The management of Parkinson’s disease (PD) is frequently compromised by complications induced by dopaminergic treatment such as involuntary movements (dyskinesias) and psychosis. Mesdopetam (IRL790) is a novel dopamine D3 receptor antagonist developed for the management of complications of therapy in PD. Aim To evaluate safety, tolerability and pharmacokinetics of escalating single and multiple doses of mesdopetam Method We conducted a prospective, single-centre, randomized, double-blind, placebo-controlled phase I, first in human (FIH) study with mesdopetam administered to healthy male subjects. Results Overall, mesdopetam was well tolerated up to 120 mg single dose and up to 80 mg upon multiple dosing. AEs were mainly related to the nervous system and were dose dependent. No SAEs occurred and no AEs led to withdrawal. The results of the SAD and the MAD parts indicated dose- and time-independent pharmacokinetics with rapid absorption, maximum plasma levels generally reached within 2 hours after dosing. The average terminal half-life of mesdopetam ranged from 6.4 to 7.1 hours in the SAD part, and 6.3 to 7.3 hours in the MAD part. No accumulation was observed upon multiple dosing. Safety findings were unremarkable with no changes demonstrated in vital signs, ECG parameters or physical examination. Mesdopetam produced a dose-dependent increase in plasma prolactin, compatible with target engagement. Conclusion Mesdopetam was safe and well tolerated in healthy male volunteers. Pharmacokinetic analysis indicated rapid absorption and dose-linear pharmacokinetics of mesdopetam, with a plasma half-life around 7 hours, upon single and repeated dosing. The pharmacokinetics of mesdopetam supports twice daily use in patients.

Background. Acute myeloid leukemia (AML) accounts for approximately 25% of pediatric leukemia. The long term overall survival rate now approaches 70%, but up 30% relapse. The anti-leukemia properties of Natural Killer (NK) cells and its safety profile has been reported previously at different phases of AML treatment. We proposed a phase II open, a prospective multicenter, non-randomized clinical trial for adoptive infusion of haploidentical K562-mb15-41BBL activated and expanded Natural Killer (NKAE) cells as a consolidation strategy in children with favorable and intermediate-risk AML who were in first complete remission after chemotherapy (NCT02763475). Previous to NKAE cell infusion, patients received a lymphodepleting regimen. After NKAE cell infusion, patients received low doses (1×106/IU/m2) of IL-2 subcutaneously every 48 hours for 2 weeks. Procedure. Seven patients, median age 7.4 years (range, 0.78–15.98), received 13 infusions of NKAE cells, with a median of 36.44×106 NKAE cells/kg (range, 6.92–193.2×106 cells/kg). Results. Three pair donor-recipient were KIR–HLA-mismatched. Donor KIR haplotype score was better in two cases, and neutral in the rest of the cases. Chimerism was observed in 4 patients median chimerism 0.065%, (range 0.05-0.27%). With a median of follow up of 33 moths, 6 (85.7%) patients remain alive and in complete remission. The 3-year overall survival was 83.3% (95% confidence interval 68.1-98.5), and the 3-year relapse cumulative incidence was 28.6% (95% confidence interval 11.5-45.7). Conclusions. This study shows that NKAE cell infusion as a consolidation strategy was feasible and safe but could not improve the pediatric AML relapse rate in this small cohort.

Abstract: Immune thrombocytopenic purpura (ITP) is an autoimmune disease presents with isolated thrombocytopenia (thrombocyte count < 100.000/mm3) and develops due to increased thrombocyte destruction by autoantibodies. ITP is the most common cause of pediatric thrombocytopenia. Usually a self-limiting disease with an acute course of 70% - 80%. However, 20% - 25% cases are chronical. These cases are follow-up and management difficult and expensive. It is important to distinguish events that may become chronic at the time of initial diagnosis. In this study, we sought clues to be able to choose, which the patient will be chronicle?

