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Background The pediatric HIV follow-up is challenging, and treatment indicators are markedly distant from UNAIDS goals. In this study, we describe the 2019 Brazilian HIV cascade according to age categories and sociodemographic variables and address temporal trends between 2009-2019. Methods We obtained data from the Brazilian Ministry of Health monitoring database. Cascade outcomes included retention in care, antiretroviral use, and viral suppression. The effect of age on timely initiation of antiretroviral treatment (ART, initiation with CD4+ T cell count ≥350 cells/mm3 or a first ART dispensation ≤30 days after the first CD4+ T cell measurement) and detectable HIV viral load (>50 copies/mL) was assessed in univariable and multivariable analysis adjusted for gender, race, and Social Vulnerability Index (SVI). Temporal trends in timely ART initiation and viral suppression were evaluated graphically. Results Among 771,774 people living with HIV (PLHIV), those from youngest age categories had poorer indicators in the care cascade (Figure 1). PLHIV in younger age groups, those with higher SVI, and those declaring black and native Brazilian race/ethnicity, had higher odds of having detectable viral load and delayed ART initiation (Table 1).Social aspects are also associated with worse outcomes. Although children living with HIV tend to start ART with higher CD4+T cell counts, time-series analysis suggest that improvements observed in the adult population do not extend to the pediatric population (Figure 2) Continuum of care in Brazil, 2019 Retention in care, antiretroviral use and viral load suppression in people living with HIV under care in the Brazilian Unified Health System in 2019, overall and by age category (N=771,774). Temporal trends, Brazil (2009-2019) Temporal trends of timely initiation of ART based on a CD4+ T cell count ≥500m/mm3 (panel A), timely initiation of ART based on a first ART dispensation ≤30 days after the first CD4+ T cell count measurement (panel B) and viral load suppression (panel C) overall and according to age categories between 2009 and 2019 in Brazil. Table 1Associations between demographic variables and timely initiation of ART (based on a CD4+ T cell count ≥350m/mm3 or ≤30 days after the first CD4+ T cell count measurement) and detectable viral load using univariable and multivariable logistic regression models in the 2019 dataset. Conclusion Our results highlight the challenge faced by children and adolescents living with HIV to achieve UNAIDS goals. Lower access to ART among children is a central barrier to improve pediatric care. Disclosures All Authors: No reported disclosures.

Background Multivalvular surgery (MV) requires prolonged extracorporeal circulation (ECC) and aortic cross-clamp times (X-Ao). Rapid-deployment aortic prosthesis (RD-AV) allow lower ECC and X-Ao times in isolated aortic valve surgery (AVR), but have not been studied in MV surgery. Purpose To determine if RD-AV use influences early outcomes when compared to biological stented or mechanical aortic valves in MV surgery. Methods Retrospectively collected pre, intra and immediate post-operatory data on all MV adult patients with AVR operated on our Department from January 2016 to February 2022. Bentall surgery and aortic dissection patients were excluded. A propensity score matching (PSM) of patients receiving RD-AV (Group A) compared to patients with non-RD-AV (Group B) was performed using sex, age, Euroscore II, type of surgery (involved valves, CABG, ascending aortic replacement), active endocarditis, ventricular function and redo surgery. After PSM, we compared outcomes until death or discharge. Normal distribution of samples was tested using the Kolmogorov-Smirnov test. Normal data was analysed with unpaired t-testing and non-normal data with non-parametric Mann Whitney U test. Categorical data were analysed with Fisher test. A significance level of p Results 205 patients received non-RD-AV and 58 patients RD-AV. After PSM, 57 pairs of patients were obtained. Sex, BMI, Euroscore II, age, redo surgery, insulin dependent DM, baseline creatinine, left ventricle ejection fraction, right ventricle dysfunction, pulmonary artery systolic pressure, and active endocarditis were similar in both groups. Intra-operatory, RD-AV valves (Group A) were associated with shorter surgery duration (167.3±52 vs 206.6±91 min, p=0.005), shorter ECC duration (89.5±36.5 vs. 118.9±56.5 min, p=0.002), and aortic X-clamp time (71.6±28 vs. 98.9±38.2 min, p Conclusion Despite shorter surgery duration, ECC duration and aortic X-clamp duration, RD-AV have similar early outcomes when compared with non-RD-AV in multivalvular surgery. Funding Acknowledgement Type of funding sources: None.

