[Genotype and phenotype of gastrointestinal symptoms analysis in children with cystic fibrosis].
Cystic fibrosis is the most common autosomal recessive genetic defect of one gene CFTR, where a variety of mutations were revealed. Cystic fibrosis is a variable disease and to date the genotype-phenotype correlation is difficult to clarify. The aim of the study was to analyse retrospectively the genotype and phenotype of children with cystic fibrosis and to search the correlation between type of mutation in CFTR and clinical manifestation of the gastrointestinal tract. The study group comprised 52 patients. Molecular DNA analyses were performed in 43 cases. Statistical analysis was done by using Fisher test. In 34 (79%) cases two mutations in the CFTR gene were identified. In this group 21 cases were identified as a homozygous for AF508 mutation, in single case other mutations were found. A mutation of one CFTR allel was revealed in 11 patients, cystic fibrosis was not confirmed by genetic test in 9 children. Mean age of diagnosis was 34 months. In 38 children (73%) pancreatic insufficiency in the course of disease was found. Exocrine insufficiency of pancreas was showed significant frequently in homozygous group. Liver dysfunction in 20 children (38.5%) was revealed. In this group 12 patients was identified as a homozygous for deltaF508 mutation. On the base of oral glucose tolerance test the diabetes mellitus and glucose intolerance was diagnosed in 4 cases with homozygous genotype. Seven patients died in the endstage of the illness, in two of them homozygous mutation deltaF508 was found, in next 5 patients genetic analysis was not performed. The frequency and severity of clinical manifestation of the gastrointestinal tract correlates with deltaF508 mutation. Early genetic test and demonstration of molecular defect in CFTR gene confirms the clinical diagnosis of cystic fibrosis and improves a quality of life and prolongs survival time of cystic fibrosis patients.


Redesigning Implementation Measurement for Monitoring and Quality Improvement in Community Delivery Settings.
The field of prevention has established the potential to promote child adjustment across a wide array of outcomes. However, when evidence-based prevention programs have been delivered at scale in community settings, declines in implementation and outcomes have resulted. Maintaining high quality implementation is a critical challenge for the field. We describe steps towards the development of a practical system to monitor and support the high-quality implementation of evidence-based prevention programs in community settings. Research on the implementation of an evidence-based parenting program for divorcing families called the "New Beginnings Program" serves as an illustration of the promise of such a system. As a first step, we describe a multidimensional theoretical model of implementation that links aspects of program delivery with improvements in participant outcomes. We then describe research on the measurement of each of these implementation dimensions and test their relations to intended program outcomes. As a third step, we develop approaches to the assessment of these implementation constructs that are feasible to use in community settings and to establish their reliability and validity. We focus on the application of machine learning algorithms and web-based data collection systems to assess implementation and provide support for high quality delivery and positive outcomes. Examples are presented to demonstrate that valid and reliable measures can be collected using these methods. Finally, we envision how these measures can be used to develop an unobtrusive system to monitor implementation and provide feedback and support in real time to maintain high quality implementation and program outcomes.


Cutaneous Protothecosis in a Patient with Chronic Lymphocytic Leukemia: A Case Report and Literature Review.
Protothecosis is a rare infection, which has the potential to cause severe disease in patients with underlying immunosuppression. We describe a case of an elderly female with chronic lymphocytic leukemia (CLL), as well as other risk factors, who presented with pustular and erythematous plaques, initially presumed to be leukemia cutis. A biopsy with special stains revealed the lesions to be cutaneous protothecosis, thus presenting a most unusual concurrence of disease entities. The literature to date on this rare infection will be reviewed.


Trigeminal brainstem modulation of persistent orbicularis oculi muscle activity in a rat model of dry eye.
Altered corneal reflex activity is a common feature of dry eye disease (DE). Trigeminal sensory nerves supply the ocular surface and terminate at the trigeminal interpolaris/caudalis (ViVc) transition and spinomedullary (VcC1) regions. Although both regions contribute to corneal reflexes, their role under dry eye conditions is not well defined. This study assessed the influence of local inhibitory and excitatory amino acid neurotransmission at the ViVc transition and VcC1 regions on hypertonic saline (HS) evoked orbicularis oculi muscle activity (OOemg) in urethane-anesthetized male rats after exorbital gland removal (DE). HS increased the magnitude of long-duration OOemg activity (OOemgL, >200ms) in DE compared to sham rats, while short-duration OOemg activity (OOemgS, <200ms) was similar for both groups. Inhibition of the ViVc transition by muscimol, a GABAA receptor agonist, greatly reduced HS-evoked OOemgL activity in DE rats, whereas injections at the VcC1 region had only minor effects in both groups. Blockade of GABAA receptors by bicuculline methiodide at the ViVc transition or VcC1 region increased HS-evoked OOemgL activity in DE rats. Blockade of N-methyl-D-aspartate (NMDA) receptors at either region reduced HS-evoked OOemgL activity in DE and sham rats. GABAαβ3 receptor density was reduced at the ViVc transition, while NMDA receptor density was increased at both regions in DE rats. Loss of GABAergic inhibition at the ViVc transition coupled with enhanced NMDA excitatory amino acid neurotransmission at the ViVc transition and the VcC1 region likely contribute to altered corneal reflexes under dry eye conditions.


Structural requirements for beta1 integrin-mediated tyrosine phosphorylation in human T cells.
The beta1 integrin adhesion receptors activate signal transduction pathways that induce tyrosine phosphorylation of a variety of substrates. Increased tyrosine phosphorylation is mediated by the beta1 subunit cytoplasmic domain, which consists of 46 amino acids and contains no intrinsic kinase activity. In the H9 T cell line, beta1 integrin engagement leads to the increased tyrosine phosphorylation of three 105 to 115-kDa substrates that are distinct from focal adhesion kinase (FAK): HEF1 (human enhancer of filamentation 1), a protein with structural homology to p130Cas, and two novel substrates, pp105 and pp115. DNA-mediated gene transfer was used to explore the role of the beta1 cytoplasmic domain in integrin-mediated tyrosine phosphorylation of HEF1, pp105, and pp115 in human T cells. Using a chimeric receptor composed of the cytoplasmic domain of the beta1 integrin subunit and the extracellular and transmembrane domains of the CD2 Ag, we demonstrate that the beta1 cytoplasmic domain is necessary and sufficient for inducing tyrosine phosphorylation of each of these three substrates in H9 T cells. Analysis of a series of beta1 cytoplasmic domain truncations reveals that a truncation of only five amino acids from the carboxyl-terminal end of the beta1 cytoplasmic domain abrogates the ability of the CD2/beta1 chimera to activate tyrosine phosphorylation of HEF1, pp105, or pp115. Thus, the carboxyl-terminal five amino acids, Lys-Tyr-Glu-Gly-Lys (KYEGK), of the beta1 integrin cytoplasmic domain are critical for the coordinate tyrosine phosphorylation of three non-FAK substrates in human T cells.


[Liver injury in idiopathic CD4+T-cell lymphocytopenia].
A 48 years old patient was admitted to the Internal Medicine ward due to progressive weakness and abnormal liver function tests. During three months of hospitalization she developed opportunistic infections with Cryptococcus and Pneumocystic jiroveci pneumonia. The CD4+ T-cell lymphocyte count was very low with no evidence of infection with human immunodeficiency virus. Liver disease deteriorated with the appearance of profound jaundice and severe hepatitis. The patient's laboratory and clinical presentation were compatible with the diagnosis of idiopathic CD4 + T-cell lymphocytopenia--ICL. The authors reviewed the literature on ICL and discuss the rare hepatic presentation of this uncommon syndrome.


Framework for estimating renal function using magnetic resonance imaging.
Purpose: Nephrologists have empirically predicted renal function from renal morphology. In diagnosing a case of renal dysfunction of unknown course, acute kidney injury and chronic kidney disease are diagnosed from blood tests and an imaging study including magnetic resonance imaging (MRI), and an examination/treatment policy is determined. A framework for the estimation of renal function from water images obtained using the Dixon method is proposed to provide information that helps clinicians reach a diagnosis by accurately estimating renal function on the basis of renal MRI. Approach: The proposed framework consists of four steps. First, the kidney area is extracted by MRI using the Dixon method with a U-net by deep learning. Second, the extracted renal region is registered with the target mask. Third, the kidney features are calculated based on the target mask classification information created by a specialist. Fourth, the estimated glomerular filtration rate (eGFR) representing the renal function is estimated using a regression support vector machine from the calculated features. Results: For the accuracy evaluation, we conducted an experiment to estimate the eGFR when MRI was performed and the eGFR slope, which is the annual rate of decline in eGFR. When the accuracy was evaluated for 165 subjects, the eGFR was estimated to have a root mean square error (RMSE) of 11.99 and a correlation coefficient of 0.83. Moreover, the eGFR slope was estimated to have an RMSE of 4.8 and a correlation coefficient of 0.5. Conclusions: Therefore, the proposed method shows the possibility of estimating the prognosis of renal function based on water images obtained by the Dixon method.


Excellent mid-term durability of the On-X mechanical aortic valve in the pulmonary position with a low international normalized ratio.
Although the pulmonary position has been preferred for the placement of homografts or bioprosthetic valves, the limited longevity of these implants makes reoperation almost unavoidable. Good durability of mechanical valves in the pulmonary position has been reported. The mid-term outcomes were analyzed of patients who received an On-X mechanical heart valve for pulmonary valve replacement (PVR) with a relatively low International Normalized Ratio (INR). Between February 2008 and February 2011, mechanical On-X valves (size range: 19 to 25 mm) were implanted for PVR in six patients. Tetralogy of Fallot (ToF) was the most common diagnosis (n = 6). Postoperatively, warfarin was used to maintain the INR at 1.5-2.0. The surgical results and follow up were reviewed retrospectively, with valve failure, thrombosis, embolism, bleeding, reoperation and death being defined as end-points. There was no intraoperative or in-hospital mortality. The mean age of patients at the time of PVR was 31 +/- 19.7 years (range: 16-61 years). In patients who underwent repair of ToF (n = 4) the average duration between PVR and previous right ventricular outflow tract (RVOT) reconstruction was 8.75 +/- 3.3 years (range: 5-12 years). The mean follow up period was 3.13 +/- 1.31 years (range: 2-5 years). There was no 30-day mortality, late death, thromboembolism, major bleeding event or valve dysfunction, and no patient needed reoperation. All survivors were categorized as NYHA class I or II. A three-year experience with the On-X bileaflet mechanical valve in the pulmonary position demonstrated excellent mid-term durability, with no thromboembolisms or bleeding events when the INR was maintained at 1.5-2.0. For patients who require PVR, either as primary procedure or reoperation, the On-X mechanical heart valve might represent an appropriate option.


