetric) ancestors as a consequence of strong selection exerted by specialized pollinators. Most studies focused on unraveling the developmental genetics of flower symmetry, but little is known about the adaptive significance of intraspecific flower shape variation under natural conditions. We provide the first evidence for natural selection favoring zygomorphy in a wild population of Erysimum mediohispanicum (Brassicaceae), a plant showing extensive continuous variation in flower shape, ranging from actinomorphic to zygomorphic flowers. By using geometric morphometric tools to describe flower shape, we demonstrate that plants bearing zygomorphic flowers received more pollinator visits and had the highest fitness, measured not only by the number of seeds produced per plant but also by the number of seeds surviving to the juvenile stage. This study provides strong evidence for the existence of significant fitness differences associated with floral shape variation in E. mediohispanicum, thus illuminating a pathway for the evolution of zygomorphy in natural populations.


Nonconverged Constraints Cause Artificial Temperature Gradients in Lipid Bilayer Simulations.
Molecular dynamics (MD) simulations have become an indispensable tool to investigate phase separation in model membrane systems. In particular, simulations based on coarse-grained (CG) models have found widespread use due to their increased computational efficiency, allowing for simulations of multicomponent lipid bilayers undergoing phase separation into liquid-ordered and liquid-disordered domains. Here, we show that a significant temperature difference between molecule types can artificially arise in CG MD membrane simulations with the standard Martini simulation parameters in GROMACS. In particular, the linear constraint solver (LINCS) algorithm does not converge with its default settings, resulting in serious temperature differences between molecules in a time step-dependent manner. We demonstrate that the underlying reason for this behavior is the presence of highly constrained moieties, such as cholesterol. Their presence can critically impact numerous structural and dynamic membrane properties obtained from such simulations. Furthermore, any preference of these molecules toward a certain membrane phase can lead to spatial temperature gradients, which can amplify the degree of phase separation or even induce it in compositions that would otherwise mix well. We systematically investigated the effect of the integration time step and LINCS settings on membrane properties. Our data show that for cholesterol-containing membranes, a time step of 20 fs should be combined with at least lincs_iter = 2 and lincs_order = 12, while using a time step of 30 fs requires at least lincs_iter = 3 and lincs_order = 12 to bring the temperature differences to a level where they do not perturb central membrane properties. Moreover, we show that in cases where stricter LINCS settings are computationally too demanding, coupling the lipids in multiple groups to the temperature bath offers a practical workaround to the problem, although the validity of this approach should be further verified. Finally, we show that similar temperature gradients can also emerge in atomistic simulations using the CHARMM force field in combination with settings that allow for a 5 fs integration step.


Effects of water on reactions for waste treatment, organic synthesis, and bio-refinery in sub- and supercritical water.
Current research analyzing the effects of water in the field of homogeneous and heterogeneous reactions of organics in sub- and supercritical water are reviewed in this article. Since the physical properties of water (e.g., density, ion product and dielectric constants) can affect the reaction rates and mechanisms of various reactions, understanding the effects that water can have is important in controlling reactions. For homogeneous reactions, the effects of water on oxidation, hydrolysis, aldol condensation, Beckman rearrangement and biomass refining were introduced including recent experimental results up to 100 MPa using special pressure-resistance equipment. For heterogeneous reactions, the effects of ion product on acid/base-catalyzed reactions, such as hydrothermal conversion of biomass-related compounds, organic synthesis in the context of bio-refinery, and hydration of olefins were described and how the reaction paths are controlled by the concentration of water and hydrogen ions was summarized.