Aim This study evaluates the versatility and performance of a novel adhesive for atraumatic hernia mesh fixation. The TISSIUM adhesive is a biodegradable and biocompatible viscous liquid that can be precisely applied to different tissue and mesh.1 Once in place, the surgeon utilizes a light probe to polymerize the adhesive, creating a flexible elastomeric connection that provides strong, durable and atraumatic mesh fixation. Materials and Methods The performance of the TISSIUM adhesive when used with a range of marketed mesh and against peritoneum (n=7) and muscle (n=3) was evaluated using a standardized lap-shear bench method using porcine tissues. The shear strength was compared to resorbable tacks (n=8) (against peritoneum as standard of care in IPOM) and self-adhesive meshes (n=4) and fibrin glue (n=3) (against muscle as classically used in the retromuscular approach). Results Lap-shear data revealed that the TISSIUM adhesive performance was equivalent to resorbable tacks when fixing meshes to the peritoneum. Similar testing protocol demonstrated that the TISSIUM adhesive shear strength was 6 to 13 times superior to non- penetrating fixation devices such as fibrin glue or self-adhesive mesh. Conclusions The use of the TISSIUM Adhesive for hernia mesh fixation is compatible with various mesh materials used in hernia repair and, in a bench model, outperforms existing non-penetrating methods in diverse tissue planes demonstrating the potential to help the surgeon achieve more effective and efficient atraumatic repair in a range of hernia procedures.

Study question Are the embryological, clinical and newborn outcomes using aspirated testicular sperm improved in cases with recurrent implantation failure previously treated with ejaculated sperm? Summary answer Aspirated testicular sperm enabled to obtain significant higher embryological, clinical and newborn outcomes in cases with recurrent implantation failure previously treated with ejaculated sperm. What is known already High levels of sperm DNA fragmentation (SDF) were associated to poor clinical outcomes (1-Simon et al., 2017). Testicular sperm display lower SDF than ejaculated sperm (2-Sakas and Alvarez, 2010), improving clinical outcomes in cases with abnormal semen parameters (3-Awaga et al., 2018; 4-Kang et al., 2018), recurrent implantation failure (RIF) and pregnancy loss (RPL) (5-Esteves et al., 2017), and elevated SDF (6-Ambar et al., 2021). As only a few studies are specifically dedicated to RIF, we expanded the number of cases and first provided full demographic, stimulation, embryological, clinical and newborn outcomes. References 1-(https://doi.org/10.4103/1008-682X.182822); 2-(https://doi.org/10.1016/j.fertnstert.2009.10.046); 3-(https://doi.org/10.1016/j.rbmo.2018.08.017); 4-(https://doi.org/10.1038/s41598-018-26280-0); 5-(https://doi.org/10.1016/j.fertnstert.2017.06.018); 6-(https://doi.org/10.5534/wjmh.200084 Study design, size, duration We retrospectively evaluated during consecutive years (2010-2020) 63 patients with recurrent implantation failure, which accepted to perform testicular sperm aspiration (TESA) as an alternative treatment. These patients presented a long history of failed treatments (153 cycles) using ejaculated sperm. From these cycles, no pregnancy ensued. The present study compares 127 treatment cycles, 80 with testicular sperm (17 cases repeated TESA) and 47 with ejaculated sperm from the same patients performed at the present IVF clinic. Participants/materials, setting, methods Patients were screened for karyotype abnormalities, for Y-chromosome microdeletions (7-Gonçalves et al., 2016), and for SDF with the TUNEL assay (8-Sá et al., 2015). Conventional semen analysis was performed according to World Health Organization guidelines (9-WHO, 2010). Male evaluation and TESA was performed by the same experienced urologist (LF) according to established protocols (10-Madureira et al 2014). The procedure was performed entirely on an outpatient basis, with no complications reported. References 7-(https://doi.org/10.4103/1008-682X.172827); 8-(https://doi.org/10.1016/j.rbmo.2015.06.019); 9-(https://apps.who.int/iris/handle/10665/44261); 10-(https://doi.org/10.1111/j.2047-2927.2014.00231.x). Main results and the role of chance The mean ages were 35.5±3.4 (26-42)-female and 38.1±5.7 (29-59)-male. There were 4 abnormal karyotypes (3-female, 1-male), all without known relevance. Most cases had asthenozoospermia and teratozoospermia (65.1%), or oligoasthenoteratozoospermia (41.8%). Of the 19 cases with 20%; 8, >36%). Female basal characteristics and testicular evaluation were under normal values. The TESA procedure took about 15-20 min, and the time of laboratorial search around 30-60 min. Cases using testicular sperm showed significant higher rates of fertilization (64% vs 73%-p=0.005), blastocyst development (47% vs 62%-p=0.010), implantation (6% vs 27%-p=0.000), clinical pregnancy (10% vs 39%-p=0.001), live birth delivery (5% vs 28%-p=0.005) and newborn (5% vs 32%-p=0.000) than ejaculated sperm. No significant differences were observed regarding the rates of embryo cleavage (95% vs 94.8%) and high quality embryos (89.4% vs 94%), in the mean number of transferred embryos (1.8±0.4 vs 1.9±0.4), or in the abortion rate (2 cases-50% vs 7 cases-25.9%). Cases using testicular sperm had 22 frozen-thawed embryo transfer cycles, enabling per initiated cycle a cumulative pregnancy rate of 45%, live birth delivery rate of 31.3% and newborn rate of 37.5% (32 newborn). Limitations, reasons for caution Although presenting the higher number of cycles using TESA in the treatment of RIF, this number needs to be increased for drawing more definitive conclusions, as these women present a diversity of conditions, rendering subgrouping difficult. In the future, it would also be important to evaluate SDF in all cases. Wider implications of the findings In conclusion, the present results gave further evidence for the superiority of using testicular sperm instead of ejaculated sperm in cases with recurrent implantation failure. Data also evidences the security of using testicular sperm aspiration, as there were no pregnancy or delivery complications, or congenital anomalies among the 32 newborn. Trial registration number Not Applicable

