Total hip arthroplasty outcomes in morbidly obese patients: A systematic review.
The increasing prevalence of obesity has resulted in a marked increase in the number of total hip arthroplasties (THAs) carried out in patients with a high body mass index (BMI).THA in morbidly obese patients is often technically challenging owing to the associated co-morbidities and anatomical factors. Furthermore, the long-term clinical and functional outcomes of the procedure in these patients are not clear.The aim of this systematic review was to compare the long-term failure rate and functional outcomes of THA in morbidly obese versus non-obese patients.A literature search of PubMed, EMBASE and PubMed Central was conducted to identify studies that compared the outcomes of THA in patients defined as morbidly obese (BMI ≥ 35) to a control group (BMI < 30). The primary and secondary outcome measures were rate of revision and functional outcome, respectively, in the long term.Eight studies were included in this review. There were 66,238 THAs in morbidly obese patients and 705,619 THAs in patients with a BMI < 30. The overall revision rate was 7.99% in the morbidly obese patients versus 2.75% in the non-obese controls. The functional outcome was at least comparable to non-obese patients.This review suggests that morbidly obese patients have a slightly increased revision rate following THA. Importantly, these patients have a functional recovery at least comparable to those with a BMI < 30. Morbidly obese patients should be fully informed of these issues prior to undergoing surgery. Cite this article: EFORT Open Rev 2018;3:507-512. DOI: 10.1302/2058-5241.3.180011.


Inhibition of Adipocyte Differentiation by Anthocyanins Isolated from the Fruit of Vitis coignetiae Pulliat is Associated with the Activation of AMPK Signaling Pathway.
Anthocyanins are naturally occurring water-soluble polyphenolic pigments in plants that have been shown to protect against cardiovascular diseases, and certain cancers, as well as other chronic human disorders. However, the anti-obesity effects of anthocyanins are not fully understood. In this study, we investigated the effects of anthocyanins isolated from the fruit of Vitis coignetiae Pulliat on the adipogenesis of 3T3-L1 preadipocytes. Our data indicated that anthocyanins attenuated the terminal differentiation of 3T3-L1 preadipocytes, as confirmed by a decrease in the number of lipid droplets, lipid content, and triglyceride production. During this process, anthocyanins effectively enhanced the activation of the AMP-activated protein kinase (AMPK); however, this phenomenon was inhibited by the co-treatment of compound C, an inhibitor of AMPK. Anthocyanins also inhibited the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein a and b, and sterol regulatory element-binding protein-1c. In addition, anthocyanins were found to potently inhibit the expression of adipocyte-specific genes, including adipocyte fatty acid-binding protein, leptin, and fatty acid synthase. These results indicate that anthocyanins have potent anti-obesity effects due to the inhibition of adipocyte differentiation and adipogenesis, and thus may have applications as a potential source for an anti-obesity functional food agent.


The relationship of gastroesophageal reflux and gastric emptying in infants and children: concise communication.
One hundred twenty-six pediatric patients (0-16 yr of age) with clinically suspected gastroesophageal reflux (GER) were evaluated using radionuclide scintigraphy. Although 46 of the patients (38.3%) had abnormal studies exhibiting evidence of GER, there were no significant differences in gastric emptying between patients with and without GER. At 60 min after ingestion, the 76 patients less than 2 yr old had a mean residual of 54%, whereas those over 2 yr of age had a value of 29% (P less than 0.0001). Gastric emptying values may be age-related.


Bordetella bronchiseptica flagellin is a proinflammatory determinant for airway epithelial cells.
Motility is an important virulence phenotype for many bacteria, and flagellin, the monomeric component of flagella, is a potent proinflammatory factor. Of the three Bordetella species, Bordetella pertussis and Bordetella parapertussis are nonmotile human pathogens, while Bordetella bronchiseptica expresses flagellin and causes disease in animals and immunocompromised human hosts. The BvgAS two-component signal transduction system regulates phenotypic-phase transition (Bvg+, Bvg-, and Bvg(i)) in bordetellae. The Bvg- phase of B. bronchiseptica is characterized by the expression of flagellin and the repression of adhesins and toxins necessary for the colonization of the respiratory tract. B. bronchiseptica naturally infects a variety of animal hosts and constitutes an excellent model to study Bordetella pathogenesis. Using in vitro coculture models of bacteria and human lung epithelial cells, we studied the effects of B. bronchiseptica flagellin on host defense responses. Our results show that B. bronchiseptica flagellin is a potent proinflammatory factor that induces chemokine, cytokine, and host defense gene expression. Furthermore, we investigated receptor specificity in the response to B. bronchiseptica flagellin. Our results show that B. bronchiseptica flagellin is able to signal effectively through both human and mouse Toll-like receptor 5.


Gesture and the processing of speech: neuropsychological evidence.
Patterns of speech-related ('coverbal') gestures were investigated in three groups of right-handed, brain-damaged patients and in matched controls. One group had anomic aphasia with a primarily semantic impairment ('semantic'); one group had a primarily phonological impairment, reflected in both repetition and naming ('phonologic'); a third group had a primarily conceptual impairment, with relatively good naming ('conceptual'). Coverbal gestures were video recorded during the description of complex pictures and analyzed for physical properties, timing in relation to speech and ideational content. The semantic and phonologic subjects produced a large number of ideational gestures relative to their lexical production, while the related production of the conceptual subjects was similar to that of the unimpaired controls. The composition of ideational gestures in the semantic and phonologic groups was similar to that of the control groups, while conceptual subjects produced fewer iconic gestures (i.e., gestures that show in their form the content of a word or phrase). The iconic gestures of the conceptual patients tended to start further from their lexical affiliates than those of all other subjects. We conclude that ideational gestures probably facilitate word retrieval, as well as reflect the transfer of information between propositional and non-propositional (visual and motoric) representations during message construction. We suggest that conceptual and lexical processes differ in the way they constrain ideational gestures.


Cytogenetic and molecular characterization of inverted duplicated chromosomes 15 from 11 patients.
We have studied the inverted duplicated chromosomes 15 (inv dup(15)) from 11 individuals--7 with severe mental retardation and seizures, 3 with a normal phenotype, and 1 with Prader-Willi syndrome (PWS). Through a combination of FISH and quantitative DNA analyses, three different molecular sizes of inv dup(15) were identified. The smallest inv dup(15) was positive only for the centromeric locus D15Z1 (type 1); the next size was positive for D15Z1 and D15S18 (type 2); and the largest inv dup(15) was positive for two additional copies of loci extending from D15Z1 and D15S18 through D15S12 (type 3). Type 1 or type 2 was observed in the three normal individuals and the PWS patient. Type 3 was observed in all seven individuals with mental retardation and seizures but without PWS or Angelman Syndrome (AS). The PWS patient, in addition to being mosaic for a small inv dup(15), demonstrated at D15S63 a methylation pattern consistent with maternal uniparental inheritance of the normal chromosomes 15. The results from this study show (a) two additional copies of proximal 15q loci, D15S9 through D15S12, in mentally retarded patients with an inv dup(15) but without AS or PWS and (b) no additional copies of these loci in patients with a normal phenotype or with PWS.


The 1999 Helene Fuld Health Trust Fellowship. Promoting leadership development in undergraduate nursing students.
In 1999, based on the recommendation of The Conservation Company. The Helene Fuld Health Trust selected New York University's Robert F. Wagner Graduate School of Public Service, in partnership with the Division of Nursing in the School of Education, to restructure its fellowship program for undergraduate nursing students. Bringing together an interdisciplinary team with experience in leadership development, nursing and health policy, and health care administration, NYU designed and delivered an innovative and state-of-the-art leadership development program for the 1999 Fuld Fellowship program. The new program started in June 1999 with 21 nursing students from all over the country. This article describes the goals and methods of the program; it also discusses early observations of the program's success that could be relevant to nursing education.


Unified view of quantum and classical correlations.
We discuss the problem of the separation of total correlations in a given quantum state into entanglement, dissonance, and classical correlations using the concept of relative entropy as a distance measure of correlations. This allows us to put all correlations on an equal footing. Entanglement and dissonance, whose definition is introduced here, jointly belong to what is known as quantum discord. Our methods are completely applicable for multipartite systems of arbitrary dimensions. We investigate additivity relations between different correlations and show that dissonance may be present in pure multipartite states.


Review of Noninvasive Continuous Glucose Monitoring in Diabetics.
For diabetics, taking regular blood glucose measurements is crucial. However, traditional blood glucose monitoring methods are invasive and unfriendly to diabetics. Recent studies have proposed a biofluid-based glucose sensing technique that creatively combines wearable devices with noninvasive glucose monitoring technology to enhance diabetes management. This is a revolutionary advance in the diagnosis and management of diabetes, reflects the thoughtful modernization of medicine, and promotes the development of digital medicine. This paper reviews the research progress of noninvasive continuous blood glucose monitoring (CGM), with a focus on the biological liquids that replace blood in monitoring systems, the technical principles of continuous noninvasive glucose detection, and the output and calibration of sensor signals. In addition, the existing limits of noninvasive CGM systems and prospects for the future are discussed. This work serves as a resource for further promoting the development of noninvasive CGM systems.


Characterization of the 16S-23S rRNA intergenic spacer regions among strains of the Fusobacterium necrophorum cluster.
The 16S-23S rRNA intergenic spacer regions (ISRs) of Fusobacterium necrophorum subsp. necrophorum and F. necrophorum subsp. funduliforme were characterized. Products of two sizes, about 360 bp (small) and 530 bp (large), were generated by PCR amplification from the 16S-23S rRNA ISR of all the strains tested. The large and small 16S-23S rRNA ISRs of F. necrophorum exhibited a level of sequence similarity of 93.9% to 99.7% and 94.2% to 98.6% homologies within the species, respectively. Only the large spacer regions in these bacteria contained one or two tRNA genes. F. necrophorum subsp. necrophorum contains the isoleucine and alanine tRNA gene, whereas F. necrophorum subsp. funduliforme contains the isoleucine tRNA gene.


Direct Observation of Entropic Stabilization of bcc Crystals Near Melting.
Crystals with low latent heat are predicted to melt from an entropically stabilized body-centered cubic symmetry. At this weakly first-order transition, strongly correlated fluctuations are expected to emerge, which could change the nature of the transition. Here we show how large fluctuations stabilize bcc crystals formed from charged colloids, giving rise to strongly power-law correlated heterogeneous dynamics. Moreover, we find that significant nonaffine particle displacements lead to a vanishing of the nonaffine shear modulus at the transition. We interpret these observations by reformulating the Born-Huang theory to account for nonaffinity, illustrating a scenario of ordered solids reaching a state where classical lattice dynamics fail.


