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Hypoplastic left heart syndrome (HLHS) is a relatively rare severe congenital heart defect (CHD) closely linked to other left ventricular outflow tract (LVOT) lesions including bicuspid aortic valve (BAV), one of the most common heart defects. While HLHS, BAV, and other LVOT lesions have a strong genetic underpinning, their genetic etiology remains poorly understood. Findings from a large-scale mouse mutagenesis screen showed HLHS has a multigenic etiology and is genetically heterogenous, explaining difficulties in identifying the genetic causes of HLHS. In Ohia mice, HLHS shows incomplete penetrance. Some mice exhibited small LV with normal aorta, and others a normal LV with hypoplastic aorta, indicating the LV hypoplasia is not hemodynamically driven. In Ohia mutants, HLHS was found to have a digenic modular construction, with mutation in a chromatin modifier causing the small LV phenotype and mutation in Pcdha9 causing the aorta/aortic valve hypoplasia. The Pcdha9 mutation alone can cause BAV, and in the human genome two common deletion copy number variants spanning PCDHA7-10 are associated with BAV. Hence the digenic etiology of HLHS can account for the close association of HLHS, a rare CHD, with BAV, one of the most common CHD. Functional analysis of Ohia HLHS heart tissue showed severe mitochondrial dysfunction in the small LV, while the normal size RV is also affected but milder, suggesting possible role in vulnerability of surgically palliated HLHS patients to heart failure. These findings suggest insights into the genetics of HLHS may yield new therapies for improving outcome for patients with HLHS.

Tauopathies, including Alzheimer’s disease, are characterized by retinal ganglion cell loss associated with amyloid and phosphorylated tau deposits. We investigated the functional impact of these histopathological alterations in the murine P301S model of tauopathy. Visual impairments were demonstrated by a decrease in visual acuity already detectable at 6 months, the onset of disease. Visual signals to the cortex and retina were delayed at 6 and 9 months, respectively. Surprisingly, the retinal output signal was delayed at the light onset and advanced at the light offset. This antagonistic effect, due to a dysfunction of the cone photoreceptor synapse, was associated with changes in the expression of the vesicular glutamate transporter and a microglial reaction. This dysfunction of retinal glutamatergic synapses suggests a novel interpretation for visual deficits in tauopathies and it highlights the potential value of the retina for the diagnostic assessment and the evaluation of therapies in Alzheimer’s disease and other tauopathies.

ObjectiveTerm congenital heart disease (CHD) neonates display abnormalities of brain structure and maturation, which are possibly related to underlying patient factors, abnormal physiology and perioperative insults. Our primary goal was to delineate associations between clinical factors and postnatal brain microstructure in term CHD neonates using diffusion tensor imaging (DTI) magnetic resonance (MR) acquisition combined with complementary data-driven connectome and seed-based tractography quantitative analyses. Our secondary goal was to delineate associations between mild dysplastic structural brain abnormalities and connectome and seed-base tractography quantitative analyses. These mild dysplastic structural abnormalities have been derived from prior human infant CHD MR studies and neonatal mouse models of CHD that were collectively used to calculate to calculate a brain dysplasia score (BDS) that included assessment of subcortical structures including the olfactory bulb, the cerebellum and the hippocampus.MethodsNeonates undergoing cardiac surgery for CHD were prospectively recruited from two large centers. Both pre- and postoperative MR brain scans were obtained. DTI in 42 directions was segmented into 90 regions using a neonatal brain template and three weighted methods. Clinical data collection included 18 patient-specific and 9 preoperative variables associated with preoperative scan and 6 intraoperative (e.g., cardiopulmonary bypass and deep hypothermic circulatory arrest times) and 12 postoperative variables associated with postoperative scan. We compared patient specific and preoperative clinical factors to network topology and tractography alterations on a preoperative neonatal brain MRI, and intra and postoperative clinical factors to network topology alterations on postoperative neonatal brain MRI. A composite BDS was created to score abnormal findings involving the cerebellar hemispheres and vermis, supratentorial extra-axial fluid, olfactory bulbs and sulci, hippocampus, choroid plexus, corpus callosum, and brainstem. The neuroimaging outcomes of this study included (1) connectome metrics: cost (number of connections) and global/nodal efficiency (network integration); (2) seed based tractography methods of fractional anisotropy (FA), radial diffusivity, and axial diffusivity. Statistics consisted of multiple regression with false discovery rate correction (FDR) comparing the clinical risk factors and BDS (including subcortical components) as predictors/exposures and the global connectome metrics, nodal efficiency, and seed based- tractography (FA, radial diffusivity, and axial diffusivity) as neuroimaging outcome measures.ResultsA total of 133 term neonates with complex CHD were prospectively enrolled and 110 had analyzable DTI. Multiple patient-specific factors including d-transposition of the great arteries (d-TGA) physiology and severity of impairment of fetal cerebral substrate delivery (i.e., how much the CHD lesion alters typical fetal circulation such that the highest oxygen and nutrient rich blood from the placenta are not directed toward the fetal brain) were predictive of preoperative reduced cost (p < 0.0073) and reduced global/nodal efficiency (p < 0.03). Cardiopulmonary bypass time predicted postoperative reduced cost (p < 0.04) and multiple postoperative factors [extracorporeal membrane oxygenation (ECMO), seizures and cardiopulmonary resuscitation (CPR)] were predictive of postoperative reduced cost and reduced global/nodal efficiency (p < 0.05). Anthropometric measurements (weight, length, and head size) predicted tractography outcomes. Total BDS was not predictive of brain network topology. However, key subcortical components of the BDS score did predict key global and nodal network topology: abnormalities of the cerebellum predicted reduced cost (p < 0.0417) and of the hippocampus predicted reduced global efficiency (p < 0.0126). All three subcortical structures predicted unique alterations of nodal efficiency (p < 0.05), including hippocampal abnormalities predicting widespread reduced nodal efficiency in all lobes of the brain, cerebellar abnormalities predicting increased prefrontal nodal efficiency, and olfactory bulb abnormalities predicting posterior parietal-occipital nodal efficiency.ConclusionPatient-specific (d-TGA anatomy, preoperative impairment of fetal cerebral substrate delivery) and postoperative (e.g., seizures, need for ECMO, or CPR) clinical factors were most predictive of diffuse postnatal microstructural dysmaturation in term CHD neonates. Anthropometric measurements (weight, length, and head size) predicted tractography outcomes. In contrast, subcortical components (cerebellum, hippocampus, olfactory) of a structurally based BDS (derived from CHD mouse mutants), predicted more localized and regional postnatal microstructural differences. Collectively, these findings suggest that brain DTI connectome and seed-based tractography are complementary techniques which may facilitate deciphering the mechanistic relative contribution of clinical and genetic risk factors related to poor neurodevelopmental outcomes in CHD.