Rare populations, such as endangered animals and plants, drug users and individuals with rare diseases, tend to cluster in regions. Adaptive cluster sampling is generally applied to obtain information from clustered and sparse populations since it increases survey effort in areas where the individuals of interest are observed. This work proposes a unit-level model which assumes that counts are related to auxiliary variables, improving the sampling process by assigning different weights to the cells, besides referring to them spatially. The proposed model fits rare and grouped populations arranged on a regular grid in a Bayesian framework. The approach is compared to alternative methods using simulated data and a real experiment in which adaptive samples were drawn from an African buffalo population in a 24,108 square kilometer area in East Africa. Simulation studies show that the model is efficient in several settings, validating the method proposed in this paper for practical situations.

Background The perturbation of the symbiotic relationship between microbes and the intestinal immune system contributes to Inflammatory Bowel Disease (IBD) development even years before diagnosis. However, the causes underlying the loss of gut microbial equilibrium (dysbiosis) associated with inflammation still remain unknow. The host glycocalyx (repertoire of glycans/sugar-chains at the surface of gut mucosa) constitutes a major biological interface between gut mucosa and microorganisms1. In this study we aimed to evaluate whether and how an altered host glycome perturbs microbiome composition associated with dysbiosis and initiation of intestinal inflammation. Methods We have modulated the glycosylation profile at the level of gut mucosa using specific glycoengineered mouse models (KO) that exhibit specific alterations (deficiencies) in glycosylation composition. Colitis was induced using DSS and microbiome analysis was performed by 16S rDNA sequencing both in WT and KO mice. The mucosa glyco-immunoprofile was characterized. Results We first demonstrated in different glycoengineered mice that changes in the composition of glycans at gut mucosa resulted in dysbiosis characterized by a significant decrease in beneficial members of the Firmicutes phylum compared with WT mice. These mice with deficiency in mucosa glycosylation exhibited a higher susceptibility to colitis2. Then, and to determine the causal effect of mucosa glycosylation-induced microbiota modulation, we co-housed KO and WT mice. After 5 weeks of cohousing with WT mice, the KO mice exhibited a much less severe colitis and an increased proportion of bacteria from Firmicutes phylum compared to single housed KO mice. Inferred metagenomics analysis further revealed an alteration of the glycosylation biosynthetic pathway that was apparently shared and gained upon co-housing the KO mice with WT. The analysis of colonic inflammatory infiltrate from cohoused KO mice showed an increased expression of IL17 and IL22 production in gut mucosa, at baseline and before DSS. This pinpoints a potential protective effect of the enhancement of glycosylation biosynthesis (through microbiome sharing with WT) for preventing dysbiosis and dysregulation of gut immune response. Conclusion In this study, we demonstrate that changes in composition of glycans at the gut mucosa level is associated with dysbiosis and susceptibility to colitis. These results illustrate the relevance of the gut glycome in shaping the gut microbiota, highlighting its role in maintaining a homeostatic crosstalk between the microbiome and host immunity. This study was funded by ECCO Pioneer Award. 1. Verhelst, Gastroenterology 2020. PMID: 31626754 2. Dias et al PNAS 2018 PMID: 29720442