Two Cases of Acute Kidney Injury Due to Multiple Wasp Stings.
Acute kidney injury (AKI) is an unusual complication of wasp stings. Treatment of established AKI is largely supportive but the preventive strategies are not well documented. This is a report of 2 human cases that developed AKI after multiple wasp stings (Vespa magnifica). Each patient reached the hospital early in their clinical course and was treated with intravenous hydration and urine alkalization. In both the cases the severity of AKI, morbidity, and duration of hospitalization were reduced. The requirement of dialysis therapy was avoided. We propose early treatment with intravenous hydration, diuretic administration, and urine alkalization in such cases to prevent systemic and renal complications.


Electromyographic activity and thickness of masticatory muscles in children with unilateral posterior crossbite.
The aim of this study was to assess the electromyographic (EMG) activity and thickness of the masseter and anterior temporalis muscles in children with unilateral posterior crossbite (PCB). Thirty-six children (22 boys, 14 girls, and mean age of 8.8 +/- 1.1 years) were divided into the following groups: The case group with 20 PCB patients (10 on the left side, 10 on the right side); the control group with 16 normal occlusion (NOccl) subjects. EMG activity was recorded with bipolar surface electrodes at rest and during maximal clenching. The muscle thickness was measured with real-time ultrasound. Data were compared between groups and between sides. The correlation between EMG activity and muscle thickness was also evaluated. The data were analyzed using the Shapiro-Wilks test, Pearson's correlation and Spearman as appropriate, paired and unpaired t- test, and Mann-Whitney test. The results revealed that the masseter of the crossbite side was more active than that of the non-crossbite side in PCB group during maximal clenching. The comparisons of EMG activity between PCB and NOccl groups revealed some variability in the results, depending on the crossbite side. The ultrasonographic evaluation did not show statistically significant differences between groups, nor between sides in the PCB and NOccl groups. Significant correlation between EMG activity and thickness was observed only in the left masseter in the NOccl group. In conclusion, these findings showed that asymmetric muscle activity of the masticatory muscles was not related to the thickness of these muscles in children with PCB.


Developing a national dental education research strategy: priorities, barriers and enablers.
This study aimed to identify national dental education research (DER) priorities for the next 3-5 years and to identify barriers and enablers to DER. Scotland. In this two-stage online questionnaire study, we collected data with multiple dental professions (eg, dentistry, dental nursing and dental hygiene) and stakeholder groups (eg, learners, clinicians, educators, managers, researchers and academics). Eighty-five participants completed the Stage 1 qualitative questionnaire and 649 participants the Stage 2 quantitative questionnaire. Eight themes were identified at Stage 1. Of the 24 DER priorities identified, the top three were: role of assessments in identifying competence; undergraduate curriculum prepares for practice and promoting teamwork. Following exploratory factor analysis, the 24 items loaded onto four factors: teamwork and professionalism, measuring and enhancing performance, dental workforce issues and curriculum integration and innovation. Barriers and enablers existed at multiple levels: individual, interpersonal, institutional structures and cultures and technology. This priority setting exercise provides a necessary first step to developing a national DER strategy capturing multiple perspectives. Promoting DER requires improved resourcing alongside efforts to overcome peer stigma and lack of valuing and motivation.


Palladium-Catalyzed Formylation of Arylzinc Reagents with S-Phenyl Thioformate.
The first example of palladium-catalyzed direct formylation of arylzinc reagents using S-phenyl thioformate is reported. The reaction proceeded under mild conditions, allowing high functional group tolerance. In addition, the developed formylation method was used to prepare deuterated and 13C-labeled aryl aldehydes from isotope-labeled S-phenyl thioformates. Moreover, this procedure was applied to an alkenylzinc halide, affording the corresponding enal.


Surface plasmon resonance biosensor for enzymatic detection of small analytes.
Surface plasmon resonance (SPR) biosensing is based on the detection of small changes in the refractive index on a gold surface modified with molecular recognition materials, thus being mostly limited to detecting large molecules. In this paper, we report on a SPR biosensing platform suitable to detect small molecules by making use of the mediator-type enzyme microperoxidase-11 (MP11) in layer-by-layer films. By depositing a top layer of glucose oxidase or uricase, we were able to detect glucose or uric acid with limits of detection of 3.4 and 0.27 μmol l-1, respectively. Measurable SPR signals could be achieved because of the changes in polarizability of MP11, as it is oxidized upon interaction with the analyte. Confirmation of this hypothesis was obtained with finite difference time domain simulations, which also allowed us to discard the possible effects from film roughness changes observed in atomic force microscopy images. The main advantage of this mediator-type enzyme approach is in the simplicity of the experimental method that does not require an external potential, unlike similar approaches for SPR biosensing of small molecules. The detection limits reported here were achieved without optimizing the film architecture, and therefore the performance can in principle be further enhanced, while the proposed SPR platform may be extended to any system where hydrogen peroxide is generated in enzymatic reactions.


Conversion of [U-14C] glucose to lipid in the American cockroach, Periplaneta americana L.
The incorporation of D-[U-14C] glucose into fat body acylglycerols was studied in fed and starved adult cockroaches, Periplaneta americana. About 7-10% of injected glucose is incorporated into the triacylglycerol component of fat body within three hours of injection. The capacity for conversion of glucose to triacylglycerol is greater in fed than starved Insects and the differences in lipogenic capacity of fat body from fed and starved cockroaches are retained in vitro. Incubation of fat body in the presence of haemolymph enhances the lipogenic capacity of fat body.


An International Survey of Veterinary Students to Assess Their Use of Online Learning Resources.
Today's veterinary students have access to a wide range of online resources that support self-directed learning. To develop a benchmark of current global student practice in e-learning, this study measured self-reported access to, and use of, these resources by students internationally. An online survey was designed and promoted via veterinary student mailing lists and international organizations, resulting in 1,070 responses. Analysis of survey data indicated that students now use online resources in a wide range of ways to support their learning. Students reported that access to online veterinary learning resources was now integral to their studies. Almost all students reported using open educational resources (OERs). Ownership of smartphones was widespread, and the majority of respondents agreed that the use of mobile devices, or m-learning, was essential. Social media were highlighted as important for collaborating with peers and sharing knowledge. Constraints to e-learning principally related to poor or absent Internet access and limited institutional provision of computer facilities. There was significant geographical variation, with students from less developed countries disadvantaged by limited access to technology and networks. In conclusion, the survey provides an international benchmark on the range and diversity in terms of access to, and use of, online learning resources by veterinary students globally. It also highlights the inequalities of access among students in different parts of the world.


Formulation of olfactory-targeted microparticles with tamarind seed polysaccharide to improve nose-to-brain transport of drugs.
Targeted delivery and retention of drug formulations in the olfactory mucosa, the target site for nose-to-brain drug absorption is a major challenge due to the geometrical complexity of the nose and nasal clearance. Recent modelling data indicates that 10μm-sized microparticles show maximum deposition in the olfactory mucosa. In the present study we tested the hypothesis that 10μm-sized mucoadhesive microparticles would preferentially deposit on, and increase retention of drug on, the olfactory mucosa in a novel 3D-printed human nasal-replica cast under simulated breathing. The naturally occurring mucoadhesive polymer, tamarind seed polysaccharide (TSP) was used to formulate the microparticles using a spray drying technique. Physicochemical properties of microparticles such as size, morphology and mucoadhesiveness was investigated using a combination of laser diffraction, electron microscopy and texture-analysis. Furthermore, FITC-dextrans (5-40kDa) were incorporated in TSP-microparticles as model drugs. Size-dependent permeability of the FITC-dextrans was observed ex vivo using porcine nasal mucosa. Using the human nasal-replica cast, greater deposition of 10μm TSP-microparticles in the olfactory region was observed compared to TSP-microparticles 2μm in size. Collectively, these findings support our hypothesis that 10μm-sized mucoadhesive microparticles can achieve selective deposition and retention of drug in the olfactory mucosa.


Effect of upright tilt on ventricular/vascular coupling in chronically instrumented primates.
Studies of the hydraulic loading conditions on the heart in humans, especially pulsatile load, have primarily been limited to the supine state. Therefore, we have chosen a nonhuman primate model, the baboon, to assess left ventricular/vascular coupling in both supine and upright positions. Primate subjects were studied by catheterization under sedation and then after surgical implantation of transducers. This allowed the evaluation of postural stress in the chronically instrumented conscious baboon and then after light dissociative doses of ketamine. Basic hemodynamic variables were evaluated for baboons in supine and upright positions. Fourier analysis was applied to aortic pressure and flow to obtain input and characteristic impedance and the ratio of pulsatile (Wp) to total (Wt) left ventricular power (Wp/Wt). The aortic reflected, or backward, pressure was also calculated. Peripheral resistance increased (P = 0.01) and reflected pressure decreased (17.74 +/- 1.50 vs. 15.21 +/- 2 mmHg; P < 0.01) in upright subjects. Characteristic impedance and Wp/Wt were unchanged. Postoperatively, peripheral resistance increased (2,651 +/- 311 vs. 3,667 +/- 276; P < 0.05) and mean power and Wt decreased (P < 0.01) without changes in reflected pressure. All variables were unchanged after light dissociative doses of ketamine. Thus there is no significant change in efficiency of left ventricular/vascular coupling formulated in terms of Wp/Wt or input impedance with postural stress.


Spresso: an ultrafast compound pre-screening method based on compound decomposition.
Recently, the number of available protein tertiary structures and compounds has increased. However, structure-based virtual screening is computationally expensive owing to docking simulations. Thus, methods that filter out obviously unnecessary compounds prior to computationally expensive docking simulations have been proposed. However, the calculation speed of these methods is not fast enough to evaluate ≥ 10 million compounds. In this article, we propose a novel, docking-based pre-screening protocol named Spresso (Speedy PRE-Screening method with Segmented cOmpounds). Partial structures (fragments) are common among many compounds; therefore, the number of fragment variations needed for evaluation is smaller than that of compounds. Our method increases calculation speeds by ∼200-fold compared to conventional methods. Spresso is written in C ++ and Python, and is available as an open-source code (http://www.bi.cs.titech.ac.jp/spresso/) under the GPLv3 license. email@example.com. Supplementary data are available at Bioinformatics online.