Locust retinoid X receptors: 9-Cis-retinoic acid in embryos from a primitive insect.
The retinoid X receptor (RXR) is activated by its often elusive cognate ligand, 9-cis-retinoic acid (9-cis-RA). In flies and moths, molting is mediated by a heterodimer ecdysone receptor consisting of the ecdysone monomer (EcR) and an RXR homolog, ultraspiracle (USP); the latter is believed to have diverged from its RXR origin. In the more primitive insect, Locusta migratoria (Lm), RXR is more similar to human RXRs than to USPs. LmRXR was detected in early embryos when EcR transcripts were absent, suggesting another role apart from ecdysone signaling. Recombinant LmRXRs bound 9-cis-RA and all-trans-RA with high affinity (IC(50) = 61.2-107.7 nM; K(d) = 3 nM), similar to human RXR. To determine whether specific binding had functional significance, the presence of endogenous retinoids was assessed. Embryos were extracted by using modified Bligh and Dyer and solid-phase protocols to avoid the oily precipitate that makes this material unsuitable for assay. These extracts contained retinoids (5.4 nM) as assessed by RA-inducible Cyp26A1-promoter luciferase reporter cell lines. Furthermore, the use of HPLC and MS confirmed the presence of retinoids and identified in any embryo, 9-cis-RA, in addition to all-trans-RA. We estimate that whole embryos contain 3 nM RA, including 9-cis-RA at a concentration of 1.6 nM. These findings strongly argue for a functional role for retinoids in primitive insects and favor a model where signaling through the binding of 9-cis-RA to its RXR is established relatively early in evolution and embryonic development.


Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies.
Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.


Rationale for periodic reporting on the use of adult clinical preventive services of public health priority--United States.
This supplement introduces a CDC initiative to monitor and report periodically on the use of a set of selected clinical preventive services in the U.S. adult population in the context of recent national initiatives to improve access to and use of such services. Increasing the use of these services has the potential to lead to substantial reductions in the burden of illness, death, and disability and to lower treatment costs. The majority of clinical preventive services are provided by the health-care sector, and public health agencies play important roles in helping to support increases in the use of these services (e.g., by identifying and implementing policies that are effective in increasing use of the services and by collaborating with stakeholders to conduct programs to improve use). Recent health reform initiatives, including efforts to increase the accessibility and affordability of preventive services, fund community prevention programs, and improve the use of health information technologies, offer opportunities to enhance use of preventive services. This supplement provides baseline information on a set of selected clinical preventive services before implementation of these recent reforms and discusses opportunities to increase the use of such services. This information can help public health practitioners collaborate with other stakeholders that have key roles to play in improving public health (e.g., employers, health plans, health professionals, and voluntary associations), understand the potential benefits of the recommended services, address the problem of underuse, and identify opportunities to apply effective strategies to improve use and foster accountability among stakeholders.


Trends in deaths and disability-adjusted life-years of stroke attributable to high body-mass index worldwide, 1990-2019.
High body mass index (HBMI) is an independent risk factor for stroke. Previous studies on the incremental burden of the rapid growth of stroke attributable to HBMI are incomplete and lag behind. We aim to assess the global burden of stroke attributable to HBMI based on a public database online. Study data were taken from the Global Burden of Disease, Injuries, and Risk Factors Study; deaths, the Disability-Adjusted Life-Years (DALYs), and their age-standardized rates were screened. The join point regression was used, wherein age-standardized rates were referred to as temporal trends in disease burden. Deaths from stroke attributable to HBMI worldwide were on the rise during 1990-2019, with an increase of 88.75%. Age-standardized DALYs were on the rise during 1990-2003 but declined during 2003-2013, with a turning point in 2013 and an increasing trend since then [the Annual Percentage Change (APC) = 0.30%, p < 0.05]. China, India, Indonesia, the Russian Federation, and the United States of America shared in sequence the rate of leading deaths and DALYs in 2019. The Socio-Demographic Index (SDI) was associated with an increasing trend in age-standardized deaths (R = -0.24, p < 0.001) and age-standardized DALYs (R = -0.22, p = 0.0018). A range of indicators for the global burden of stroke attributable to HBMI have been on the rise for the past three decades. Tremendous efforts worldwide should be in place to control and treat stroke attributable to HBMI, especially in regions with high-middle and middle SDIs and among middle-aged and aged populations.


Reiterative template switching: the effect of single-strand homopolymeric DNA on non-template-directed nucleotide addition by DNA polymerase.
Template switching occurs when DNA polymerase juxtaposes two discontinuous DNA molecules with 3'-terminally complementary ends generated through non-template-directed nucleotide addition. We examined whether juxtaposition of homopolymeric single-stranded oligonucleotides affects non-templated addition. We hypothesized that if DNA polymerase first juxtaposed the two substrates, then the non-template-directed nucleotide addition of any deoxynucleotide would decrease in the presence of its non-complementary template. For dATP, product formation was unaffected by non-complementary substrates. In contrast, dCTP and dGTP incorporation decreased to varying degrees while dTTP incorporation increased in the presence of oligodeoxythymidine but decreased for other non-complementary homopolymers. Interestingly, the presence of complementary templates strongly influenced the formation of highly periodic products indicative of reiterative template switching. Transient template synapsis was observed and found to be dependent on the non-templated sequence added: 3-4 A:T or 1-2 G:C base pairs were needed for stable synapsis, suggesting that base pairing plays a more important role in the active site of the enzyme than previously thought.


Integrated Intimate Partner Violence and Human Immunodeficiency Virus Interventions in Sub-Saharan Africa: A Systematic Review Targeting or Including Adolescents.
Adolescents in Sub-Saharan Africa are at disproportionately high risk for intimate partner violence (IPV) and human immunodeficiency virus (HIV). The interconnected risks for IPV and HIV present the opportunity for interventions to concurrently seek to reduce violence and sexual risk behaviors among young people. Accordingly, the present systematic review evaluates interventions that concomitantly address IPV and HIV risk among adolescents in Sub-Saharan Africa. The authors systematically reviewed electronic databases for studies meeting the following criteria: use of randomized control trials (RCT) or quasi-RCT in Sub-Saharan African countries; inclusion of adolescents aged 13-18 years; use of a comparison group (wait listed, designated to a comparative treatment, or treatment as usual); and incorporation of IPV and HIV outcome assessments. Results suggested that six studies have utilized rigorous research methodologies to evaluate integrated IPV/HIV interventions; however, few have targeted adolescents. The six studies meeting inclusion criteria indicate that current research on IPV/HIV is conducted with rigorous study designs among target populations with high IPV/HIV risk, using gender-specific risk reduction activities. The authors' findings indicate there is also the need for consistent application of valid and reliable outcome measurements of IPV and HIV risk. Additional research is needed to identify best practices for reducing IPV and HIV incidence among vulnerable adolescent populations in Sub-Saharan Africa.


Motor control differentiates children's from adults' drawings for child and adult judges.
In two exploratory studies, motor skill as a possible distinctive feature for differentiating drawings made by second-grade children and by college students was tested by having child and adult judges sort drawings made by children and by adults. Adults drew with their preferred (motorically skilled) or nonpreferred (nonmotorically skilled) hand. Children and adults were equally accurate in discriminating children's from adults' preferred-hand drawings, but child judges confused children's and adults' non-preferred-hand drawings. Child, but not adult, judges confused adults' preferred-hand and adults' non-preferred-hand drawings. Thus, children were sensitive to characteristics of drawings that depended on motor skill when it was an additional feature of difference but not when it was the only distinctive feature. Motor control effects in constructing drawings and evidence of motor control in responding to drawings warrant further study and perhaps greater emphasis in theories of drawing development.


Fine structure of the synaptic discs separated from the goldfish medulla oblongata.
Synaptic discs are structures localized in the club ending synapses on the Mauthner cell lateral dendrite of the goldfish medulla oblongata. The synaptic discs present a hexagonal array of particles approximately 8.5 nm center-to-center when observed in en face view. This lattice covers the entire surface Divalent cations are important in the stabilization of this particular hexagonal array of particles When a synaptic disc-rich fraction is treated with chelating agents (EDTA or EGTA), definite changes occur in the hexagonal lattice. First, the synaptic membranes show zones without particles interspersed with zones covered with the hexagonal array of particles Second, the synaptic discs break down and a new structure characterized by two parallel dense bands (7 nm each), separated by a 4 nm gap, is observed. The negative stain fills the gap region showing striations spaced approximately 10 nm center-to-center crossing the gap, but it does not penetrate the dense bands This "double band" structure is interpreted as an edge on view of a fragment of the synaptic membrane complex. Further treatment of this fraction with a chelating agent plus 0.3% deoxycholate produces an increase in the number of double band structures. However, EDTA plus Triton X-100 (a treatment known to produce solubilization of membrane proteins) never shows such double band structure An ordered material was observed associated with the cytoplasmic leaflets of the double bands This material consists of rows of beads approximately 4 nm in diameter and spaced at intervals of approximately 7 nm. Each of these beads is joined to the band by a thin stalk.