Background Coronavirus disease 2019 is a systemic entity, where cardiac involvement has been described. The echocardiogram is a diagnostic tool that describes myocardial damage with good certainty. Objectives Determine which echocardiographic parameters are predictors of mortality. Analyze if there is a difference in clinical, laboratory and echocardiographic variables in terms of patients who died versus those who survived. Investigate the cut-off point of the echocardiographic parameters that is best associated with mortality. Methods Prospective, analytical, comparative study. Patients admitted to the hospital with Coronavirus 2019 infection. Clinical, laboratory and echocardiographic variables will be assessed. The association with three-month mortality of the different variables will be determined. We used ROC-curves for the best cut-off associated with mortality. The association with three-month mortality was analized using Cox regression, unadjusted analysis of the variables was performed, as well as adjusted analysis for age and gender. Results 84 patients were included, a mortality of 29% was documented. Significant differences were found in the left atrial volumen index, the E/e', the proportion of dilatation of the right ventricle and diastolic dysfunction. Tricuspid annulus anterior systolic excursion (TAPSE), pulmonary artery acceleration time (PAA), tricuspid regurgitation velocity (TRV), pulmonary artery systolic pressure (PASP), left ventricular longitudinal strain (LVGLS), of the left atrium (LAGLS) and the right ventricular free wall longitudinal strain (RVFWLS). Right ventricular dilation, right ventricular shortening fraction, TAPSE, PASP, TRV, LVGLS, LAGLS, and RVFWLS were associated with mortality. Conclusion Right ventricular dilation, right ventricular shortening fraction, TAPSE, PASP, TRV, LVGLS, LAGLS, and RVFWLS are the echocardiographic parameters that were associated with three-month mortality. Funding Acknowledgement Type of funding sources: None. Table 2

Summary Among the many disparities for which Brazil is known is the difference in performance across students who attend the three administrative levels of Brazilian public schools: federal, state and municipal. Our main goal is to investigate whether student performance in the Brazilian Mathematical Olympics for Public Schools is associated with school administrative level and student gender. For this, we propose a hurdle hierarchical beta model for the scores of students who took the examination in the second phase of these Olympics, in 2013. The mean of the beta model incorporates fixed and random effects at the student and school levels. We explore different distributions for the random school effect. As the posterior distributions of some fixed effects change in the presence, and distribution, of the random school effects, we also explore models that constrain random school effects to the orthogonal complement of the fixed effects. We conclude that male students perform slightly better than female students and that, on average, federal schools perform substantially better than state or municipal schools. However, some of the best municipal and state schools perform as well as some federal schools. We hypothesize that this is due to individual teachers who successfully motivate and prepare their students to perform well in the mathematical Olympics.

The ensilage of total mixed ration (TMR) is a technology designed to help farmers with limitations to provide a balanced diet for their herds. Our aim was to evaluate the conservation of TMR ensiled in round bales with or without holes in the wrapping plastic film. Eight round bales of a corn silage-based TMR of 1,000 kg (370 kg DM/m3) were prepared. Ten days (d) after ensiling, four bales were randomly punctured with two holes of 25 cm2 each in opposite sides of the bale. The temperature in the center of the bales was recorded during the storage using dataloggers. After 60 d of storage, bales were weighted to assess dry matter (DM) recovery. Silages were sampled for measuring DM content, chemical composition, pH, lactic acid, and microbial counts. The temperature of the sliced bale face was assessed by infrared thermography. The holes in the plastic affected the DM content, DM recovery, and pH, whereas lactic acid, microbial counts, and temperature were not affected by treatments. The holes in the sealing plastic film should be avoided. However, holes of 25 cm2 each were not capable of causing expressive losses in TMR silage stored in 1,000 kg bales.