The recent health crisis experienced by all nations in the world created detrimental change in the countenance of educational sector especially in the new mode of delivering the instructions as measure in containing the virus and as well as continuing education. In the works of literature, little to no attention was given to the formulation of the most essential learning competencies (MELCs) as strategic measure for modular learning. This paves the way to probe the lived experiences of the teachers pertaining to the compromised competencies under MELCs. Anchoring to the Sociocultural Theory of Cognitive Development by Vgotsky, this study utilized Interpretative Phenomenological Research Design with Interpretative Phenomenological Analysis (IPA) popularized by Moustakas and modified by Van Kaam as approach to analyzed the transcripts. Using purposive sampling, there were 7 informants participated the study. They are all qualified according to the inclusion criteria set by the study. The study generated three themes which are: The Compromised, The Cut-short, and The Champion. These themes elaborated the lived experiences of the teachers using the Most Essential Learning Competencies forwarded to the students. It is recommended that the learning support should be magnified in the new learning modality. Hence, the Most Essential Learning Competencies will be not be compromised.

Background Effective contact tracing, vaccination, and isolation of cases of SARS-CoV-2 infection and their high-risk contacts constituted measures to contain the spread of COVID-19. In Portugal, in October 2021, low-risk cohabitants were lifted the obligation to isolate. The aim of this study was to estimate the relative risk of infection for close contacts, regarding the type of close contact and being cohabitants. Methods A descriptive longitudinal study, with an analytical component was performed. Sociodemographic and epidemiologic data from close contacts and confirmed cases in Loures and Odivelas, between October and November 2021, was collected from a regional database and from Trace COVID-19 platform. We performed a descriptive analysis and estimated the relative risk of SARS-CoV-2 positive test, stratified by type of contact and cohabitation, with 95% confidence level. Results We identified 200 confirmed cases and 428 people who were close contacts, corresponding to 502 different close contacts (59 people had contact with more than a case). From 502 close contacts, 268 were classified as low-risk and 230 as high-risk. Full time cohabitation was present in 310 of close contacts. Between contact tracing day and the next 4 weeks, 58 (10.9%) of close contacts tested positive. Risk of high-risk contacts testing positive was 2.7 [1.5-4.6], compared with low-risk contacts. Risk of cohabitants testing positive was 3.5 [1.6-7.7], compared with non-cohabitants. Risk of a high-risk cohabitant testing positive was 2.2 [1.1-4.4], compared with low-risk cohabitants. There was no higher risk of high-risk cohabitants testing positive compared with high-risk non-cohabitants. Same was true for low-risk cohabitants and non-cohabitants. Conclusions These results allow us to understand how to better stratify close contacts and apply isolation measures, according to the risk of testing positive. Further studies should be developed to assess the impact of other variables. Key messages • We identified an increased risk of testing positive in high-risk contacts, and in cohabitants. • Cohabitants could be stratified regarding being high or low-risk, with different measures being applied.

The pig is an ideal model system for studying human development and disease due to its similarities to human anatomy, physiology, size, and genome. Further, advances in CRISPR gene editing have made genetically engineered pigs viable models for the study of human pathologies and congenital anomalies. However, a detailed atlas illustrating pig development is necessary for identifying and modeling developmental defects. Here we describe normal development of the pig abdominal system and show examples of congenital defects that can arise in CRISPR gene edited SAP130 mutant pigs. Normal pigs at different gestational ages from day 20 (D20) to term were examined and the configuration of the abdominal organs was studied using 3D histological reconstructions with episcopic confocal microscopy, magnetic resonance imaging (MRI) and necropsy. This revealed prominent mesonephros, a transient embryonic organ present only during embryogenesis, at D20, while the developing metanephros that will form the permanent kidney are noted at D26. By D64 the mesonephroi are absent and only the metanephroi remain. The formation of the liver and pancreas was observed by D20 and complete by D30 and D35 respectively. The spleen and adrenal glands are first identified at D26 and completed by D42. The developing bowel and the gonads are identified at D20. The bowel appears completely rotated by D42, and testes in the male were descended at D64. This atlas and the methods used are excellent tools for identifying developmental pathologies of the abdominal organs in the pig at different stages of development.

Deep brain stimulation (DBS) is indisputable in improving motor symptoms of Parkinson's Disease (PD) and X-Linked Dystonia Parkinsonism (XDP)(4,9,22,23,26). However, a discrepancy between this improvement and the perceived quality of life (QoL) has been observed. This study aims to investigate changes and correlation between quality of life, motor symptoms and medication dosing.This prospective observational study enrolled 13 patients (6 PD, 7 XDP) who underwent DBS from 2017 to 2018. Quality of life changes were determined by Parkinson's Disease - 39 (PDQ-39 English and Filipino versions) at baseline, 6 months and 12 month after DBS. Motor symptoms and medication dosing were also evaluated within the same period and correlated with QoL changes.There is a significant reduction of PDQ-39 mean scores[F(1.06,11.64) = 18.235; p = 0.001; ηp2 = 0.624] between baseline and 6 months among XDP patients (p = 0.018) and baseline and 12 months among PD patients (p = 0.027) and XDP patients (p 0.001). Specific domains with significant improvement were stigma, cognition, mobility, ADLs, communication and bodily discomfort. Correlating these with changes in motor symptoms, only mobility for PD and ADLs for XDP were positively related.This study has shown the positive impact of DBS in improving QoL among PD and XDP patients over a 12-month period.

Background Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection. Methods A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2–4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts. Findings From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13–0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days. Interpretation A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. Funding Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments.

An essential role for cilia in the pathogenesis of congenital heart disease (CHD) has emerged from findings of a large-scale mouse forward genetic screen. High throughput screening with fetal ultrasound imaging followed by whole exome sequencing analysis recovered a preponderance of cilia related genes and cilia transduced cell signaling genes among mutations identified to cause CHD. The perturbation of left-right patterning in CHD pathogenesis is suggested by the association of CHD with heterotaxy, but also by the finding of the co-occurrence of laterality defects with CHD in birth defect registries. Many of the cilia and cilia cell signaling genes recovered were found to be related to Hedgehog signaling. Studies in mice showed cilia transduced hedgehog signaling coordinates left-right patterning with heart looping and differentiation of the heart tube. Cilia transduced Shh signaling also regulates later events in heart development, including outflow tract septation and formation of the atrioventricular septum. More recent work has shown mutations in cilia related genes may also contribute to valve disease that largely manifest in adult life. Overall, these and other findings show cilia play an important role in CHD and also in more common valve diseases.