Lack of efficacy of ergocalciferol repletion.
Vitamin D has become an area of intensive scrutiny, both in medical and lay literature. However, there are limited data to suggest proper repletion regimens for those patients who have hypovitaminosis D. Consequently, various methods are used in clinical practice. The aim of this study was to assess the efficacy of various treatment strategies for hypovitaminosis D in an ambulatory internal medicine practice. A retrospective chart review between October 2005 and June 2010 of a suburban internal medicine practice was performed via query of the electronic medical record (Centricity, General Electric Healthcare, UK). Patients with a 25-hydroxyvitamin D concentration less than 32 mg/dl were identified and treated. Treatment success was defined as 25-hydroxyvitamin D concentrations greater than 32 mg/dl. Statistical analysis to assess changes in vitamin D level controlling for season, comorbidities, and demographics were used. A total of 607 treatment episodes were identified, with 395 excluded due to lack of follow-up vitamin D level within 16 weeks, no treatment documented, topical treatment, doxercalciferol treatment, or non-compliance. Of the remaining patients, there were 212 treatment instances on 178 patients. Ergocalciferol 50,000 international units (IU) was used most frequently (71.4% of the time.). A higher initial vitamin D level was positively associated with treatment success (adjusted odds ratio = 1.11, p=0.002). Increased doses of ergocalciferol increased the likelihood of treatment success (p=0.0011). Seasonal variation was related to posttreatment 25-hydroxyvitamin D concentration as was body mass index (BMI) (p=0.003 and p=0.044). Pretreatment levels of 25-hydroxyvitamin D, BMI, season, and vitamin D dose are predictors of successful hypovitaminosis D treatment. Our data suggest that patients with initial 25-hydroxyvitamin D concentrations of <20 should be treated with a higher total dose of ergocalciferol than 50,000 IU for 8 weeks. Further studies, including prospective, randomized trials, are needed to determine an optimal treatment protocol to account for the numerous variables.


Nonlinear defects separating spiral waves in Taylor-Couette flow.
Stable domain walls which are realized by a defect between oppositely traveling spiral waves in a pattern-forming hydrodynamic system, i.e., Taylor-Couette flow, are studied numerically as well as experimentally. A nonlinear mode coupling resulting from the nonlinearities in the underlying momentum balance is found to be essential for the stability of the defects. These nonlinearly driven defects separate spiral domains and act either as a phase generating or annihilating defect. Specific phase differences of either 0 or pi between the participating traveling waves are a characteristic feature of this defect. The influence of a symmetry breaking externally imposed flow on the spiral domains and the defects is studied. The numerical and experimental results are in excellent agreement.


[Lateral sinus thrombosis in the first three months of pregnancy].
Thrombosis of the cerebral venous sinuses is characterized by clinical pleomorphism and variable pathogenesis. Although there is a relationship with pregnancy and especially with the puerperium, occurrence during the first trimester of pregnancy is unusual and this may effect the diagnosis and treatment. We describe the case of a 33 years-old patient with lateral sinus thrombosis in the first trimester of pregnancy. This was diagnosed and followed-up by magnetic resonance. Investigations as to its aetiology were inconclusive and it followed a benign course without anticoagulation. Thrombosis of the venous sinuses has been found empirically to be related to states of deficiency of S protein, hypercoagulability, anaemia and deshydration during pregnancy, to having previously taken contraceptive pills. Behçet's disease, other coagulopathies, central or systemic vasculitis, collagen disorders, septic and neoplastic disorders and a large number of cases of unknown aetiology. In our patient neurological deterioration secondary to a venous infarct or intraparenchymatous haemorrhage was not seen. There was full recovery and complete spontaneous canalization of the sinus, as shown on posterior cranial angiography. The controversial decision to use heparin in thrombosis of the cerebral venous sinuses should probably depend on the possible risks and benefits in each individual case, taking into account the clinical findings, aetiology and topography of the thrombosed sinus.


A comparison of the effects of temporary hippocampal lesions on single and dual context versions of the olfactory sequence memory task.
In recent years, many animal models of memory have focused on one or more of the various components of episodic memory. For example, the odor sequence memory task requires subjects to remember individual items and events (the odors) and the temporal aspects of the experience (the sequence of odor presentation). The well-known spatial context coding function of the hippocampus, as exemplified by place cell firing, may reflect the "where" component of episodic memory. In the present study, we added a contextual component to the odor sequence memory task by training rats to choose the earlier odor in one context and the later odor in another context and we compared the effects of temporary hippocampal lesions on performance of the original single context task and the new dual context task. Temporary lesions significantly impaired the single context task, although performance remained significantly above chance levels. In contrast, performance dropped all the way to chance when temporary lesions were used in the dual context task. These results demonstrate that rats can learn a dual context version of the odor sequence learning task that requires the use of contextual information along with the requirement to remember the "what" and "when" components of the odor sequence. Moreover, the addition of the contextual component made the task fully dependent on the hippocampus.


The efficacy of Kinesio taping on lymphedema following head and neck cancer therapy: a randomized, double blind, sham-controlled trial.
The aim was to investigate the effectiveness of Kinesio taping for lymphedema following head and neck cancer therapy and its effect on patient compliance and quality of life. A total of 66 patients with lymphedema following head and neck cancer therapy were randomly allocated to the therapeutic Kinesio taping group (n = 33) and the sham Kinesio taping group (n = 33). All participants received manual lymphatic drainage, Kinesio taping, and home exercises for the first four weeks, and only home exercises for the second four weeks. The tape measurements, a scale of external lymphedema, a scale of the internal lymphedema, and quality of life were evaluated in both groups. The perceived discomfort consisting of limitation of daily living activities, pain, tightness, stiffness, and heaviness were also recorded. When the group x time effect was evaluated, it was observed that external lymphedema was significantly reduced in both groups according to neck and face composite measurements (p < .001). However, in these measurements, a significant difference was found between the groups in favor of the KT group (p = .001, p = .032, respectively). At the end of the study, there was no significant difference in terms of internal lymphedema in both groups (p = .860). The quality of life parameters such as global health status and swallowing were significantly better in the Kinesio taping group (p < .001). There was no significant difference in the parameters of perceived discomfort between the two groups (p = .282, p = .225, p = .090, p = .155, p = .183, respectively). Kinesio taping is effective in tape measurements and positively affects the quality of life in lymphedema following head and neck cancer therapy.


Recent advances in palmoplantar pustulosis.
Palmoplantar pustulosis (PPP) is a chronic inflammatory condition where crops of sterile pustules with erythematous keratotic lesions causing bleeding and pain appear on the palms and soles. Recently, the European Rare and Severe Expert Network considered PPP as a variant of pustular psoriasis with or without psoriasis vulgaris. The prevalence of PPP varies from 0.050 to 0.12%. PPP occurs more frequently in women and the highest prevalence occurred between the ages of 50 and 69 years. Nail psoriasis seems to be frequent in PPP, ranging from 30 to 76%, and psoriatic arthritis in 8.6 to 26% of PPP patients. Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and pustulotic arthro-osteitis are considered PPP-associated disorders. PPP has been reported with other co-morbidities such as psychiatric disorders, thyroid-associated disease, altered calcium homeostasis, gluten sensitivity diabetes, obesity, and dyslipidemia, but larger studies are required to prove such associations. Environmental exacerbating factors might contribute to the onset or worsening of PPP such as cigarette smoking, stress, focal infections, metal allergies, and drug intake. Genetic predisposition plays an important role in PPP. In PPP, both the innate and the adaptive immune systems are activated. The acrosyringeal expression of IL-17 has been demonstrated, indicating that the eccrine sweat gland is an active component of the skin barrier and an immune-competent structure. Increased levels of several inflammatory molecules, including IL-8, IL-1α, IL-1β, IL-17A, IL-17C, IL-17D, IL-17F, IL-22, IL-23A, and IL-23 receptor, have been detected in PPP biopsies. Increased serum levels of TNF-α, IL-17, IL-22, and IFN-γ have been detected in patients with PPP in comparison to healthy subjects, suggesting a similar inflammatory pattern to psoriasis vulgaris. Oral and tonsillar infections serve as trigger factors for PPP. Long-term therapy is required for many patients, but high-quality data are limited, contributing to uncertainty about the ideal approach to treatment.


[State of non-specific activating and inhibitory systems of the brain under hypoxic conditions].
The functional state of the rabbit brain activating system was evaluated by the activation reaction, and the thalamic inhibitory system, by the recruiting response. At the initial phase of hypoxia, excitability of the activating system was enhanced, while at the same time the eugmenting phase of the recruiting response diminished and its inhibitory phase was prolonged. At the "altitude" of about 7000 m, against the background of a gradual weakening of the ascending activating influence of the reticular formation and the hypthalamus, the recruiting response assumed the form of regular; equally negative potentials, which testifies to the activie synchronizing influence of the inhibitory system. At a "rise" to 8500 m, against the background of slow synchronized EEG waves, in most cases there was no activation reaction to the stimulation of the reticular formation and hypothalamus. Neither was there any recruiting response to the stimulation of non-specific thalamic nuclei.


Preliminary assessment of an image analysis method for the evaluation of pharmaceutical coatings.
This article describes the development and preliminary assessment of an innovative image analysis method for the evaluation of pharmaceutical coatings. Nonpareils previously hot-melt coated with a red water-soluble dye incorporated into polyethylene glycol were employed to develop and evaluate the new method. Digital images of batch samples were acquired and transferred to a PC for evaluation by image analysis software. Standard deviations generated for the optical densities of individual nonpareils in each batch sample were utilized to evaluate coating uniformity. Mean optical densities generated for each batch sample were used to evaluate the mean coating thickness. Method precision determinations, using an average sample size of 221 nonpareils, returned a relative standard deviation of 2.47% for coating uniformity and 1.71% for coating thickness. The new method is rapid, objective, and relatively inexpensive. It proved to be both qualitative and quantitative for coating uniformity, qualitative for coating thickness, and maintained a high degree of precision. The method can be used independently or in conjunction with other methods to eliminate their subjective aspects regarding sample selection.


Nomograms for clinically localized disease. Part III: watchful waiting.
Patients with newly diagnosed, clinically localized prostate cancer need information concerning long-term outcomes to make informed decisions regarding treatment options. Several nomograms have been developed that can help in this decision process. By using a nomogram originally published in 1998, patients and clinicians can predict the 15-year clinical outcomes in the absence of aggressive treatment based on age and Gleason score at diagnosis. These predictions are based on patients diagnosed and treated before the routine use of PSA that has accelerated the diagnosis of prostate cancer by at least 5 years. Longer follow-up of contemporary patients will determine whether this nomogram remains accurate in the prostate-specific antigen (PSA) era. In view of the lead-time bias resulting from PSA testing, the outcomes of contemporary patients are likely to be better rather than worse than the results shown.