Issue In the state of São Paulo (SSP), the rate of mother-to-child transmission of HIV (MTCT) was estimated at 2.7%, in 2006. However, for reaching elimination, its level should be Description of the Problem The occurrence of MTCT cases shows failures of healthcare system. The aim of this study was to assess the response of the Sao Paulo State STI/AIDS Program to prevent MTCT, from 2010 to 2018. A descriptive analysis of clinical monitoring indicators of the PWLH was performed. The National Surveillance Data System was used to estimate the underreporting of cases. Data from antiretroviral drug delivery, viral load (VL) and genotyping results were used to calculate the indicators and were obtained through database of the National Antiretroviral Drug System, Laboratory Control System and Genotyping System. Results In the period, despite identifying 15,463 PWLH in the systems, only 11,316 were notified (26.8% underreporting). Comparing 2010 and 2018, there was an improvement in accessing combined antiretroviral therapy (cART) from 81.2% (1,366/1,683) to 86.6% (1,543/1,782); in performing of VL before delivery from 70.8% (1.192/1.683) to 72.8% (1.298/1.782); in VL suppression Lessons The decrease in the number of cases suggests improvement in preventing MTCT in the SSP. However, many challenges remain, such as breaking down individual, social and programmatic barriers to expand access to cART, pretreatment genotyping, VL suppression before delivery, retention in care and adherence to cART over time. Key messages The National Systems of surveillance, antiretroviral drugs, laboratory and genotyping network are important for performing clinical monitoring, reducing treatment gaps and underreporting. The integration of the Sexually Transmitted Infections and HIV/AIDS Program with the Primary Care and the Maternal and Child Health Program is essential to achieve the goals of eliminating MTCT.

Although it is recognized that mental disorders are more likely to occur in adulthood, especially in university period, and result in damage to health and incapacity for work, researches with university population are scarce in Brazil. We aimed to evaluate the prevalence of Minor Mental Disorders (MMD) among undergraduate students of a public university of São Paulo state, and investigate its association with social and economic conditions, sexuality and gender. This is a cross-sectional study conducted in 2018 with 376 undergraduate students who were halfway through the course. Data were collected from an anonymously and self-administered questionnaire, and MMD was evaluated from Self Report Questionnaire (SRQ-20). Associations were estimated through logistic regression, and odds ration calculated. We found prevalence of 53.9% of MMD among the students, and associated with gender (OR, 3.66; 95% CI, 2.37-5.67), being LGBT + (e.g Bisexuals OR, 2.92; 95% CI, 1.56-5.50), not receiving necessary family support (OR, 5.6; 95% CI, 2.00 - 15.68), not being satisfied with the course (OR, 23.69 95% CI, 2.95 - 190,03) and not practicing physical activities regularly (OR, 2.05; 95% IC, 1.33 - 3.17). Minor mental disorders prevalence found was high, reaching more than 70% in some courses (e.g 77.8% among Biomedicine students), mainly associated with gender, sexual orientation and emotional support. Our study draws attention to the urgency of monitoring the mental health status of undergraduate students, and implementing mental health centers at universities, as well as facilitating access and improve existing centers. Key messages The high prevalence of minor mental disorders found among undergraduate students indicates the urgent need for interventions in this populations. Women and LGBT+ students are groups at higher risk for the development of minor mental disorders at university. Strategies must be created to reduce the higher prevalence in this populations.

Background To estimate median survival time of AIDS patients, with and without tuberculosis (TB), in a cohort in Sao Paulo, Brazil, and to investigate survival predictors. Methods Retrospective cohort study of AIDS patients above 12 years old, registered at the Ministry of Health AIDS surveillance system between 2003-2007, and followed until 2014. Survival analysis used the Kaplan-Meier method and Cox proportional hazards model to estimate hazard ratios (HR), with respective 95% confidence intervals (CI = 95%). Results 35,515 patients were included, being 4,581 (12.9%) co-infected with TB. Among the latter, probability of survival 12 years after AIDS diagnosis was 95.2%, 82.9%, and 21.9%, respectively for patients receiving at least one third line ARV (HAART2), receiving triple therapy (HAART1) and the last one not on ARV. In the same period, the probability of survival for patients without TB, in the same order as for the therapeutic regimens, was 95.2%, 90.5%, and 40.9%, respectively. The main factors associated with survival, adjusted for the year of diagnosis, were: Living in the city of Sao Paulo (HR = 1,16;IC95% 1,01-1,32), living away from the capital city (HR = 1.43; 95%CI 1.25-1.62); or on the coast (HR = 1.49; 95%CI 1.21-1.82); having TB (HR = 1.70; 95%CI 1.49-1.87); above 49 years old (HR = 1.35; 95%CI 1.18-1.54); black (HR = 1.27; 95%CI 1.12-1.45); IV drug use (HR = 1.73; 95%CI 1.49-2.02); CD4+ below 200 cell/mm³ at AIDS diagnosis (HR = 2.31; 95%CI 1.97-2.72); viral load above 500 copies at AIDS diagnosis (HR = 1.99; 95%CI 1.72-2.30); HAART1 scheme (HR = 1.94; 95%CI 1.47-2.55); no ARV (HR = 8.22; 95%CI 2.95-22.87). Conclusions A large proportion of patients did not receive ARVs or were late diagnosed with AIDS, especially those with TB, whose survival was shorter. Survival is heterogeneous in the state, being lower in regions with higher TB rates. The results point to the need for specific strategies for patients with TB-HIV co-infection. Key messages Tuberculosis is the main cause of death among HIV-infected people, being responsible for one third of deaths in this group and causing a great impact on the survival of this population. The Brazilian policy of universal access to ARV and treatment for TB has increased the survival of AIDS-TB from 22% to 95% and in patients without TB from 50% to 95% up to 12 years after diagnosis.