We examined the association between perceived racial discrimination and hypertension among African Americans and whites who live in a low-income, racially integrated, urban community. Hypertension was defined as having a systolic blood pressure 140 mm Hg or more, a diastolic blood pressure 90 mm Hg or more, or taking antihypertensive medication(s). Perceived racial discrimination was based on self-reported responses of experiencing racial discrimination in various settings. Using modified Poisson multivariable regression models, we found no association between perceived racial discrimination and hypertension (prevalence ratio: 0.96, 95% confidence interval: 0.90-1.04). Findings suggest that social context may play a role in the relationship between perceived racial discrimination and hypertension.

Individuals with bipolar disorder (BD) have higher rates of unhealthy lifestyles and risk for medical comorbidities Research currently suggests that dietary factors may play a role in the development of depression and anxiety. Therefore, nutritional approaches are potential strategies for the treatment of BD. The aim of this review is to summarize the available evidence on nutrition and BD.The paper was developed based on PRISMA 2020 guidelines. The search was conducted in Sep-2021 using PubMed and Cochrane Library, augmented by manually checked references lists. The search found 986 studies, of which 47 were included, combined with 13 from reference lists, totaling 60 studies.There were 33 observational trials, of which 15 focused on fatty acids, 9 on micronutrients, 5 on specific foods, 4 on macro and micronutrients. The 27 interventional studies mainly focused on fatty acids, micronutrients and N-acetylcysteine (NAC).Dietary intake or supplementation of unsaturated fatty acids, mainly Omega-3 seems to be associated with improved BD symptoms, along with seafood, folic acid and zinc. Studies found variable, mainly non-significant impacts of creatine, carnitine, vitamin D, inositol or NAC supplementation on BD. There are promising results associated with Coenzyme Q10 (Coq10) and probiotics. Taken together, these preliminary findings suggest that dietetic approaches might be included as part of BD treatment. Also considering the high risk of metabolic disorders in individuals with BD, they should be encouraged to choose healthy dietary lifestyles, including daily intake of fruits, vegetables, seafood and whole grains.

Trapeziometacarpal (TM) Osteoarthritis is one of the most common osteoarthritis. It causes pain, loss of mobility and strength and affected function in daily life. Splint is one of the conservative treatments proposed to patients. The purpose of this study was to assess the effect of this conservative treatment on pain, function and quality of life at long-term. We sent 193 questionnaires to patients who received a CMC splint for their TM osteoarthritis. The CMC splint immobilizes only the TM joint and leaves free the interphalangeal joint of the thumb and the wrist. First, we comptuted how many patients had finally undergone surgical treatment. On the non-operated patients, we analyzed the pain (VAS), the function (QuickDASH score) and the quality of life (SF-12). We compared the results to literature and norms. Finally, 186 people could be included in the study ,115 we answered and 28 were operated on (24%). After 4 years (3.8±1.7 yrs) of conservative treatment, The VAS and QuickDASH scores were significantly worse comparatively to a cohort of healthy patients, trapezectomy and arthrodesis patients. The SF-12 scores were reduced from 20% comparative to norms. In conclusion, few patients had surgery after splinting as a conservative treatment. However, these non- operated patients do not provide good results.

Nutritional therapy should follow evidence-based practice, thus several societies regarding nutrition and critical care have developed specific Clinical Practice Guidelines (CPG). However, to be regarded as trustworthy the quality of the CPG for critically ill patients and its recommendations need to be high. This systematic review aimed to appraise the methodology and recommendations of nutrition CPGs for critically ill patients. We performed a systematic review (protocol number CRD42020184199) with literature search conducted on Pubmed, Embase, Cochrane Library, and other four specific databases of guidelines up to October 2021. Two reviewers, independently, assessed titles and abstracts and potentially eligible full text reports to determine eligibility and subsequently four reviewers appraised the guidelines quality using the Advancing Guideline Development, Reporting and Evaluation in Health Care instrument II (AGREE-II) and AGREE-Recommendation Excellence (AGREE-REX). Ten CPG for nutrition in critically ill patients were identified. Only Academy of Nutrition and Dietetics and European Society of Intensive Care Medicine had a total acceptable quality and were recommended for daily practice according AGREE-II. None of the CPG recommendations had an overall quality score above 70%, thus being classified as moderate quality according AGREE-REX. The methodological evaluation of the critically ill adult patient CPGs revealed significant discrepancies and showed a need for improvement in its development and/or reporting. In addition, recommendations about nutrition care process presented a moderate quality.

Adapting to sea level rise, climate change, and associated effects is especially challenging in sensitive small-island environments where false adaptation can lead to adverse impacts on natural and societal dynamics. Framing and interest play a decisive role for the successful implementation of any adaptation measures. An interdisciplinary perspective on the interaction of natural dynamics, societal demands, and political decisions is crucial. This study scrutinizes the coastal processes and socio-political dimensions of erosion on the reef island Fuvahmulah, the Maldives. The national government and Fuvahmulah's population have opposed perception and attribution about the cause and effect of the retreating shoreline. To review these perceptions and determine the drivers and processes behind Fuvahmulah's most pressing coastal issue, natural dynamics are recreated with process-based numerical methods and discussed regarding the present and projected sea levels and wave climate. The numerical results are based on high resolution digital elevation models from airborne imagery and in-situ bathymetric measurements. Interviews with national and local actors in coastal development and population surveys complement the physical insights into erosion on the island and scrutinize the socio-political dimension of climate change adaptation on small islands. The results of the interdisciplinary approach demonstrate how small-islands' adaptive capacities are typically impaired in dealing with climate-related changes, they reveal the structural challenges of top-down processes, and disclose the potential of local knowledge to overcome maldevelopment.