Parental age can affect offspring telomere length through heritable and epigenetic-like effects, but at what stage during development these effects are established is not well known. To address this, we conducted a cross-fostering experiment in common gulls (Larus canus) that enabled us distinguish between pre- and post-natal parental age effects on offspring telomere length. Whole clutches were exchanged after clutch completion within and between parental age classes (young and old) and blood samples were collected from chicks at hatching and during the fastest growth phase (11 days later) to measure telomeres. Neither the ages of the natal nor the foster parents’ predicted the telomere length or the change in telomere lengths of their chicks. Telomere length was repeatable within chicks, but increased across development (repeatability = 0.55, Intraclass Correlation Coefficient within sampling events 0.934). Telomere length and the change in telomere length were not predicted by post-natal growth rate. Taken together, these findings suggest that in common gulls, telomere length during early in life is not influenced by parental age or growth rate, which may indicate that protective mechanisms buffer telomeres from external conditions during development in this relatively long-lived species.

An abundance of data indicate there are sex differences in endogenous opioid peptides and opioid receptors, leading to functional differences in sensitivity to opioid-mediated behaviors between males and females. Many of these sex differences are mediated by the effects of gonadal hormones on the endogenous opioid system. Whereas much research has examined the role of ovarian hormones on opioid-mediated endpoints, comparatively less research has examined the role of androgens. This review describes what is currently known regarding the influence of androgens on opioid-mediated endpoints and how androgens may contribute to sex differences in opioid-mediated effects. The review also addresses the clinical implications of androgenic modulation of opioid-mediated behaviors and suggests future lines of research for preclinical and clinical investigators, We conclude that further investigation into androgenic modulation of opioid-mediated effects may lead to new options for addressing conditions such as chronic pain and substance use disorders.

Background and Purpose: Drug induced liver injury is an emerging form of acute and chronic liver disease that may manifest as fatty liver. Amiodarone (AMD), a widely used anti-arrhythmic drug, can cause hepatic injury and steatosis by a variety of mechanisms, which are not completely understood. Experimental Approach: Chronic damage was induced by daily gavage of 180mg/kg body weight AMD for four consecutive days to C57Bl/6OlaHsd male mice. Key Results: Chronic AMD administration induced endoplasmic reticulum (ER) stress in both liver and adipose tissue. In adipose tissue, AMD reduced lipogenesis and increased lipolysis. Moreover, AMD treatment induced ER stress and ER stress-dependent lipolysis in 3T3L1 adipocytes in vitro. In the liver, AMD caused increased expression of genes encoding proteins involved in fatty acid (FA) uptake and transfer (Cd36, Fabp1 and Fabp4) and resulted in increased hepatic accumulation of free FAs, but not of triacylglycerols. In line with this, there was increased expression of hepatic de novo FA synthesis genes (Srebp1 and FA synthase encoded by Fasn). However, AMD significantly reduced the expression of the desaturase Scd1 and elongase Elovl6, detected at mRNA and protein levels. Accordingly, the FA profile of hepatic total lipids revealed increased accumulation of palmitate, a SCD1 and ELOVL6 substrate, and reduced levels of palmitoleate and cis-vaccenate, products of the enzymes. In addition, AMD-treated mice displayed increased hepatic apoptosis, known to be induced by lipotoxic palmitate. Conclusions and Implications: Chronic AMD induced ER stress and aggravated lipolysis in adipose tissue, while inducing a lipotoxic hepatic lipid environment.

Background and Purpose: Recent biochemical and pharmacological studies have reported that in several tissues and cell types, microsomal prostaglandin E2 synthase (mPGES) and peroxisome proliferator-activated receptor-γ (PPAR-γ) expression are modulated by a variety of inflammatory factors and stimuli Considering that very little is known about the biological effects promoted by IL-17 in the context of mPGES-1/PPAR-γ modulation, we sought to investigate the contribution of this unique cytokine on these integrated pathways during the onset of inflammation. Experimental Approach: We evaluated PF 9184 (mPGES-1 antagonist) and Troglitazone (PPAR-γ agonist) activity utilising integrated in vitro and in vivo approaches. The dorsal air pouch model was employed, and inflammatory infiltrates were analysed by flow cytometry. Locally produced cyto-chemokines and prostaglandins were assessed using ELISA assays. Western blots were also employed to determine the activity of various enzymes involved in downstream signalling pathways. Key Results: PF 9184 and Troglitazone, in a time and dose-dependent manner, were shown to significantly modulate leukocyte infiltration, myeloperoxidase activity, and the expression of COX-2/mPGES-1, NF-кB/IкB-α and mPGDS-1/PPAR-γ induced by IL-17. Moreover, both compounds were found to modulate prostaglandins (PGE2, PGD2, and PGJ2) production, the expression of different pro-inflammatory cyto-chemokines and the recruitment of inflammatory monocytes in response to IL-17. Conclusions and Implications: Collectively, the data presented suggests that IL-17 may constitute a specific modulator of inflammatory monocytes during later phases of the inflammatory response. Therefore, the results of this study show, for the first time, that IL-17/mPGES-1/PPAR-γ “axis” could represent a potential therapeutic target for inflammatory-based and immune-mediated diseases.