Recurrent ventricular tachydisrhythmias (VT) episodes have a negative impact in the outcome of patients (P) already with an implantable cardioverter-defibrillator (ICD). Elimination of arrhythmic reentry circuits represents a difficult challenge, mainly due to the induction of intolerable VTs, with multiple ECG morphologies, requiring rapid interruption. Substrate guided ablation has been used as a promising approach strategy to treat recurrent VTs. Aim: to assess long-term results of a VT substrate-based ablation using high-density mapping in P with an ICD, severe left ventricular (LV) dysfunction and recurrent appropriate ICD therapy. Methods: 16P (12 men, non-ischemic cardiomyopathy 67%, 55 ± 13 years, LV ejection fraction 32 ± 6%) and recurrent appropriate shocks despite antiarrhythmic drug therapy and optimal heart failure medication. All P underwent a protocol of ventricular programmed stimulation (600 ms/S3) to obtain baseline VT documentation. A sinus rhythm (SR) voltage map was created using a 3D electroanatomic mapping system (CARTO) with a high-density mapping catheter (PentaRay) to delineate areas of scarred myocardium (ventricular bipolar voltage ≤0,5 mV – dense scar; 0,5-1,5 mV – border zone; ≥1,5 mV – healthy tissue) and provide high-resolution electrophysiological mapping. The substrate modification included catheter elimination of local abnormal ventricular activities (LAVA) - fractionated, splited, low-amplitude/long-lasting, late potentials, pre-systolic potentials - and linear ablation to obtain scars homogenization and scar dechanneling. Pace-mapping techniques were used when capture was possible. LV approach was retrograde in 6 cases, transeptal in 4 and endo-epicardial in 2 cases. In 2P the ablation was performed in the right ventricle. Results: VTs were induced and interrupted with bursts or external DC shocks. LAVA were identified and ablated in all P. Eleven P underwent modification of scar areas. The mean duration of the procedure was 153 mn (103-218 mn), with radiofrequency ranging from 18 to 60 mn (mean 33 min), and a mean fluoroscopy time of 16 mn. Non-inducibility was achieved in 75% of the cases. There was 1 pericardial tamponade drained successfully. During a follow-up of 48 ± 18 months, 75% had no VT recurrences, 2P underwent redo ablation, 1P died from stroke. Conclusion: Catheter ablation of VT based on substrate modification guided by high-density mapping is feasible and safe in P with LV dysfunction. This approach may be of clinical relevance, with potential benefits in reducing VT burden.

Understanding short-range cues (e.g., host odorants, heat, moisture) of host-seeking female Aedes aegypti L. is very important for attempts to reduce mosquito bites, to complement current control strategies, and to develop potential spatial repellents. We investigated behavior under semi-field conditions utilizing a new portable uni-port taxis box with a caged chicken host. The combined influences of airflow regimes (0, 1.5, 3, 5, and 6 m/s), distance from host odor (10, 50, 100 cm), host-odor confinement (partial confinement/unconfined), and foraging periodicity (day/evening) were studied. Statistical regression analysis was used to delineate the significant factors that predict upwind flight behavior and short-range source location. Almost 15% of host-seeking Ae. aegypti were activated by an unconfined chicken odor in still air. This was double the number of attracted mosquitoes to confined host odor. The maximum behavioral response was reported with airflow of 5 m/s during daytime (76.7% ± 2.85) at a distance of 10 (70.7% ± 2.47) and 50 cm (56.7% ± 8.88). However, airflow of 6 m/s activated host-seeking orientation during evening assays. The host-seeking response between indoor and outdoor experiments was not significantly different and demonstrated the reliability of the portable taxis box in evaluating mosquito short-range behavioral response toward hosts.