The non-pharmacological measures to contain the COVID-19 pandemic may lead to considerable psychological distress. The aim of the CoCo-Fakt study was to investigate possible coping strategies and their effects on psychological distress during legally enforced quarantine of infected persons (IPs) and their close contacts (CPs).This was a cross-sectional cohort study.From 12 December 2020 to 6 January 2021, all IPs and their CPs (n = 8232) registered by the public health department (Cologne, Germany) were surveyed online. Psychosocial distress and coping were measured using sum scores; free-text answers related to specific strategies were subsequently categorised.Psychosocial distress was higher in IPs than in CPs (P .001). Although the mean coping score did not differ between both groups, it was influenced by the reason for quarantine (IP vs CP) besides gender, age, socio-economic status, living situation, psychological distress, resilience, physical activity and eating behaviour. This final regression model explained 25.9% of the variance. Most participants used active coping strategies, such as contact with the social environment, a positive attitude and hobbies.Although psychological distress was higher in IPs than in CPs during the quarantine period, the mean coping score did not differ. The strategies most frequently used by IPs and CPs were activating social networks, a healthy lifestyle and professional support systems, such as the health department helpline. Appropriate advice should be implemented to prevent long-term psychological consequences when supporting affected people.

Summary Bicuspid aortic valve (BAV) with ∼1%–2% prevalence is the most common congenital heart defect (CHD). It frequently results in valve disease and aorta dilation and is a major cause of adult cardiac surgery. BAV is genetically linked to rare left-heart obstructions (left ventricular outflow tract obstructions [LVOTOs]), including hypoplastic left heart syndrome (HLHS) and coarctation of the aorta (CoA). Mouse and human studies indicate LVOTO is genetically heterogeneous with a complex genetic etiology. Homozygous mutation in the Pcdha protocadherin gene cluster in mice can cause BAV, and also HLHS and other LVOTO phenotypes when accompanied by a second mutation. Here we show two common deletion copy number variants (delCNVs) within the PCDHA gene cluster are associated with LVOTO. Analysis of 1,218 white individuals with LVOTO versus 463 disease-free local control individuals yielded odds ratios (ORs) at 1.47 (95% confidence interval [CI], 1.13–1.92; p = 4.2 × 10−3) for LVOTO, 1.47 (95% CI, 1.10–1.97; p = 0.01) for BAV, 6.13 (95% CI, 2.75–13.7; p = 9.7 × 10−6) for CoA, and 1.49 (95% CI, 1.07–2.08; p = 0.019) for HLHS. Increased OR was observed for all LVOTO phenotypes in homozygous or compound heterozygous PCDHA delCNV genotype comparison versus wild type. Analysis of an independent white cohort (381 affected individuals, 1,352 control individuals) replicated the PCDHA delCNV association with LVOTO. Generalizability of these findings is suggested by similar observations in Black and Chinese individuals with LVOTO. Analysis of Pcdha mutant mice showed reduced PCDHA expression at regions of cell-cell contact in aortic smooth muscle and cushion mesenchyme, suggesting potential mechanisms for BAV pathogenesis and aortopathy. Together, these findings indicate common variants causing PCDHA deficiency play a significant role in the genetic etiology of common and rare LVOTO-CHD.

Congenital heart defect is one of the most common structural birth defects in the human population. It is highly associated with heterotaxy, a birth defect involving randomized left-right patterning of visceral organ situs. Large scale mouse forward genetics have led to the finding of a central role for cilia in CHD pathogenesis, with some cilia and non-cilia mutations causing CHD with heterotaxy. Interestingly, many of the mutations causing CHD with heterotaxy can give rise to three laterality outcomes comprising normal situs solitus, mirror symmetric situs inversus totalis, or randomized situs with heterotaxy. Given CHD is largely observed only with heterotaxy, this suggests a new paradigm is needed for investigating the genetics of CHD associated with heterotaxy. Furthermore, analysis of data from multiple large birth cohorts have independently confirmed a broader involvement of laterality disturbance in CHD. This was demonstrated by the common cooccurrence of rare laterality defects with CHD lesions of a wide spectrum. These findings suggest left-right patterning is tightly intertwined with the developmental processes that regulate cardiac morphogenesis and its disturbance may contribute to all types of CHD even in the absence of laterality defects.

This study focused in determining the Perception, Awareness, Acceptance and Understanding of Nueva Ecija University of Science and Technology San Isidro Campus Community towards the its Vision, Mission, Goals and Objectives of programs offered (VMGO). The survey instrument used in this study was a modified survey questionnaire from previous studies conducted by Castillo (2016). The items regarding the perception, awareness, acceptance and understanding on VMGO included in the survey instrument were based on the 2010 AACCUP Revised Instruments. The respondents of the survey were the NEUST-SIC (1325) internal stakeholders and (565) external stakeholders respectively. Findings show that External Stakeholders generally were least aware, least accept and understand the Vision, Mission, Golas and Objectives of NEUST. It is also revealed that the external stakeholders believed that the vision, mission, goals and objectives are not clearly stated and consistent with each other. However, they all agreed that the program objectives are clearly stated in terms of aesthetic and cultural values. Thus, it is recommended that widest dissemination of the VMGO through various forms of communication media, conduct campaigns or other related activities should be done by the NEUST-SIC community to further raise awareness among external stakeholders and thereby strengthen support.

Aim: Steroidal prodrugs of nitrogen mustards such as estramustine and prednimustine have proven effective anticancer agents in clinical use since the 1970s. In this work, we aimed to develop steroidal prodrugs of the novel nitrogen mustard POPAM-NH2. POPAM-NH2 is a melphalan analogue that was coupled with three different steroidal lactams. Methodology: The new conjugates were preclinically tested for anticancer activity against nine human and one rodent cancer experimental models, in vitro and in vivo. Results & conclusion: All the steroidal alkylators showed high antitumor activity, in vitro and in vivo, in the experimental systems tested. Moreover, these hybrid compounds showed by far superior anticancer activity compared with the alkylating agents, melphalan and POPAM-NH2.

The purpose of this systematic review is to analyze the available evidence linking short-chain fatty acids (SCFA) to leptin's levels and production. We performed a systematic review using the PubMed/Medline database including primary articles written in English that measured leptin production or levels as well as SCFA used as an intervention, mechanism or outcome. The search yielded a total of 573 citations; 36 studies were included in the final analysis. The quality of the studies was analyzed through two validated tools based on objective criteria. Overall, the studies presented low risk of bias to construct and statistical validity. However, the majority presented a high risk of attrition and detection bias. In vitro studies (n = 8) consistently demonstrated that SCFA stimulate leptin expression in adipocytes through activation of free fatty acid receptor 3 (FFAR3). In animal studies (n = 24), interventions to modulate high-fat diet outcomes predominantly caused a decrease in circulating leptin levels and increased SCFA, associated with suppressed weight gain. Control of dysbiosis through administration of prebiotics and probiotics also played a role in leptin synthesis in animal studies. In human studies (n = 4) leptin was mainly correlated with adiposity but dysbiosis interfered with this relationship. We conclude that the association between SCFA and leptin remains incompletely understood but occurs mainly through the activation of FFAR3 in adipocytes. However, body fat rather than SCFA remains the main driver for leptin synthesis in vivo. Future studies should aim to better clarify the role of SCFA in regulating leptin production in vivo.