Synthesis and characterization of Black Au nanoparticles deposited over g-C3N4 nanosheets: enhanced photocatalytic degradation of methylene blue.
Black AuNPs, prepared by a facile seeding growth method under ambient conditions, displayed efficient broadband absorption of the incident light over the entire visible and near-infrared regions of the solar spectrum. The spherical black AuNPs with the size of 2-4 nm were deposited over mesoporous g-C3N4 nanosheets. Novel black AuNPs/g-C3N4 plasmonic photocatalysts were used to remove methylene blue (MB) dye from an aqueous solution. The degradation efficiency for the optimal coupling of 1.3 wt.% black AuNPs with g-C3N4 (1.2 g) was found to be 85% within 60 min under visible light irradiation. The calculated kinetic constant was 0.0186 min-1 which was 6.4 and 2.9 times greater than those for g-C3N4 and AuNPs/g-C3N4 nanocomposite, respectively. The excellent potential in photocatalysis was attributed to the synergistic interactions of the g-C3N4 conduction band and the localized surface plasmon resonance effect of black AuNPs. These properties were responsible for the generation of high-energy electrons, a negative shift in the Fermi level of black AuNPs, and the migration of charge carriers. This work studied a new insight into black gold nanoparticles via the design of a visible-light-driven photocatalyst and provided a perspective on valuable photo-related applications such as water treatment.


Translating evidence into practice in acute respiratory distress syndrome: teamwork, clinical decision support, and behavioral economic interventions.
Although the treatment of the acute respiratory distress syndrome (ARDS) with low tidal volume (LTV) mechanical ventilation improves mortality, it is not consistently administered in clinical practice. This review examines strategies to improve LTV and other evidence-based therapies for patients with ARDS. Despite the well established role of LTV in the treatment of ARDS, a recent multinational study suggests it is under-utilized in clinical practice. Strategies to improve LTV include audit and feedback, provider education, protocol development, interventions to improve ICU teamwork, computer decision support, and behavioral economic interventions such as making LTV the default-ventilator setting. These strategies typically target all patients receiving invasive mechanical ventilation, effectively avoiding the problem of poor ARDS recognition in clinical practice. To more effectively administer advanced ARDS therapies, such as prone positioning, better approaches for ARDS recognition will also be required. Multiple strategies can be utilized to improve adherence to LTV ventilation in ARDS patients.


Extended Efficacy of Low-Dose Valganciclovir for Prevention of Cytomegalovirus Disease in Intermediate-Risk Kidney Transplant Recipients: Two-Year Follow-Up.
In a previous study, we evaluated 1-year outcomes of using low-dose valganciclovir prophylaxis for cytomegalovirus infection in intermediate-risk kidney transplant recipients. Whether this effect persists in the long term is unknown. We aimed to evaluate the 2-year follow up of such adopted prophylaxis. We randomized 2 matched groups of kidney transplant recipients (1:1) to receive valganciclovir as 450 mg daily (group 1) or 900 mg daily (group 2) for the first 6 months after kidney transplant. The final analysis included 196 patients as intermediate-risk patients (98 in each treatment group) after exclusion of 5 high-risk patients. Serologically, all patients were at moderate risk for cytomegalovirus infection. Long-term outcomes including cytomegalovirus disease, acute rejection, new-onset diabetes after transplant, graft loss, and patient survival were assessed. Through year 2 of follow-up, cytomegalovirus infection was reported in only 1 patient in group 1 (at month 13) and 1 patient in group 2 (at month 19) (not significant). Biopsy-proven acute rejection episodes were not statistically different between the groups (2 episodes in group 1 and 6 in group 2; P = .431). New-onset diabetes posttransplant was reported in 8.1% in group 1 and 13.2% in group 2 (P = .535). Graft failure was equal in both groups (1 in each group) at 2 years of follow up (not significant). Patient survival was comparable in both groups (100% in group 1 versus 97.9% in group 2; P = .661). The total number of cytomegalovirus infections at 2 years was numerically less in group 1 (P = .128). Low-dose valganciclovir prophylaxis for 6 months was associated with sustained reduction of cytomegalovirus infection up to 2 years after kidney transplant without significant impact on the acute rejection, new-onset diabetes posttransplant, or patient and graft outcomes.


Depression and Mobility Among Older Adults in Mexico: ENSANUT 2012.
Depression among older people can be associated with limitations in physical mobility. The ENSANUT 2012 data set was used. A secondary data analysis was conducted on a total sample of 6,525 Mexicans 60 years and older. Findings indicate that depressive symptoms among older people derive from their limitations in mobility rather than from their age. In Mexico, the prevalence of major depressive disorders is higher among older adults than among the rest of the adults. Hence, as the prevalence of this problem grows, the need for appropriate mental health attention will increase in Mexico.


Acute and chronic effects of adriamycin on fatty acid oxidation in isolated cardiac myocytes.
This study was designed to determine if acute (in vitro) or chronic (in vivo) adriamycin inhibits cardiac fatty acid oxidation and if so at what sites in the fatty acid oxidation pathway. In addition, the role of L-carnitine in reversing or preventing this effect was examined. We determined the effects of adriamycin in the presence or absence of L-carnitine on the oxidation of the metabolic substrates [1-14C]palmitate. [1(-14)C] octanoate. [1(-14)C]butyrate, [U-14C]glucose, and [2(-14)C]pyruvate in isolated cardiac myocytes. Acute exposure to adriamycin caused a concentration- and time-dependent inhibition of carnitine palmitoyl transferase 1 (CPT 1) dependent long-chain fatty acid, palmitate, oxidation. Chronic exposure to (18 mg/kg) adriamycin inhibited palmitate oxidation 40% to a similar extent seen in vitro with 0.5 mM adriamycin. Acute or chronic administration of L-carnitine completely abolished the adriamycin-induced inhibition of palmitate oxidation. Interestingly, medium- and short-chain fatty acid oxidation, which are independent of CPT 1, were also inhibited acutely by adriamycin and could be reversed by L-carnitine. In isolated rat heart mitochondria, adriamycin significantly decreased oxidation of the CPT 1 dependent substrate palmitoyl-CoA by 50%. However, the oxidation of a non-CPT 1 dependent substrate palmitoylcarnitine was unaffected by adriamycin except at concentrations greater than 1 mM. These data suggest that after in vitro or in vivo administration, adriamycin, inhibits fatty acid oxidation in part secondary to inhibition of CPT 1 and/or depletion of its substrate, L-carnitine, in cardiac tissue. However, these findings also suggest that L-carnitine plays an additional role in fatty acid oxidation independent of CPT 1 or fatty acid chain length.


Oxidative stress and excitotoxicity: a therapeutic issue in multiple sclerosis?
There is increasing evidence that multiple sclerosis (MS) is not only characterized by immune mediated inflammatory reactions but also by neurodegenerative processes. In neurodegenerative diseases, neuronal and axonal loss is mediated by oxidative stress and excitotoxicity which constitute a final common toxic pathway. Importantly, peroxynitrite is the key mediator of those two intertwined pathomechanisms. In MS, peroxynitrite is consistently associated with active lesions and produces highly toxic nitrating and oxidizing radical species that alter lipid, protein, DNA and mitochondrial structures and functions. During the remitting phase, peroxynitrite participates to neuron and oligodendrocyte damage in association with inflammatory processes. During the chronic phase, peroxynitrite contributes to self-perpetuating mechanisms responsible for disease progression. Neutralization of oxidative stress and excitotoxicity, and in particular of peroxynitrite derived free radicals, might represent a therapeutic approach to provide neuroprotection in MS.


More than just a gut feeling: constraint-based genome-scale metabolic models for predicting functions of human intestinal microbes.
The human gut is colonized with a myriad of microbes, with substantial interpersonal variation. This complex ecosystem is an integral part of the gastrointestinal tract and plays a major role in the maintenance of homeostasis. Its dysfunction has been correlated to a wide array of diseases, but the understanding of causal mechanisms is hampered by the limited amount of cultured microbes, poor understanding of phenotypes, and the limited knowledge about interspecies interactions. Genome-scale metabolic models (GEMs) have been used in many different fields, ranging from metabolic engineering to the prediction of interspecies interactions. We provide showcase examples for the application of GEMs for gut microbes and focus on (i) the prediction of minimal, synthetic, or defined media; (ii) the prediction of possible functions and phenotypes; and (iii) the prediction of interspecies interactions. All three applications are key in understanding the role of individual species in the gut ecosystem as well as the role of the microbiota as a whole. Using GEMs in the described fashions has led to designs of minimal growth media, an increased understanding of microbial phenotypes and their influence on the host immune system, and dietary interventions to improve human health. Ultimately, an increased understanding of the gut ecosystem will enable targeted interventions in gut microbial composition to restore homeostasis and appropriate host-microbe crosstalk.


The effects of self-induced mood states on behavior and physiological arousal.
The effects of reading emotionally loaded statements on behavioral tasks and physiological measures were investigated. Statements were constructed to arouse elation, depression, or neutrality. Ss were both pre- and posttested on Writing Speed, Reaction Time, Decision Time, and Spontaneous Verbalizations. Base rates were obtained for heart rate and galvanic skin response. Elation Ss significantly outperformed both Neutral and Depression Ss on the Reaction Time task. Scores for Neutral Ss fell between those of Elation and Depression Ss on three of the four behavioral measures. No significant differneces were found on the physiological measures.


Endosymbiotic bacteria in honey bees: Arsenophonus spp. are not transmitted transovarially.
Intracellular endosymbiotic bacteria are common and can play a crucial role for insect pathology. Therefore, such bacteria could be a potential key to our understanding of major losses of Western honey bees (Apis mellifera) colonies. However, the transmission and potential effects of endosymbiotic bacteria in A. mellifera and other Apis spp. are poorly understood. Here, we explore the prevalence and transmission of the genera Arsenophonus, Wolbachia, Spiroplasma and Rickettsia in Apis spp. Colonies of A. mellifera (N = 33, with 20 eggs from worker brood cells and 100 adult workers each) as well as mated honey bee queens of A. cerana, A. dorsata and A. florea (N = 12 each) were screened using PCR. While Wolbachia, Spiroplasma and Rickettsia were not detected, Arsenophonus spp. were found in 24.2% of A. mellifera colonies and respective queens as well as in queens of A. dorsata (8.3%) and A. florea (8.3%), but not in A. cerana The absence of Arsenophonus spp. from reproductive organs of A. mellifera queens and surface-sterilized eggs does not support transovarial vertical transmission. Instead, horizontal transmission is most likely.