Inflammatory bowel disease (IBD) comprises Crohn’s disease and ulcerative colitis. In patients with IBD, intestinal inflammation and psychological comorbidities affect the quality of life. Evidence for the effectiveness of antipsychotics drugs or psychological therapies in patients with IBD is currently lacking. However, several studies have reported that intranasal oxytocin (OT) administration is effective in individuals with psychological disorders. Therefore, in this study, we evaluated the effects of intranasal OT on psychological disorders, using an IBD mouse model established via dextran sodium sulfate (DSS). Our results showed that intranasal OT improved DSS- induced abnormal stress-related behavior and restored the DSS-induced alterations in nNOS/NO, oxytocin receptor (OTR), pERK/ERK and BDNF expression in the hippocampus. Intranasal OT also ameliorated intestinal inflammation. The activity of the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal medulla axis were also altered by intranasal OT, without affecting the peripherally-secreted OT. Thus, while intranasal OT administration increased the concentration of OT in the hypothalamus compared to that in the untreated IBD mouse, the OT levels in the serum did not change. Intranasal OT increased the percentages of the M1 and M2 type macrophages and regulatory T (Treg) cells in the IBD mice, in contrast it decreased the M1/M2 ratio and the percentage of NKp46+NK cells in the spleen. We found that the protective effects of intranasal OT administration on impaired stress-coping behavior and intestinal inflammation could be abolished by splenectomy. In conclusion, the present study demonstrates that intranasal OT can ameliorate DSS-induced abnormal stress-related behavior and intestinal inflammation.

Pseudorabies virus (PRV) causes Aujeszky’s disease or pseudorabies (PR) in pigs worldwide, which leads to heavy economic losses to the swine industry. Since 2011, the emerging PRV variant led to the outbreak of PR in Bartha-K61-vaccinated pigs. The PR outbreaks demonstrated that Bartha-K61 vaccine did not provide full protection against the emerging PRV variant. PRV live-attenuated vaccines could control PRV infection, which has become a consensus. In this study, a Bartha-K61-like vaccine based on emerging PRV variant was generated by the CRISPR/Cas9 method, which has deleted the gI, gE, US9, and US2 genes. Safety experiments have confirmed that PRV GDFS-delgI/gE/US9/US2 was safe for 5-7 days-old suckling piglets. The piglets immunized with PRV GDFS-delgI/gE/US9/US2 vaccine did not produce PRV gE-specific antibodies but could generate PRV gB-specific antibodies and high neutralizing titers against PRV GDFS strain (variant PRV strain) or PRV Ea strain (older PRV strain). After emerging PRV GDFS variant challenge, all piglets immunized with PRV GDFS-delgI/gE/US9/US2 vaccine did not show any clinical signs, and the rectal temperature was normal. Moreover, the autopsy and histopathological analyses revealed that the piglets in the PRV GDFS-delgI/gE/US9/US2 vaccine group did not show apparent gross and pathological lesions. Furthermore, the piglets did not present weight loss in the PRV GDFS-delgI/gE/US9/US2 vaccine groups. According to the criteria of OIE terrestrial manual, the results of the experiment confirmed that the PRV GDFS-delgI/gE/US9/US2 vaccine could provide full protection against emerging PRV variant strain in piglets. Therefore, PRV GDFS-delgI/gE/US9/US2 strain is a potential live-attenuated vaccine against emerging PRV variant strain infection in China.