Resume Introduction Dans notre etablissement, la conciliation des traitements medicamenteux (CTM) d’entree est mise en place depuis 2012 et concerne l’ensemble des patients admis. Objectif L’objectif de l’etude est de definir une organisation pour la mise en place de la conciliation de sortie et assurer la transmission des informations necessaires a la poursuite du traitement et des surveillances initiees durant l’hospitalisation. Materiels et methodes Un audit sur les modalites de sortie d’hospitalisation a permis d’etablir une chronologie du parcours de soins d’un patient apres decision de sortie d’hospitalisation. Resultats Une organisation a ete testee puis reajustee. L’activite commence proactivement des la conciliation d’entree. Puis au cours de l’hospitalisation, un suivi pharmaceutique personnalise est redige en continu. L’ensemble est synthetise et consigne dans la lettre de conciliation de sortie qui pourra ainsi etre rapidement transmise aux professionnels de sante de ville. De plus, celle-ci repond a la partie medicamenteuse de la lettre de liaison decrite dans le decret no 2016-995 du 20 juillet 2016 relatif aux lettres de liaison. Apres 12 mois de mise en place sur site pilote, 92 % des patients eligibles ont ete concilies en sortie d’hospitalisation.

Cadmium is a metallotoxin, amply encountered in the environment and derived through physical and anthropogenic activities. Its entry in various organisms leads through water and the food chain to humans, thereby inducing a plethora of pathophysiologies. Delineation of the interactive role of cadmium with physiological and physiologically relevant substrates, requires well-defined forms of cadmium arising from such interactions along with the ensuing chemical reactivity amounting to toxic manifestations and health aberrations. To implement such efforts, low molecular mass substrate metal ion binders are needed, forming species with enhanced solubility and bioavailability. To that end, α-hydroxy isobutyric acid (HIBAH2) was used in pH-specific synthetic efforts involving bulky aromatic chelators 2,2′-bipyridine (2,2′-bipy) and 1,10-phenanthroline (phen), thus leading to new crystalline materials [Cd(C4H7O3)2]n(1), [Cd(C4H7O3)2(H2O)2](2), [{Cd2(C4H7O3)2(C10H8N2)2(H2O)2}(NO3)2]n·nH2O(3), and [{Cd2(C4H7O3)2(C12H8N2)2(H2O)2}(NO3)2]n·2nH2O(4), which were physicochemically characterized (elemental analysis, FT-IR, NMR, ESI-MS, and X-ray crystallography) in the solid state and solution. Their physicochemical characteristics led to their employment in tissue-specific biological toxicity studies in three different cell lines. Their toxicity profile (cell viability, morphology, chemotacticity) was correlated through genetic biomarkers to apoptotic-necrotic processes, thereby shedding light on cadmium cellular toxicity processes. Finally, the cytoprotective action of specific chelators was examined, lending credence to the notion that appropriately structured chelators and antioxidants may be used as effective deterrent to cadmium toxicity. Collectively, structure-specificity linked to tissue-specific toxicity profiling in well-defined binary-ternary Cd(II)-HIBAH2 systems exemplifies that metal ion's aberrant interactions in the cellular milieu, meriting further probing into the development of efficient chelators in cadmium detoxification.

We recently conducted a large-scale mouse mutagenesis screen and uncovered a central role for cilia in the pathogenesis of congenital heart disease (CHD). Though our screen was phenotype based, most of the genes recovered were cilia-related, including genes encoding proteins important for ciliogenesis, cilia-transduced cell signaling, and vesicular trafficking. Also unexpected, many of the cilia related genes recovered are known direct protein-protein interactors, even though each gene was recovered independently in unrelated mouse lines. These findings suggest a cilia-based protein-protein interactome network may provide the context for congenital heart disease pathogenesis. This could explain the incomplete penetrance and variable expressivity of human CHD, and account for its complex non-Mendelian etiology. Supporting these findings in mice, a preponderance of cilia and cilia related cell signaling genes were observed among de novo pathogenic variants identified in a CHD patient cohort. Further clinical relevance unfolded with the observation of a high prevalence of respiratory cilia dysfunction in CHD patients. This was associated with increased postsurgical respiratory complications. Together these findings highlight the importance of cilia in CHD pathogenesis and suggest possible clinical translation with instituting pulmonary therapy to improve outcome for CHD patients undergoing congenital cardiac surgeries.

In this case report we present a Family cluster of amoebiasis in a nonendemic region. A 46-year-old women, diagnosed with Crohn's disease for which she received no maintenance therapy, was evaluated for the suspicion of a flare. At colonuscopy however, atypical findings for Crohn's disease were seen. Histopathologic examination revealed micro-organisms compatible with amoebiasis. Interestingly, 4 years before this event she started a new relationship with a 38-year-old man who was diagnosed with liver-amoebiasis 3 months after the start of their start of their relationship. On top of this, her 18-year-old daughter was diagnosed with amoebiasis 2 years after her diagnosis. The source of the infection remains unknown, but we speculate that the infection was transmitted feco-orally between the different members of this family. These cases illustrate that we should be aware of parasitological causes of colitis, especially in patients with atypical endoscopic images or when a close "relative" is diagnosed with amoebiasis.

