Diagnosis of potential stressors adversely affecting benthic communities in New Bedford Harbor, MA (USA).
Diagnosing the causes of impaired ecosystems in the marine environment is critical for effective management action. When ecological impairment is based on toxicological or biological criteria (i.e., degraded benthic community composition or toxicity test results), managers are faced with the additional problem of diagnosing the cause of impairment before plans can be initiated to reduce the pollutant loading. We evaluated a number of diagnostic tools to determine their ability to identify pollutants in New Bedford Harbor (NBH), Massachusetts (USA), using a modified version of the US Environmental Protection Agency's (USEPA) stressor identification (SI) guidance. In this study, we linked chemical sources and toxic chemicals in the sediment with spatial concentration studies; we also linked toxic chemicals in the sediment with toxicity test results using toxicity identification and evaluation (TIE) studies. We used geographical information systems (GIS) maps to determine sources and to aid in determining spatially integrated inorganic nitrogen (SIIN). The SIIN values of reference and test estuaries were quantified and compared. Using this approach, we determined that toxic chemicals continue to be active stressors in NBH and that a moderate nutrient stress exists, but we were unable to link the nutrient stressor with a source. Also excess sedimentation was evaluated, but it does not appear to be an active stressor in this harbor. The research included an evaluation of the effectiveness of tools under development that may be used to evaluate stressors in water bodies. We found that the following tools were useful in diagnosing active stressors: toxicity tests, toxicity identification and evaluation (TIE) methods, comparison of grain size-normalized total organic carbon (TOC) ratios with reference sites, and comparison of SIIN with reference sites. This approach allowed us to successfully evaluate stressors in NBH retrospectively; however, a limitation in using retrospective data sets is that the approach may underestimate current or newly emerging stressors.


A survey of practices during cardiopulmonary bypass in India: An Indian association of cardiovascular and thoracic anesthesiologist endeavor.
Cardiac anesthesiologists play a key role during the conduct of cardiopulmonary bypass (CPB). There are variations in the practice of CPB among extracorporeal technologists in India. Aims: The aim of this survey is to gather information on variations during the conduct of CPB in India. This was an online conducted survey by Indian College of Cardiac Anaesthesia, which is the research and academic wing of the Indian Association of Cardiovascular Thoracic Anaesthesiologists. Senior consultants heading cardiac anesthesia departments in both teaching and nonteaching centers (performing at least 15 cases a month) were contacted using an online questionnaire fielded using SurveyMonkey™ software. There were 33 questions focusing on institute information, perfusion practices, blood conservation on CPB; monitoring and anesthesia practices. The response rate was 74.2% (187/252). Fifty-one (26%) centers were teaching centers; 18% centers performed more than 1000 cases annually. Crystalloid solution was the most common priming solution used. Twenty-three percent centers used corticosteroids routinely; methylprednisone was the most commonly used agent. The cardioplegia solution used by most responders was the one available commercially containing high potassium St. Thomas solution (55%), followed by Del Nido cardioplegia (33%). Majority of the responders used nasopharyngeal site to monitor intraoperative patient temperature. Antifibrinolytics were commonly used only in patients who were at high risk for bleeding by 51% of responders, while yet, another 39% used them routinely, and 11% never did. About 59% of the centers insist on only fresh blood (<7 days old) when blood transfusion was indicated. The facility to use vaporizer on CPB was available in 62% of the centers. All the teaching centers or high volume centers in India had access to transesophageal echocardiography probe and echo machine, with 51% using them routinely and 38% using them at least sometimes. There is a wide heterogeneity in CPB management protocols among various Indian cardiac surgery centers. The survey suggests that adherence to evidence-based and internationally accepted practices appears to be more prevalent in centers that have ongoing teaching programs and/or have high volumes, strengthening the need to devise guidelines by appropriate body to help bring in uniformity in CPB management to ensure patient safety and high quality of clinical care for best outcomes.


Vitamin D Deficiency Is Associated With an Increased Likelihood of Incident Depression in Community-Dwelling Older Adults.
To examine the prospective relationship between vitamin D status and incident depression in a large cohort of nondepressed community-dwelling older people. Longitudinal study examining the relationship between vitamin D levels at baseline (wave 1) and incident depression at 2 and 4 years (waves 2 and 3), embedded within the Irish Longitudinal Study on Aging. Participants with depression at wave 1 were excluded. Logistic regression models reporting odds ratios were used to analyze the longitudinal association of vitamin D categories with incident depression. Analysis was weighted for attrition. Almost 4000 community-dwelling people aged ≥50 years. A score ≥9 on the Center for Epidemiologic Studies Depression Scale-8 at wave 2 or 3 was indicative of incident depression. Vitamin D analysis was performed using liquid chromatography-tandem mass spectrometry and deficiency, insufficiency, and sufficiency were defined as <30, 30-50, and >50 nmol/L, respectively. The incident depression group (400/3965) had a higher likelihood of baseline vitamin D deficiency (proportional estimation 19.4) [95% confidence interval (CI) 15.1-24.7] vs [12.4 (95% CI 11.1-14.0); Z = 3.93; P < .001]. Logistic regression models demonstrated that participants with vitamin D deficiency had a significantly higher likelihood of incident depression (odds ratio 1.75, 95% CI 1.24-2.46; t = 3.21; P = .001). This finding remained robust after controlling for relevant covariates including physical activity, chronic disease burden, cardiovascular disease and antidepressant use. This study demonstrates that vitamin D deficiency is associated with a significant increase in the likelihood of developing depression in later life. These findings are important, given the high prevalence of vitamin D deficiency among older people, the fact that supplementation has a low risk of toxicity or side effects, as well as the significant adverse effect depression can have on functional status and longevity in later life.


Interannual atmospheric variability forced by the deep equatorial Atlantic Ocean.
Climate variability in the tropical Atlantic Ocean is determined by large-scale ocean-atmosphere interactions, which particularly affect deep atmospheric convection over the ocean and surrounding continents. Apart from influences from the Pacific El Niño/Southern Oscillation and the North Atlantic Oscillation, the tropical Atlantic variability is thought to be dominated by two distinct ocean-atmosphere coupled modes of variability that are characterized by meridional and zonal sea-surface-temperature gradients and are mainly active on decadal and interannual timescales, respectively. Here we report evidence that the intrinsic ocean dynamics of the deep equatorial Atlantic can also affect sea surface temperature, wind and rainfall in the tropical Atlantic region and constitutes a 4.5-yr climate cycle. Specifically, vertically alternating deep zonal jets of short vertical wavelength with a period of about 4.5 yr and amplitudes of more than 10 cm s(-1) are observed, in the deep Atlantic, to propagate their energy upwards, towards the surface. They are linked, at the sea surface, to equatorial zonal current anomalies and eastern Atlantic temperature anomalies that have amplitudes of about 6 cm s(-1) and 0.4 °C, respectively, and are associated with distinct wind and rainfall patterns. Although deep jets are also observed in the Pacific and Indian oceans, only the Atlantic deep jets seem to oscillate on interannual timescales. Our knowledge of the persistence and regularity of these jets is limited by the availability of high-quality data. Despite this caveat, the oscillatory behaviour can still be used to improve predictions of sea surface temperature in the tropical Atlantic. Deep-jet generation and upward energy transmission through the Equatorial Undercurrent warrant further theoretical study.


Development and characterization of eight polymorphic microsatellite loci from Pistacia lentiscus L. (Anacardiaceae).
We have developed a set of eight polymorphic nuclear microsatellite markers for the Mediterranean shrub Pistacia lentiscus by means of an enriched library method. Characterization for the eight loci was carried out on 42 individuals from two populations sampled in southern Spain. The overall number of alleles detected was 59, ranging from three to 13 per locus. Expected heterozygosity per locus and population ranged from 0.139 to 0.895. Two loci albeit only in one population (Seville) departed significantly from Hardy-Weinberg equilibrium expectations and no linkage disequilibrium between pairs of loci was detected. These markers will be used in studies of gene flow across a fragmented landscape.


Phase I and pharmacologic study of SNS-032, a potent and selective Cdk2, 7, and 9 inhibitor, in patients with advanced chronic lymphocytic leukemia and multiple myeloma.
SNS-032 is a highly selective and potent inhibitor of cyclin-dependent kinases (Cdks) 2, 7, and 9, with in vitro growth inhibitory effects and ability to induce apoptosis in malignant B cells. A phase I dose-escalation study of SNS-032 was conducted to evaluate safety, pharmacokinetics, biomarkers of mechanism-based pharmacodynamic (PD) activity, and clinical efficacy. Parallel cohorts of previously treated patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) received SNS-032 as a loading dose followed by 6-hour infusion weekly for 3 weeks of each 4-week course. There were 19 patients with CLL and 18 with MM treated. Tumor lysis syndrome was the dose-limiting toxicity (DLT) for CLL, the maximum-tolerated dose (MTD) was 75 mg/m(2), and the most frequent grade 3 to 4 toxicity was myelosuppression. One patient with CLL had more than 50% reduction in measurable disease without improvement in hematologic parameters. Another patient with low tumor burden had stable disease for four courses. For patients with MM, no DLT was observed and MTD was not identified at up to 75 mg/m(2), owing to early study closure. Two patients with MM had stable disease and one had normalization of spleen size with treatment. Biomarker analyses demonstrated mechanism-based PD activity with inhibition of Cdk7 and Cdk9, decreases in Mcl-1 and XIAP expression level, and associated CLL cell apoptosis. SNS-032 demonstrated mechanism-based target modulation and limited clinical activity in heavily pretreated patients with CLL and MM. Further single-agent, PD-based, dose and schedule modification is warranted to maximize clinical efficacy.