Aedes aegypti (L.) (Diptera: Culicidae) are known to flourish in a variety of natural and residential habitats and are competent vectors of at least 22 different arboviruses, including dengue, chikungunya, and Zika. Their global distribution, anthropophilic nature, and vector competency make them species of interest for control. A novel durable dual-action lethal ovitrap (DDALO) with combined larviciding and adulticiding effects, as well as a slow-release polymer (isobutyl methacrylate), was designed to target Ae. aegypti. The use of the DDALO resulted in high adult mosquito mortality (~95-100%) in no-choice laboratory cage studies targeting gravid females and successfully prevented all deposited eggs from hatching. Aging of the traps caused some loss in activity over time, but they still caused adult mortality (~50%) and continued to prevent successful hatching of eggs for 6 mo. Oviposition preference studies resulted in ~4.5 times as many larvae developing in untreated DDALOs compared with the other containers combined. Small-cage multigenerational studies resulted in significantly lower populations of adult mosquitoes in cages containing treated DDALOs after 4 wk. Successful laboratory studies show that the DDALO appears to be a promising tool that could be used for controlling wild vector populations of Ae. aegypti in combination with other mosquito control practices.

Many decision-makers are looking to science to clarify how nature supports human well-being. Scientists' responses have typically focused on empirical models of the provision of ecosystem services (ES) and resulting decision-support tools. Although such tools have captured some of the complexities of ES, they can be difficult to adapt to new situations. Globally useful tools that predict the provision of multiple ES under different decision scenarios have proven challenging to develop. Questions from decision-makers and limitations of existing decision-support tools indicate three crucial research frontiers for incorporating cutting-edge ES science into decision-support tools: (1) understanding the complex dynamics of ES in space and time, (2) linking ES provision to human well-being, and (3) determining the potential for technology to substitute for or enhance ES. We explore these frontiers in-depth, explaining why each is important and how existing knowledge at their cutting edges can be incorporated to improve ES decision-making tools.

We conducted a study in which body composition, energy and protein requirements, and efficiency of MP and ME were determined in F1 Boer × Saanen goat kids of 5 to 25 kg BW by using the comparative slaughter technique. Two experiments were performed: Exp. 1 estimated the maintenance requirements of kids from 15 to 25 kg BW, and Exp. 2 estimated the gain requirements of kids from 5 to 25 kg BW. In Exp. 1, 28 intact male F1 Boer × Saanen goat kids were utilized, with 7 kids slaughtered (BW of 15.0 ± 0.35 kg) at the onset for estimation of initial body composition and the remaining 21 kids assigned to a randomized block design. Within each block, kids were subjected to 3 levels of feed intake treatments (ad libitum [100%] or restricted to 70% or 40% ad libitum). All kids in each block were slaughtered when the animals fed ad libitum reached 25 kg BW. The NE, ME for maintenance, and partial efficiency of use of ME for NE were 321.6 kJ/kg BW, 525.9 kJ/kg BW, and 0.61, respectively. The net protein and MP for maintenance were 2.43 g/kg of BW and 4.41 g/kg of BW, respectively; thus, the estimated partial efficiency of MP for maintenance was 0.55. In Exp. 2, 32 intact male F1 Boer × Saanen goat kids were distributed in a completely randomized design and slaughtered at 5.6 ± 0.85 kg BW ( = 6), 10.0 ± 0.35 kg BW ( = 6), 15.3 ± 0.52 kg BW ( = 7), 20.4 ± 0.66 kg BW ( = 6), and 25 ± 0.46 kg BW ( = 7). Body composition was then fitted to allometric equations. Body fat composition increased from 37 to 114 g/kg empty BW (EBW; < 0.001), and body protein composition decreased by 10% (from 203.2 to 180.6 g/kg EBW; < 0.001) when kids grew from 5 to 25 kg BW. The NE increased by approximately 60% (from 7.2 to 11.5 MJ/kg of empty BW gain [EWG]; < 0.001), and the net protein for gain decreased by 10% (from 186 to 166 g/kg of EWG; < 0.001). The partial efficiency of the utilization of ME to NE for growth was 0.32 ( < 0.0001), and the partial efficiencies of the utilization of ME for the synthesis of protein and fat were 0.19 and 0.59 ( < 0.011), respectively. These results demonstrate that the protein and energy maintenance requirements in young crossbred goat kids are greater than values reported previously in feeding system studies. In addition, their requirements for gain depend on body composition and are driven by efficiencies of deposition.