Analysis of large-scale human genomic data has yielded unexplained mutations known to cause severe disease in healthy individuals. Here, we report the unexpected recovery of a rare dominant lethal mutation in

In this study, the exposome paradigm has been applied on a mother-child cohort adopting an optimised untargeted metabolomics approach for human urine followed by advanced bioinformatics analysis. Exposome-wide association algorithms were used to draw links between in utero co-exposure to metals and phthalates, metabolic pathways deregulation, and clinically observed phenotypes of neurodevelopmental disorders such as problems in linguistic, motor development and cognitive capacity. Children (n = 148) were tested at the first and second year of their life using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Their mothers had been exposed to metals and phthalates during the pregnancy, according to human biomonitoring results from previously performed studies. Untargeted metabolomics analysis of biobanked urine samples from the mothers was performed using a combination of the high throughput analytical methods liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). Most perturbed metabolic pathways from co-exposure heavy metals and phthalates were pathways related to the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation, indicating the possibility of disruption of mitochondrial respiration. Overproduction of reactive oxygen species (ROS); the presence of glutathione peroxidase 3 (GPx3) during pregnancy and presence of glutathione peroxidase 1 (GPx1) in the umbilical cord were linked to verbal development problems. Another finding of the study is that in real life, adverse outcomes occur as a combination of environmental and social factors, all of them acting synergistically towards the deployment of an observed phenotype. Finally, the two-steps association process (exposure to pathways and pathways to adverse outcomes) was able to (a) provide associations that are not evident by directly associating exposure to outcomes and (b) provides additional insides on the mechanisms of environmental disease.

Analysis of large scale human genomic data has yielded unexplained mutations known to cause severe disease in healthy individuals. Here we report the unexpected recovery of a rare dominant lethal mutation in TPM1, a sarcomeric actin-binding protein, in 8 individuals with large atrial septal defect (ASD) in a 5-generation pedigree. Mice with TPM1 mutation exhibited early embryonic lethality with disrupted myofibril assembly and no heartbeat. However, patient induced pluripotent stem cell derived cardiomyocytes showed normal beating with mild myofilament defect, indicating disease suppression. A variant in TLN2, another myofilament actin-binding protein, was identified as a candidate suppressor. Mouse CRISRP knockin of both the TLN2/TPM1 variants rescued heart beating, with near term fetuses exhibiting large ASD. Thus, the role of TPM1 in ASD pathogenesis unfolded with the suppression of its embryonic lethality by a TLN2 protective variant. These findings provide evidence that genetic resiliency can arise with genetic suppression of a deleterious mutation.

Hypertension affects more than one billion people worldwide. There has been much discussion about clinical practice guidelines (CPGs) following the proposal of lower thresholds for starting pharmacological treatment. Some smaller groups or institutions could benefit from adapting CPGs to their local context, a process that requires high-quality CPGs with few points of conflict in their recommendations. To address this issue, we have compared high-quality hypertension CPGs and highlighted conflicting recommendations.CPGs were searched in MEDLINE, Embase, the Cochrane Library, as well as specific websites. Only CPGs published between 2016 and 2019 were included. We defined CPGs as high-quality if the 'rigor of development' and 'editorial independence' AGREE II domains were scored at least 60%. We compared recommendations made by high-quality CPGs and highlighted areas of conflict (defined as disagreements between more than two CPGs).Nineteen CPGs were identified. The highest scoring domain was 'scope and purpose' (74.3%) and the lowest scoring was 'applicability' (40.0%). Eight CPGs were rated as high quality. Most CPG recommendations on the management of hypertension were consistent. Conflicting recommendations were regarding blood pressure (BP) levels to initiate pharmacotherapy and therapeutic goals, particularly in patients with low cardiovascular risk and older patients.It is possible to adapt hypertension CPGs once high-quality documents have been identified with agreement between most recommendations. Guideline developers can focus on the adaption process and concentrate efforts on implementation.

Transmissible viral proventriculitis (TVP) is a disease of chickens, mostly in broilers of 2-8 wk of age. Chicken proventricular necrosis virus (CPNV), a birnavirus, is the etiologic agent. Characteristic gross lesions are enlargement, atony, and pallor of the proventriculus. Cases diagnosed in California between 2000 and 2018 (n = 477), originating from 93 different farms representing all major companies in the region, were analyzed. Frequency of cases varied widely between years, with no recognizable seasonality. The flocks were between 6 and 61 days of age; the average age was 34.0 days, and the median age was 35 days. In 166 cases, between 6.3% and 100% of the submitted birds had gross lesions in the proventriculus. The most common findings were enlarged or dilated proventriculi, thickened walls, and pale or mottled serosal appearance. Histopathologically, inflammation of the glands was the most frequent finding. Other lesions included necrosis, hyperplasia, or both conditions of the glandular epithelium; dilated glands; and occasionally fibrin deposition, fibrosis, and hemorrhages. Twenty-three proventriculi from six cases were tested by immunohistochemistry for the presence of CPNV antigen; 21 stained positive. In 209 cases, birds also had lesions in the bursa fabricii attributed to infectious bursal disease, but with no significant difference in the mean percentage of birds with gross lesions in the proventriculus between cases with or without lesions in the bursa fabricii. The results show that TVP is a common disease of broiler flocks in California and confirms that CPNV is the likely causative agent.