Warmer Environments Increase Implicit Mental Workload Even If Learning Efficiency Is Enhanced.
Climate change is one of the most important issues for humanity. To defuse this problem, it is considered necessary to improve energy efficiency, make energy sources cleaner, and reduce energy consumption in urban areas. The Japanese government has recommended an air conditioner setting of 28°C in summer and 20°C in winter since 2005. The aim of this setting is to save energy by keeping room temperatures constant. However, it is unclear whether this is an appropriate temperature for workers and students. This study examined whether thermal environments influence task performance over time. To examine whether the relationship between task performance and thermal environments influences the psychological states of participants, we recorded their subjective rating of mental workload along with their working memory score, electroencephalogram (EEG), heart rate variability, skin conductance level (SCL), and tympanum temperature during the task and compared the results among different conditions. In this experiment, participants were asked to read some texts and answer questions related to those texts. Room temperature (18, 22, 25, or 29°C) and humidity (50%) were manipulated during the task and participants performed the task at these temperatures. The results of this study showed that the temporal cost of task and theta power of EEG, which is an index for concentration, decreased over time. However, subjective mental workload increased with time. Moreover, the low frequency to high frequency ratio and SCL increased with time and heat (25 and 29°C). These results suggest that mental workload, especially implicit mental workload, increases in warmer environments, even if learning efficiency is facilitated. This study indicates integrated evidence for relationships among task performance, psychological state, and thermal environment by analyzing behavioral, subjective, and physiological indexes multidirectionally.


Spontaneous and catheter-induced secondary coronary artery dissection: a single-centre experience.
6497 consecutive patients who underwent coronary angiography in our institution in a three-year period were analysed. Spontaneous coronary artery dissection was noted in five, and unexpected dissection secondary to coronary arteriography in three patients. All patients with spontaneous dissection presented clinically as myocardial infarction. Three patients (two of them with spontaneous dissection) underwent urgent coronary artery bypass grafting. Percutaneous coronary intervention was successful in two patients with spontaneous and in one with unexpected secondary dissection. One patient with spontaneous and one with secondary dissection were treated medically after failed intervention. In conclusion, spontaneous coronary artery dissection is rare, but not exceptional. Its true incidence might have been underestimated before the advent of coronary interventions in acute myocardial infarction. Survival of all our patients, in contrast to earlier reports on mortality rates up to 50%, may be attributed to the benefits of modern surgery and interventional cardiology.


Potential role of the intestinal microbiota in programming health and disease.
The composition of the microbiota varies according to prenatal events, delivery methods, infant feeding, infant care environment, and antibiotic use. Postnatal gut function and immune development are largely influenced by the intestinal microbiota. Emerging evidence has shown that early microbiota colonization may influence the occurrence of later diseases (microbial programming). The vast majority of microbial species (commensals) give rise to symbiotic host-bacterial interactions that are fundamental for human health. However, changes in the composition of the gut microbiota (dysbiosis) may be associated with several clinical conditions, including obesity and metabolic diseases, autoimmune diseases and allergy, acute and chronic intestinal inflammation, irritable bowel syndrome (IBS), allergic gastroenteritis (e.g., eosinophilic gastroenteritis and allergic IBS), and necrotizing enterocolitis. Based on recent advances, modulation of gut microbiota with probiotics, prebiotics, or fermented dairy products has been suggested as a treatment of, or prevention for, different disorders such as IBS, infectious diarrhea, allergic disease, and necrotizing enterocolitis.


Dyrk1A phosphorylates p53 and inhibits proliferation of embryonic neuronal cells.
Down syndrome (DS) is associated with many neural defects, including reduced brain size and impaired neuronal proliferation, highly contributing to the mental retardation. Those typical characteristics of DS are closely associated with a specific gene group "Down syndrome critical region" (DSCR) on human chromosome 21. Here we investigated the molecular mechanisms underlying impaired neuronal proliferation in DS and, more specifically, a regulatory role for dual-specificity tyrosine-(Y) phosphorylation-regulated kinase 1A (Dyrk1A), a DSCR gene product, in embryonic neuronal cell proliferation. We found that Dyrk1A phosphorylates p53 at Ser-15 in vitro and in immortalized rat embryonic hippocampal progenitor H19-7 cells. In addition, Dyrk1A-induced p53 phosphorylation at Ser-15 led to a robust induction of p53 target genes (e.g. p21(CIP1)) and impaired G(1)/G(0)-S phase transition, resulting in attenuated proliferation of H19-7 cells and human embryonic stem cell-derived neural precursor cells. Moreover, the point mutation of p53-Ser-15 to alanine rescued the inhibitory effect of Dyrk1A on neuronal proliferation. Accordingly, brains from embryonic DYRK1A transgenic mice exhibited elevated levels of Dyrk1A, Ser-15 (mouse Ser-18)-phosphorylated p53, and p21(CIP1) as well as impaired neuronal proliferation. These findings suggest that up-regulation of Dyrk1A contributes to altered neuronal proliferation in DS through specific phosphorylation of p53 at Ser-15 and subsequent p21(CIP1) induction.


Gracilone, a new sesquiterpene lactone from Tanacetum gracile (Tansies).
The methanolic extract of the Tanacetum gracile afforded the isolation of new sesquiterpene lactone, named gracilone (1) along with four known compounds as 14α-taraxeran-3-one (2), 14α-taraxeran-3-ol (3), apigenin (4) and β-sitosterol (5). The structure of compound 1 was elucidated on the basis of 1D, 2D NMR and MS spectroscopic analysis. Antimicrobial, antioxidant and anticancer activities of all compounds were evaluated, from which gracilone (1) showed a moderate antibacterial activity, while apigenin (4) showed comparatively more antibacterial activity against both gram-positive and gram-negative tested strains.


Donor-Acceptor Properties of a Single-Molecule Altered by On-Surface Complex Formation.
Electron donor-acceptor molecules are of outstanding interest in molecular electronics and organic solar cells for their intramolecular charge transfer controlled via electrical or optical excitation. The preservation of their electronic character in the ground state upon adsorption on a surface is cardinal for their implementation in such single-molecule devices. Here, we investigate by atomic force microscopy and scanning tunneling microscopy a prototypical system consisting of a π-conjugated tetrathiafulvalene-fused dipyridophenazine molecule adsorbed on thin NaCl films on Cu(111). Depending on the adsorption site, the molecule is found either in a nearly undisturbed free state or in a bound state. In the latter case, the molecule adopts a specific adsorption site, leading to the formation of a chelate complex with a single Na+ alkali cation pulled out from the insulating film. Although expected to be electronically decoupled, the charge distribution of the complex is drastically modified, leading to the loss of the intrinsic donor-acceptor character. The chelate complex formation is reversible with respect to lateral manipulations, enabling tunable donor-acceptor molecular switches activated by on-surface coordination.


Mechanism of complement-dependent haemolysis via the lectin pathway: role of the complement regulatory proteins.
Mannan-binding lectin (MBL) is an acute phase protein which activates the classical complement pathway at the level of C4 and C2 via two novel serine proteases homologous to C1r and C1s. We recently reported that haemolysis via this lectin pathway requires alternative pathway amplification. The present experiments sought to establish the basis for this requirement, and hence focused on the activity and regulation of the C3 convertases. Complement activation was normalized between the lectin and classical pathways such that identical amounts of bound C4 and of haemolytically active C4,2 sites were present on the indicator cells. Under these conditions, there was markedly less haemolysis, associated with markedly less C3 and C5 deposited, via the lectin pathway than via the classical pathway, particularly when alternative pathway recruitment was blocked by depletion of factor D. Lectin pathway activation was associated with enhanced binding in the presence of MBL of complement control proteins C4bp and factor H to C4b and C3b, respectively, with decreased stability of the C3-converting enzyme C4b,2a attributable to C4bp. Immunodepletion of C4bp and/or factor H increased lectin pathway haemolysis and allowed lysis to occur in absence of the alternative pathway. Thus, the lectin pathway of humans is particularly susceptible to the regulatory effects of C4bp and factor H, due at least in part to MBL enhancement of C4bp binding to C4b and factor H binding to C3b.


Clinical, Bacterial, and Prosthodontic Parameters After Implant Abutment Disinfection Using Nd:YAG, Er,Cr:YSGG, Chlorhexidine, and Conventional Steam Before Prosthesis Delivery.
Objective: This 1-year prospective clinical trial was designed to assess the microbial, clinical, radiographic, and prosthetic parameters after disinfection of the implant abutment connection using Er,Cr:YSGG (erbium, chromium-doped: yttrium, scandium, gallium, and garnet) and Nd:YAG (neodymium-doped yttrium, aluminum, garnet). Materials and methods: All the patients were divided into four groups; Group I: Nd:YAG laser, Group II: Er,Cr:YSGG laser, Group III: 0.2% chlorhexidine (CHx), and Group IV: steam disinfection. Peri-implant parameters assessed included peri-implant bleeding scores (PIBS), peri-implant plaque scores (PIPS), peri-implant pocket depth (PIPD), and crestal bone loss (CBL). The peri-implant plaque samples were acquired to perform microbiological analysis to assess Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, respectively. All measurements were completed at baseline, 6 months, and 12 months postsurgery. Multiple groups were compared with the help of the Bonferroni post-hoc adjustment test (p < 0.01). Logistic regression models were utilized to assess the association between age, oral hygiene practices (brushing and flossing), and duration of implant function. Results: At the baseline level, there were no discernible differences in the peri-implant parameters between the study groups (p > 0.05). At the 6-month (p < 0.01) and 12-month (p < 0.001) follow-ups, all four study groups demonstrated a significant improvement in PIPS and PIBS, with no significant differences between the groups at baseline (p > 0.05). Based on an intergroup comparison, Group I (Nd:YAG) showed a significant decrease in PIBS when compared with the other groups. Group II showed a considerable decrease in PIPD and enhancements in CBL when compared with Groups I, III, and IV (p < 0.01). At the 6- and 12-month follow-up periods, P. gingivalis and T. denticola reduction were found to be statistically higher in Group II, whereas P. gingivalis and T. forsythia mean log CFU/mL were found to be statistically higher in Group I. Conclusions: Nd:YAG and Er,Cr:YSGG lasers both outperformed CHx and steam disinfection in terms of clinical, peri-implant, and prosthetic results when used to clean implant abutments.


The temporary colostomy.
The indications for a temporary transverse colostomy are examined in the light of a year's experience of the Stomatherapy Service at Groote Schuur Hospital. A surgical technique, which employs primary colocutaneous suture and which may be used in both emergency and elective situations, is described.