Neural Responses to Rapid Facial Expressions of Fear and Surprise.
Facial expression recognition is mediated by a distributed neural system in humans that involves multiple, bilateral regions. There are six basic facial expressions that may be recognized in humans (fear, sadness, surprise, happiness, anger, and disgust); however, fearful faces and surprised faces are easily confused in rapid presentation. The functional organization of the facial expression recognition system embodies a distinction between these two emotions, which is investigated in the present study. A core system that includes the right parahippocampal gyrus (BA 30), fusiform gyrus, and amygdala mediates the visual recognition of fear and surprise. We found that fearful faces evoked greater activity in the left precuneus, middle temporal gyrus (MTG), middle frontal gyrus, and right lingual gyrus, whereas surprised faces were associated with greater activity in the right postcentral gyrus and left posterior insula. These findings indicate the importance of common and separate mechanisms of the neural activation that underlies the recognition of fearful and surprised faces.


Prazosin in acute anthracyclene cardiomyopathy.
A 32-year-old woman with a 14-month history of acute lymphoblastic leukemia received 300 mg/sq m of doxorubicin. Shortly after the last course of therapy, congestive failure developed that was attributed to anthracyclene cardiomyopathy. Three weeks later, an acute septic episode was complicated by hypotension and low cardiac output. Adequate blood pressure and cardiac output were restored with a combined intravenous infusion of dopamine hydrochloride and nitroglycerine. Within 24 hours, oral therapy with prazosin and digitalis was initiated, and two days later, the intravenous infusions could be discontinued. Acute anthracyclene cardiomyopathy can be successfully treated with a combination of oral inotropic and vasodilating agents.


Long-term predictive factors of the morphology based outcome in bare platinum coiled intracranial aneurysms: Evaluation by pre- and post-contrast 3D time-of-flight MR angiography.
Our aim was to identify long-term predictive factors of the morphology-based outcome (MBO) of bare platinum coiled intracranial aneurysms. A retrospective analysis of 96 bare platinum coiled intracranial aneurysms followed up from 1997 to 2016 using pre- and post-contrast 3D time-of-flight MR angiography (MRA) was performed. Logistic regression analysis was used to identify factors associated with a positive history of surrounding coil mass enhancement (SCME) and poor MBO. Spearman's rank correlation test was used to analyze the relationship between the initial angiographic result (IAR) class, sequential change of the SCME category, and MBO grade. Factors independently associated with poor MBO were incomplete IAR (OR=14.94, 95%CI: 2.46, 289.21, P=0.002) and a history of SCME (OR=4.13, 95% CI: 1.05, 18.65, P=0.043). The MBO grade strongly correlated with the IAR class (correlation coefficient [r]=0.84, P<0.0001). MBO grade correlated with sequential change of the SCME category (r=0.56, P<0.0001). The sequential change of the SCME category correlated with IAR class (r=0.53, P<0.0001). Although IAR and its class were strong long-term predictive factors of MBO, a history of SCME and upgrading of sequential change of SCME category were also long-term predictive factors of the MBO of bare platinum coiled intracranial aneurysms.


Maternity Leave Length and Workplace Policies' Impact on the Sustainment of Breastfeeding: Global Perspectives.
Breastfeeding is a global initiative of the World Health Organization and the U.S. domestic health agenda, Healthy People 2020; both recommend exclusive breastfeeding, defined as providing breast milk only via breast or bottle, through the first 6 months of an infant's life. Previous literature has shown the correlation between socioeconomic status and breastfeeding, with higher maternal education and income as predictors of sustained breastfeeding. This same population of women is more likely to be employed outside the home. PubMed and the Cochrane Database of Systematic Reviews were searched using inclusion and exclusion criteria to identify the effect of maternity leave length and workplace policies on the sustainment of breastfeeding for employed mothers. Common facilitators to sustainment of breastfeeding included longer length of maternity leave as well as adequate time and space for the pumping of breast milk once the mother returned to the workplace. Barriers included inconsistency in policy and the lack of enforcement of policies in different countries. There is a lack of consistency globally on maternity leave length and workplace policy as determinants of sustained breastfeeding for employed mothers. A consistent approach is needed to achieve the goal of exclusive breastfeeding for infants.


The neurobiology of drug addiction: cross-species insights into the dysfunction and recovery of the prefrontal cortex.
A growing preclinical and clinical body of work on the effects of chronic drug use and drug addiction has extended the scope of inquiry from the putative reward-related subcortical mechanisms to higher-order executive functions as regulated by the prefrontal cortex. Here we review the neuroimaging evidence in humans and non-human primates to demonstrate the involvement of the prefrontal cortex in emotional, cognitive, and behavioral alterations in drug addiction, with particular attention to the impaired response inhibition and salience attribution (iRISA) framework. In support of iRISA, functional and structural neuroimaging studies document a role for the prefrontal cortex in assigning excessive salience to drug over non-drug-related processes with concomitant lapses in self-control, and deficits in reward-related decision-making and insight into illness. Importantly, converging insights from human and non-human primate studies suggest a causal relationship between drug addiction and prefrontal insult, indicating that chronic drug use causes the prefrontal cortex damage that underlies iRISA while changes with abstinence and recovery with treatment suggest plasticity of these same brain regions and functions. We further dissect the overlapping and distinct characteristics of drug classes, potential biomarkers that inform vulnerability and resilience, and advancements in cutting-edge psychological and neuromodulatory treatment strategies, providing a comprehensive landscape of the human and non-human primate drug addiction literature as it relates to the prefrontal cortex.


New Approaches to Fetal Growth Restriction: The Time for Metabolomics Has Come.
Fetal growth restriction (FGR) diagnosis is often made by fetal biometric ultrasound measurements or Doppler evaluation, but most babies are only diagnosed after birth, using the birth weight as a proxy for intrauterine development. The higher risks of neurodevelopmental delay, metabolic syndrome, and cardiovascular illness associated with FGR impose a shift on the focus during pregnancy. New methodological approaches, like metabolomics, can provide novel biomarkers for intrauterine fetal development. Recent evidence on metabolites involved with fetal growth and weight show a consistent role played by lipids (especially fatty acids), amino acids, vitamin D and folic acid. Fetal energy source and metabolism, structural functions, and nervous system functioning need further evaluations in different populations. In the near future, the establishment of a core set of outcomes for FGR studies may improve the identification of the role of each metabolite in its development. Thus, we will concretely progress with the perspective of a translational capacity of metabolomics for this condition.


Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide.
Dedicator-of-cytokinesis 8 (DOCK8) deficiency, a primary immunodeficiency disease, can be reversed by allogeneic hematopoietic stem cell transplantation (HSCT); however, there are few reports describing the use of alternative donor sources for HSCT in DOCK8 deficiency. We describe HSCT for patients with DOCK8 deficiency who lack a matched related or unrelated donor using bone marrow from haploidentical related donors and post-transplantation cyclophosphamide (PT/Cy) for graft-versus-host disease (GVHD) prophylaxis. Seven patients with DOCK8 deficiency (median age, 20 years; range, 7 to 25 years) received a haploidentical related donor HSCT. The conditioning regimen included 2 days of low-dose cyclophosphamide, 5 days of fludarabine, 3 days of busulfan, and 200 cGy total body irradiation. GVHD prophylaxis consisted of PT/Cy 50 mg/kg/day on days +3 and +4 and tacrolimus and mycophenolate mofetil starting at day +5. The median times to neutrophil and platelet engraftment were 15 and 19 days, respectively. All patients attained >90% donor engraftment by day +30. Four subjects developed acute GVHD (1 with maximum grade 3). No patient developed chronic GVHD. With a median follow-up time of 20.6 months (range, 9.5 to 31.7 months), 6 of 7 patients are alive and disease free. Haploidentical related donor HSCT with PT/Cy represents an effective therapeutic approach for patients with DOCK8 deficiency who lack a matched related or unrelated donor.


[Multiplex genotyping of single nucleotide polymorphisms by MALDI-TOF mass-spectrometry: ferequencies of 56 SNP in immune response genes in human populations].
Single nucleotide polymorphism (SNP) are the most common type of genetic polymorphisms. Despite the progress in sequencing and postgenomic technologies, point genotyping of SNPs remains the most demanded approach in human and medical genetics. In this paper, the experience in the application of multiple SNP genotyping using MALDI-TOF mass-spectrometry for the analysis of genetic diversity of immune response genes in human populations has been described. It is demonstrated that MALDI-TOF mass-spectrometry is rapid, accurate and efficient method for medium-scale SNP genotyping. In four populations (Russian, Komi, Khant, and Buryat) the similar spectrum of allelic frequencies for 56 SNPs in 41 genes implicated in the regulation of immune response was found. Populations under study have the similar level of genetic diversity and are clustered according their geographic location. Economic effectiveness of MALDI-TOF mass-spectrometry in comparison with a real time PCR technology is estimated.


Dramatic Improvement of Diabetes Mellitus Following the Treatment of Coexisting Acromegaly and Cushing's Syndrome.
Endocrine diseases are frequently accompanied by diabetes mellitus and treatment of an underlying endocrine disease often improves glucose control. The co-occurrence of acromegaly and Cushing's syndrome is extremely rare. We herein describe a patient who showed a dramatic improvement in glucose control following treatment for co-existing acromegaly and Cushing's syndrome. An adrenal mass was incidentally discovered during a routine evaluation of a 56-year-old woman who was subsequently diagnosed with acromegaly and a unilateral cortisol-producing adrenal adenoma. Her blood glucose was poorly controlled despite receiving high-dose insulin therapy. After undergoing adrenalectomy for Cushing's syndrome, her insulin dosage was decreased by almost 50%. The insulin treatment was discontinued following the treatment of acromegaly.


A perspective of mitochondrial dysfunction in rats treated with silver and titanium nanoparticles (AgNPs and TiNPs).
Nanotechnology is a growing branch of science that deals with the development of structural features bearing at least one dimension in the nano range. More specifically, nanomaterials are defined as objects with dimensions that range from 1 to 100 nm, which give rise to interesting properties. In particular, silver and titanium nanoparticles (AgNPs and TiNPs, respectively) are known for their biological and biomedical properties and are often used in consumer products such as cosmetics, food additives, kitchen utensils, and toys. This situation has increased environmental and occupational exposure to AgNPs and TiNPs, which has placed demand for the risk assessment of NPs. Indeed, the same properties that make nanomaterials so attractive could also prove deleterious to biological systems. Of particular concern is the effect of NPs on mitochondria because these organelles play an essential role in cellular homeostasis. In this scenario, this work aimed to study how AgNPs and TiNPs interact with the mitochondrial respiration chain and to analyze how this interaction interferes in the bioenergetics and oxidative state of the organelles after sub-chronic exposure. Mitochondria were exposed to the NPs by gavage treatment for 21 days to check whether co-exposure of the organelles to the two types of NPs elicited any mitochondrion-NP interaction. More specifically, male Wistar rats were randomly assigned to four groups. Groups I, II, III, and IV received mineral oil, TiNPs (100 μg/kg/day), AgNPs (100 μg/kg/day), and TiNPs + AgNPs (100 μg/kg/day), respectively, by gavage. The liver was immediately removed, and the mitochondria were isolated and used within 3 h. Exposure of mitochondria to TiNPs + AgNPs lowered the respiratory control ratio, causing an uncoupling effect in the oxidative phosphorylation system. Moreover, both types of NPs induced mitochondrial swelling. Extended exposure of mitochondria to the NPs maintained increased ROS levels and depleted the endogenous antioxidant system. The AgNPs and TiNPs acted synergistically-the intensity of the toxic effect on the mitochondrial redox state was more significant in the presence of both types of NPs. These findings imply that the action of the NPs on mitochondria underlie NP toxicity, so future application of NPs requires special attention.