BackgroundRLS-0071-101 was a first in human clinical trial to evaluate safety of the peptide RLS-0071 in healthy volunteers in a single ascending dose and multiple ascending dose format. RLS-0071, previously referred to as Peptide Inhibitor of Complement C1 (PIC1) is a dual-targeting peptide being developed for clinical use to moderate humoral and cellular inflammation via inhibition of complement activation and neutrophil effectors including myeloperoxidase (MPO) and Neutrophil extracellular trap formation (NETosis).1,2 Humans that are otherwise asymptomatic are considered at risk for cardiovascular complications if they have a plasma MPO level of > 420 pmol.3 A post hoc analysis of plasma samples from subjects participating in RLS-0071-101 identified an individual with mildly elevated baseline MPO level (142 pmol/L).ObjectivesEvaluate if RLS-0071 dosing would change MPO level or activity in a subject with elevated baseline MPO.MethodsFrozen plasma samples prepared from blood collected by venipunture into K2EDTA tubes (BD) was utilized to determine MPO quantity and activity levels. MPO quantity in the plasma was analyzed using a human MPO ELISA kit (BMS2038INST, Invitrogen) and MPO activity within the plasma was analyzed using a fluorescence-based myeloperoxidase assay kit (K745-100, BioVision).ResultsUpon screening 54 subjects from RLS-0071-101 we identified one individual with a mildly elevated MPO level at baseline, a 21-year-old white female with BMI of 21.7. The subject received 9 intravenous infusions of RLS-0071 each at a dose of 10 mg/kg. Her vital signs and body temperature remained normal throughout the study and the only blood laboratory abnormality were a mildly low plasma protein concentration of Day 2 and Day 4 which was noted both among recipients of the peptide and placebo subjects. Analysis of MPO blood concentrations demonstrated a mildly elevated baseline plasma MPO concentration that decreased after multiple doses of RLS-0071 with partial recovery to baseline 24 hours after cessation of dosing. MPO activity analyzed using a fluorescence-based myeloperoxidase assay kit demonstrated an elevated baseline plasma MPO activity level that decreased after multiple doses of RLS-0071 with partial recovery after 24 hours.ConclusionThese results suggest promise for RLS-0071 to reversibly moderate plasma MPO activity and potentially affect MPO-mediated diseases including acute coronary syndrome (ACS), atheromatous plaque vulnerability and auto immune conditions.4,5,6,7.References[1]Sharp, Julia A., et al. “Peptide inhibitor of complement c1, a novel suppressor of classical pathway activation: mechanistic studies and clinical potential.” Frontiers in immunology 5 (2014): 406.[2]Hair, Pamela S., et al. “Inhibition of myeloperoxidase activity in cystic fibrosis sputum by peptide inhibitor of complement C1 (PIC1).” PLoS One 12.1 (2017): e0170203.[3]Tang WH, Wu Y, Nicholls SJ, Hazen SL. Plasma myeloperoxidase predicts incident cardiovascular risks in stable patients undergoing medical management for coronary artery disease. Clin Chem. 2011;57(1):33-9.[4]Malle, E.; Marsche, G.; Panzenboeck, U.; Sattler, W. Myeloperoxidase-mediated oxidation of high-density lipoproteins: Fingerprints of newly recognized potential proatherogenic lipoproteins. Arch. Biochem. Biophys., 2006, 445 (2), 245-255.[5]Nurcombe, H. L.; Bucknall, R. C.; Edwards, S. W. Activation of the neutrophil myeloperoxidase-H2O2 system by synovial fluid isolated from patients with rheumatoid arthritis. Ann. Rheum. Dis., 1991, 50 (4), 237-242[6]Malle, E.; Buch, T.; Grone, H. J. Myeloperoxidase in kidney disease. Kidney Int., 2003, 64 (6), 1956-1967.[7]Nicholls, S. J.; Hazen, S. L. Myeloperoxidase and cardiovascular disease. Arterioscler., Thromb., Vasc. Biol., 2005, 25 (6), 1102- 1111.Disclosure of InterestsParvathi Kumar Shareholder of: I have stock options available, Consultant of: Served as a consultant for ReAlta life Sciences INC from April- July 2020, Employee of: I am employed by ReAlta Life Sciences, Kenji Cunnion Shareholder of: Shareholder of ReAlta life sciences, Employee of: ReAlta Life Sciences, Neel Krishna Employee of: I am an employee of ReAlta Life Sciences., Ulrich Thienel Shareholder of: Shareholder of ReAlta and JNJ, Employee of: ReAlta Life Sciences, Pamela Hair Employee of: ReAlta Life Sciences, Jessica Goss Employee of: ReAlta Life Sciences, Christos Gabriel: None declared

In order to investigate the structure-specific bioactivity of Cd(II) in a cellular environment and delve into the associated biomolecular interactions, binary systems of that metal ion in the presence of the physiological naturally-occurring α-hydroxycarboxylic acid quinic acid were examined synthetically in a pH-specific mode. Two discrete polymeric compounds [Cd(C7H11O6)2]n·n/2H2O (1) and [Cd(C7H11O6)2]n·nH2O (2) were isolated and characterized through elemental analysis, FT-IR, NMR, TGA, and X-ray crystallography. Despite their discrete solid state metal-binding ligand coordination modes and lattice architecture, ESI-MS studies on 1 and 2 showed that both give rise to the same species upon dissolution in water. In vitro biological investigation of the toxicity profile of 2 in two cell lines, 3 T3-L1 and Saos-2, point out the influence of the coordination environment of Cd(II) on cell survival, migration and cellular morphology. The in vitro cytotoxic work showed a concentration- and tissue-specific pattern for the Cd-quinate system. Finally, the cytoprotective role of the chelator agent EDTA was investigated in these cell lines at various concentrations of 2, thereby providing insight into Cd(II) interactions with cellular targets compromising cellular integrity. The collective results, signify the a) importance of the aqueous chemistry of Cd(II) with biologically significant substrates, leading to discrete and isolable architectures reflecting binary Cd(II)-quinate composition, b) formulation of the cytotoxicity profile, based on well-defined Cd(II) species, and c) selection and use of appropriately configured organic chelators into future research linked to the development of preventive and/or therapeutic approaches pertaining to Cd(II) (de)toxification processes.

Diabetes mellitus comprises a group of metabolic abnormalities due to insulin deficiency and/or resistance. Obesity contributes to diabetes, with a strong causal relationship existing between diabetes and insulin resistance, especially in patients with Diabetes mellitus II. Adipocytes emerge as key constituents of adipose tissue physiology. In their pre-mature form to mature state transformation, adipocytes fully exemplify one of the key adipogenic actions of insulin. Poised to a) gain insight into adipogenesis leading to antidiabetic factors, and b) investigate adipogenesis through careful examination of insulin contributions to interwoven mechanistic pathways, a systematic comparative study was launched involving well-defined metal-citrates (zinc and vanadium), the chemical reactivity of which was in line with their chemistry under physiological conditions. Selection of the specific compounds was based on their common aqueous coordination chemistry involving the physiological chelator citric acid. Cellular maturation of pre-adipocytes to their mature form was pursued in the presence-absence of insulin and employment of closely linked genetic targets, key to adipocyte maturation (Peroxisome proliferator-activated receptor gamma (PPAR-γ), Glucose transporter 1,3,4 (GLUT 1,3,4), Adiponectin (ADIPOQ), Glucokinase (GCK), and Insulin receptor (INS-R)). The results show a) distinct adipogenic biological profiles for the metalloforms involved in a dose-, time- and nature-dependent manner, and b) metal ion-specific adipogenic response-signals at the same or higher level than insulin toward all selected targets. Collectively, the foundations have been established for future exploitation of the distinct metal-specific adipogenic factors contributing to the functional maturation of adipose tissue and their use toward hyperglycemic control in Diabetes mellitus.