Inhibition of membrane-type serine protease 1/matriptase by natural and synthetic protease inhibitors.
Membrane-type serine protease 1 (MT-SP1), identical to matriptase, is a recently identified type II transmembrane serine protease. MT-SP1/matriptase is of considerable interest for the development, homeostasis, and cancer invasion and metastasis of epithelial tissues. The administration of inhibitors for MT-SP1/matriptase may be effective to suppress the development of tumors where the enzyme may be involved. In the present study, we produced a secreted form of recombinant MT-SP1/matriptase (ekMT-SP1s) that can be activated by enterokinase in vitro and investigated the inhibitory ability of various protease inhibitors toward the recombinant enzyme. The enterokinase-treated ekMT-SP1s (active ekMT-SP1s) cleaved various peptidyl-4-methylcoumaryl-7-amide (MCA) substrates with arginine (or lysine) residue at position P1, and the best substrate was t-butyloxycarbonyl (Boc)-Gln-Ala-Arg-MCA. The specificity for the synthetic and natural substrates of the active ekMT-SP1s was in good agreement with that of the natural enzyme. Endogenous protease inhibitors tested, except for antithrombin III, showed no or little inhibition on the cleavage of Boc-Gln-Ala-Arg-MCA by the active ekMT-SP1s. Aprotinin showed strong inhibitory activity toward the cleavage. Food-derived inhibitors, such as soybean trypsin inhibitor, Bowman-Birk inhibitor, and lima bean trypsin inhibitor inhibited it, while chicken ovomucoid did not. Synthetic inhibitors tested inhibited it, and among them, the inhibitory effect of FOY-305 was strongest. The present findings provide important information for the suppression of cancer invasion and metastasis for which MT-SP1/matriptase is responsible.


Voyager pour apprendre : les Canadiens reçus docteurs en médecine à Paris au XIXe siècle.
Thirteen Canadians obtained a doctoral degree from the Faculty of Medicine of Paris between 1822 and 1905. Their studies in France played a decisive role in some of the major trends of 19th-century Canadian history: the formation of a French-Canadian professional bourgeoisie, the formalization of diplomatic ties between Canada and France, the development of bacteriology in America, and the rise of French-Canadian nationalism at the turn of the 20th century. This article traces the careers of these medical doctors by using unpublished sources, mainly their student files and doctoral theses, located through the Pierre Moulinier database and made available by the Bibliothèque Interuniversitaire de Santé of the Université Paris-Descartes. By examining these doctors' travels to Paris, it shows the impact on the Canadian medical profession of the relationship between a former North American colony and its former imperial capital.


LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function.
We have determined the cistrome and transcriptome for the nuclear receptor liver receptor homolog-1 (LRH-1) in exocrine pancreas. Chromatin immunoprecipitation (ChIP)-seq and RNA-seq analyses reveal that LRH-1 directly induces expression of genes encoding digestive enzymes and secretory and mitochondrial proteins. LRH-1 cooperates with the pancreas transcription factor 1-L complex (PTF1-L) in regulating exocrine pancreas-specific gene expression. Elimination of LRH-1 in adult mice reduced the concentration of several lipases and proteases in pancreatic fluid and impaired pancreatic fluid secretion in response to cholecystokinin. Thus, LRH-1 is a key regulator of the exocrine pancreas-specific transcriptional network required for the production and secretion of pancreatic fluid.


Longitudinal Policy and Systems Change as a Component of Community Power.
Community power represents the ability of communities to develop, sustain, and grow the capacity to participate in and advance systems change that addresses health inequities but is difficult to assess because of its multifaceted, longitudinal nature. Using California's school-based Local Control Funding Formula (LCFF) as an example, this article examines the interconnectedness of longitudinal policy and systems changes as one approach to understanding and visualizing evolving community power. Data on policy and systems changes were collected during the 10-year, place-based Building Healthy Communities initiative and coded using thematic analysis. Related changes within sites and between community and state levels were linked to show how changes built and overlapped over time. Around 45% of changes were interconnected and cascaded to build momentum within sites; in addition, a substantial proportion of statewide changes (68%) overlapped with community ones. The state-level LCFF policy led to multiple community-based changes over time, involving ongoing engagement from various community groups across communities. Local implementation of the LCFF policy change was used to illustrate the usefulness of connecting community-driven policy and systems changes over time to explore the dynamics of community power and address some of the limitations of that approach.


Improving Vertical Jump Profiles Through Prescribed Movement Plans.
Mayberry, JK, Patterson, B, and Wagner, P. Improving vertical jump profiles through prescribed movement plans. J Strength Cond Res 32(6): 1619-1626, 2018-Developing practical, reliable, and valid methods for monitoring athlete wellness and injury risk is an important goal for trainers, athletes, and coaches. Previous studies have shown that the countermovement vertical jump (CMJ) test is both a reliable and valid metric for evaluating an athlete's condition. This study examines the effectiveness of prescribed workouts on improving the quality of movement during CMJ. The data set consists of 2,425 pairs of CMJ scans for high school, college, and professional athletes training at a privately owned facility. During each scan, a force plate recorded 3 ground reaction force (GRF) measurements known to impact CMJ performance: eccentric rate of force development (ERFD), average vertical concentric force (AVCF), and concentric vertical impulse (CVI). After an initial scan, coaches either assigned the athlete a specific 1- or 2-strength movement plan (treatment group) or instructed the athlete to choose their own workouts (control group) before returning for a follow-up scan. A multivariate analysis of covariance (MANCOVA) revealed significant differences in changes to GRF measurements between athletes in the 2 groups after adjusting for the covariates sex, sport, time between scans, and rounds of workout completed. A principal component analysis of GRF measurements further identified 4 primary groups of athlete needs and the results provide recommendations for effective workout plans targeting each group. In particular, split squats increase CVI and decrease ERFD/AVCF; deadlifts increase AVCF and decrease CVI; alternating squats/split squats increase ERFD/CVI and decrease AVCF; and alternating squats/deadlifts increase ERFD/AVCF and decrease CVI.


Automatic 3D segmentation of individual facial muscles using unlabeled prior information.
Segmentation of facial soft tissues is required for surgical planning and evaluation, but this is laborious using manual methods and has been difficult to achieve with digital segmentation methods. A new automatic 3D segmentation method for facial soft tissues in magnetic resonance imaging (MRI) images was designed, implemented, and tested. A region growing algorithm based on local energy functions, using intensity similarities among neighboring regions as criteria, was developed. This local energy function includes the neighborhood relationships not only in the same dataset but from other training datasets. This approach differs from previous studies where the prior information was represented as manual segmented atlases. In this study, a consensus of many datasets, none of which was labeled a priori, is used to guide the segmentation. The method was tested in MRI scans for adult facial structures. MRI scans were obtained from the Alzheimer's disease neuroimaging initiative database. Comparison was made to results from expert manual segmentation and region growing techniques. The volumetric overlap between automated 3D segmentation results and the ground truth was 82.6% for masseter and 78.8% for temporalis tissues. A new automated method to segment various facial soft tissues was implemented and the results compared with standard region growing results. The proposed method shows 3.9% improvement in accuracy over the standard method. Reduction in segmentation errors was consistently achieved in MRI scans.


Longitudinal changes in domains of physical activity during childhood and adolescence: A systematic review.
Physical activity (PA) participation is prone to decline during adolescence. An understanding of the domains of PA that are susceptible to decline may support a more targeted approach to PA and health promotion. The aim of this study was to review longitudinal trends in participation in four PA domains during childhood and adolescence: organized PA, non-organized PA, active transport and active chores. Systematic review. 5517 research articles were sourced from five electronic databases (covering January 1997-April 2018). Eligibility criteria included repeated measurements of at least one PA domain among the same participants (5-18years of age). 23 studies were included, cumulatively reporting data from 27,231 participants. Few studies had a low risk of bias (n=6). Most studies of active transport reported an increase in participation during childhood, no change in the transition to adolescence, and no change or decline during adolescence. Most studies of organized PA reported an increase during childhood, an increasing or stable pattern in the transition to adolescence, and no change or decline during adolescence. Non-organized PA participation tended to remain stable among adolescent girls and decline among adolescent boys. Active chores increased during the transition to adolescence and then stabilized. Potential strategies for PA promotion among youth may include targeting non-organized PA among adolescent boys or organized PA among late adolescent boys and girls. However, there is a continuing need for high-quality, longitudinal studies of participation in PA domains, particularly non-organized PA and active chores. PROSPERO Registration: CRD42017076888.


Effects of temporal association on recognition memory.
The influence of temporal association on the representation and recognition of objects was investigated. Observers were shown sequences of novel faces in which the identity of the face changed as the head rotated. As a result, observers showed a tendency to treat the views as if they were of the same person. Additional experiments revealed that this was only true if the training sequences depicted head rotations rather than jumbled views; in other words, the sequence had to be spatially as well as temporally smooth. Results suggest that we are continuously associating views of objects to support later recognition, and that we do so not only on the basis of the physical similarity, but also the correlated appearance in time of the objects.


Robust tests for treatment effects based on censored recurrent event data observed over multiple periods.
We derive semiparametric methods for estimating and testing treatment effects when censored recurrent event data are available over multiple periods. These methods are based on estimating functions motivated by a working "mixed-Poisson" assumption under which conditioning can eliminate subject-specific random effects. Robust pseudoscore test statistics are obtained via "sandwich" variance estimation. The relative efficiency of conditional versus marginal analyses is assessed analytically under a mixed time-homogeneous Poisson model. The robustness and empirical power of the semiparametric approach are assessed through simulation. Adaptations to handle recurrent events arising in crossover trials are described and these methods are applied to data from a two-period crossover trial of patients with bronchial asthma.


Therapeutic effect of cevimeline on dry eye in patients with Sjögren's syndrome: a randomized, double-blind clinical study.
Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by salivary and lacrimal glandular destruction leading to symptoms of dry mouth and dry eye. Dryness can also occur in the absence of glandular destruction. Patients with SS have autoantibodies that bind to muscarinic acetylcholine receptors in the exocrine glands. Recently, a muscarinic acetylcholine receptor agonist, cevimeline, has been approved for use against symptoms of dry mouth in patients with SS. In this study, the efficacy of cevimeline in improving symptoms of dry eye was examined. Prospective, randomized, double-blind, multi-center clinical study. Sixty patients were randomly assigned to three groups-placebo; cevimeline, 20 mg three times daily; or cevimeline, 30 mg three times daily-and received treatment for 4 weeks. Patients were evaluated before treatment, at week 2, at the end of treatment, and at the end of a 2- to 4-week follow-up period. Compared with the placebo, statistically significant differences were seen with cevimeline, 20 mg three times daily, in subjective symptoms, tear dynamics, condition of the corneoconjunctival epithelium, and global improvement rating. No difference was found among the three groups regarding the safe use of the drug. These results indicate that cevimeline, 20 mg three times daily, is safe and effective in improving symptoms of dry eye in patients with SS. Additional studies, with larger patient populations, are needed to further assess the effectiveness of cevimeline for dry eye.