Night-to-night variability of polysomnography in children with suspected obstructive sleep apnea.
To determine whether a single polysomnographic night was a valid measure of obstructive sleep apnea syndrome (OSAS) in children with symptoms of sleep-disordered breathing. The night-to-night variability of respiratory and sleep parameters was measured prospectively in 30 snoring children aged 1.6 to 11.3 years (mean +/- SD, 4.1 +/- 2) by using 2 nocturnal polysomnograms performed 7 to 27 days apart (14 +/- 5 days). The mean of the respiratory variables including apnea index, apnea/hypopnea index, arterial oxygen saturation, and end-tidal partial pressure of carbon dioxide were not significantly different from night to night. Among the sleep parameters, there was no significant night-to-night difference in sleep efficiency, arousal index, percent rapid eye movement, or percent of slow wave sleep. Only the percentage of stage 2 was significantly different between the nights. The polysomnographic clinical diagnosis remained the same on both nights for all children, although the disease severity differed slightly in 2 patients. There is little clinically significant night-to-night variability in pediatric polysomnography, and no first-night effect. These data suggest that a single polysomnographic night is an adequate measure of the OSAS in children with symptoms of sleep-disordered breathing.


Low-frequency collective dynamics in deep eutectic solvents of acetamide and electrolytes: a femtosecond Raman-induced Kerr effect spectroscopic study.
In this study, we have investigated the ion concentration dependent collective dynamics in two series of deep eutectic solvent (DES) systems by femtosecond Raman-induced Kerr effect spectroscopy, as well as some physical properties, e.g., shear viscosity (η), density (ρ), and surface tension (γ). The DES systems studied here are [0.75CH3CONH2 + 0.25{f KSCN + (1 - f )NaSCN}] and [0.78CH3CONH2 + 0.22{f LiBr + (1 - f )LiNO3}] with f = 0, 0.2, 0.4, 0.6, 0.8, and 1.0. γ of these DES systems shows near insensitivity to f, while ρ shows a moderate dependence on f. Interestingly, η exhibits a strong dependence on f. In the low-frequency Kerr spectra, obtained via the Fourier transform of the collected Kerr transients, a characteristic band at ∼70 cm(-1) is clear in [0.78CH3CONH2 + 0.22{f LiBr + (1 - f )LiNO3}] DES especially at the larger f. The band is attributed to the intermolecular hydrogen bond of acetamide. Because of less depolarized Raman activities of intermolecular/interionic vibrational motions, which are mostly translational (collision-induced or interaction-induced) motions, of spherical ions, the intermolecular hydrogen-bonding band is clearly observed. In contrast, the intermolecular hydrogen-bonding band is buried in the other intermolecular/interionic vibrational motions, which includes translational and reorientational (librational) motions and their cross-terms, in [0.75CH3CONH2 + 0.25{f KSCN + (1 - f )NaSCN}] system. The first moment (M1) of the intermolecular/interionic vibrational band in these DES systems is much higher than that in typical neutral molecular liquids and shows a weak but contrasting dependence on the bulk parameter √γ/ρ. The time constants for picosecond overdamped Kerr transients in both the DES systems, which are obtained on the basis of the analysis fitted by a triexponential function, are rather insensitive to f for both the DES systems, but all the three time constants (fast: ∼1-3 ps; intermediate: ∼7-20 ps; and slow: ∼100 ps) are different between the [0.78CH3CONH2 + 0.22{f LiBr + (1 - f )LiNO3}] and [0.75CH3CONH2 + 0.25{f KSCN + (1 - f )NaSCN}] systems. These results indicate that the intermolecular/interionic interactions in DES systems is strongly influenced by the ionic species present in these DES systems.


Primary endocardial fibroelastosis and nonimmune hydrops fetalis: case report with autopsy.
Endocardial fibroelastosis is an important cause of congestive heart failure and death in infancy and early childhood. When present, it is commonly associated with non immune hydrops fetalis. The aim of this study is to draw attention for possible cardiac abnormalities in cases of fetal hydrops, and report a case of premature death by primary endocardial fibroelastosis with autopsy.


Endarterectomy versus angioplasty in the treatment of localized stenosis of the abdominal aorta.
To compare the outcome after aortoiliac endarterectomy and percutaneous transluminal angioplasty (PTA) of the aorta for localized stenosis of the lower abdominal aorta. Chart review of patients treated over a 5-year period. A university centre. Sixteen women, all of whom were smokers; 5 had hyperlipidemia, 4 had evidence of coronary artery disease, 3 were hypertensive, and 1 was diabetic. Aortoiliac endarterectomy (eight women) and PTA (eight women). Ankle-brachial pressure index (ABI), degree of claudication and clinical outcome. Angiography showed localized stenosis of the lower aorta in all patients, aortic hypoplasia in nine patients and associated common iliac disease in seven. None of the eight patients managed by aortoiliac endarterectomy had complications or died. All were free of claudication at a mean follow-up of 29 months and had durable improvement in their ABI: mean ABI preoperatively was 0.69 (standard deviation [SD] 0.1) and postoperatively was 1.06 (SD 0.07). Of the eight patients treated by PTA, only one had partial dilatation; another had a subintimal tear with worsening symptoms and a fall in ABI, requiring surgery within 18 months. The remaining six were symptom free after a mean follow-up of 13.4 months. Aortic PTA resulted in improvement of the ABI: mean ABI before PTA was 0.69 (SD 0.19) and after PTA was 1.06 (SD 0.15). Endarterectomy is a safe and effective method of treating occlusive disease limited to the distal aorta. PTA appears to be less reliable. However, it is recommended as the initial treatment of choice in patients with angiographically suitable lesions because it is less invasive.


[Ileo-ileal and ileocecal invagination due to intestinal lipomatosis].
Intestinal lipomatosis is a rare entity and few cases have been reported in the literature. The condition is usually asymptomatic. Symptomatic cases usually present as obstruction or, less frequently, as bleeding. Intestinal barium studies, ultrasonography and computed tomography are useful diagnostic techniques. We present the case of a 47-year-old man with no relevant medical history who presented with intestinal obstruction of several months' duration. Complementary investigations yielded a diagnosis of intestinal obstruction due to ileocecal invagination secondary to endoluminal tumors of the ileum. Surgery and pathological analysis revealed the latter to be intestinal lipomatosis. This rare clinical entity has been associated with diverticulosis and intestinal volvulus.


Fungal mycobiome-mediated immune response: a non-negligible promoter in pancreatic oncogenesis and chemoresistance.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in humans due to late diagnosis and poor response to treatments. The tumor microenvironment (TME) of PDAC is characterized by a distinctive, suppressive immune profile, which inhibits the protective functions of anti-tumor immunity and thereby contributes to PDAC progression. Recently, the study of Alam et al. discovered for the first time that the intratumoral fungal mycobiome could contribute to the recruitment and activation of type 2 immune cells in the TME of PDAC via enhancing the secretion of a chemoattractant, interleukin (IL-) 33. In this article, we reviewed the important findings of this study. Together with our findings, we synthetically discussed the role of the fungal mycobiome in orchestrating the immune response and thereby modulating tumor progression.


Estimates of Ripple-Density Resolution Based on the Discrimination From Rippled and Nonrippled Reference Signals.
Rippled-spectrum stimuli are used to evaluate the resolution of the spectro-temporal structure of sounds. Measurements of spectrum-pattern resolution imply the discrimination between the test and reference stimuli. Therefore, estimates of rippled-pattern resolution could depend on both the test stimulus and the reference stimulus type. In this study, the ripple-density resolution was measured using combinations of two test stimuli and two reference stimuli. The test stimuli were rippled-spectrum signals with constant phase or rippled-spectrum signals with ripple-phase reversals. The reference stimuli were rippled-spectrum signals with opposite ripple phase to the test or nonrippled signals. The spectra were centered at 2 kHz and had an equivalent rectangular bandwidth of 1 oct and a level of 70 dB sound pressure level. A three-alternative forced-choice procedure was combined with an adaptive procedure. With rippled reference stimuli, the mean ripple-density resolution limits were 8.9 ripples/oct (phase-reversals test stimulus) or 7.7 ripples/oct (constant-phase test stimulus). With nonrippled reference stimuli, the mean resolution limits were 26.1 ripples/oct (phase-reversals test stimulus) or 22.2 ripples/oct (constant-phase test stimulus). Different contributions of excitation-pattern and temporal-processing mechanisms are assumed for measurements with rippled and nonrippled reference stimuli: The excitation-pattern mechanism is more effective for the discrimination of rippled stimuli that differ in their ripple-phase patterns, whereas the temporal-processing mechanism is more effective for the discrimination of rippled and nonrippled stimuli.


Introducing a photo-switchable azo-functionality inside Cr-MIL-101-NH2 by covalent post-synthetic modification.
For the first time an azo functionality was covalently introduced into a MOF by post-synthetic modification. The reaction of Cr-MIL-101-NH(2) with p-phenylazobenzoylchloride (1) and 4-(phenylazo)phenylisocyanate (2) as the reactants led to the compounds Cr-MIL-101_amide and Cr-MIL-101_urea, with the azo groups protruding into the mesoporous cages. XRPD and N(2) sorption measurements confirm the intactness of the framework and the successful covalent modification was proven by IR- and NMR-spectroscopy. Furthermore, cis/trans isomerisation upon irradiation with light was demonstrated by UV/Vis spectroscopy. More distinct changes in the UV/Vis spectra were observed for Cr-MIL-101_amide compared to Cr-MIL-101_urea, while the degree of functionalization, i.e. the number of reacted NH(2)-groups, seems to have a less pronounced effect. The variation of the sorption properties due to the cis/trans isomerisation was proven by methane adsorption measurements.