Molecular diagnosis of bovine tuberculosis plays an essential role in the epidemiological knowledge of the disease. Bovine tuberculosis caused by Mycobacterium bovis represents a risk to human health. This study aimed to perform the genotypic characterization of M. bovis isolated from bovines diagnosed as tuberculosis from dairy herds in the state of Pernambuco, Brazil. Granulomas from 30 bovines were sent for microbiological culture and colonies compatible with Mycobacterium spp were obtained in at least one culture from 17/30 granulomas. All isolates were confirmed to be M. tuberculosis bovis by spoligotyping and 24loci MIRU-VNTR typing. While spoligotyping characterized the isolates as SB0121, SB0295, SB0852, SB0120 and an unclassified genotype, 24loci MIRU-VNTR rendered two clusters of two isolates each and 13 unique profiles. Loci ETR-A showed higher discriminatory power, and loci (ETR-B, ETR-C, MIRU16, MIRU27 and QUB26) showed moderate allelic diversity. This is the first study on genetic variability of the infectious agent cause of bovine TB in Pernambuco and demonstrates variability of strains in the state. Thus, it corroborates the importance of this microorganism as agent of bovine tuberculosis and its zoonotic potential, being this epidemiological tool determinant in the rigor of the sanitary practices of disease control in dairy herds.

Adequate nasal breathing is indispensable for athletes and nasal symptoms have been shown to inter-fere with their subjective feeling of comfortable breathing and quality of life. Nasal symptoms are caused by either structural abnormalities or mucosal pathology. Structural pathologies are managed differently from mucosal disease and therefore adequate diagnosis is of utmost importance in athletes in order to choose the correct treatment option for the individual. Literature suggests that nasal symp-toms are more prevalent in athletes compared to the general population and certain sport environments might even trigger the development of symptoms. Given the high demands of respiratory function in athletes, insight into triggering factors is of high importance for disease prevention. Also, it has been suggested that athletes are more neglectful to their symptoms and hence remain undertreated, meaning that special attention should be paid to education of athletes and their caregivers. This review aims at giving an overview of nasal physiology in exercise as well as the possible types of nasal pathology. Additionally, diagnostic and treatment options are discussed and we focus on un-met needs for the management and prevention of these symptoms in athletes within the concept of precision medicine.

The ability of S. aureus to infect bone and osteoblasts is correlated to its incredible virulence armamentarium that can mediate the invasion/internalization process, cytotoxicity, membrane damage and intracellular persistence. We comparatively analyzed the interaction, persistence and modulation of expression of selected genes as well as cell viability in an ex-vivo model using human MG-63 osteoblasts of two previously studied and well-characterized S. aureus clinical strains belonging to ST239-SCCmecIII-t037 and ST228-SCCmecI-t041 clones at 3h and 24h post-infection (p.i). ATCC12598 was used as a control strain. Using Imaging Flow Cytometry analysis, we found that strains differently invaded osteoblasts after 3h and 24h: ATCC12598 internalized in 70% and 50% of cells, ST239-SCCmecIII in 50% and 45% and ST228-SCCmecI in 30% and 20%, respectively. ST239-III, during the infection period, exerted a significative cytotoxic activity due to the over-expression of hla and psmA and the increased expression of the genes involved in adhesion, probably due to the release and re-entry of bacteria inside MG-63 at 24h p.i. The lower invasiveness of ST228-I was also correlated with the non-cytotoxic activity inside osteoblasts. This clone was not able to activate a sufficient cellular reaction and succumbed in-side the MG-63 cells.

Calculating spatial ranges of species and individuals is a crucial problem throughout ecology. However, sample size biases can be strong, and defining range boundaries can be difficult. These hurdles can be overcome by calculating areas without calculating boundaries. The first step is to algorithmically define a graph that connects the spatial points where observations have been made. The routine generates a small number of short edges that form a pattern resembling a mosaic. The edge lengths are summed, squared, divided by the edge count, and multiplied by a known constant to obtain a total area estimate for the shape. This non-parametric mosaic area method can work with irregular outlines and clumped point distributions. It is more accurate than convex hull, kernel density, and hypervolume estimation according to simulation analyses. Mosaic area calculations can be used in areas ranging all the way from conservation biology to morphometrics.