The effect of high energy (HZE) particle radiation (40Ar) on aging parameters of mouse hippocampus and retina.
Eight month old C57BL6 mice were exposed (head only) to 0.5 rad or 50 rads of Argon particles at the Lawrence Berkeley Radiation Facility, CA. Neuromotor performance was assessed monthly for six months beginning twelve weeks post-irradiation using a "string test". The decline in motor performance was dose-related and none of the animals was able to complete the task after four months of testing. Morphological changes were monitored six and twelve months post-irradiation by light and electron microscopy. The synaptic density in the CA-1 area of the hippocampus decreased six and twelve months after irradiation. The decrease after twelve months was less than after six months. The width of the outer nuclear layer (ONL) of the retina increased with increasing dose. The number of blood vessels between the ONL and the ganglion layer decreased twelve months after irradiation and this area did not show significant accumulation of age pigment.


Cortical and thalamic connectivity to the second auditory cortex of the cat is resilient to the onset of deafness.
It has been well established that following sensory loss, cortical areas that would normally be involved in perceiving stimuli in the absent modality are recruited to subserve the remaining senses. Despite this compensatory functional reorganization, there is little evidence to date for any substantial change in the patterns of anatomical connectivity between sensory cortices. However, while many auditory areas are contracted in the deaf, the second auditory cortex (A2) of the cat undergoes a volumetric expansion following hearing loss, suggesting this cortical area may demonstrate a region-specific pattern of structural reorganization. To address this hypothesis, and to complement existing literature on connectivity within auditory cortex, we injected a retrograde neuronal tracer across the breadth and cortical thickness of A2 to provide the first comprehensive quantification of projections from cortical and thalamic auditory and non-auditory regions to the second auditory cortex, and to determine how these patterns are affected by the onset of deafness. Neural projections arising from auditory, visual, somatomotor, and limbic cortices, as well as thalamic nuclei, were compared across normal hearing, early-deaf, and late-deaf animals. The results demonstrate that, despite previously identified changes in A2 volume, the pattern of projections into this cortical region are unaffected by the onset of hearing loss. These results fail to support the idea that crossmodal plasticity reflects changes in the pattern of projections between cortical regions and provides evidence that the pattern of connectivity that supports normal hearing is retained in the deaf brain.


Quantitative phase microscopy using dual-plane in-line digital holography.
We present detailed theoretical evaluation and thorough experimental investigation of quantitative phase imaging using our previously demonstrated dual-plane in-line digital holographic microscopy technique [Opt. Lett. 35, 3426 (2010)]. This evaluation is based on the recording of two interferograms at slightly different planes and numerically reconstructing the object information. The zero-order diffracted wave is eliminated by using the method of subtraction of average intensity of the entire hologram, and the twin-image diffracted wave is removed by Fourier domain processing of the two recorded holograms. Experiments are performed using controlled amplitude and phase objects and human muscle cells to demonstrate the potential of this technique.


Analysis of type IV pilus and its associated motility in Myxococcus xanthus using an antibody reactive with native pilin and pili.
Myxococcus xanthus possesses a social gliding motility that requires type IV pili (TFP). According to the current model, M. xanthus pili attach to an external substrate and retract, pulling the cell body forward along their long axis. By analogy with the situation in other bacteria employing TFP-dependent motility, M. xanthus pili have been assumed to be composed of pilin (PilA) subunits, but this has not previously been confirmed. The first 28 amino acids of the M. xanthus PilA protein share extensive homology with the N-terminal oligomerization domain of pilins in other bacterial species. To facilitate purification, the authors engineered a truncated form of M. xanthus PilA lacking the first 28 amino acids and purified this protein in soluble form. Polyclonal antibody generated against this protein was reactive with native pilin and pili. Using this antibody, it was confirmed that TFP of M. xanthus are indeed composed of PilA, and that TFP are located unipolarly and required for social gliding motility via retraction. Using tethering as well as motility assays, details of pili function in M. xanthus social motility were further examined.


Escherichia coli alkaline phosphatase fails to acquire disulfide bonds when retained in the cytoplasm.
The cysteines of the Escherichia coli periplasmic enzyme alkaline phosphatase, which are involved in disulfide bonds in the native enzyme, were found to be fully reduced when the protein was retained in the cytoplasm. Under these circumstances the cysteines remained reduced for at least several minutes after the synthesis of the protein was completed. This contrasted with the normally exported protein, wherein disulfide bonds formed rapidly. Disulfide bond formation accompanied export and processing. The implications of these findings for the inactivity of the enzyme in the cytoplasm are discussed.


NADH reoxidation does not control glycolytic flux during exposure of respiring Saccharomyces cerevisiae cultures to glucose excess.
Introduction of the Lactobacillus casei lactate dehydrogenase (LDH) gene into Saccharomyces cerevisiae under the control of the TPI1 promoter yielded high LDH levels in batch and chemostat cultures. LDH expression did not affect the dilution rate above which respiro-fermentative metabolism occurred (Dc) in aerobic, glucose-limited chemostats. Above Dc, the LDH-expressing strain produced both ethanol and lactate, but its overall fermentation rate was the same as in wild-type cultures. Exposure of respiring, LDH-expressing cultures to glucose excess triggered simultaneous ethanol and lactate production. However, the specific glucose consumption rate was not affected, indicating that NADH reoxidation does not control glycolytic flux under these conditions.


TNF-like weak inducer of apoptosis inhibition is comparable to IL-13 blockade in ameliorating atopic dermatitis inflammation.
Targeting IL-13 is highly efficacious in patients with Th2-biased atopic dermatitis (AD), but inhibition of other inflammatory molecules might also limit disease. We investigated the importance of the TNF family cytokine TNF-like weak inducer of apoptosis (TWEAK; TNFSF12) to keratinocyte dysregulation and the pathogenesis of AD in mice and also tested if blocking TWEAK has a similar therapeutic effect as targeting IL-13. Conditional knockout mice lacking Fn14 (TNFRSF12A), the receptor for TWEAK, only in keratinocytes, were repetitively sensitized with house dust mite allergen and analyzed for AD-like skin inflammation. To determine the translational potential, wild-type mice with AD were therapeutically treated with anti-TWEAK and/or anti-IL-13 antibodies, and skin inflammation was assessed. Mice deficient in Fn14 in keratinocytes were resistant to developing maximal clinical features of AD, exhibiting reduced epidermal hyperplasia and dermal thickening, less skin infiltration of immune cells, and downregulated inflammatory gene expression. Moreover, therapeutic neutralization of TWEAK in wild-type mice with AD reduced all of the pathological features to a comparable extent as blocking IL-13. The activity of TWEAK in keratinocytes contributes to AD development, and neutralizing TWEAK represents a future potential therapeutic option in human AD similar to targeting IL-13.


Thromboxane synthase deficiency improves insulin action and attenuates adipose tissue fibrosis.
Thromboxane A2, an arachidonic acid-derived eicosanoid generated by thromboxane synthase (TBXAS), plays critical roles in hemostasis and inflammation. However, the contribution of thromboxane A2 to obesity-linked metabolic dysfunction remains incompletely understood. Here, we used in vitro and mouse models to better define the role of TBXAS in metabolic homeostasis. We found that adipose expression of Tbxas and thromboxane A2 receptor (Tbxa2r) was significantly upregulated in genetic and dietary mouse models of obesity and diabetes. Expression of Tbxas and Tbxa2r was detected in adipose stromal cells, including macrophages. Furthermore, stimulation of macrophages with interferon-γ or resistin factors known to be upregulated in obesity induced Tbxas and Tbxa2r expression. Mice lacking Tbxas had similar weight gain, food intake, and energy expenditure. However, loss of Tbxas markedly enhanced insulin sensitivity in mice fed a low-fat diet. Improvement in glucose homeostasis was correlated with the upregulated expression of multiple secreted metabolic regulators (Ctrp3, Ctrp9, and Ctrp12) in the visceral fat depot. Following a challenge with a high-fat diet, Tbxas deficiency led to attenuated adipose tissue fibrosis and reduced circulating IL-6 levels without adipose tissue macrophages being affected; however, these changes were not sufficient to improve whole body insulin action. Together, our results highlight a novel, diet-dependent role for thromboxane A2 in modulating peripheral tissue insulin sensitivity and adipose tissue fibrosis.


Life expectancy estimation with breast cancer: bias of the declining exponential function and an alternative to its use.
Life expectancy gain (LEG) is an outcome measure commonly estimated with a declining exponential function in a Markov model. The accuracy of such estimates has not been objectively evaluated. To compare LEGs from declining exponential function estimates with those calculated from population data, using published screening mammography studies as examples. SEER-based population data are used to compare LEG calculation with declining exponential function estimation and empiric population data in a new model, the "nested" Markov. Analyses of the LEG of mammographic screening based on the declining exponential function significantly overestimate LEGs for younger women and underestimate them for older women. Because of offsetting errors, all-age analyses paradoxically appear accurate. Declining exponential function estimates of LEGs for chronic diseases with low mortality rates and long time horizons are liable to significant bias, especially with limited age cohorts.


Anterior entrapment syndromes.
The anterior tarsal tunnel syndrome is best described as a chronic irritation or compression of the deep peroneal nerve. The pathogenesis, etiology, and diagnostic features of the anterior tarsal tunnel as it effects the foot are discussed with its complexities. Case histories are presented.


Snap-buckling in asymmetrically constrained elastic strips.
When a flat elastic strip is compressed along its axis, it is bent in one of two possible directions via spontaneous symmetry breaking, forming a cylindrical arc. This is a phenomenon well known as Euler buckling. When this cylindrical section is pushed in the other direction, the bending direction can suddenly reverse. This instability is called "snap-through buckling" and is one of the elementary shape transitions in a prestressed thin structure. Combining experiments and theory, we study snap-buckling of an elastic strip with one end hinged and the other end clamped. These asymmetric boundary constraints break the intrinsic symmetry of the strip, generating mechanical behaviors, including largely hysteretic but reproducible force responses and switchlike discontinuous shape changes. We establish the set of exact analytical solutions to fully explain all our major experimental and numerical findings. Asymmetric boundary conditions arise naturally in diverse situations when a thin object is in contact with a solid surface at one end. The introduction of asymmetry through boundary conditions yields new insight into complex and programmable functionalities in material and industrial design.