Despite the great diversity of plant growth-promoting bacteria (PGPB) with potential to partially replace the use of N fertilisers in agriculture, few PGPB have been explored for the production of commercial inoculants, reinforcing the importance of identifying positive plant-bacteria interactions. Aiming to better understand the influence of PGPB inoculation in plant development, two PGPB species with distant phylogenetic relationship were inoculated in maize. Maize seeds were inoculated with Bacillus sp. or Azospirillum brasilense. After germination, the plants were subjected to two N treatments: full (N+) and limiting (N-) N supply. Then, anatomical, biometric and physiological analyses were performed. Both PGPB species modified the anatomical pattern of roots, as verified by the higher metaxylem vessel element (MVE) number. Bacillus sp. also increased the MVE area in maize roots. Under N+ conditions, both PGPB decreased leaf protein content and led to development of shorter roots; however, Bacillus sp. increased root and shoot dry weight, whereas A. brasilense increased photosynthesis rate and leaf nitrate content. In plants subjected to N limitation (N-), photosynthesis rate and photosystem II efficiency increased in maize inoculated with Bacillus sp., whilst A. brasilense contained higher ammonium, amino acids and total soluble sugars in leaves, compared to the control. Plant developmental and metabolical patterns were switched by the inoculation, regardless of the inoculant bacterium used, producing similar as well as distinct modifications to the parameters studied. These results indicate that even non-diazotrophic inoculant strains can improve the plant N status as result of the morpho-anatomical and physiological modifications produced by the PGPB.

We investigated exposure to infectious diseases in wild (n=33) and pen-reared (n=12) Ring-necked Pheasants (Phasianus colchicus) in the Central Valley of California, US during 2014 and 2015. Serologic tests were positive for antibodies against hemorrhagic enteritis, infectious bursal disease, and Newcastle disease viruses in both wild and pen-reared pheasants.

Wide-spread implementation of carbon capture and storage has the potential to decrease carbon emissions and aid in meeting global climate change mitigation goals. Data availability is one of the biggest challenges faced by the carbon capture and storage (CCS) community for modeling risks associated with CCS, necessary for wide-spread implementation in coming years. Collecting, integrating, and intuitively managing data is a time-consuming process, but one which is fundamental to establishing necessary access to carbon storage data. The US Department of Energy (US DOE) has been a major supporter of energy research in the US, including significant investment into carbon capture and storage research and technology development over the last ten years. The US DOE investments into the Regional Carbon Sequestration Partnerships, the National Risk Assessment Partnership, and other CCS related research has resulted in a large volume of data, of which much has been made public through the National Energy Technology Laboratories data repository, the Energy Data eXchange (EDX). Researchers at the National Energy Technology Laboratory have developed workflows, tools, and other methods that leverage EDX, open-source software, machine learning, and natural language processing to discover, curate, label, organize and visualize available data. This paper describes the available data on EDX for carbon storage applications, describes the results of a spatial and temporal analysis of the data, describes where it is most geographically available, makes a general assessment of the quality of the available data, and discusses visualization tools and natural language processing tools developed for understanding, discovering and reusing the data.

Among transition and non-transition metals, thallium is a unique case of an element which, despite its known toxicity, provides interesting challenges through its biology and chemistry linked to diagnosis of human pathophysiologies. Poised to investigate in-depth the structural and electronic aspects of thallium involvement in physiological processes, the synthetic exploration of aqueous binary systems of Tl(I) with physiological binders from the family of hydroxycarboxylic acids (glycolic, lactic, mandelic and citric acid) was pursued in a pH-specific fashion. The isolated crystalline coordination polymers, emerging from that effort, were physicochemically characterized through elemental analysis, FT-IR, ESI-MS, 1H-/13C-NMR, and X-ray crystallography. The coordination environment of thallium in each molecular Tl(I) assembly, along with lattice dimensionality (2D 3D), reflects the contributions of the ligands, collectively exemplifying interactions probed into though BVS and Hirshfeld surface analysis. The results portray a well-defined solid-state and solution profile for all species investigated, thereby providing the basis for their subsequent selection into in vitro biological studies involving the (patho)physiological cell lines 3T3-L1, Saos-2, C2C12, and MCF-7. Biotoxicity profiles, encompassing cell viability, morphology, and cell growth support clearly a concentration-, time-, and cell tissue-specific behavior for the chosen Tl(I) compounds in a structure-specific fashion. Collectively, the chemical experimental data support the biological results in formulating a structure-specific behavior for Tl(I)-hydroxycarboxylato species with respect to biotoxicity mechanisms in a (patho)physiological environment. The accrued knowledge stands as the foreground for further investigation into the relevant biological chemistry of Tl(I) and molecular technologies targeting its sequestration and removal from cellular media.

Helcococcus ovis is a slow-growing, pyridoxal-dependent, Gram-positive coccus belonging to the Peptostreptococcaceae family. Bacteria belonging to the genus Helcococcus are considered normal inhabitants of keratinized epithelium in humans; however, several reports support their role as pathogens in humans and several animal species. This case report describes the identification of H. ovis in a white leghorn rooster with valvular vegetative endocarditis and hepatitis. In February 2017 one dead, 7-yr-old, white leghorn rooster was submitted to the California Animal Health and Food Safety Turlock laboratory for diagnostic testing. Postmortem and microscopic examination revealed vegetative endocarditis and aortic thrombosis associated with large numbers of Gram-positive cocci. Myocarditis and extensive necrotic hepatitis were also noticed. Helcococcus ovis was isolated in large numbers from the aortic endothelium and confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Bacterial colonies become evident 48 hr postincubation and exhibited a satellite growth around Escherichia coli on blood agar plates. A similar relationship has been described between Helcococcus spp. and Staphylococcus aureus. The primary site of infection in this chicken was not determined. To our understanding this is the first report of H. ovis infection in an avian species. The fastidious nature and nutritional requirements of Helcococcus spp. must be considered in order to allow proper identification and avoid misdiagnosis. Further studies are needed to define pathogenesis, virulence factors, and predisposing conditions associated with this microorganism.

Ship-borne waves are of significant interest for the design of port and waterway infrastructure and the maintenance of its surrounding environment. Computation of these nonlinear and dispersive waves has mainly been focusing on their near-field generation as a fluid-body interaction problem. This study presents an approach for the computation of ship waves generated by a moving pressure disturbance with phase-resolving and depth-averaged equations. To support a wide range of applicability, the paper deals with the evolution of the vessel wedge compared to an analytical solution for sub-to supercritical speeds and the assessment of wave patterns from a broad range of pressure term dimensions, including cross-references to findings in other studies. The conducted numerical experiments showcase the typical response of a Boussinesq-type model to a simplified moving pressure disturbance and identify the main factors and criteria for ship-wave propagation in the far-field of a vessel. Finally, a unique field dataset underlines the capability of an extended Boussinesq-type model to compute the propagation of vessel waves over an irregular bathymetry.