Objective: To describe the use of local hospital guidelines on maternal care and fetal post-mortem work-up following intrauterine fetal death (IUFD) in Austria and to evaluate epidemiological factors influencing the availability of such in secondary and tertiary referral hospitals Design: Prospective national survey Setting: 75 secondary and tertiary referral hospitals providing obstetrical care in Austria Population: Obstetrical departments Methods: National survey with a paper-based questionnaire covering nine general questions regarding local hospital facilities and four comprehensive questions regarding medical approach following IUFD Main Outcome measures: Epidemiological data Results: 46 (61.3%) obstetrical departments [37 (80.4%) secondary; 9 (19.6%) tertiary referral hospitals] participated in this survey, of which 17 (37.0%) had local hospital guidelines on care after IUFD, whilst 29 (63.0%) denied. Availability of a local guideline was strongly correlated with the regular practice of post-mortem consultations (p=0.012). 16 (34.8%) hospitals replied to always schedule a follow-up consultation with affected parents, whilst 7 (15.2%) denied. In 8 (17.4%) hospitals post-mortem consultations would only be scheduled, if post-mortem examinations had been conducted. Neither type of institution (p=0.613), on-site pathology department (p=0.177), nor institutional annual live birth (p=0.291) and stillbirth rates (p=0.438) were found to influence the availability of local hospital guidelines. 26 (56.5%) participants considered a national guideline on IUFD necessary. Conclusion: Less than half of the surveyed institutions, regardless of annual live- or stillbirth rate and type of referral centre, have implemented a local guideline at their department. Availability of such may be influenced by regular conduction of post-mortem follow-up consultations.

The oceans face a range of complex challenges for which the impacts on society are highly uncertain but mostly negative. Tackling these challenges is testing society’s capacity to mobilise large-scale transformative action and engendering a sense of ‘doom and gloom’. Envisaging positive but realistic visions of the future, and considering how current knowledge, resources, and technology could be used to achieve these futures, may lead to greater action to achieve sustainable transformations. The Future Seas project (www.FutureSeas2030.org) aims to leverage interdisciplinary knowledge to improve society’s capacity to purposefully shape the direction of marine social-ecological systems over the UN Decade of Ocean Science for Sustainable Development (2021-2030). Teams comprising researchers across career stages, Indigenous Peoples and environmental managers, collaborated over a series of workshops to develop narrative futures for 12 Key Challenges facing the oceans. We focused the narratives on two futures: our current trajectory based on published evidence, and a more sustainable future, consistent with the UN’s Sustainable Development Goals, which is technically achievable using existing and emerging knowledge. Presentation of Business-as-usual and More Sustainable futures - together - allows communication of both trajectories, whilst also highlighting achievable , sustainable versions of the future. The advantages of the interdisciplinary approach taken here include: (1) integrating different perspectives on actions and solutions, (2) capacity to explore the interactions between Life Under Water (Goal 14) and other SDGs, and (3) cross-disciplinary learning. This approach allowed participants to conceptualise shared visions of the future and co-design transformative pathways to achieving those futures.

The concentration of human population along coastlines has far-reaching effects on ocean and societal health. The oceans provide benefits to humans such as food, coastal protection and improved mental well-being, but can also impact negatively via natural disasters. At the same time, humans influence ocean health, for example, via coastal development or through environmental stewardship. Given the strong feedbacks between ocean and human health there is a need to promote desirable interactions, while minimising undesirable interactions. To this end, we articulate two scenarios for 2030. First, Business-as-Usual, named ‘Command & (Out of) Control ’, focuses on the anticipated future based on our current trajectory. Second, a more sustainable scenario called ‘Living & Connecting ’, emphasises the development of interactions between oceans and society consistent with achieving the Sustainable Development Goals. We describe a potential pathway to achieving the ‘Living & Connecting’ scenario, centred on improving marine citizenship, achieving a more equitable distribution of power among stakeholders, and more equitable access to resources and opportunities. The constituent actions of this pathway can be categorised into four groups: (i) improved approaches to science and health communication that account for society’s diverse values, beliefs and worldviews, (ii) a shift towards more trusted relationships among stakeholders to enable two-way knowledge exchange, (iii) economic incentives that encourage behavioural changes necessary for achieving desired sustainability outcomes, and (iv) stronger regulations that simultaneously focus on ocean and human health. We contend that these changes will provide improved outcomes for both oceans and society over the UN Decade of Ocean Science.