Small RNAs Are Implicated in Regulation of Gene and Transposable Element Expression in the Protist Trichomonas vaginalis.
Trichomonas vaginalis is the causative agent of trichomoniasis, the most prevalent nonviral sexually transmitted infection worldwide. Repetitive elements, including transposable elements (TEs) and virally derived repeats, comprise more than half of the ∼160-Mb T. vaginalis genome. An intriguing question is how the parasite controls its potentially lethal complement of mobile elements, which can disrupt transcription of protein-coding genes and genome functions. In this study, we generated high-throughput RNA sequencing (RNA-Seq) and small RNA-Seq data sets in triplicate for the T. vaginalis G3 reference strain and characterized the mRNA and small RNA populations and their mapping patterns along all six chromosomes. Mapping the RNA-Seq transcripts to the genome revealed that the majority of genes predicted within repetitive elements are not expressed. Interestingly, we identified a novel species of small RNA that maps bidirectionally along the chromosomes and is correlated with reduced protein-coding gene expression and reduced RNA-Seq coverage in repetitive elements. This novel small RNA family may play a regulatory role in gene and repetitive element expression. Our results identify a possible small RNA pathway mechanism by which the parasite regulates expression of genes and TEs and raise intriguing questions as to the role repeats may play in shaping T. vaginalis genome evolution and the diversity of small RNA pathways in general.IMPORTANCE Trichomoniasis, caused by the protozoan Trichomonas vaginalis, is the most common nonviral sexually transmitted infection in humans. The millions of cases each year have sequelae that may include complications during pregnancy and increased risk of HIV infection. Given its evident success in this niche, it is paradoxical that T. vaginalis harbors in its genome thousands of transposable elements that have the potential to be extremely detrimental to normal genomic function. In many organisms, transposon expression is regulated by the activity of endogenously expressed short (∼21 to 35 nucleotides [nt]) small RNA molecules that effect gene silencing by targeting mRNAs for degradation or by recruiting epigenetic silencing machinery to locations in the genome. Our research has identified small RNA molecules correlated with reduced expression of T. vaginalis genes and transposons. This suggests that a small RNA pathway is a major contributor to gene expression patterns in the parasite and opens up new avenues for investigation into small RNA biogenesis, function, and diversity.


Pasteurella canis osteomyelitis and cutaneous abscess after a domestic dog bite.
The genus Pasteurella is part of the normal oral flora of many animals, including domestic cats and dogs. In humans, Pasteurella may cause complications ranging from cellulitis to septicemia but rarely causes osteomyelitis or septic arthritis after bites and/or scratches by cats and dogs. Although Pasteurella multocida is a common cause of infection, other Pasteurella species have also been cultured from wounds in humans. We describe here, a case of a cutaneous abscess and acute osteomyelitis associated with P canis after a domestic dog bite. To our knowledge, no previous case of P canis has been reported as the cause of acute osteomyelitis in humans.


Real-Time Personalised Pharmacokinetic-Pharmacodynamic Modelling in Propofol Anesthesia through Bayesian Inference.
Pharmacological models describe a patient's response to the administration of a medicinal drug based on parameters derived from population studies. However, considerable inter-patient variability exists, such that population models may underperform when used to predict the actual response of a specific individual. In applications which demand predictive accuracy-such as target-controlled infusion of anesthetic agents-modeling uncertainty may reduce system dependability and introduce clinical risk. Our work investigates the use of Bayesian inference, implemented through a particle filter algorithm, to refine a prior model of propofol pharmacokinetics-pharmacodynamics and estimate patient-specific parameters in real-time. We report here on an observational clinical study conducted on 40 adults undergoing general anesthesia, where we evaluated the performance of Bayesian inference-personalized models in forecasting forward trends of depth of anesthesia (Bispectral Index) measurements and compared it with that of a traditional population-based pharmacological model. Our results show a significant reduction in prediction error metrics for the patient-specific models. Our study demonstrates the viability and practical implementability of Bayesian inference as a tool for real-time intra-operative estimation of personalized pharmacological models in anesthesia applications.


Linear Instability of Turbulent Channel Flow.
Laminar-turbulent pattern formation is a distinctive feature of the intermittency regime in subcritical plane shear flows. By performing extensive numerical simulations of the plane channel flow, we show that the pattern emerges from a spatial modulation of the turbulent flow, due to a linear instability. We sample over many realizations the linear response of the fluctuating turbulent field to a temporal impulse, in the regime where the turbulent flow is stable, just before the onset of the instability. The dispersion relation is constructed from the ensemble-averaged relaxation rates. As the instability threshold is approached, the relaxation rate of the least damped modes eventually reaches zero. The method allows, despite the presence of turbulent fluctuations and without any closure model, for an accurate estimation of the wave vector of the modulation at onset.


Water management improvement in PEM fuel cells via addition of PDMS or APTES polymers to the catalyst layer.
Water management is one of the obstacles in the development and commercialization of proton exchange membrane fuel cells (PEMFCs). Sufficient humidification of the membrane directly affects the PEM fuel cell performance. Therefore, 2 different hydrophobic polymers, polydimethylsiloxane (PDMS) and (3-Aminopropyl) triethoxysilane (APTES), were tested at different percentages (5, 10, and 20 wt.%) in the catalyst layer. The solution was loaded onto the surface of a 25 BC gas diffusion layer (GDL) via the spraying method. The performance of the obtained fuel cells was compared with the performance of the commercial catalyst. Characterizations of each surface, including different amounts of PDMS and APTES, were performed via scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) analyses. Molecular bond characterization was examined via Fourier transform infrared spectroscopy (FTIR) analysis and surface hydrophobicity was measured via contact angle measurements. The performance of the fuel cells was evaluated at the PEM fuel cell test station and the 2 hydrophobic polymers were compared. Surfaces containing APTES were found to be more hydrophobic. Fuel cells with PDMS performed better when compared to those with APTES. Fuel cells with 5wt.% APTES with a current density of 321.31 mA/cm 2 and power density of 0.191 W/cm 2 , and 10wt.% PDMS with a current density of 344.52 mA/cm 2 and power density of 0.205 W/cm 2 were the best performing fuel cells at 0.6V.


Inhibition of substance-P-induced histamine release from rat peritoneal mast cells by 8-methoxypsoralen plus long-wave ultraviolet light irradiation: decreased intracellular calcium as a possible mechanism.
Rat peritoneal mast cells purified on a Percoll gradient were activated by substance P (SP) and the effect of 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet light (UVA) irradiation (8-MOP/UVA) on SP-induced histamine release from the cells was investigated. At a concentration of 10(-5) M SP caused a significant histamine release. 8-MOP or UVA irradiation alone at the doses used in the present study neither induced a histamine release nor had any significant effects on SP-induced histamine release from mast cells. On the other hand, 8-MOP/UVA inhibited SP-induced histamine release; this inhibition was dependent on the UVA doses (0.5-3.0 J/cm2) and was accompanied by a reduction in the rise in intracellular calcium concentrations ([Ca2+]i). These data suggest that 8-MOP/UVA inhibits histamine release from SP-activated rat peritoneal mast cells by suppressing the rise in [Ca2+]i.


[Effectiveness of 3 ways method in intra-arterial infusion chemotherapy for advanced or recurrent cervical cancer with or without radiotherapy].
We analyzed 58 cases of advanced or recurrent cervical cancer treated with intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. Two separate IAIC regimens were administered since 1985: group I consisted of 5-FU + MMC +/- ADR (30 patients) and group II consisted of CDDP + MMC +/- 5-FU (28 patients). The tip of a catheter was placed in the bifurcation of the abdominal aorta (1 way method: 45 patients regimen II: 15) between 1977-1984. We have used selective catheterization (2 ways method: 9) since 1995 in order to get good drug distribution. However we experienced grade 4 toxic effect of cutaneous and pain with this method, so we have used a 3 ways method (4 patients) since 1998. The two-year survival rete was 60% with the 1 way method, and 67% with the 2 ways method and regimen II. Severe adverse effects (grade 3 + 4) were found in 53, 56, 0%, respectively, by each of the three methods (1, 2, 3 ways) hematologically, 13, 22, 0% in gastrointestinally, 0, 44, 0% in cutaneously and 0, 56, 0% in pain or neurotoxicity. These data suggest that IAIC by the 3 ways method is a useful treatment for advanced or recurrent cervical cancer. However, one should check the blood flow distribution periodically, and control concentration of drugs.


Platinum complexes act as shielding agents against virus infection.
We determine that the substitution-inert polynuclear platinum complex (PPC) TriplatinNC is an antiviral agent and protects cells from enterovirus 71 and human metapneumovirus infection. This protection occurs through the formation of adducts with cell-surface glycosaminoglycans. Our detailed mechanistic investigation demonstrates that TriplatinNC blocks viral entry by shielding cells from virus attack, opening new directions for metalloshielding antiviral drug development.


Predictive utility of prior positive urine cultures.
A patient's prior urine cultures are often considered when choosing empiric antibiotic therapy for a suspected urinary tract infection. We sought to evaluate how well previous urine cultures predict the identity and susceptibility of organisms in a patient's subsequent urine cultures. We conducted a multinational, multicenter, retrospective cohort study, including 22 019 pairs of positive urine cultures from 4351 patients across 2 healthcare systems in Toronto, Ontario, and Chicago, Illinois. We examined the probability of the same organism being identified from the same patient's positive urine culture as a function of time elapsed from the previous positive urine specimen; in cases where the same organism was identified we also examined the likelihood of the organism exhibiting the same or better antimicrobial susceptibility profile. At 4-8 weeks between cultures, the correspondence in isolate identity was 57% (95% confidence interval [CI], 55%-59%), and at >32 weeks it was 49% (95% CI, 48%-50%), still greater than expected by chance (P < .001). The susceptibility profile was the same or better in 83% (95% CI, 81%-85%) of isolate pairs at 4-8 weeks, and 75% (95% CI, 73%-77%) at >32 weeks, still greater than expected by chance (P < .001). Despite high local rates of ciprofloxacin resistance in urine isolates across all patients (40%; 95% CI, 39.5%-40.5%), ciprofloxacin resistance was <20% among patients with a prior ciprofloxacin sensitive organism and no subsequent fluoroquinolone exposure. A patient's prior urine culture results are useful in predicting the identity and susceptibility of a current positive urine culture. In areas of high fluoroquinolone resistance, ciprofloxacin can be used empirically when prior urine culture results indicate a ciprofloxacin-susceptible organism and there has been no history of intervening fluoroquinolone use.