Cardiovascular effects of SK&F 104078, a novel alpha-adrenoceptor antagonist, in normotensive and hypertensive rats.
SK&F 104078 is a novel alpha-adrenoceptor antagonist derived from the 3-benzazepine alpha 2-adrenoceptor antagonist SK&F 86466. SK&F 104078 will block both alpha 1- and vascular postjunctional alpha 2-adrenoceptors but does not block most prejunctional alpha 2-adrenoceptors. Intravenous (i.v.) administration of SK&F 104078 decreased blood pressure (BP) in both spontaneously hypertensive and DOCA-salt hypertensive rats. SK&F 104078 potentiated the hypotensive response to tilt in anesthetized spontaneously hypertensive rats (SHR). Although SK&F 104078 had no effect on BP in normotensive rats, the tilt-induced decrease in BP in these animals was also potentiated. In this regard, SK&F 104078 resembled the selective alpha 1-adrenoceptor antagonist prazosin, rather than the alpha 2-adrenoceptor antagonists rauwolscine or SK&F 86466. Oral administration of SK&F 104078 had no significant effect on BP in SHR unless extremely high doses were administered. This was consistent with low plasma concentrations of SK&F 104078 observed after oral administration. After i.v. administration, the clearance of SK&F 104078 from plasma was 123 ml/min/kg, the steady-state volume of distribution was 17 L/kg, and the fraction excreted unchanged in urine was less than 1%. The low oral bioavailability of SK&F 104078 did not appear to be due to high first-pass oxidative metabolism, since pretreatment of SHR with the suicide substrate inhibitor of cytochrome P-450, 1-aminobenzotriazole (ABT), did not result in increased oral efficacy. SK&F 101253, a close structural analogue of SK&F 104078, was an effective antihypertensive when administered orally. Comparison of the stability of SK&F 101253 and SK&F 104078 in acid media showed SK&F 104078, but not SK&F 101253, to be rapidly degraded.(ABSTRACT TRUNCATED AT 250 WORDS)


Functional adaptation of nephrons in dogs with acute progressing to chronic experimental glomerulonephritis.
Although a diminished fractional excretion of sodium (FENa) is the hallmark of acute proliferative glomerulonephritis (APGN), an enhanced natriuresis per glomerular filtration rate (GFR) in the chronic phases of this disease has been reported. We studied this adaptive response utilizing two different split-bladder dog models with unilateral, and a third group of dogs with bilateral Masugi's nephritis. Group I. Six dogs with unilateral nonaccelerated APGN studied a mean of 6 days after induction had a mean base-line APGN/intact kidney GFR of 31/50 ml/min (P less than 0.005) and FENa of 0.2/0.75% (P less than 0.005). Acute volume expansion caused a smaller absolute increase in FENa from the APGN kidney, 1.6%, than from the intact kidney, 4.0%, (P less than 0.01). Maximum tubular secretion of rho-aminohippuric acid/GFR (TmPAH/GFR) measured in three dogs was higher in the APGN kidney than intact kidney, 13.1 vs. 9.3 mg/dl. Subsequent studies on three of the six dogs when the disease had become chronic demonstrated a reversal in the pattern of sodium excretion in response to volume expansion. Group II. Six dogs with accelerated unilateral APGN (dogs presensitized to antibody source) studied a mean of 5 days after induction had a mean base-line APGN/intact kidney GFR of 16/57 ml/min and FENa of 0.22/0.12% (P less than 0.1). Contrary to group I, volume expansion caused a greater absolute increase in FENa from the APGN kidney, 5.8%, than from the intact kidney, 2.9% (P less than 0.05). TmPAH/GFR studied in four dogs was similar for both kidneys, 17.9 and 18.5 mg/dl for the APGN kidney and intact kidney, respectively. Group III. Sequential studies were performed on seven dogs with bilateral nonaccelerated APGN. Initially each demonstrated sodium retention and a smaller absolute increase in FENa in response to volume expansion compared to a predisease control study. With disease progression, volume expansion induced a greater absolute increase in FENa than in the control study. We concluded that (a) the fractional excretion of sodium from the APGN kidney will be less or greater than the contralateral intact kidney or control study depending on the severity and/or chronicity of the disease, possibly as the result of morphologic alterations; (b) the degree of extracellular fluid volume expansion is an important variable influencing similarity of glomerulotubular balance between the APGN and contralateral intact kidney; and (c) the "intact nephron hypothesis" applies in a limited fashion to kidneys with APGN in the absence of volume expansion just as it does for kidneys with chronic glomerulonephritis or pyelonephritis.


Same day discharge after thyroidectomy is safe and effective.
Historically, thyroidectomies have been performed as inpatient operations due to concerns of postoperative bleeding and symptomatic hypocalcemia. We aim to demonstrate that outpatient thyroidectomy can be performed safely. This report outlines a 7-year retrospective analysis (2009-2016) of outpatient vs inpatient thyroidectomies, with outcomes including hematoma, blood loss, recurrent laryngeal nerve injury, symptomatic hypocalcemia, and postoperative emergency room (ER) visits. A total of 1460 thyroidectomies were performed: 1272 (87%) outpatient and 188 (13%) inpatient. Five outpatients: 4 total thyroidectomies (TT), 1 TT with a central lymph node dissection (CLND), and 1 partial thyroidectomy (PT) developed postoperative hematomas (0.34%) at post-discharge hour 3, 9, 10, 13, and 42. Average time to discharge was 2 hours and 37 minutes. Hematomas were evacuated successfully in the operating room under local anesthesia with a 2-day average hospital stay. There were no differences between TT, thyroid lobectomy (TL), and PT procedures for postoperative hematoma (p=0.17). Outpatient compared to inpatient thyroidectomy was more likely to have been performed in patients with lower American Society of Anesthesia scores (2.3 vs 2.9, p<0.0001), less mean blood loss (74 vs 227 ml, p<0.0001), lesser age (52 vs 56 years, p=0.0012), less extensive dissection (p<0.0001), and fewer RLN injuries (2.4% vs 8.5%, p<0.0001). There was no difference between outpatient and inpatient symptomatic hypocalcemia (6.3% vs 9.6%, p=0.09), 30-day postoperative ER visits (8.8% vs 9.6%, p=0.73), and postoperative hematoma (0.39% vs 0%, p=0.39). There was one inpatient mortality from stroke. Postoperative hematomas can be managed safely without life-threatening complications suggesting outpatient thyroidectomy can be performed safely by an experienced surgeon, and adverse sequelae dealt with in a safe and effective manner.


Risk of ocular manifestations in patients with giant cell arteritis: a nationwide study in Sweden.
No large-scale nationwide study has determined the risk of ocular manifestations in patients with giant cell arteritis (GCA). The aim was to study the incidence and risk factors of ocular manifestations in patients with GCA in Sweden. A national cohort was created by linking Swedish nationwide registers. GCA patients were identified from the Swedish Hospital Inpatient and Outpatient Registers between 2002 and 2010, and were followed until the development of ocular manifestations. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for ocular manifestations in patients with GCA compared to those without GCA. We identified 3737 males and 8311 females with GCA. A total of 1618 individuals had subsequent ocular manifestations, representing 13.4% of the GCA patients. The overall SIR of ocular manifestations was 6.96 (95% CI 6.63-7.31). The risk for disorders of the optic nerve or visual tract was particularly high (SIR = 51.68, 95% CI 46.12-57.73). Men with GCA had a higher risk than women, and GCA patients without polymyalgia rheumatica (PMR) symptoms had a higher risk than those with PMR symptoms. Living outside big cities was negatively associated with ocular manifestations in GCA patients, whereas hypertension and diabetes were associated with an increased risk of ocular manifestations. The overall risk of ocular manifestations was higher in GCA patients than in the general population, especially for men and for those without PMR symptoms.


Selective adaptation to linear frequency-modulated sweeps: evidence for direction-specific FM channels?
Psychometric functions were obtained for detection of linear frequency-modulated pure tones which were preceded by either a pure tone or a linear FM pure-tone adaptor. The results of Gardner and Wilson [J. Acoust. Soc. Am. 66, 704-709(1979)] were generally confirmed: Thresholds were larger by about a factor of 1.7 when the adaptor and test sweeps rose in frequency. This increase in threshold corresponds to a change in performance from 75% to 65% correct. As an alternative to feature-selective channels, we propose that this small effect is due to nonsensory factors, specifically, the use of an adaptor-like reference in the "adapted" condition. Performance similar to that obtained in humans is shown by an ideal receiver that uses an inappropriate reference to match the signal in the detection task.


Isomeric solid enols on ring- and amide-carbonyls of substituted 2-carbanilido-1,3-indandiones.
Both isomeric enols on ring carbonyl (5b) and on amide carbonyl (6b) derived from N-p-methoxyphenyl-2-carbamido-1,3-indandione (4b) were isolated, and their X-ray structures were determined. X-ray diffraction of the N-o,p-dimethoxy analogue indicated a disorder ascribed to the presence of a 6:4 mixture of 5c and 6c. Calculation (B3LYP/6-31+G*) gave good agreement with observed geometries. The calculated energies indicated that enols 6 are more stable by <1 kcal/mol than enols 5 and much more stable than amides 4.


Acute myocardial infarction following an arthropod bite: is hereditary thrombophilia a contributing factor?
Acute myocardial infarction (AMI) due to arthropod envenomation has rarely been reported in the literature. In the present report, we describe two cases who developed AMI following an arthropod bite. Coronary angiograms revealed normal coronary arteries in both patients. Both events were probably secondary to coronary artery thrombosis and/or coronary artery vasospasm. Both patients were subsequently found to be heterozygous for prothrombin mutation (G20210A). As a result, we recommend ruling out the possibility of hereditary thrombophilias in young patients with AMI developing after an arthropod bite.


Hyperhomocysteinemia Exacerbates Cisplatin-induced Acute Kidney Injury.
Hyperhomocysteinemia (HHcy) has been linked to several clinical manifestations including chronic kidney disease. However, it is not known whether HHcy has a role in the development of acute kidney injury (AKI). In the present study, we reported that HHcy mice developed more severe renal injury after cisplatin injection and ischemia-reperfusion injury shown as more severe renal tubular damage and higher serum creatinine. In response to cisplatin, HHcy mice showed more prevalent tubular cell apoptosis and decreased tubular cell proliferation. Mechanistically, a heightened ER stress and a reduced Akt activity were observed in kidney tissues of HHcy mice after cisplatin injection. Stimulating cultured NRK-52E cells with Hcy significantly increased the fraction of cells in G2/M phase and cell apoptosis together with decreased Akt kinase activity. Akt agonist IGF-1 rescued HHcy-induced cell cycle arrest and cell apoptosis. In conclusion, the present study provides evidence that HHcy increases the sensitivity and severity of AKI.