Introduction: The AFQPHALS Survey (Adult Food Quality and Physical Activity Level Survey), is a semi-structured instrument consisting of 35 questions that evaluate food quality, level of physical activity and provision of health education in adults. Purpose: Evaluation of the content and logical validity of the AFQPHALS survey by a group of experts. Methodology: The evaluation of the content and logical validity of the AFQPHALS survey was conducted on May 17, 2020, by a group of experts, who evaluated the instrument independently. Each expert answered 9 questions in relation to the content and logical of the AFQPHALS survey, on a Likert scale from 1 to 5. After the evaluation of the content and logical validity of the AFQPHALS survey was performed AFQPHALS pilot test on an adult sample, who also assessed if they had encountered difficulties during the completion of the AFQPHALS survey and if the AFQPHALS survey questions needed further modifications, adjustments or improvements. Results: From the evaluation of experts resulted that, the average points of all the questions of the evaluation instrument of the AFQPHALS survey were 4.81 points (between I agree and completely agree). After AFQPHALS pilot test, in relation to the difficulties encountered during the completion of the survey and the need for further modifications, adjustments or improvements of instrument, resulted with no difficulties during the completion of the survey and with no need for further modifications, adjustments or improvements of instrument. Conclusions: After evaluating the AFQPHALS survey by a group of experts, and after AFQPHALS pilot test and evaluation of difficulty and need to improvements of the instrument by an adult sample, the AFQPHALS survey proved to be suitable for use in the population.  Keywords: AFQPHALS survey, content validity, logical validity, experts.

Background: Many patients with mild asthma are undiagnosed and untreated for low diagnostic sensitivity of the bronchodilation test (BDT). Objective: Investigating whether airway reversibility in BDT alone or together with fractional exhaled nitric oxide (FENO) can predict the response to anti-asthma therapy (RAT) in suspected asthma patients. Methods: This study included patients with chronic recurrent asthma symptoms, normal forced expiratory volume in 1 second (FEV1), and negative BDT. Inhaled corticosteroid (ICS) and long-acting β agonist (LABA) were given for 4 weeks. Positive RAT (PRAT) was defined as improved symptoms and increase of FEV1 > 200 mL after ICS/LABA. Lung tissues from 19 patients with lung nodules, grouped by predicted RAT, were also analyzed. Results: Of 102 patients, the PRAT group had higher FENO and greater absolute (∆) and (∆%) percent improvements of forced vital capacity, FEV1, and forced expiratory flows (FEFs) in BDT than the negative RAT group. The AUCs of FENO, ∆FEV1%, ∆FEF25-75%, and ∆FEF75% for PRAT were 0.703, 0.824, 0.736, and 0.710, with the optimal cut-off values of 33 ppb, 3.50%, 15.26%, and 26.04%. A joint model of FENO and ∆FEV1% increased the AUC to 0.880. IL-4, IL-5, IL-13, and NFκB were higher in lung tissues of patients with predicted PRAT than with predicted NRAT. Conclusion: ∆FEV1% > 3.50% in BDT together with FENO > 33 ppb predicted PRAT and an asthma diagnosis in patients with normal FEV1 and negative BDT. Evidence of pathological changes in the early stage of asthma increased the credibility of the predictive model.