Characterization of the effects of the vasopressin V2 receptor on sweating, fluid balance, and performance during exercise.
A regulatory effect of arginine vasopressin (AVP) on sweat water conservation has been hypothesized but not definitively evaluated. AVP-mediated insertion of sweat and salivary gland aquaporin-5 (AQP5) water channels through activation of the vasopressin type 2 receptor (V2R) remains an attractive, yet unexplored, mechanism that could result in a more concentrated sweat with resultant decreased water loss. Ten runners participated in a double-blind randomized control treadmill trial under three separate pharmacological conditions: a placebo, V2R agonist (0.2 mg desmopressin), or V2R antagonist (30 mg tolvaptan). After a familiarization trial, runners ran for 60 min at 60% of peak speed followed by a performance trial to volitional exhaustion. Outcome variables were collected at three exercise time points: baseline, after the steady-state run, and after the performance run. Body weight losses were <2% across all three trials. Significant pharmacological condition effects were noted for urine osmolality [F = 84.98; P < 0.0001] and urine sodium concentration ([Na(+)]) [F = 38.9; P < 0.0001], which verified both pharmacological activation and inhibition of the V2R at the kidney collecting duct. Plasma osmolality and [Na(+)] demonstrated significant exercise (F = 26.0 and F = 11.1; P < 0.0001) and condition (F = 5.1 and F = 3.8; P < 0.05) effects (osmolality and [Na(+)], respectively). No significant exercise or condition effects were noted for either sweat or salivary [Na(+)]. Significant exercise effects were noted for plasma [AVP] (F = 22.3; P < 0.0001), peak core temperature (F = 103.3; P < 0.0001), percent body weight change (F = 6.3; P = 0.02), plasma volume change (F = 21.8; P < 0.0001), and thirst rating (F = 78.2; P < 0.0001). Performance time was not altered between conditions (P = 0.80). In summary, AVP acting at V2R does not appear to regulate water losses from body fluids other than renal excretion during exercise.


Feeling Hurt: Pain Sensitivity is Correlated With and Modulated by Social Distress.
Social distress, resulting from loss or threat to social relationships, shares similar psychological and neuronal processes with physical pain. Recent evidence demonstrated that social distress may have an impact on pain. The current study aimed to further assess the relationship between these 2 phenomena. Sixty healthy participants were randomly assigned to inclusion, noninclusion, or exclusion conditions of Cyberball, a virtual ball tossing game used to induce social distress. Pain and unpleasantness in response to noxious electrical stimuli were assessed before and after Cyberball manipulation. Psychological characteristics were evaluated by the Experiences in Close Relationships Questionnaire and the neuroticism scale of Big Five Inventory. Significant correlations were found between social distress and pre-Cyberball unpleasantness thresholds: those who perceived the Cyberball task as more distressing demonstrated lower unpleasantness thresholds. Post-Cyberball manipulation pain intensity ratings, but not unpleasantness ratings, were lower in the inclusion condition. No associations were found between the psychological characteristic and the effects of Cyberball on pain or unpleasantness ratings. The current study results indicate that participants' pre-Cyberball unpleasantness threshold is related to their responsiveness to social distress and that physical pain may be modulated by social events. Further studies are needed to clarify the clinical relevance of these results.


Penetration of CD4 T cells by HIV-1. The CD4 receptor does not internalize with HIV, and CD4-related signal transduction events are not required for entry.
Receptor binding of HIV to the CD4 molecule is required for efficient infection of T cells, but the post-binding steps that result in penetration of HIV are not well understood. CD4 is induced to internalize upon T cell activation, and mAb to CD4 modify signal transduction and T cell activation as does HIV in some systems. It is not known whether HIV binding triggers CD4 endocytosis or whether signal transduction events are required for penetration. Selected inhibitors of signal transduction were evaluated for their effects on penetration using two assays that are dependent on penetration. After short term exposure to inhibitor and HIV, cells were analyzed for reverse-transcribed HIV DNA (DNA amplification assay), or productive infection is monitored (infectivity assay). Viral penetration was tested in the presence of H7 (protein kinase C inhibition), EGTA (extracellular Ca2+ chelation), cyclosporine A (inhibition of Ca2+/calmodulin-dependent activation), or pertussis toxin (inhibition of G protein function). All agents were used at concentrations that were inhibitory for their respective signal transduction pathways. None of the inhibitors affected viral penetration. We tracked the CD4 molecule with fluorescent probes that do not interfere with HIV binding in a system where CD4 T cells were saturated with HIV and the penetration event was relatively synchronized. Under conditions where detection of CD4 was more sensitive than the detection of HIV, HIV internalization was readily detected but CD4 internalization was not.


Exercise echocardiography.
Exercise echocardiography has been used for 30 years. It is now considered a consolidated technique for the diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). Of the stress echocardiography techniques, it represents the first choice for patients who are able to exercise. Given that the cost-effectiveness and safety of stress echocardiography are higher than those of other imaging techniques, its use is likely to be expanded further. Recent research has also proposed this technique for the evaluation of cardiac pathology beyond CAD. Although the role of new technology is promising, the assessment of cardiac function relies on good quality black and white harmonic images.


Common reasons for non-participation during the outcome measurement process: wheeled mobility service delivery quality improvement reporting.
The purpose of this paper is to describe non-participation during the outcome measurement step of the wheeled mobility service delivery process (WMSDP) based on the Functional Mobility Assessment (FMA)-Uniform Dataset (UDS) Registry. The WMSDP is a standard framework for the provision of wheeled mobility devices, and several factors influence the client's experience throughout the process. Patient-reported outcomes are one way to measure the client's experience as part of a quality improvement program. A retrospective descriptive study was conducted on the FMA-UDS Registry to measure the response rate during the outcome measurement step of the WMSDP and describe the reasons an individual did not complete the FMA-UDS. The FMA-UDS was examined at two time points: pre-delivery and post-delivery of the wheeled mobility device. As of September 2, 2021, 10,253 cases have been entered into the FMA-UDS Registry. 2,247 cases were no longer participating pre-delivery, and an additional 3,905 cases were no longer participating post-delivery. The most common reasons for non-participation in the FMA-UDS pre-delivery and post-delivery included: equipment not delivered; provider no longer participating in the FMA-UDS; funding issues; no new equipment; client opted out; loss in contact; deceased; returned equipment; and other. The type and frequency of non-participation in the outcome measurement step of the WMSDP is critical to understanding why individuals participate in outcome measures and provides insight into the barriers and facilitators for the implementation of quality improvement programs.


Adhesivity and rigidity of erythrocyte membrane in relation to wheat germ agglutinin binding.
Binding of the plant lectin wheat germ agglutinin (WGA) to erythrocyte membranes causes membrane rigidification. One of our objectives has been to directly measure the effects of WGA binding on membrane rigidity and to relate rigidification to the kinetics and levels of WGA binding. Our other objective has been to measure the strength of adhesion and mechanics of cell separation for erythrocytes bound together by WGA. The erythrocyte membrane rigidity was measured on single cells by micropipette aspiration. The slope of the suction pressure-length data for entry into the pipette provided the measure of the membrane extensional modulus. Data were collected for cells equilibrated with WGA solutions in the range of concentrations of 0.01-10 micrograms/ml. Erythrocyte-erythrocyte adherence properties were studied by micropipette separation of two-cell aggregates. First, a "test" cell was selected from a WGA solution by aspiration into a small micropipette, then transferred to a separate chamber that contained erythrocytes in WGA-free buffer. Here, a second cell was aspirated with another pipette and maneuvered into close proximity of the test cell surface, and adhesive contact was produced. The flaccid cell was separated from the test cell surface in steps at which the force of attachment was derived from the pipette suction pressure and cell geometry. In addition, we measured the time-dependent binding and release of fluorescently labeled WGA to single erythrocytes with a laser microfluorometry system. The results showed that the stiffening of the erythrocyte membrane and binding of fluorescently labeled WGA to the membrane surface followed the same concentration and time dependencies. The threshold concentration for membrane stiffening was at approximately 0.1 microgram/ml where the time course to reach equilibrium was close to 1 h. The maximal stiffening (almost 30-fold over the normal membrane elastic modulus) occurred in concentrations greater than 2 micrograms/ml where the time to reach equilibrium took less than 1 min. The WGA binding also altered the normal elastic membrane behavior into an inelastic, plastic-like response which indicated that mechanical extension of the membrane caused an increase in cross-linking within the surface plane. Similar to the stiffening effect, we observed that the membrane adhesivity of cells equilibrated with WGA solutions greatly increased with concentration greater than 0.1 microgram/ml.(ABSTRACT TRUNCATED AT 400 WORDS)


[Predominant Leptospira spp. serovars in serological diagnosis of canines and humans in the City of Uberlândia, State of Minas Gerais, Brazil].
This study aimed to verify the occurrence of the principal Leptospira spp. serovars in domestic dogs and humans, notified in 2008, and the main risk factors in a geographic approach to the disease in the City of Uberlândia, State of Minas Gerais, Brazil. Canine blood serum samples (n=268) from different districts, belonging to the Northern, Southern, Eastern, Western and Central Sanitary Districts of Uberlandia, were collected during an animal vaccination campaign against rabies, in August 2008. A geographic approach to the city was conducted, including evaluation of locations in peripheral areas, waste landfills, garbage collection, rodent notification, human leptospirosis cases and overflow flood areas, during 2008. Leptospirosis was diagnosed using the microscopic agglutination test (MAT), the gold standard for animal and human leptospirosis diagnosis. Dogs mainly reacted to Autumnalis (34.2%) and Tarassovi (23.7%) serovars, while in humans, predominance of Tarassovi serovars occurred in the cases registered. The occurrence of these serovars could be related to an infection source common to both species, or dogs could be the infection source for humans. The Eastern Sanitary District showed a greater number of reactive dogs. Leptospirosis occurred in dogs and humans of the City of Uberlandia in 2008. This often neglected disease must be prevented because represents a public health risk and resembles other endemic illness like dengue.