Trends and Cut-Point Changes in Obesity Parameters by Age Groups Considering Metabolic Syndrome.
Non-communicable diseases (NCDs) are an important issue worldwide. Obesity has a close relationship with NCDs. Various age-related changes should be considered when evaluating obesity. National representative cohort data from the National Health Insurance Service National Sample Cohort from 2012 to 2013 were used. Sex-specific and age group-specific (10-year intervals) means for body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WtHR) were calculated. Optimal cut-points for obesity parameters were defined as the value predicting two or more components of metabolic syndrome (except WC). The mean value and optimal cut-point for BMI decreased with age for men. The mean BMI value for women increased with age, but optimal cut-points showed no remarkable difference. The mean WC of men increased with age, but the optimal cut-points were similar for age groups. For women, the mean value and optimal cut-point for WC increased with age. Regarding WtHR, the mean value and optimal cut-point increased with age for men and women. Differences across age groups were larger for women. The mean values of the obesity indices and the optimal cut-points were changed according to age groups. This study supports the necessity of applying age group-specific cut-points for the various obesity parameters.


Need for Hepatitis B Vaccination in Medical Students.
Hepatitis B is a global acute and chronic life-threatening liver infection caused by the hepatitis B virus. During cadaveric dissection, clinical rotations, and autopsy posting, medical students get exposed to patients' blood and body fluids, which increases the risk of hepatitis B infection. Hepatitis B can be prevented by vaccines that are safe, easily available, and effective, however many medical students are still unvaccinated. This results in the need for attention to prevent early exposure and provide vaccination at regular intervals during clinical training and professional practice. autopsy; hepatitis B vaccine; medical students.


Further delineation of Hennekam syndrome.
We report four children from four inbred Arab families with varying manifestations of Hennekam syndrome and additional features that have not been previously reported. These include abnormalities of the middle ear, anomalous pulmonary venous drainage, interrupted inferior vena cava, polysplenia, crossed renal ectopia, median position of the liver and multiple cavernous haemangiomas. In addition, in one case lymphoedema was absent and oedema due to hypoproteinaemia appeared at 6 years of age. Since anomalies of the veins and the consequent developmental abnormalities of the lymphatics might lead to alterations in the fluid balance of the embryo, we hypothesize that altered fluid dynamics due to defective vascular and lymphatic development might disrupt critical events in craniofacial morphogenesis resulting in Hennekam syndrome.


Comparison of self- and balloon-expandable valves in patients with dilatated ascending aorta undergoing transcatheter aortic valve replacement.
Limited studies have focused on the performance of self-expandable valves (SEVs) and balloon-expandable valves (BEVs) in patients with dilatated ascending aorta (AA) undergoing transcatheter aortic valve replacement (TAVR). The present study compared the performance of widely used Edwards BEVs and domestic SEVs in patients with dilatated AA among Chinese population. We identified and reviewed 207 patients who had baseline AA diameter ≥40 mm and underwent transfemoral TAVR. Patients were divided into two groups: SEV and BEV. The SEVs were locally manufactured valves that have received Chinese regulatory approval (Venus-A, Taurus One, and VitaFlow), while the BEVs were Edwards Sapien XT and Sapien3. Procedural device success and post-procedural changes of AA diameters were compared. The sample size of SEV group was larger than that of BEV group because BEVs were not available in China in the early clinical practice. The overall device success was slightly lower in SEV group compared with BEV group (84.2% vs. 95.8%, P=0.213). However, in the univariable and multivariable logistic regression analyses, only bicuspid aortic valve (BAV) was found to be an independent risk factor for device failure (OR: 2.632, CI: 1.107-6.257, P=0.029). During the median follow-up of 21 months, no statistical difference was found between the two groups regarding the overall survival (83.1%±4.7% vs. 95.8%±4.1%, P=0.533), and no aortic dissection nor rupture was observed. In a subgroup of patients who had follow-up CTs ≥12-month intervals, the AA diameter appeared to remain stable in SEV group with an aortic expansion rate of 0 (-0.4 to 0.8) mm (P=0.102), while it slightly enlarged in BEV group with an aortic expansion rate of 0.4 (-0.4 to 0.6) mm/y (P=0.038). In addition, the AA diameter also slightly enlarged in patients with BAV [0.2 (0 to 1.0) mm/y, P=0.015], while it remained stable in patients with tricuspid aortic valve (TAV) [0 (-0.8 to 0.6) mm/y, P=0.640]. In patients with dilatated AA who underwent TAVR, the type of THVs did not affect the procedural device success. BAV appeared to be a risk factor for both device failure and higher aortic expansion rate in these patients.


Monitoring aging-associated structural alterations in Caenorhabditis elegans striated muscles via polarization-dependent second-harmonic generation measurements.
The in-vivo elucidation of the molecular mechanisms underlying muscles dysfunction due to aging via non-invasive label free imaging techniques is an important issue with high biological significance. In this study, polarization-dependent second-harmonic generation (PSHG) was used to evaluate structural alterations in the striated muscles during Caenorhabditis elegans lifespan. Young and old wild-type animals were irradiated. The obtained results showed that it was not feasible to detect differences in the structure of myosin that could be correlated with the aging of the worms, via the implementation of the classical, widely used, cylindrical symmetry model and the calculation of the SHG anisotropy values. A trigonal symmetry model improved the extracted results; however, the best outcome was originated from the application of a general model. Myosin structural modifications were monitored via the estimation of the difference in spectral phases derived from discrete Fourier transform analysis. Age classification of the nematodes was achieved by employing both models, proving the usefulness of the usage of PSHG microscopy as a potential diagnostic tool for the investigation of muscle diseases.


Safety and efficacy of percutaneous atrial appendage closure followed by antiplatelet therapy in a high-risk population: single-center experience with a WATCHMAN device.
In our everyday practice we encounter many patients with non-valvular atrial fibrillation with either a contraindication to oral anticoagulation or with its inefficiency. To investigate whether left atrial appendage closure (LAAC) followed by post-procedure antiplatelet therapy is safe and efficient in a high-risk population. Ninety-one (48 males) consecutive patients with non-valvular atrial fibrillation (NVAF) underwent an LAAC procedure using a first-generation WATCHMAN 2.5 device followed by antiplatelet therapy. Clinical and transesophageal echocardiography data were collected at baseline and at the follow-up visit. The median (IQR) CHA2DS2-VASc score was 5 (4.0-6.0) and the HAS-BLED score was 3 (3.0-4.0); the mean (SD) age was 74.4 (8.4). A bleeding history was observed in 89% of patients and 24.2% of patients had a history of stroke or transient ischemic attack (TIA). The procedure was successful in 98.9%. Post-procedure therapy was dual antiplatelet therapy in 85 patients; 3 patients received single antiplatelet therapy and the therapy was maintained until the follow-up visit. Peri-procedural complications were tamponade (3.3%), pericardial effusion (2.2%) and two deaths (2.2%) with no bleeding or vascular complications. The median follow-up was 67 (52.75-84.75) days. Primary safety endpoint (bleeding BARC type 3 or more, tamponade, pericardial effusion, and device embolization) and primary efficacy endpoint (stroke or TIA, hemorrhagic stroke, peripheral embolism, cardiovascular (CV) and non-CV death) were observed in 2 and 4 patients, respectively. The LAAC procedure followed by antiplatelet therapy seems to be safe and efficient in the high-risk population. Further studies in this field are required.


O-acetylserine (thiol) lyase: an enigmatic enzyme of plant cysteine biosynthesis revisited in Arabidopsis thaliana.
The synthesis of cysteine is positioned at a decisive stage of assimilatory sulphate reduction, marking the fixation of inorganic sulphide into a carbon skeleton. O-acetylserine (thiol) lyase (OAS-TL) catalyses the reaction of inorganic sulphide with O-acetylserine (OAS). Despite its prominent position in the pathway OAS-TL is generally regarded as a non-limiting enzyme without regulatory function, due to low substrate affinities and semi-constitutive expression patterns. To resolve this apparent contradiction, the kinetic properties of three OAS-TLs from Arabidopsis thaliana, localized in the cytosol (A), plastids (B), and mitochondria (C), were analysed. The recombinant expressed OAS-TLs were purified to apparent homogeneity without any fusion tag to maintain their native forms. The proteins displayed high specific activities of 550-900 micromol min(-1) mg(-1). Using an improved and highly sensitive assay method for cysteine determination, the apparent K(m)(sulphide) was 3-6 microM for OAS-TL A, B, and C and thus 10-100 times lower than previously reported for plant OAS-TLs. K(m)(OAS) was between 310 microM and 690 microM for OAS-TL isoform A, B, and C, whereas the apparent dissociation binding constant for OAS was much lower (K(d)<1 microM OAS). A HPLC method was developed for OAS quantification that revealed fast increases of the cellular OAS concentration in response to sulphate deprivation. The observed fluctuations of intracellular OAS concentrations, combined with the OAS dissociation constant and the catalytic properties of OAS-TL, support the model of a dynamic cysteine synthesis system with regulatory function as can be expected from the position of the reaction in the sulphur assimilation pathway.


The left-right coordinator: the role of Vg1 in organizing left-right axis formation.
The asymmetries of internal organs are consistently oriented along the left-right axis in all vertebrates, and perturbations of left-right orientation lead to significant congenital disease. We propose a model in which a "left-right coordinator" interacts with the Spemann organizer to coordinate the evolutionarily conserved three-dimensional asymmetries in the embryo. The Vg1 cell-signaling pathway plays a central role in left-right coordinator function. Antagonists of Vg1 alter left-right development; antagonists of other members of the TGFbeta family do not. Cell-lineage directed expression of Vg1 protein can fully invert the left-right axis (situs inversus), can randomize left-right asymmetries, or can "rescue" a perturbed left-right axis in conjoined twins to normal orientation (situs solitus), indicating that Vg1 can mimic left-right coordinator activity. These are the first molecular manipulations in any vertebrate by which the left-right axis can be reliably controlled.