Monolingual and bilingual children's processing of coarticulation cues during spoken word recognition.
Bilingual children cope with a significant amount of phonetic variability when processing speech, and must learn to weigh phonetic cues differently depending on the cues' respective roles in their two languages. For example, vowel nasalization is coarticulatory and contrastive in French, but coarticulatory-only in English. In this study, we extended an investigation of the processing of coarticulation in two- to three-year-old English monolingual children (Zamuner, Moore & Desmeules-Trudel, 2016) to a group of four- to six-year-old English monolingual children and age-matched English-French bilingual children. Using eye tracking, we found that older monolingual children and age-matched bilingual children showed more sensitivity to coarticulation cues than the younger children. Moreover, when comparing the older monolinguals and bilinguals, we found no statistical differences between the two groups. These results offer support for the specification of coarticulation in word representations, and indicate that, in some cases, bilingual children possess language processing skills similar to monolinguals.


Multi-omics of 34 colorectal cancer cell lines - a resource for biomedical studies.
Colorectal cancer (CRC) cell lines are widely used pre-clinical model systems. Comprehensive insights into their molecular characteristics may improve model selection for biomedical studies. We have performed DNA, RNA and protein profiling of 34 cell lines, including (i) targeted deep sequencing (n = 612 genes) to detect single nucleotide variants and insertions/deletions; (ii) high resolution DNA copy number profiling; (iii) gene expression profiling at exon resolution; (iv) small RNA expression profiling by deep sequencing; and (v) protein expression analysis (n = 297 proteins) by reverse phase protein microarrays. The cell lines were stratified according to the key molecular subtypes of CRC and data were integrated at two or more levels by computational analyses. We confirm that the frequencies and patterns of DNA aberrations are associated with genomic instability phenotypes and that the cell lines recapitulate the genomic profiles of primary carcinomas. Intrinsic expression subgroups are distinct from genomic subtypes, but consistent at the gene-, microRNA- and protein-level and dominated by two distinct clusters; colon-like cell lines characterized by expression of gastro-intestinal differentiation markers and undifferentiated cell lines showing upregulation of epithelial-mesenchymal transition and TGFβ signatures. This sample split was concordant with the gene expression-based consensus molecular subtypes of primary tumors. Approximately ¼ of the genes had consistent regulation at the DNA copy number and gene expression level, while expression of gene-protein pairs in general was strongly correlated. Consistent high-level DNA copy number amplification and outlier gene- and protein- expression was found for several oncogenes in individual cell lines, including MYC and ERBB2. This study expands the view of CRC cell lines as accurate molecular models of primary carcinomas, and we present integrated multi-level molecular data of 34 widely used cell lines in easily accessible formats, providing a resource for preclinical studies in CRC.


Diagnosis and management of the oral manifestations of HIV infection and AIDS.
The oral manifestations of HIV infection present as a variety of opportunistic infections, neoplasms, and other lesions. Some of these are common, perhaps the most common, features of HIV disease and are highly predictive of the development of AIDS. Clinicians caring for HIV-infected persons should become familiar with the diagnosis and management of this group of conditions. The oral lesions of HIV infection present challenges of diagnosis and therapy. As the epidemic progresses, it can be expected that further lesions will be observed and that additional rational and effective therapeutic approaches will be developed.


Non-destructive methodologies applied to track the occurrence of natural micropollutants in watering: Glycine max as a biomonitor.
Groundwater is habitually used for watering purposes in rural areas where the rainfall is not enough to adequately cover the crop requirements. However, groundwater sources could be naturally contaminated with trace micropollutants like As and associated elements (B, V and F) adversely affecting the plant health. In this work, non-destructive methodologies based on reflectance and chlorophyll emission processes were applied to assess the presence of micropollutants in watering by using a widespread crop (soybean plant). One of the most substantial results is that the co-occurrence of As, V, B and F in the watering solution clearly produced a synergistic effect in the plants. In fact, both reflectance and fluorescence techniques were proved in this work to be effective in detecting non-destructively stress by multielement treatment. Particularly, for reflectance measurements the most sensitive parameters were the derivative peak area between 480 and 560 nm and the chlorophyll content. Furthermore, it was demonstrated that it is possible to successfully use a portable hyperspectral spectroradiometer instead of a conventional spectrophotometer as the determinations performed with both instruments were positively correlated. Concerning fluorescence, variable emission of chlorophyll-a was more sensitive to stress than steady-state emission. The parameter Fv/F0 was a valuable indicator of stress but the quantum yields of PSII and NPQ stood out as the most sensitive indices with variations of around 60 and 100% respectively.


Immunosuppressive therapy of childhood idiopathic nephrotic syndrome.
Childhood nephrotic syndrome (NS) is a distressing chronic renal disorder with potentially life threatening complications. Over 80% of cases in children are due to minimal change disease and the majority will respond to corticosteroid therapy. Steroid-sensitive NS is considered a relatively benign condition, since progression to end stage renal failure (ESRF) is extremely rare and > 80% will enter spontaneous long-term remission in later childhood. However, the disease is characterised by a relapsing course, placing the child at risk of acute complications, such as infection, hypovolaemia and thrombosis. Frequent relapses can result in a not inconsequential corticosteroid burden or prescription of cytotoxic immunosuppressive therapy to control the disease. In contrast, steroid-resistant and -refractory NS has an unfavourable outcome with a propensity to progress to ESRF. While these clinical entities have an unpredictable response to cytotoxic immunosuppressive therapy, the favourable long-term renal survival associated with children who enter sustained remission has revived the enthusiasm to treat steroid-resistant NS with more aggressive immunosuppressive regimens.


Votucalis, a Novel Centrally Sparing Histamine-Binding Protein, Attenuates Histaminergic Itch and Neuropathic Pain in Mice.
Votucalis is a biologically active protein in tick (R. appendiculatus) saliva, which specifically binds histamine with high affinity and, therefore, has the potential to inhibit the host's immunological responses at the feeding site. We hypothesized that scavenging of peripherally released endogenous histamine by Votucalis results in both anti-itch and anti-nociceptive effects. To test this hypothesis, adult male mice were subjected to histaminergic itch, as well as peripheral nerve injury that resulted in neuropathic pain. Thus, we selected models where peripherally released histamine was shown to be a key regulator. In these models, the animals received systemic (intraperitoneal, i.p.) or peripheral transdermal (subcutaneous, s.c. or intraplantar, i.pl.) administrations of Votucalis and itch behavior, as well as mechanical and thermal hypersensitivity, were evaluated. Selective histamine receptor antagonists were used to determine the involvement of histamine receptors in the effects produced by Votucalis. We also used the spontaneous object recognition test to confirm the centrally sparing properties of Votucalis. Our main finding shows that in histamine-dependent itch and neuropathic pain models peripheral (s.c. or i.pl.) administration of Votucalis displayed a longer duration of action for a lower dose range, when compared with Votucalis systemic (i.p.) effects. Stronger anti-itch effect was observed after co-administration of Votucalis (s.c.) and antagonists that inhibited peripheral histamine H1 and H2 receptors as well as central histamine H4 receptors indicating the importance of these histamine receptors in itch. In neuropathic mice, Votucalis produced a potent and complete anti-nociceptive effect on mechanical hypersensitivity, while thermal (heat) hypersensitivity was largely unaffected. Overall, our findings further emphasize the key role for histamine in the regulation of histaminergic itch and chronic neuropathic pain. Given the effectiveness of Votucalis after peripheral transdermal administration, with a lack of central effects, we provide here the first evidence that scavenging of peripherally released histamine by Votucalis may represent a novel therapeutically effective and safe long-term strategy for the management of these refractory health conditions.


Overproduction of discoidin I by a temperature-sensitive motility mutant of Dictyostelium discoideum.
Dictyostelium discoideum MC2 is a temperature-sensitive motility mutant of AX3. Mutant cells are incapable of growth, phagocytosis, and migration under restrictive conditions (Kayman et al., J. Cell Biol. 92:705-711, 1982). We show here that at the restrictive temperature MC2 cells grown axenically or on bacteria synthesized excessive quantities of the lectin discoidin I. By two-dimensional gel electrophoresis and peptide mapping, the proteins overproduced by MC2 cells were indistinguishable from discoidin I synthesized at lower levels in AX3 cells. At least two of the three species of discoidin I were overproduced. This protein family constituted 9% of the total protein in cells that were incubated overnight at 27 degrees C in axenic medium. Although MC2 cells are defective in nutrient uptake under restrictive conditions, the overproduction of discoidin I did not appear to be part of a pleiotropic response to starvation. We propose that transcription of the coordinately regulated discoidin I genes is altered in mutant cells. This alteration may be related to the motility defects manifested by MC2.


Functional assessment of problem behavior: dispelling myths, overcoming implementation obstacles, and developing new lore.
Hundreds of studies have shown the efficacy of treatments for problem behavior based on an understanding of its function. Assertions regarding the legitimacy of different types of functional assessment vary substantially across published articles, and best practices regarding the functional assessment process are sometimes difficult to cull from the empirical literature or from published discussions of the behavioral assessment process. A number of myths regarding the functional assessment process, which appear to be pervasive within different behavior-analytic research and practice communities, will be reviewed in the context of an attempt to develop new lore regarding the functional assessment process. Frequently described obstacles to implementing a critical aspect of the functional assessment process, the functional analysis, will be reviewed in the context of solutions for overcoming them. Finally, the aspects of the functional assessment process that should be exported to others versus those features that should remain the sole technological property of behavior analysts will be discussed.


Arthrotomography of the wrist. The palmar radiocarpal ligaments.
Twenty-one fresh cadaver wrists were studied by arthrography and arthrotomography. Arthrography was unreliable in accurately delineating the palmar radiocarpal ligaments. However, lateral arthrotomograms predictively and precisely outlined the radiolucent radiocapitate and radiotriquetral ligaments. The radial and more distant radiolucent area was the radiocapitate ligament, and the ulnar and more proximal area was the radiotriquetral ligament. A constant radiopaque invagination between the outlines of contrast material demonstrated the sulcus anatomically separating these two ligaments. When the ligaments were transected contrast material entered the substance of the ligaments, rendering them radiopaque and, thus, visible on the radiographs. The authors believe that arthrotomography may be a useful clinical tool in the evaluation of post-traumatic injuries to the palmar radiocarpal ligaments of the wrist.