Abstract: Introduction: Efficacious screening of severe obstructive sleep apnea (OSA) is important for children with sleep-disordered breathing before time-consuming nocturnal polysomnography. However, the predictive performance of clinical variables, nocturnal unattended pulse oximetry, and snoring sound analysis to screen for severe pediatric OSA has not been comprehensively investigated. Methods: Forty-two consecutive children (11 [26%] girls and 31 [74%] boys; median age, 9 years; median body-mass index of 19.0 kg/m2) with loud snoring were prospectively recruited to undergo standard polysomnography, nocturnal pulse oximetry, and snoring sound analysis. Results: Binary logistic regression models showed that oxygen desaturation index ≥ 3% (> 5.9 events/h), adenoidal‐nasopharyngeal ratio (> 0.782), snoring sound energy of 801-1000 Hz (> 22.1 dB), and tonsil size (> 3) significantly predicted severe OSA, in descending order of odds ratio. Multivariate analysis showed that oxygen desaturation index ≥ 3%, adenoidal‐nasopharyngeal ratio, and tonsil size independently predicted severe OSA, and that their combination best predicted severe OSA (sensitivity = 91%; specificity = 84%; area under the curve = 0.92; p < 0.001). Conclusions: Our results suggested that pulse oximetry is better than snoring sound analysis to screen for severe OSA in children with loud snoring. A combination of oxygen desaturation index ≥ 3%, adenoidal‐nasopharyngeal ratio, and tonsil size can be used to efficiently screen for severe pediatric OSA.

Background and Purpose: Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF) with unknown mechanisms. Due to sudden and unpredictable features of AF, detection or prediction of anthracycline-induced AF at early phase is difficult. Experimental Approach: Breast cancer patients (post-surgery) with an anthracycline-containing regimen were recruited for echocardiography at pre-, and 3 and 6 months post-chemotherapy. Mice were injected with doxorubicin or vehicle and the following parameters were determined: left atrial diameter, electrical transmission, AF inducibility. Meanwhile, oxidative stress, cardiomyocyte size, vacuolization, inflammation and fibrosis were measured in mouse atria. The therapeutic effect of dexrazoxane on doxorubicin-induced changes in the aforementioned parameters were also determined. Key Results: Whilst ventricular parameters and functions were unchanged in cancer patients pre- and post-chemotherapy, strain and strain rate of left atrial reservoir function and conduit function were decreased at 3 months post-chemotherapy vs pre-chemotherapy. Doxorubicin-induced atrial dilatation and susceptibility to AF occurred in mice prior to onset of ventricular dysfunction. Doxorubicin-induced AF was via inducing structural remodeling (i.e. cardiomyocyte death, hypotrophy and vacuolization) and electrical remodeling (i.e. reduction and redistribution of connexin 43) in the atrium, which was effectively prevented by dexrazoxane. Atrial remodeling and AF inducibility were induced after doxorubicin injection, which can be inhibited by dexrazoxane. Conclusions and Implications: Clinically, we tested whether anthracycline-induced early atrial remodeling in patients could be detected by echocardiography. Experimentally, we investigated the mechanisms of doxorubicin-induced atrial remodeling and AF in mice, and the protective effect of the free radical scavenger dexrazoxane.

ABSTRACT Nowadays , thrombophilia is one of the leading causes of RPL which has negative side effects due to psychological effect and the high expenses of investigations and attempts to get normal full term pregnancy up to ICSI trials in some cases. So as early as possible we try to diagnose the cause of abortion and treat it to avoid another bad experience of abortion. Aim of the work: to evaluate the correlation of factor V Leiden and MTHFR C677T gene mutation in primigravida late first trimester abortion and to identify candidates for anticoagulation therapy to improve pregnancy outcome .METHODOLOGY: polymerase chain reaction (PCR) and reverse-hybridization were used to assess MTHFR and FV leiden mutations . Results: MTHFR C 677T mutations were 42.5 %. While factor V leiden gene mutation were 20%. Combined MTHFR C 677T mutations and factor V leiden was 10 %, normal cases were 27.5%. The cases without MTHFR C 677Tgene mutations were 47.5% . While The cases with MTHFR C 677T mutations were 52.5%. Heterozygous MTHFR C 677T mutations cases were 37.5 % , homozygous cases were 15% .The cases without Factor V Leiden gene mutations were 70 %, cases with Factor V Leiden mutations were 30%. All cases with Factor V Leiden mutations were heterozygous and there was no homozygous cases. Conclusion: MTHFR mutation is highly expected in late first trimester missed abortions in primigravida specially the heterotype so significantly affect the pregnancy adversely while FACTOR V LEIDEN mutation is less likely to be found.