Factors influencing potent antagonistic effects of Escherichia coli and Bacteroides ovatus on Staphylococcus aureus in anaerobic continuous flow cultures.
We examined factors related to the potent antagonistic effect of Escherichia coli and Bacteroides ovatus on Staphylococcus aureus in anaerobic continuous flow cultures. In the presence of sugars fermentable by E. coli alone or both E. coli and S. aureus, motile E. coli strains exerted a potent antagonistic effect and S. aureus was expelled from the culture vessel within a few days. Conversely, in the presence of a sugar fermentable by S. aureus alone, the antagonistic effect of E. coli was diminished and S. aureus persisted at ca. 5 x 10(5) cfu/mL. B. ovatus alone exerted only a weak antagonistic effect on S. aureus in any culture conditions; however, when B. ovatus was cocultivated with E. coli and S. aureus, even in the presence of a sugar fermentable by S. aureus but not by E. coli, the potent antagonistic effect was restored. Escherichia coli showed the same level of antagonistic effect either in the presence of acetic acid (ca. 32 mM), propionic acid (4 mM), butyric acid (17 mM) and hydrogen sulfide (5 x 10(-1) mM) or when these metabolic products, except for a small amount of acetic acid (1.2 mM) were not present. In these culture conditions, S. aureus populations were lost at rates much higher than theoretical wash out rates of resting cells. These results indicate the presence of some bactericidal factors other than the volatile fatty acids and hydrogen sulfide. The bactericidal factors were not found in cultures of E. coli heated in boiling water for 10 min and in cell-free culture filtrates. Thus, the bactericidal factors seem to be associated with live E. coli cells. The nature of the bactericidal factors is not clear at present.


Changes in temporomandibular disc position during growth in young Japanese.
To detect the initial changes in temporomandibular disc position during growth with MRI examination in a prospective longitudinal study of a young Japanese population. Forty-four temporomandibular joints in 22 healthy asymptomatic volunteers, mean age 11.8 years, age range 9-16 years, were examined by MRI. They were re-examined 2-3 years later. The mean age and age range at the second examination were 14.5 years and 12-19 years, respectively. The discs were assessed at three different locations by oblique sagittal planes at the lateral, central and medial parts, and the displacement was evaluated as a partial anterior or total anterior position. Six joints already had a partial anterior position of the disc at the initial examination and no developmental change in disc position was observed during the examination period. Nine joints developed partial disc displacement during the examination period. Every partial displacement was observed at the lateral part of the disc. One joint developed a total anterior position from the lateral to the medial images. Initial changes in the disc position are likely to start from the lateral part of the joint in the early teenage years and are often asymptomatic.


Computational investigation of the time-dependent contact behaviour of the human tibiofemoral joint under body weight.
The knee joint is one of the most common sites for osteoarthritis, the onset and progression of which are believed to relate to the mechanical environment of cartilage. To understand this environment, it is necessary to take into account the complex biphasic contact interactions of the cartilage and menisci. In this study, the time-dependent contact behaviour of an intact and a meniscectomized human tibiofemoral joint was characterized under body weight using a computational model. Good agreement in the contact area and femoral displacement under static loads were found between model predictions of this study and published experimental measurements. The time-dependent results indicated that as loading time progressed, the contact area and femoral vertical displacement of both intact and meniscectomized joints increased. More load was transferred to the cartilage-cartilage interface over time. However, the portions of load borne by the lateral and medial compartments did not greatly vary with time. Additionally, during the whole simulation period, the maximum compressive stress in the meniscectomized joint was higher than that in the intact joint. The fluid pressure in the intact and meniscectomized joints remained remarkably high at the condyle centres, but the fluid pressure at the cartilage-meniscus interface decreased faster than that at the condyle centres as loading time progressed. The above findings provide further insights into the mechanical environment of the cartilage and meniscus within the human knee joint.


Use of glucose starvation to limit growth and induce protein production in Escherichia coli.
The use of glucose starvation to uncouple the production of recombinant beta-galactosidase from cell growth in Escherichia coli was investigated. A lacZ operon fusion to the carbon starvation-inducible cst-1 locus was used to control beta-galactosidase synthesis. beta-Galactosidase induction was observed only under aerobic starvation conditions, and its expression continued for 6 h following the onset of glucose starvation. The cessation of beta-galactosidase expression closely correlated with the exhaustion of acetate, an overflow metabolite of glucose, from the culture medium. Our results suggest the primary role of acetate in cst-1-controlled protein expression is that of an energy source. Using this information, we metered acetate to a glucose-starved culture and produced a metabolically sluggish state, where growth was limited to a low linear rate and production of recombinant beta-galactosidase occurred continuously throughout the experiment. The cst-1 controlled beta-galactosidase synthesis was also induced at low dilution rates in a glucose-limited chemostat, suggesting possible applications to high-density cell systems such as glucose-limited recycle reactors. This work demonstrates that by using an appropriate promoter system and nutrient limitation, growth can be restrained while recombinant protein production is induced and maintained.


Finite-Size Scaling of a First-Order Dynamical Phase Transition: Adaptive Population Dynamics and an Effective Model.
We analyze large deviations of the time-averaged activity in the one-dimensional Fredrickson-Andersen model, both numerically and analytically. The model exhibits a dynamical phase transition, which appears as a singularity in the large deviation function. We analyze the finite-size scaling of this phase transition numerically, by generalizing an existing cloning algorithm to include a multicanonical feedback control: this significantly improves the computational efficiency. Motivated by these numerical results, we formulate an effective theory for the model in the vicinity of the phase transition, which accounts quantitatively for the observed behavior. We discuss potential applications of the numerical method and the effective theory in a range of more general contexts.


Solitary Collagenoma of the Labium Majus: A Rare Occurrence.
Collagenomas are connective tissue nevi representing hamartomatous proliferation of collagen. Isolated collagenomas are of rare occurrence. They are sporadically acquired, and lesions are often localized to a single body region. We described a case of solitary collagenoma in a 23-year-old woman, confirmed on histopathology and special stains for collagen, involving an uncommon site such as labium majus. A high index of suspicion for a skin-colored circumscribed solitary growth and a low threshold for biopsy often help to arrive at a final diagnosis.


Characterization of Equine Infectious Anemia Virus Long Terminal Repeat Quasispecies In Vitro and In Vivo.
The equine infectious anemia virus (EIAV) attenuated vaccine was developed by long-term passaging of a field-isolated virulent strain in cross-species hosts, followed by successive cultivation in cells in vitro To explore the molecular mechanism underlying the evolution of the EIAV attenuated vaccine, a systematic study focusing on long-terminal-repeat (LTR) variation in numerous virus strains ranging from virulent EIAV to attenuated EIAV was performed over time both in vitro and in vivo Two hypervariable regions were identified within the U3 region in the enhancer region (EHR) and the negative regulatory element (NRE) and within the R region in the transcription start site (TSS) and the Tat-activating region (TAR). Among these sites, variation in the U3 region resulted in the formation of additional transcription factor binding sites; this variation of the in vitro-adapted strains was consistent with the loss of pathogenicity. Notably, the same LTR variation pattern was observed both in vitro and in vivo Generally, the LTR variation in both the attenuated virus and the virulent strain fluctuated over time in vivo Interestingly, the attenuated-virus-specific LTR variation was also detected in horses infected with the virulent strain, supporting the hypothesis that the evolution of an attenuated virus might have involved branching from EIAV quasispecies. This hypothesis was verified by phylogenetic analysis. The present systematic study examining the molecular evolution of attenuated EIAV from EIAV quasispecies may provide an informative model reflecting the evolution of similar lentiviruses.IMPORTANCE The attenuated EIAV vaccine was the first lentiviral vaccine used to successfully control for equine infectious anemia in China. This vaccine provides an important reference for studying the relationship between EIAV gene variation and changes in biological characteristics. Importantly, the vaccine provides a model for the investigation of lentiviral quasispecies evolution. This study followed the "natural" development of the attenuated EIAV vaccine by use of a systematic analysis of LTR evolution in vitro and in vivo The results revealed that the increase in LTR variation with passaging was accompanied by a decrease in virulence, which indicated that LTR variability might parallel the attenuation of virulence. Interestingly, the attenuated-virus-specific LTR variation was also detected in virulent-strain-infected horses, a finding consistent with those of previous investigations of gp90 and S2 evolution. Therefore, we present a hypothesis that the evolution of the attenuated virus may involve branching from EIAV quasispecies present in vivo.


German registry for acute aortic dissection type A (GERAADA)--lessons learned from the registry.
A German registry for acute aortic dissection type A (GERAADA) was initiated by the Working Group for Aortic Surgery and Interventional Vascular Surgery of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) in July 2006. This web-based database was developed to record the data of patients who had undergone surgery for aortic dissection type A. From analyzing the data, we aim to learn how to improve surgical treatment and to identify parameters affecting patient outcome. In the beginning, 33 cardiac centers participated via online access to the registry on the GSTCVS' homepage. Since then, 43 centers in Germany, Switzerland and Austria have begun entering data on the pre- and intraoperative status of their patients, postoperative complications, mid-term results and circumstances of death. We have succeeded in interpreting the initial results and trends from the registry now available to all of the participating centers, which benefit from this shared pool of analyzed data by optimizing their therapy regimes and comparing their success with that in the other centers.


Evolution of sexual dimorphism and Rensch's rule in the beetle genus Limnebius (Hydraenidae): is sexual selection opportunistic?
Sexual size dimorphism (SSD) is widespread among animals, with larger females usually attributed to an optimization of resources in reproduction and larger males to sexual selection. A general pattern in the evolution of SSD is Rensch's rule, which states that SSD increases with body size in species with larger males but decreases when females are larger. We studied the evolution of SSD in the genus Limnebius (Coleoptera, Hydraenidae), measuring SSD and male genital size and complexity of ca. 80% of its 150 species and reconstructing its evolution in a molecular phylogeny with 71 species. We found strong support for a higher evolutionary lability of male body size, which had an overall positive allometry with respect to females and higher evolutionary rates measured over the individual branches of the phylogeny. Increases in SSD were associated to increases in body size, but there were some exceptions with an increase associated to changes in only one sex. Secondary sexual characters (SSC) in the external morphology of males appeared several times independently, generally on species that had already increased their size. There was an overall significant correlation between SSD, male body size and male genital size and complexity, although some lineages with complex genitalia had low SSD, and some small species with complex genitalia had no SSD. Our results suggest that the origin of the higher evolutionary variance of male body size may be due to lack of constraints rather than to sexual selection, that may start to act in species with already larger males due to random variation.