Combination of Energetic Tetrazole and Triazole: Promising Materials with Exceptional Stability and Low Mechanical Sensitivity as Propellants and Gas Generators.
An innovative synthesis of 5-((1H-tetrazol-5-yl)methyl)-4H-1,2,4-triazole-3,4-diamine (TMT) based on triazole and tetrazole frameworks bearing double amino groups was reported. It is worth mentioning that TMT is insensitive to impact and friction (IS > 40 J, FS > 360 N), thus enabling it to have an exceptional thermal decomposition behavior that is superior to RDX and TNT. Meanwhile, it also has relatively high energetic performance (Dv = 8.417 km/s). A series of energy-containing salts TMT-1-8 were also investigated for their potential applications. Except for TMT-4 and TMT-7, the remaining nitrogen-rich salts have initial decomposition temperatures above 200 °C. Furthermore, the salts with positive heat generation all have extraordinary gas production, especially for TMT-1 (Vo = 840.5 dm3/kg), TMT-2 (Vo = 803.9 dm3/kg), and TMT-7 (Vo = 844.3 dm3/kg). The low mechanical sensitivities of the TMT series were discovered, and a majority of them have impact sensitivities exceeding 40 J with friction sensitivities exceeding 360 N which are superior to TNT (IS = 15 J, FS = 353 N). The intermolecular and intramolecular interactions of the crystals TMT-1-3 were explored by Hirshfeld surfaces, 2D fingerprint plots, noncovalent interaction (NCI) analysis, and electrostatic potential surface analysis to understand the physicochemical property changes in relation to the structure. Consequently, this novel tri/tetrazole and polyamine system as a promising material provides the impetus for the development of gas generators and propellants.


Combined ossification of the posterior longitudinal ligament at C2-3 and invagination of the posterior axis resulting in myelopathy.
Spinal stenosis at the C2-3 segment is a rare occurrence, and when it occurs myelopathy infrequently results. Furthermore, only a handful of cases involving congenital abnormalities of the posterior arch of the axis have been described resulting in cervical myelopathy many of which described simultaneous congenital abnormalities at adjacent levels and none of which identified ossification of the posterior longitudinal ligament (OPLL) at the same level. We report a case of a previously undescribed combination of abnormalities at the C2-3 segment resulting in clinical myelopathy. A 49-year-old Chinese male presented with a progressive cervical myelopathy (C-JOA score 11 immediately pre-op). Segmental OPLL at the C2-3 disk space was visible, together with invagination of the bilaterally hypoplastic C2 lamina into the spinal canal. Signal abnormalities of the spinal cord were evident on both T1 and T2 sequences. The patient underwent a posterior decompression and instrumented fusion at C2-3 using pars screws at C2 and lateral mass screws at C3. Following surgery there was a rapid and significant improvement in the neurological symptoms, with the C-JOA score improving to 14 at final follow-up. A successful fusion was evident. Deficiencies in the posterior arch of the axis are rare and have not previously been reported in conjunction with OPLL. Advanced imaging is helpful to define the abnormality and site of compression. In the setting of a progressive neurological dysfunction, surgical decompression and stabilization is a reasonable intervention and can be associated with neurological and symptomatic improvement.


Endothelin receptors in teleost fishes: cardiovascular effects and branchial distribution.
By observing gill blood flow using epi-illuminating microscopy, in parallel with cardiovascular recordings and immunohistochemistry, we have tried to identify the receptor mediating endothelin (ET) type 1 (ET1)-induced pillar cell contraction in the lamellae of the Atlantic cod (Gadus morhua). Intra-arterial injection of the specific ET(B) receptor agonist BQ-3020 induced dose-dependent increases in ventral aortic blood pressure, gill vascular resistance, and pillar cell area (indicating contraction). The specific ET(A) receptor antagonist BQ-610 did not prevent either pillar cell contraction or increased gill vascular resistance induced by ET-1 injection. The cardiovascular responses were corroborated by the detection of ET(B) receptor-like immunoreactivity (IR) associated with pillar cells in the lamellar region and in neuroendocrine cells. ET(B) receptor-like IR was also found lining the muscle layer of lamellar arterioles and filament arteries. In contrast, strong ET(A) receptor-like IR was found on branchial nerves throughout the filaments. In addition, ET-like IR was concentrated in neuroendocrine cells in the filament and lamellae. We also present data suggesting that ET-mediated pillar cell contraction is widespread among teleost fish, including Atlantic cod, rainbow trout (Oncorhynchus mykiss), sculpin (Myoxocephalus scorpius), and mackerel (Scomber scombrus). Taken together, our results suggest that an ET(B)-like receptor mediates pillar cell contraction in fishes, whereas ET(A)-like receptors may serve another function in the gill, inasmuch as ET(A) receptor-like IR is found on branchial nerves.


Equine infectious anemia viral vector-mediated codelivery of endostatin and angiostatin driven by retinal pigmented epithelium-specific VMD2 promoter inhibits choroidal neovascularization.
Equine infectious anemia virus (EIAV) is a nonprimate lentivirus that does not cause human disease. Subretinal injection into mice of a recombinant EIAV lentiviral vector in which lacZ is driven by a CMV promoter (EIAV CMV LacZ) resulted in rapid and strong expression of LacZ in retinal pigmented epithelial (RPE) cells and some other cells including ganglion cells, resulting in the presence of 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside within the optic nerve. Substitution of the RPE-specific promoter from the vitelliform macular dystrophy (VMD2) gene for the CMV promoter resulted in prolonged (at least 1 year) expression of LacZ that was restricted to RPE cells, albeit reduced 6- to 10-fold compared with the CMV promoter. Similarly, the amount of FLAG-tagged endostatin detected in eyes injected with the EIAV VMD2 Endo(FLAG) vector was similar to that seen in eyes injected with a vector that expressed both endostatin and angiostatin [EIAV VMD2 Endo(FLAG)/Angio]; expression was approximately 6-fold lower than with identical vectors in which the CMV promoter drove expression. Compared with murine eyes treated with a control EIAV vector, subretinal injection of EIAV vectors expressing murine endostatin alone or in combination with angiostatin driven by either the CMV or VMD2 promoter caused significant suppression of choroidal neovascularization (NV) at laser-induced rupture sites in Bruch's membrane. These data support proceeding toward clinical studies with EIAV-based gene therapy for choroidal NV, using the VMD2 promoter to selectively drive expression of a combination of endostatin and angiostatin in RPE cells.


Calibrating machine learning approaches for probability estimation: A comprehensive comparison.
Statistical prediction models have gained popularity in applied research. One challenge is the transfer of the prediction model to a different population which may be structurally different from the model for which it has been developed. An adaptation to the new population can be achieved by calibrating the model to the characteristics of the target population, for which numerous calibration techniques exist. In view of this diversity, we performed a systematic evaluation of various popular calibration approaches used by the statistical and the machine learning communities for estimating two-class probabilities. In this work, we first provide a review of the literature and, second, present the results of a comprehensive simulation study. The calibration approaches are compared with respect to their empirical properties and relationships, their ability to generalize precise probability estimates to external populations and their availability in terms of easy-to-use software implementations. Third, we provide code from real data analysis allowing its application by researchers. Logistic calibration and beta calibration, which estimate an intercept plus one and two slope parameters, respectively, consistently showed the best results in the simulation studies. Calibration on logit transformed probability estimates generally outperformed calibration methods on nontransformed estimates. In case of structural differences between training and validation data, re-estimation of the entire prediction model should be outweighted against sample size of the validation data. We recommend regression-based calibration approaches using transformed probability estimates, where at least one slope is estimated in addition to an intercept for updating probability estimates in validation studies.


Risk of specific birth defects in relation to chlorination and the amount of natural organic matter in the water supply.
To assess the effect of water chlorination by-products on specific birth defects, the authors conducted a nationwide cross-sectional study of 285,631 Norwegian births in 1993-1998. Risks of birth defects according to four chlorination by-product exposure categories were compared on the basis of chlorination (yes/no) and level of water color (mg Pt/liter), representing the amount of natural organic matter: high (chlorination, < or =20), medium (chlorination, 10-19.9), and low (chlorination, <10) exposure, with no chlorination and low color (<10) as the reference category. In logistic regression analysis, the risks of any birth defect (adjusted odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.01, 1.25) and of cardiac (adjusted OR = 1.37, 95% CI: 1.00, 1.89), respiratory system (adjusted OR = 1.89, 95% CI: 1.00, 3.58), and urinary tract (adjusted OR = 1.46, 95% CI: 1.00, 2.13) defects were significantly associated with exposure (medium and high combined). Regarding risk of specific birth defects, only that for ventricular septal defects was significantly elevated, with an exposure-response pattern, yielding adjusted odds ratios of 1.63 (95% CI: 1.02, 2.58) for the medium and 1.81 (95% CI: 1.05, 3.09) for the high exposure categories. Furthermore, risk of neural tube defects was related to high color (adjusted OR = 2.60, 95% CI: 1.30, 5.26).


Arsenic trioxide: mechanisms of action.
The chimeric protein encoded by the PML-RAR alpha gene that is pathognomonic of acute promyelocytic leukemia (APL) causes the arrest of myeloid cell development at the promyelocyte stage, leading to an accumulation of abnormal promyelocytes in the bone marrow. Differentiation therapy with all-trans retinoic acid (ATRA) is used routinely in patients with APL, but ATRA is not the only agent in clinical use that promotes differentiation of the abnormal clone. Arsenic trioxide (ATO) has been shown to cause degradation of PML-RAR alpha, promoting differentiation. APL cells are extremely sensitive to ATO, which has shown good clinical activity at low doses in patients with relapsed APL. However, degradation of PML-RAR alpha may not be wholly responsible for the great sensitivity of APL cells to ATO, which also acts through the intracellular environment to influence apoptosis, differentiation, growth arrest, and angiogenesis. ATO can act at several points in mitochondrially induced apoptosis, including degradation of peroxides and interaction with glutathione (GSH)-related enzymes. Subclones that are resistant to ATO have been used to demonstrate that sensitivity can be restored by reducing the cellular GSH content. GSH can be reduced using agents such as buthionine sulfoximine (BSO) and ascorbic acid. The key factors that determine the ATO sensitivity of cells and control ATO-induced apoptosis have not yet been defined. It has been proposed that ATO acts through activation of Jun N-terminal kinase (JNK), activator protein-1, and inhibition of dual-specificity phosphatases, and evidence is accumulating that JNK activation is an important event in arsenic-induced apoptosis. Further research is required to determine the exact pathways through which the cytotoxic actions of ATO are mediated.