Objective To evaluate the total, and direct effects of vitamin D, measured by circulating 25-hydroxyvitamin D [25(OH)D] levels, on GWG after adjustment for confounding variables, and then assess the indirect effects by demonstrating the role of gestational age at birth as a mediator in this association. Design A secondary analysis of data collected in a screening program in pregnancy. Setting and population Data collected in “Khuzestan Vitamin D Deficiency Screening Program in Pregnancy” was used for the present study; it was included the data of 900 pregnant women referred to the health centers of Shushtar (Khuzestan Province, Iran), whose vitamin D status during the third trimester of pregnancy was available. Methods A mediation analysis was applied to detect the causal relationship between serum level of 25(OH)D, covariates (maternal age, parity, and baseline maternal weight), mediator (gestational age), and outcome (GWG). Main outcome measures The main outcome measure of the study was gestational weight gain. Results The adjusted total effect of vitamin D on GWG was estimated 0.0699 (95%CI: 0.0537, 0.0849; P=0.000). Although, an adjusted direct effect of vitamin D on GWG was not statistically significant, the adjusted indirect effect of this micronutrient on GWG by considering gestational age as a mediator was found to be significant [0.059 (95%CI: 0.048, 0.0708; P=0.000)]. Women with severe vitamin D deficiency had the lowest speed as compared to moderate and normal levels. Conclusion This study shows that maternal vitamin D status affects the gestational weight gain by reducing the risk of preterm delivery.

Recently, the survival of Mycobacterium bovis on livestock mineral blocks has been confirmed, but little is known about its implication in the transmission of animal tuberculosis (TB) under field conditions. The objective of this study was to describe the shared use of mineral supplements in four extensive beef cattle farms from a high TB prevalence area in South Central Spain, to identify the main factors explaining their use, and characterize its potential role for the transmission of Mycobacterium tuberculosis complex (MTC). This is relevant to design control measures at the wildlife-livestock interface. Animal activity was monitored by camera-trapping at 12 mineral supplementation points during spring and fall. Additionally, swabs were periodically taken from the mineral substrates and analyzed by PCR searching for MTC DNA. Cattle, pig, goat, sheep, wild boar and red deer were all recorded licking on mineral supplementation points. Livestock species were the main users and presented a diurnal use pattern. Wild ungulates presented a nocturnal-crepuscular use pattern, with scarce overlapping with livestock. Wild boar presence was positively related to cattle presence at mineral supplementation points, whereas red deer presence was higher in supplemental points closer to forested areas, mostly in absence of cattle. We recorded 266 indirect wildlife-livestock interactions (i.e. two consecutive visits that occurred within 78h), all of them derived from 21 unique wildlife visits. All the analyzed swabs resulted negative to MTC DNA. Comparing to other environmental sources of MTC in our study area, mainly water ponds, this research evidenced that mineral blocks are less attractive to wildlife. However, the potential for interspecific transmission of MTC or other pathogens cannot be discarded. The risk for interaction at mineral supplementation points and further transmission can be prevented by implementing specific measures in the context of integral biosecurity plans at the wildlife-livestock interface, which are proposed.

Ligand field theory (LFT) calculations of energy levels were performed for the neutral actinide monooxides (AnO) and their singly and doubly ionized cations (AnO+ and AnO2+ by treating the molecular electronic states as Anm+ free-ion energy levels (where An ∈ Th through Lr and m=1, 2, 3, or 4) perturbed by the electric field of O2- or O-. LFT parameters obtained from fits to the energy levels of ThO, ThO+, UO, and UO+ were used to compute molecular energy levels for the lowest energy (maximum Sc, maximum Lc) 5f-core states of An4+, An3+, An2+, and An+ for the majority of the An4+O2-, An3+O-, An3+O2-, An2+O-, An2+O2- , and An+O- electronic configurations. Simple linear relationships enabled predictions of the dissociation energies for AnO, AnO+ and AnO2+ (where An ∈ Bk through Lr) and ionization energies for AnO and AnO+ (where An ∈ Bk through Lr), mainly based on recent accurate experimental data for the ionization energies of An atoms (where An ∈ Fm, Md, No, and Lr) and correlations with the energetics of the atoms and ions.