Effect of daily zinc supplementation on child mortality in southern Nepal: a community-based, cluster randomised, placebo-controlled trial.
Zinc supplementation can reduce subsequent morbidity in children recovering from diarrhoea and respiratory illness in developing countries. However, whether routine supplementation would decrease morbidity and mortality in populations with zinc deficiency is unclear. We assessed the effect of daily zinc supplementation on children in southern Nepal. We did a community-based, cluster-randomised, double-masked, placebo-controlled, 2x2 factorial trial in children aged 1-35 months. Treatment groups were placebo, iron and folic acid, zinc, and iron and folic acid with zinc, with daily doses of 12.5 mg iron, 50 microg folic acid, and 10 mg zinc. Study staff gave children tablets on 2 days each week and left tablets with caregivers for other days. All children received vitamin A supplementation twice per year. Results of the iron arm of the trial have been reported previously. Between October, 2001, and January, 2006, 41,276 children were enrolled into the placebo (n=20,308) or zinc (n=20,968) groups and were followed-up for 60,636.3 person-years. The primary outcome was child mortality, and analyses were by intention to treat. Daily reports of signs and symptoms of common morbidities in stratified random subsamples of children were assessed every week for 12 months. This study is registered at ClinicalTrials.gov, number NCT00109551. 2505 children refused to continue the trial and 3219 children were lost to follow-up. There was no significant difference in mortality between the zinc and placebo groups (316 vs 333 deaths; hazard ratio 0.92, 95% CI 0.75-1.12). Zinc had no effect on mortality in children younger than 12 months (181 vs 168 deaths; 1.04, 0.83-1.31); mortality was lower, but not statistically significantly so, in older children receiving zinc (135 vs 165; 0.80, 0.60-1.06). The frequency and duration of diarrhoea, persistent diarrhoea, dysentery, and acute lower respiratory infections did not differ between the groups. Total mortality of children receiving zinc supplementation was not significantly different from that of children receiving placebo. Further data are needed from other populations with endemic zinc deficiency to confirm the potential age-specific effects reported in this study.


DNA barcoding amphibians and reptiles.
Only a few major research programs are currently targeting COI barcoding of amphibians and reptiles (including chelonians and crocodiles), two major groups of tetrapods. Amphibian and reptile species are typically old, strongly divergent, and contain deep conspecific lineages which might lead to problems in species assignment with incomplete reference databases. As far as known, there is no single pair of COI primers that will guarantee a sufficient rate of success across all amphibian and reptile taxa, or within major subclades of amphibians and reptiles, which means that the PCR amplification strategy needs to be adjusted depending on the specific research question. In general, many more amphibian and reptile taxa have been sequenced for 16S rDNA, which for some purposes may be a suitable complementary marker, at least until a more comprehensive COI reference database becomes available. DNA barcoding has successfully been used to identify amphibian larval stages (tadpoles) in species-rich tropical assemblages. Tissue sampling, DNA extraction, and amplification of COI is straightforward in amphibians and reptiles. Single primer pairs are likely to have a failure rate between 5 and 50% if taxa of a wide taxonomic range are targeted; in such cases the use of primer cocktails or subsequent hierarchical usage of different primer pairs is necessary. If the target group is taxonomically limited, many studies have followed a strategy of designing specific primers which then allow an easy and reliable amplification of all samples.


Humoral and blood pressure effects of the angiotensin converting enzyme inhibitor ramipril in essential hypertension.
The humoral and antihypertensive activities of the angiotensin converting enzyme (ACE) inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S, 3S, 5S)-2-azabicyclo[3.3.0] octane-3-carboxylic acid (ramipril, Hoe 498) were investigated in 10 patients with essential hypertension (WHO stage I or II). After a 7-day placebo period, the patients were treated with 5 mg ramipril orally once daily for 14 days. Peak serum concentrations of the active metabolite M1 (dicarboxylic acid) of 5.4-62.0 ng/ml were observed 2-6 h after the first oral dose. The maximum ACE inhibition of 95% was reached 2-4 h after the first oral dose, inhibition exceeded 70% 24 h after dosing. The maximum drop in the systolic and diastolic blood pressure (random zero sphygmomanometer) was measured 4 h after ramipril (p less than 0.02, p less than 0.01), but blood pressure on days 7 and 14 of the treatment period was not different from pretreatment values. Automatically recorded blood pressure results showed a marked reduction of both systolic and diastolic blood pressure during treatment compared to placebo. No side effects occurred. From the present data it is concluded that ramipril is a potent ACE inhibitor in hypertensive patients and that further controlled studies are required for the evaluation of the antihypertensive effect of 5 mg ramipril in essential hypertension.


Inferring models of opinion dynamics from aggregated jury data.
Jury deliberations provide a quintessential example of collective decision-making, but few studies have probed the available data to explore how juries reach verdicts. We examine how features of jury dynamics can be better understood from the joint distribution of final votes and deliberation time. To do this, we fit several different decision-making models to jury datasets from different places and times. In our best-fit model, jurors influence each other and have an increasing tendency to stick to their opinion of the defendant's guilt or innocence. We also show that this model can explain spikes in mean deliberation times when juries are hung, sub-linear scaling between mean deliberation times and trial duration, and unexpected final vote and deliberation time distributions. Our findings suggest that both stubbornness and herding play an important role in collective decision-making, providing a nuanced insight into how juries reach verdicts, and more generally, how group decisions emerge.


In vitro effector activity of Pneumocystis murina-specific T-cytotoxic-1 CD8+ T cells: role of granulocyte-macrophage colony-stimulating factor.
Human immunodeficiency virus (HIV)-related opportunistic infections continue to occur in patients who are newly diagnosed with HIV infection, those in the early course of highly active antiretroviral therapy or nonadherent to HIV care, and other immunosuppressed individuals. One of the most common opportunistic infections in these patients is Pneumocystis pneumonia. CD8+ T cells are recruited to the lung after P. carinii infection and have been associated with both lung injury and host defense. This variability may be due to subpopulations of CD8+ T cells recruited to the lung. We have previously shown using adoptive transfer studies that in vivo-generated T-cytotoxic-1 (Tc1) CD8+ T cells, defined by the secretion of gamma interferon (IFN-gamma), have effector activity against Pneumocystis spp. in vitro as well as in vivo. To better understand the mechanisms of these effects, we generated, expanded, and tested Tc1 and Tc2 CD8+ T cells specific for P. murina ex vivo. Tc1-polarized CD8+ T cells secreted higher levels of IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) and lower levels of interleukin-4 (IL-4), IL-5, IL-10, and IL-13 than Tc2 CD8+ T cells when stimulated with P. murina antigen. Moreover, Tc1 CD8+ T cells demonstrated enhanced effector activity in a macrophage-mediated killing assay which was independent of cell contact. The augmentation in macrophage-mediated P. murina killing was significantly abrogated when GM-CSF was neutralized in the Tc1 CD8+ T cells. These data support the possibility that antigen-specific GM-CSF secretion is critical for effector activity of P. murina-specific Tc1 CD8+ T cells in vitro.


Population trends in achalasia diagnosis and management: a changing paradigm.
The Chicago Classification of esophageal motility disorders improved the differentiation of achalasia subtypes and tailored treatment. Heller myotomy (HM) and pneumatic dilation are two established treatments for achalasia. Peroral endoscopic myotomy (POEM) has become a third definitive option and is on the rise. Using the National Inpatient Sample (NIS) database, we evaluated patients hospitalized with achalasia and associated surgical and endoscopic interventions from 2013 to 2017 and compared patients undergoing HM versus POEM. The NIS database was queried to include patients with achalasia. Patients who underwent HM, POEM (only 2017 due to lack of distinct procedure code in 2013), pneumatic dilation, or esophagectomy were identified. Adverse events during the hospitalization were also queried using diagnosis codes. From 2013 to 2017, patients hospitalized with achalasia increased from 16 850 to 19 485. There were reductions in the number of esophageal dilations (10.6-5.4%, P < 0.001) and HM (18.7-13.1%, P < 0.001). In 2017, 580 POEMs were performed. Compared with patients undergoing HM in 2017, patients who had POEM had higher mean age > 64 (P = 0.004), Charlson comorbidity index (P < 0.001), disease severity (P < 0.001), and likelihood of mortality (P < 0.001). There were no differences in length of stay, mortality, or total costs between the HM and POEM groups. Patients hospitalized with achlasia increased from 2013 to 2017, possibly due to the growth and accessibility of high-resolution esophageal manometry. As expertise in POEM increases, the number of POEM performed is anticipated to rise with possible further reductions in other treatment modalities for achalasia.


[Secondary treatment of digital mutilations: reconstruction or amputation].
Decision for stump improvement, shortening or reconstruction after finger mutilation is based on multiple factors. Some of them belong to the patient, age, psychological background, job and leisure activities and cosmetic expectation. Others belong to the injury, its mechanism and the anatomical lesions. Abstention, prostheses and rehabilitation are among the options. Conventional techniques are not to be forgotten as age remains an ultimate frontier in microsurgical reconstruction to obtain a good sensory result. Function and appearance are closely linked for a useful and a used hand.


Regulation and function of Cav3.1 T-type calcium channels in IGF-I-stimulated pulmonary artery smooth muscle cells.
Arterial smooth muscle cells enter the cell cycle and proliferate in conditions of disease and injury, leading to adverse vessel remodeling. In the pulmonary vasculature, diverse stimuli cause proliferation of pulmonary artery smooth muscle cells (PASMCs), pulmonary artery remodeling, and the clinical condition of pulmonary hypertension associated with significant health consequences. PASMC proliferation requires extracellular Ca(2+) influx that is intimately linked with intracellular Ca(2+) homeostasis. Among the primary sources of Ca(2+) influx in PASMCs is the low-voltage-activated family of T-type Ca(2+) channels; however, up to now, mechanisms for the action of T-type channels in vascular smooth muscle cell proliferation have not been addressed. The Ca(v)3.1 T-type Ca(2+) channel mRNA is upregulated in cultured PASMCs stimulated to proliferate with insulin-like growth factor-I (IGF-I), and this upregulation depends on phosphatidylinositol 3-kinase/Akt signaling. Multiple stimuli that trigger an acute rise in intracellular Ca(2+) in PASMCs, including IGF-I, also require the expression of Ca(v)3.1 Ca(2+) channels for their action. IGF-I also led to cell cycle initiation and proliferation of PASMCs, and, when expression of the Ca(v)3.1 Ca(2+) channel was knocked down by RNA interference, so were the expression and activation of cyclin D, which are necessary steps for cell cycle progression. These results confirm the importance of T-type Ca(2+) channels in proper progression of the cell cycle in PASMCs stimulated to proliferate by IGF-I and suggest that Ca(2+) entry through Ca(v)3.1 T-type channels in particular interacts with Ca(2+)-dependent steps of the mitogenic signaling cascade as a central component of vascular remodeling in disease.