Presence of multiple genotypes in subjects with HPV-16 infection is highly associated with anal squamous intraepithelial lesions in HIV-1 infected males.
The aim of the study was to determine the prevalence of abnormal cytological findings, high risk (HR)-HPV genotypes and to identify factors associated with an abnormal cytological findings in a cohort of HIV-infected males. Retrospective observational study on HIV-infected male patients who performed screening in the absence of clinical symptoms. Cytological abnormalities were classified as atypical squamous cells of undetermined significance (ASC-US), low-grade(LSIL) or high high-grade squamous intraepithelial lesion (HSIL). Logistic regression models were used to identify predictors of having LSIL/HSIL. Among 875 pts, abnormal cytology findings were observed in 254 (29%, 95% CI: 26.1%-32.1%) subjects: 142 (16%) had LSIL and 49 (6%) HSIL. Overall, 581 (66%, 95%CI: 63.2%-69.5%) subjects had ≥1 HR-HPV type and 269 (31%) had ≥2 HR HPV types. Multivariate logistic regression showed that subjects with multiple HR-HPV genotypes (OR = 1.351, 95%CI: 1.005-2.111) and with HPV-16 type (OR = 2.032, 95%CI: 1.313-3.146) were more likely to have LSIL/HSIL in addition to a lower CD4+/CD8+ ratio, a previous diagnosis of syphilis and a positive viral load. In another multivariate model, the presence of multiple HPV types in subjects with HPV-16 type was associated with the highest adjusted OR of having a LSIL/HSIL (OR = 2.598, 95%CI: 1.460-4.624). In HIV-infected men, the prevalence of abnormal cytological findings was of 29% and of HR-HPV was 66%. The concomitant presence of HPV-16 and multiple HR genotypes was associated with an increased risk of abnormal cytological findings. These data highlight the importance of screening multiple HPV genotypes in HIV-infected patients.


Adolescent Sleep Duration, Variability, and Peak Levels of Achievement and Mental Health.
To inform public health recommendations for adolescent sleep, the amounts of sleep associated with the highest levels of academic achievement and mental health were examined. The degree to which daily variability in sleep duration represents an underappreciated but functionally significant sleep behavior also was tested. A total of 421 adolescents (Mage = 15.03 years) with Mexican-American backgrounds reported nightly sleep times for 2 weeks; approximately 80% repeated the same protocol 1 year later. Multilevel modeling indicated that the amount of sleep associated with the lowest levels of internalizing and externalizing symptoms was more than 1 hr greater than the amount associated with the highest levels of academic performance. Greater daily variability in sleep duration predicted greater symptomatology and mixed academic outcomes.


Natural history of fetal simple renal cysts detected in early pregnancy.
In this 12-year prospective, longitudinal study we investigated the natural history of fetal simple renal cysts identified by ultrasonography in early pregnancy. A detailed sonographic examination of the fetus was performed between January 1987 and June 1998 in 29,984 consecutive pregnancies at 14 to 16 weeks of gestation. Amniocenteses and chromosomal investigations were done in all cases in which a simple renal cyst was detected in the fetus. Followup sonography was done in all cases of renal cyst during pregnancy, infancy and, when indicated, childhood. Simple renal cysts were diagnosed at 14 to 16 weeks of gestation in 28 fetuses (1/1,100 pregnancies, 0.09%). In 25 fetuses the cysts resolved during pregnancy. In 2 fetuses the cysts remained benign but persisted postnatally and in 1 a renal cyst that was initially defined as simple was the first sign of unilateral multicystic dysplastic kidney. Except for nonseptated cystic hygroma in 1 fetus, none of the others had associated anomalies of the urinary or other organ systems and no chromosomal anomalies. Postnatal followup in all cases revealed healthy children. A fetal simple renal cyst can be identified by ultrasonography in early pregnancy. In the absence of associated anatomical or chromosomal abnormalities, the majority of cysts will resolve during pregnancy without any sequelae. Given the transient nature of most fetal simple renal cysts detected in early pregnancy, it is possible that these cysts represent a distinct entity within the spectrum of cystic kidney diseases.


Simian homologues of Epstein-Barr virus.
Gamma-herpesviruses closely related to the Epstein-Barr virus (EBV) are known to naturally infect Old World non-human primates and are classified in the same lymphocryptovirus (LCV) genera. LCV infecting humans and Old World primates share similar biology, and recent studies have demonstrated that these viruses share a similar repertoire of viral genes. Surprisingly, the latent infection genes associated with cell growth transformation demonstrate the most striking sequence divergence, but the functional mechanisms for these genes are generally well conserved. The recent discovery of LCVs naturally infecting New World primates has rewritten the old paradigm of LCV host range restriction to humans and Old World non-human primates, so that these viruses are more widespread than previously believed. However, the New World LCV genome has significant and interesting differences from EBV and other Old World LCVs despite similar biological properties. Thus, the simian homologues of EBV can provide an important animal model for studying LCV pathogenesis, and the similarities and differences that have evolved among these related viruses can provide a unique perspective towards a better understanding of EBV.


Antifreeze proteins in polar sea ice diatoms: diversity and gene expression in the genus Fragilariopsis.
Fragilariopsis is a dominating psychrophilic diatom genus in polar sea ice. The two species Fragilariopsis cylindrus and Fragilariopsis curta are able to grow and divide below freezing temperature of sea water and above average sea water salinity. Here we show that antifreeze proteins (AFPs), involved in cold adaptation in several psychrophilic organisms, are widespread in the two polar species. The presence of AFP genes (afps) as a multigene family indicated the importance of this group of genes for the genus Fragilariopsis, possibly contributing to its success in sea ice. Protein phylogeny showed the potential mobility of afps, which appear to have crossed kingdom and domain borders, occurring in Bacteria, diatoms, crustaceans and fungi. Our results revealed a broad distribution of AFPs not only in polar organisms but also in taxa apparently not related to cold environments, suggesting that these proteins may be multifunctional. The relevance of AFPs to Fragilariopsis was also shown by gene expression analysis. Under stress conditions typical for sea ice, with subzero temperatures and high salinities, F. cylindrus and F. curta strongly expressed selected afps. An E/G point mutation in the Fragilariopsis AFPs may play a role in gene expression activity and protein function.


Arrhythmias presenting in neonatal lupus.
Perfusion of human foetal heart with anti-Ro/SSA antibodies induces transient heart block. Anti-Ro/SSA antibodies may cross-react with T- and L-type calcium channels, and anti-p200 antibodies may cause calcium to accumulate in rat heart cells. These actions may explain a direct electrophysiological effect of these antibodies. Congenital complete heart block is the more severe manifestation of so-called "Neonatal Lupus". In clinical practice, it is important to distinguish in utero complete versus incomplete atrioventricular (AV) block, as complete AV block to date is irreversible, while incomplete AV block has been shown to be potentially reversible after fluorinated steroid therapy. Another issue is the definition of congenital AV block, as cardiologists have considered congenital blocks detected months or years after birth. We propose as congenital blocks detected in utero or within the neonatal period (0-27 days after birth). The possible detection of first degree AV block in utero, with different techniques, might be a promising tool to assess the effects of these antibodies. Other arrhythmias have been described in NL or have been linked to anti-Ro/SSA antibodies: first degree AV block, in utero and after birth, second degree (i.e. incomplete block), sinus bradycardia and QT prolongation, both in infants and in adults, ventricular arrhythmias (in adults). Overall, these arrhythmias have not a clinical relevance, but are important for research purposes.


Probable post-traumatic stress disorder and harmful alcohol use among male members of the British Police Forces and the British Armed Forces: a comparative study.
Background: British Armed Forces' and Police Forces' personnel are trained to operate in potentially traumatic conditions. Consequently, they may experience post-traumatic stress disorder (PTSD), which is often comorbid with harmful alcohol use. Objective: We aimed to assess the proportions, and associations, of probable PTSD and harmful alcohol use among a covariate-balanced sample of male military personnel and police employees. Methods: Proportions of probable PTSD, harmful alcohol use, and daily binge drinking, were explored using data from the police Airwave Health Monitoring Study (2007-2015) (N = 23,826) and the military Health and Wellbeing Cohort Study (phase 2: 2007-2009, phase 3: 2014-2016) (N = 7,399). Entropy balancing weights were applied to the larger police sample to make them comparable to the military sample on a range of pre-specified variables (i.e. year of data collection, age and education attainment). Multinomial and logistic regression analyses determined sample differences in outcome variables, and associated factors (stratified by sample). Results: Proportions of probable PTSD were similar in military personnel and police employees (3.67% vs 3.95%), although the large sample size made these borderline significant (Adjusted Odds Ratio (AOR): 0.84; 95% Confidence Intervals (CI): 0.72 to 0.99). Clear differences were found in harmful alcohol use among military personnel, compared to police employees (9.59% vs 2.87%; AOR: 2.79; 95% CI: 2.42 to 3.21). Current smoking, which was more prevalent in military personnel, was associated with harmful drinking and binge drinking in both samples but was associated with PTSD in military personnel only. Conclusions: It is generally assumed that both groups have high rates of PTSD from traumatic exposures, however, low proportions of PTSD were observed in both samples, possibly reflecting protective effects of unit cohesion or resilience. The higher level of harmful drinking in military personnel may relate to more prominent drinking cultures or unique operational experiences.


Cellular immunity in vitro. I. Immunologically mediated enhancement of macrophage bactericidal capacity.
An in vitro model of cellular immunity in the guinea pig was established. Animals were immunized with tubercle bacilli, bovine gamma globulin, or picrylated human serum albumin in complete Freund's adjuvant. Oil-induced peritoneal exudates from immune and control animals were cultured overnight with and without specific antigen. The cultures were washed and the macrophage monolayers were infected with Listeria monocytogenes. At intervals the monolayers were lysed and the numbers of viable intracellular bacteria were quantitated by pour plate cultures. Random monolayers were also evaluated in sequence by visually counting the intracellular bacteria on Gram-stained plates. Both methods demonstrated that the macrophages from immune animals had markedly enhanced listericidal activity when the peritoneal exudates were cultured with antigen before infection. Macrophage migration inhibition was also demonstrated under these conditions. The experiments reported here describe an in vitro model of cellular immunity which will allow separation and recombination of cell types and direct assay of cell products in efforts to elucidate further the mechanisms of the immunologically mediated enhancement of macrophage bactericidal capacity.