CoraL: interpretable contrastive meta-learning for the prediction of cancer-associated ncRNA-encoded small peptides.
NcRNA-encoded small peptides (ncPEPs) have recently emerged as promising targets and biomarkers for cancer immunotherapy. Therefore, identifying cancer-associated ncPEPs is crucial for cancer research. In this work, we propose CoraL, a novel supervised contrastive meta-learning framework for predicting cancer-associated ncPEPs. Specifically, the proposed meta-learning strategy enables our model to learn meta-knowledge from different types of peptides and train a promising predictive model even with few labeled samples. The results show that our model is capable of making high-confidence predictions on unseen cancer biomarkers with only five samples, potentially accelerating the discovery of novel cancer biomarkers for immunotherapy. Moreover, our approach remarkably outperforms existing deep learning models on 15 cancer-associated ncPEPs datasets, demonstrating its effectiveness and robustness. Interestingly, our model exhibits outstanding performance when extended for the identification of short open reading frames derived from ncPEPs, demonstrating the strong prediction ability of CoraL at the transcriptome level. Importantly, our feature interpretation analysis discovers unique sequential patterns as the fingerprint for each cancer-associated ncPEPs, revealing the relationship among certain cancer biomarkers that are validated by relevant literature and motif comparison. Overall, we expect CoraL to be a useful tool to decipher the pathogenesis of cancer and provide valuable information for cancer research. The dataset and source code of our proposed method can be found at https://github.com/Johnsunnn/CoraL.


Efficacy of ozone as a novel treatment option for urovagina in dairy cows.
Urovagina is detrimental to the health and fertility of cows worldwide. Surgery, the only known treatment, is not economically pragmatic to dairy practice, and it has some medical drawbacks. The objective of this study was to determine whether reproductive problems associated with urovagina could be alleviated through more practical and less-invasive treatment options to allow successful conception and term-pregnancy. Cows diagnosed with urovagina (n = 1219) were divided into three treatment groups, each containing an equal number of cows with mild, moderate and severe urovagina. The groups received one of three treatment options: saline (group A, n = 400), streptomycin (group B, n = 400) or ozone (group C, n = 419) flush, regardless of the severity of the urovagina condition within the group. The ozone treatment was found to be the most effective treatment modality, resulting in the shortest period of days open (95, 89 and 79 days in groups A, B and C, respectively; p < 0.05), the fewest number of inseminations until pregnancy (2.38, 1.84 and 1.63 in groups A, B and C, respectively; p < 0.05) and the smallest number of culled cows (20, 23 and 12 in groups A, B and C, respectively; p < 0.05). The ozone flush coupled with intracornual insemination presents an effective treatment option for urovagina that can lead to successful conceptions and pregnancies in dairy cows.


Watson-Crick base-pairing properties of tricyclo-DNA.
Tricyclo-DNA belongs to the family of conformationally restricted oligodeoxynucleotide analogues. It differs structurally from DNA by an additional ethylene bridge between the centers C(3') and C(5') of the nucleosides, to which a cyclopropane unit is fused for further enhancement of structural rigidity. The synthesis of the hitherto unknown tricyclodeoxynucleosides containing the bases cytosine and guanine and of the corresponding phosphoramidite building blocks is described, as well as a structural description of a representative of an alpha- and a beta-tricyclodeoxynucleoside by X-ray analysis. Tricyclodeoxynucleoside building blocks of all four bases were used for the synthesis of fully modified mixed-base oligonucleotides. Their Watson-Crick pairing properties with complementary DNA, RNA, and with itself were investigated by UV melting curves, CD spectroscopy, and molecular modeling. Tricyclo-DNA was found to be a very stable Watson-Crick base-pairing system. A UV melting curve analysis of the decamers tcd(pcgtgacagtt) and tcd(paactgtcacg) showed increased thermal stabilities of up to DeltaT(m)/mod. = +1.2 degrees C with complementary DNA and +2.4 degrees C with complementary RNA. With itself, tricyclo-DNA showed an increase in stability of +3.1 degrees C/base pair relative to DNA. Investigations into the thermodynamic properties of these decamers revealed an entropic stabilization and an enthalpic destabilization for the tricyclo-DNA/DNA duplexes. CD spectroscopic structural investigations indicated that tricyclo-DNA containing duplexes preferrably exist in an A-conformation, a fact which is in agreement with results from molecular modeling.


[Advantages of reabsorbable intradermal sutures in general surgery. Experience on 201 sutures].
Surgical wound suture is often considered of minor importance compared to the whole surgical operation. The aesthetical result of a wound suture is still hardly considered in general surgical practice compared to other "traditional" wound sutures. The Authors carried a prospective study an 201 intradermal absorbable sutures in clean general surgery. The results clearly show that with a limited increase of the mean operation time of 90 seconds, for a 10 cm suture, there are such positive clinical, and aesthetical results that it is advisable to use routinely this type of suture in elective clean surgery.


Bioremediation of Wastewater by Iron Oxide-Biochar Nanocomposites Loaded with Photosynthetic Bacteria.
It has been reported that bacteria-mediated degradation of contaminants is a practical and innocuous wastewater treatment. In addition, iron oxide nanoparticles (NP) are wastewater remediation agents with great potentials due to their strong adsorption capacity, chemical inertness and superparamagnetism. Therefore, a combination of NPs and microbes could produce a very desirable alternative to conventional wastewater treatment. For this purpose, we first prepared Fe3O4/biochar nano-composites, followed by loading photosynthetic bacteria (PSB) onto them. It was found that Fe3O4/biochar nano-composites exhibited a high adsorption capacity for PSB (5.45 × 109 cells/g). The efficiency of wastewater pollutants removal by this PSB/Fe3O4/biochar agent was then analyzed. Our results indicated that when loaded onto Fe3O4/biochar nano-composites, PSB's nutrient removal capability was significantly enhanced (P < 0.05). This agent removed 83.1% of chemical oxygen demand, 87.5% of NH4+, and 92.1% of PO43- from the wastewater in our study. Our experiments also demonstrated that such composites are outstanding recyclable agents. Their nutrient removal capability remained effective even after five cycles. In conclusion, we found the PSB/Fe3O4/biochar composites as a very promising material for bioremediation in the wastewater treatment.


Cold Stress and Nitrogen Deficiency Affected Protein Expression of Psychrotrophic Dyadobacter psychrophilus B2 and Pseudomonas jessenii MP1.
Nitrogen (N) deficiency and low temperature conditions are the prominent facet of Western Himalayan agro-ecosystems. A slight change in the environment alters the protein expression of the microorganisms. Therefore, proteomes of the two psychrotrophs Dyadobacter psychrophilus B2 and Pseudomonas jessenii MP1 were analyzed using two dimensional electrophoresis and MALDI-TOF-MS, to determine the physiological response of altitudinally different but indigenous microorganisms in response to cold stress under N depleting conditions. Functional assessment of 150 differentially expressed proteins from both the psychrotrophs revealed several mechanisms might be involved in cold stress adaptation, protein synthesis/modifications, energy metabolism, cell growth/maintenance, etc. In both the proteomes, abundance of the proteins related to energy production and stress were significantly increased while, proteins related to biosynthesis and energy consuming processes decreased. ATP synthase subunit alpha, beta, ATP-dependent Clp protease, Enolase, groL HtpG and N(2)-fixation sustaining protein CowN proteins were found to be expressed in both B2 and MP1, similarly to previously studied diazotrophs under low temperature N2 fixing conditions and therefore, can be considered as a biomarker for monitoring the nitrogen fixation in cold niches. Nevertheless, in both the diazotrophs, a good fraction of the proteins were related to hypothetical proteins which are still uncharacterized, thereby, suggesting the need for in-depth studies on cold adapted diazotrophs and their adaptive mechanisms.


[Dermatopathology today--current perspectives].
In recent years dermatopathology has experienced a dynamic development and acquired highly original aspects. Even today it is possible with classical histomorphology and clinical observation to discover new diseases, to recognize etiopathogenetic relationships and to give an important impetus to modern experimental research. The application of immunohistological techniques to the diagnosis of skin diseases is one of the most remarkable trends.


A cross-sectional exploratory analysis between pet ownership, sleep, exercise, health and neighbourhood perceptions: the Whitehall II cohort study.
To explore associations between pets, and specifically dog ownership and sleep, health, exercise and neighbourhood. Cross sectional examination of 6575 participants of the Whitehall II study aged between 59 and 79 years. We used self-assessed measurement scales of the Short Form (SF36), General Health Questionnaire (GHQ), Control, Autonomy, Self-realisation and Pleasure (CASP), Centre for Epidemiologic Studies Depression Scale (CES-D), sleep, exercise, and perceptions of local neighbourhood. In addition the Mini Mental State Examination which is administered to test global cognitive status (MMSE). We found 2/7 people owned a pet and of those 64% were "very" attached to their pet. Mild exercise in metabolic equivalents (MET-hours) was significantly higher in pet owners than non-owners (median 27.8 (IQR 18.1 to 41.8) vs 25.7 (IQR 16.8 to 38.7), p = 0.0001), and in dog owners than other pets (median 32.3 (IQR 20.8 to 46.1) vs 25.6 (IQR 16.8 to 38.5), p < 0.0001). Moderate exercise was also significantly higher in pet owners than non pet owners (median 11.8 (IQR 4.2 to 21.9) vs 9.8 (IQR 2.8 to 19.5), p < 0.0001), and dog owners than owners of other pets (median 12.3 (IQR 4.2 to 22.2) vs 10.1 (3.1 to 20.0), p = 0.0002) but there were no significant differences with vigorous exercise. We found that pet owners were significantly more positive about their neighbourhood than non-owners on 8/9 questions, while dog owners were (significantly) even more positive than owners of other pets on 8/9 questions. Associations with sleep were mixed, although dog owners had less trouble falling asleep than non-dog owners, with borderline statistical significance. Dog owners feel more positive about their neighbourhood, do more exercise, and fall asleep more easily than non-dog owners. These results suggest that dog owners could be more likely to exercise by walking their dogs and therefore may be more familiar and positive about the area in which they walk their dog.