Unmet needs in paediatric psychopharmacology: Present scenario and future perspectives.
Paediatric psychopharmacology holds great promise in two equally important areas of enormous biomedical and social impact, namely the treatment of behavioural abnormalities in children and adolescents, and the prevention of psychiatric disorders with adolescent- or adult-onset. Yet, in striking contrast, pharmacological treatment options presently available in child and adolescent psychiatry are dramatically limited. The most important currently unmet needs in paediatric psychopharmacology are: the frequent off-label prescription of medications to children and adolescents based exclusively on data from randomized controlled studies involving adult patients; the frequent lack of age-specific dose, long-term efficacy and tolerability/safety data; the lack of effective medications for many paediatric psychiatric disorders, most critically autism spectrum disorder; the scarcity and limitations of randomized placebo-controlled trials in paediatric psychopharmacology; the unexplored potential for the prevention of psychiatric disorders with adolescent- and adult-onset; the current lack of biomarkers to predict treatment response and severe adverse effects; the need for better preclinical data to foster the successful development of novel drug therapies; and the effective dissemination of evidence-based treatments to the general public, to better inform patients and families of the benefits and risks of pharmacological interventions during development. Priorities and strategies are proposed to overcome some of these limitations, including the European Child and Adolescent Clinical Psychopharmacology Network, as an overarching Pan-European infrastructure aimed at reliably carrying out much needed psychopharmacological trials in children and adolescents, in order to fill the identified gaps and improve overall outcomes.


Pharmacological Treatment of Cannabis-Related Disorders: A Narrative Review.
Cannabis is the most widely used illicit psychoactive substance world-wide, yet no medication is approved for the treatment of intoxication, withdrawal, or cannabis use disorder (CUD). To comprehensively review the current state of knowledge. Search of the PubMed electronic data base and review of reference lists of relevant articles to identify controlled clinical trials of pharmacological treatment. The search identified 4 trials for specific intoxication symptoms (none for global intoxication), 7 trials for withdrawal, and 12 phase II trials for CUD. One or two trials each suggest that propranolol is effective for some intoxication symptoms, antipsychotics for cannabis-induced psychosis, and dronabinol (synthetic THC) and gabapentin for cannabis withdrawal. Of 10 medications and one medication combination studied in 12 trials for CUD, only two medications were effective (in single trials): gabapentin and Nacetylcysteine (in adolescents). Not effective were dronabinol and several antidepressants, anticonvulsants, and antianxiety medications. Three trials of antidepressants for CUD with comorbid depression gave inconsistent results. A trial of atomoxetine for CUD with comorbid ADHD showed no efficacy. Five trials of second-generation antipsychotics for CUD with comorbid schizophrenia showed none better than any other. Further research is needed to confirm the efficacy of gabapentin for withdrawal and gabapentin and N-acetylcysteine for CUD and to develop new medications for all 3 cannabis-related disorders.


The heterochronic microRNA let-7 inhibits cell motility by regulating the genes in the actin cytoskeleton pathway in breast cancer.
The heterochronic gene let-7 serves as a tumor suppressor microRNA by targeting various oncogenic pathways in cancer cells. Considerable evidence indicates that reduced expression of let-7 might be associated with poor clinical outcome in patients with cancer. Here, we report that the expression levels of three let-7 family members, let-7a, let-7b, and let-7g, were significantly decreased in the patients with breast cancer with lymph node metastasis compared with those without lymph node metastasis. Enforced expression of let-7b significantly inhibits breast cancer cell motility and affects actin dynamics. Using bioinformatic and experimental approaches, four genes in the actin cytoskeleton pathway, including PAK1, DIAPH2, RDX, and ITGB8, were identified as let-7 direct targets. Blocking the expression of PAK1, DIAPH2, and RDX significantly inhibits breast cancer cell migration induced by let-7b repression. Our results indicate that reconstitution of let-7 expression in tumor cells could provide a novel therapeutic strategy for the treatment of metastatic disease.


In vitro adhesion of Candida glabrata to denture base acrylic resin modified by glow-discharge plasma treatment.
This study evaluated the potential of plasma treatments to modify the surface chemistry and hydrophobicity of a denture base acrylic resin to reduce the Candida glabrata adhesion. Specimens (n = 54) with smooth surfaces were made and divided into three groups (n = 18): control - non-treated; experimental groups - submitted to plasma treatment (Ar/50 W; AAt/130 W). The effects of these treatments on chemical composition and surface topography of the acrylic resin were evaluated. Surface free energy measurements (SFE) were performed after the treatments and after 48 h of immersion in water. For each group, half (n = 9) of the specimens were preconditionated with saliva before the adhesion assay. The number of adhered C. glabrata was evaluated by cell counting after crystal violet staining. The Ar/50 W and AAt/130 W treatments altered the chemistry composition, hydrophobicity and topography of acrylic surface. The Ar/50 W group showed significantly lower C. glabrata adherence than the control group, in the absence of saliva. After preconditioning with saliva, C. glabrata adherence in experimental and control groups did not differ significantly. There were significant changes in the SFE after immersion in water. The results demonstrated that Ar/50 W treated surfaces have potential for reducing C. glabrata adhesion to denture base resins and deserve further investigation, especially to tailor the parameters to prolong the increased wettability.


Translational control of SCL-isoform expression in hematopoietic lineage choice.
We investigated the translational regulation of SCL protein expression and its role in hematopoietic lineage choice. We show that the expression of different SCL protein isoforms is regulated by signal transduction pathways that modulate translation initiation factor (eIF) function. A conserved small upstream open reading frame (uORF) in SCL transcripts acts as a cis-regulatory element for isoform expression. At the onset of erythroid differentiation, truncated SCL protein isoforms arise by alternative translation initiation and favor the erythroid lineage. In comparison, full-length SCL proteins are more efficient at enhancing the megakaryocyte lineage. Together, our studies unravel translational control as a novel mechanism regulating hematopoietic outcome.


Perinatal derivatives: How to best validate their immunomodulatory functions.
Perinatal tissues, mainly the placenta and umbilical cord, contain a variety of different somatic stem and progenitor cell types, including those of the hematopoietic system, multipotent mesenchymal stromal cells (MSCs), epithelial cells and amnion epithelial cells. Several of these perinatal derivatives (PnDs), as well as their secreted products, have been reported to exert immunomodulatory therapeutic and regenerative functions in a variety of pre-clinical disease models. Following experience with MSCs and their extracellular vesicle (EV) products, successful clinical translation of PnDs will require robust functional assays that are predictive for the relevant therapeutic potency. Using the examples of T cell and monocyte/macrophage assays, we here discuss several assay relevant parameters for assessing the immunomodulatory activities of PnDs. Furthermore, we highlight the need to correlate the in vitro assay results with preclinical or clinical outcomes in order to ensure valid predictions about the in vivo potency of therapeutic PnD cells/products in individual disease settings.


Development of a spanish-language version of the U.S. household food security survey module.
A survey module used to monitor the prevalence of household food insecurity and hunger in the United States was developed by a broadly based collaborative project with leadership from the USDA and the National Center for Health Statistics (NCHS). It has been administered annually since 1995 as a supplement to the Census Bureau's Current Population Survey (CPS) and is part of the National Health and Nutrition Examination Survey (NHANES) and other national surveys. Spanish is the second most common language in the United States, yet no standardized Spanish-language version of this instrument has yet been sanctioned by the relevant federal agencies. In the CPS, interviewers free-translate the questions while interviewing respondents who prefer to have the interview conducted in Spanish. National prevalence data indicate relatively high rates of food insecurity for Hispanic households, raising the question whether methodological artifacts may contribute to these rates. We analyzed eight Spanish-language versions of the instrument that have been used in published work for variability in wording and phrasing. We then conducted focus groups of low-income Spanish-speaking participants from Mexico, Central America, Puerto Rico and Cuba to refine a single Spanish-language instrument. We also employed professional translators to render the English instrument into "standard" Spanish; both instruments were then back-translated. The focus group-derived instrument uses simpler language and grammar; its back-translation integrity to the English version was slightly better than the professionally translated version. We provide the instrument for use and further testing by other investigators.


Epidemiological study to investigate potential interaction between physical and psychosocial factors at work that may increase the risk of symptoms of musculoskeletal disorder of the neck and upper limb.
To investigate potential interactions between physical and psychosocial risk factors in the workplace that may be associated with symptoms of musculoskeletal disorder of the neck and upper limb. 891 of 1514 manual handlers, delivery drivers, technicians, customer services computer operators, and general office staff reported on physical and psychosocial working conditions and symptoms of neck and upper limb disorders using a self administered questionnaire (59% return rate). Of the 869 valid questionnaire respondents, 564 workers were classified in to one of four exposure groups: high physical and high psychosocial, high physical and low psychosocial, low physical and high psychosocial, and low physical and low psychosocial. Low physical and low psychosocial was used as an internal reference group. The exposure criteria were derived from the existing epidemiological literature and models for physical and psychosocial work factors. The frequency and amplitude of lifting and the duration spent sitting while experiencing vibration were used as physical exposure criteria. Ordinal values of mental demands, job control, and social support with managers and coworkers were used as psychosocial exposure criteria. In the multivariate analyses, the highest and significant increase in risk was found in the high physical and high psychosocial exposure group for symptoms of hand or wrist and upper limb disorders after adjusting for years at the job, age, and sex. A potential interaction effect was found for the symptoms of the hand or wrist and upper limb disorders but not for the neck symptoms. This study showed that workers highly exposed to both physical and psychosocial workplace risk factors were more likely to report symptoms of musculoskeletal disorders than workers highly exposed to one or the other. The results suggest an interaction between physical and psychosocial risk factors in the workplace that increased the risk of reporting symptoms in the upper limbs. Psychosocial risk factors at work were more important when exposure to physical risk factors at work were high than when physical exposure was low. Ergonomic intervention strategies that aim to minimise the risks of work related musculoskeletal disorders of the upper limb should not only focus on physical work factors but also psychosocial work factors.