The role of free tissue transfer in posterior neck reconstruction.
Reconstruction of the posterior neck is one of the rarer procedures performed by plastic surgeons; we used free flaps for the closure of defects in this area in six cases over the past 4 years. Six patients were located requiring posterior neck reconstruction between the years 2007 and 2013. Five of these patients required reconstruction due to oncologic resections, while one underwent serial removal of a giant congenital nevus. Five of these reconstructions involved the use of a free anterolateral thigh/vastus lateralis flap, and the sixth received a pre-expanded deep inferior epigastric perforator flap. Satisfactory dorsal neck reconstruction was achieved with the free flap approach: it produced excellent healing, contour and coverage of hardware. There was only one early minor complication, allowing early return to daily activities and continuation of planned oncologic treatment. Free flap reconstruction of the posterior neck area is a safe and relatively rapidly performed procedure that yields good results both functionally and aesthetically. In this article, we review the literature on the options available for reconstruction of the posterior neck, describe our surgical experience in such cases, and suggest an algorithm to guide in choosing the optimal approach for a given patient.


lincRNA-p21 inhibits hepatic stellate cell activation and liver fibrogenesis via p21.
Long non-coding RNAs are involved in various biological processes and diseases. The biological role of long intergenic non-coding RNA-p21 (lincRNA-p21) in liver fibrosis remains unknown before this study. In this study, we observed marked reduction of lincRNA-p21 expression in mice liver fibrosis models and human cirrhotic liver. Over-expression of lincRNA-p21 suppressed activation of hepatic stellate cells (HSCs) in vitro. Lentivirus-mediated lincRNA-p21 transfer into mice decreased the severity of liver fibrosis in vivo. Additionally, lincRNA-p21 reversed the activation of HSCs to their quiescent phenotype. The mRNA levels of lincRNA-p21 and p21 were positively correlated. Our results show that over-expression of lincRNA-p21 promotes up-regulation of p21 at both the mRNA and protein levels. Furthermore, lincRNA-p21 inhibited cell-cycle progression and proliferation of primary HSCs through enhancement of p21 expression. Compared with healthy subjects, serum lincRNA-p21 levels were significantly lower in patients with liver cirrhosis, especially those with decompensation. These findings collectively indicate that lincRNA-p21 is a mediator of HSC activation, supporting its utility as a novel therapeutic target for liver fibrosis.


Efficacy of Propidium Monoazide on Quantitative Real-Time PCR-Based Enumeration of Staphylococcus aureus Live Cells Treated with Various Sanitizers.
Propidium monoazide (PMA) has been used together with quantitative real-time PCR (qPCR) to enumerate live bacteria, while discriminating against the residual DNA of dead bacterial cells. Although the effectiveness of PMA at increasing the accuracy of enumeration of live bacteria treated with heat has been investigated in a number of studies, few studies have involved bacteria treated with sanitizers. In this study, dead Staphylococcus aureus cells were prepared by treatment with six kinds of sanitizers (ethanol, isopropyl alcohol, benzalkonium chloride, sodium hypochlorite, hydrogen peroxide, and nisin) and were mixed with a culture of live bacteria in different ratios. PMA-qPCR was able to accurately enumerate live bacteria with a <0.5 CFU/500 μL difference with that of plate counts for cultures treated with ethanol, isopropyl alcohol, and nisin. For ethanol and isopropyl alcohol treatments, live cells were accurately enumerated for live/dead cell ratios of 10/1 to 0.01/1, while live cells for the nisin treatment were accurately enumerated for live/dead cell ratios of 10/1 to 0.1/1. In contrast, PMA-qPCR was not able to accurately enumerate live cells in bacterial cultures treated with benzalkonium chloride and hydrogen peroxide. In addition, qPCR without PMA was able to enumerate live cells as consistently as plate counts with a bacterial culture treated with sodium hypochlorite. The results of this study show that the use of PMA for qPCR-based enumeration of live cells is not always recommended, and its effectiveness depends on the treatment used on the cells.


Entrainment of local synchrony reveals a causal role for high-beta right frontal oscillations in human visual consciousness.
Prior evidence supports a critical role of oscillatory activity in visual cognition, but are cerebral oscillations simply correlated or causally linked to our ability to consciously acknowledge the presence of a target in our visual field? Here, EEG signals were recorded on humans performing a visual detection task, while they received brief patterns of rhythmic or random transcranial magnetic stimulation (TMS) delivered to the right Frontal Eye Field (FEF) prior to the onset of a lateralized target. TMS entrained oscillations, i.e., increased high-beta power and phase alignment (the latter to a higher extent for rhythmic high-beta patterns than random patterns) while also boosting visual detection sensitivity. Considering post-hoc only those participants in which rhythmic stimulation enhanced visual detection, the magnitude of high-beta entrainment correlated with left visual performance increases. Our study provides evidence in favor of a causal link between high-beta oscillatory activity in the Frontal Eye Field and visual detection. Furthermore, it supports future applications of brain stimulation to manipulate local synchrony and improve or restore impaired visual behaviors.


A GABAergic component in the commissure of the inferior colliculus in rat.
The commissure of the inferior colliculus is significant as the final point of interconnection between homologous structures on the two sides of the auditory pathway at the subcortical level. The presence of excitatory fibres is well established in this tract, but the existence of an inhibitory component is controversial. Using rats, we injected biotinylated dextran amine into the inferior colliculus on one side to retrogradely label cells projecting through the commissure from the contralateral inferior colliculus. Immunocytochemistry for gamma-amino-n-butyric acid in neighbouring semithin sections revealed that 20% of biotinylated dextran amine cell profiles were also labelled for gamma-amino-n-butyric acid. We conclude that monosynaptic inhibitory connections contribute to the inhibition observed in the contralateral inferior colliculus in functional studies of the commissural projection.


Parathyroid Adenomas in Adults and Adolescents. Critical Appraisal and Surgical Strategy in 18 Cases.
Background: Our study underline scarcity of isolated case reports or small case series of parathyroid adenoma (PA) published in autochthonous medical literature,their variable clinical expression among the "historic" varieties but also the diagnostic difficulties and delays of diagnosis as well consecration of surgery as the golden therapeutic standard of this disorder. Demographic, clinical presentations, laboratory and imaging data, operative findings and procedures together with pathology account and outcome from the case reports of 18 patients with documented PHP were retrospectively analyzed. Results: The male/female ratio was 1/5, with ages ranging from 16 to 58 (mean 46) years. Renal stones (n=9) and bone sufferings (n=6) were the most common modes of presentation. To these were added psychiatric and neuromuscular complaints, digestive disorders (pancreatitis and peptic ulcer) arterial hypertension and presence of a palpable nodule. Mean serum calcium and phospho-rus, alkaline phosphatase and PTH dosage together with parathyroid ultrasound and 99m Tc sestamibi scintigraphy are the most useful parameters for diagnosis. Eighteen adenomectomies were performed of which bilateral neck exploration was done in 16 patients and minimally invasive approach in the remaining two cases. In 9 situations concomitant thyroid exeresis for associated lesions or tactical purpose were done. Pathology revealed single adenoma consisting of main and oxyphil cells in 17 cases. In one case an atypical adenoma was identified and in another case three years after removal of a benign adenoma the subject presented a clinical ipsilateral recurrence which provided to be a carcinoma. Postoperative clinical and humoral outcome was favorable in all situations less the case of carcinoma which died after 14 months. Conclusions: Despite the rarity and difficulties of diagnosis in cases of PA, practitioners must be aware of potential existence of these lesions in order to apply as early and appropriate treatment where surgery is the gold standard.


Fertilization and InsP3-induced Ca2+ release stimulate a persistent increase in the rate of degradation of cyclin B1 specifically in mature mouse oocytes.
Vertebrate oocytes proceed through meiosis I before undergoing a cytostatic factor (CSF)-mediated arrest at metaphase of meiosis II. Exit from MII arrest is stimulated by a sperm-induced increase in intracellular Ca2+. This increase in Ca2+ results in the destruction of cyclin B1, the regulatory subunit of cdk1 that leads to inactivation of maturation promoting factor (MPF) and egg activation. Progression through meiosis I also involves cyclin B1 destruction, but it is not known whether Ca2+ can activate the destruction machinery during MI. We have investigated Ca2+ -induced cyclin destruction in MI and MII by using a cyclin B1-GFP fusion protein and measurement of intracellular Ca2+. We find no evidence for a role for Ca2+ in MI since oocytes progress through MI in the absence of detectable Ca2+ transients. Furthermore, Ca2+ increases induced by photorelease of InsP3 stimulate a persistent destruction of cyclin B1-GFP in MII but not MI stage oocytes. In addition to a steady decrease in cyclin B1-GFP fluorescence, the increase in Ca2+ stimulated a transient decrease in fluorescence in both MI and MII stage oocytes. Similar transient decreases in fluorescence imposed on a more persistent fluorescence decrease were detected in cyclin-GFP-injected eggs undergoing fertilization-induced Ca2+ oscillations. The transient decreases in fluorescence were not a result of cyclin B1 destruction since transients persisted in the presence of a proteasome inhibitor and were detected in controls injected with eGFP and in untreated oocytes. We conclude that increases in cytosolic Ca2+ induce transient changes in autofluorescence and that the pattern of cyclin B1 degradation at fertilization is not stepwise but exponential. Furthermore, this Ca2+ -induced increase in degradation of cyclin B1 requires factors specific to mature oocytes, and that to overcome arrest at MII, Ca2+ acts to release the CSF-mediated brake on cyclin B1 destruction.


Statins: Cholesterol guidelines and Indian perspective.
Statins have become an important drug in preventing the occurrence of atherosclerotic cardiovascular disease (ASCVD). The effectiveness of statins in reducing ASCVD has been established in large-scale clinical trials. The lipid management guidelines have been periodically modified due to accumulating evidence about the proportionate benefit achieved with a progressive reduction in cholesterol levels with higher doses of statins and even in those at low risk of development of ASCVD. The current American College of Cardiology/American Heart Association guidelines have based its recommendations from data gathered exclusively from randomized controlled trials. It has simplified the use of statins, but also raised questions regarding the validity of its cardiovascular event risk prediction tool. Epidemiology of cardiovascular disease in India differs from the western population; there is an increased the prevalence of metabolic syndrome and atherogenic dyslipidemia phenotype a group not addressed in the current guidelines. The guidelines are based on trials, which do not have a representative South Asian population. This article reviews the relevant literature, and examines the issues involved in adopting the guidelines to the Indian population.