Objective Acromegaly is a rare disease caused by excess growth hormone (GH) production by the pituitary adenoma. The skeletal complications of GH and IGF-1 excess include increased bone turnover, increased cortical bone mass and deteriorated microarchitecture of trabecular bone, associated with a high risk of vertebral fractures in the presence of relatively normal bone mineral density (BMD). We aimed to evaluate tissue-level properties of bone using impact microindentation (IMI) in well-controlled patients with acromegaly aged ≥18 years compared to 44 controls from the outpatient clinic of the Centre for Bone Quality. Design and methods In this cross-sectional study, bone material strength index (BMSi) was measured in 48 acromegaly patients and 44 controls with impact microindentation using the osteoprobe. Results Mean age of acromegaly patients (54% male) was 60.2 years (range 37.9–76.5), and 60.5 years (range 39.8–78.6) in controls (50% male). Patients with acromegaly and control patients had comparable BMI (28.2 kg/m2 ± 4.7 vs 26.6 kg/m2 ± 4.3, P = 0.087) and comparable BMD at the lumbar spine (1.04 g/cm2 ± 0.21 vs 1.03 g/cm2 ± 0.13, P = 0.850) and at the femoral neck (0.84 g/cm2 ± 0.16 vs 0.80 g/cm2 ± 0.09, P = 0.246). BMSi was significantly lower in acromegaly patients than that in controls (79.4 ± 0.7 vs 83.2 ± 0.7; P 0.001). Conclusion Our data indicates that tissue-level properties of cortical bone are significantly altered in patients with controlled acromegaly after reversal of long-term exposure to pathologically high GH and IGF-1 levels. Our findings also suggest that methods other than DXA should be considered to evaluate bone fragility in patients with acromegaly.

INTRODUCTION Prolactinomas are common pituitary adenomas managed medically or surgically. METHODS Reviewed 181 prolactinomas resected transsphenoidally 2012-2019. Tumor volumes were quantified using BrainLab Smartbrush. Pearson correlation analysis and linear regression were used to identify associations between tumor volumes and serum prolactin. Tumor density was defined as serum prolactin divided by tumor volume. RESULTS Mean tumor volume was 6.33cm3 and mean pre-op prolactin was 803.4ug/L, with men having larger (12.11 vs 2.93cm3;p< 0.001) and women having denser (173.9 vs 107.6ug/L/cm3;p=0.011) prolactinomas. Pearson correlation (R=0.688;p< 0.001) and linear regression revealed a strong association between pre-op volume and prolactin levels, with 96.9g/L increase in prolactin/cm3 increase in volume (p< 0.001); this holds true for men (R=0.584;p< 0.001) and women (R=0.939;p< 0.001), with women demonstrating greater prolactin/cm3 tumor density (186.5 vs 75.0ug/L;p< 0.001). MiB index did not correlate with pre-op volume (p=0.449) or pre-op prolactin (p=0.452). Logistic regression showed decreased biochemical remission with increasing pre-op volume (OR=0.891;p< 0.001). Increased MiB index (p=0.971) and p53 (p=0.525) staining did not affect remission rates. Positive PIT-1 staining was associated with higher remission rates (OR=2.508;p=0.005). Patients without remission had denser tumors (149.9 vs. 100.6ug/L/cm3;p=0.013), with Pearson correlation yielding R=0.736 between pre-op volume and pre-op prolactin (p< 0.001), and R=0.476 between residual volume and post-op prolactin (p< 0.001). Patients without remission exhibited 142.9ug/L increase in prolactin/cm3 of pre-op volume (p< 0.001), higher than the 58.9ug/L increase in prolactin/cm3 in patients with remission (p< 0.001). Patients without remission had residual tumors with 68.4ug/L increase in prolactin/cm3 of remaining volume after resection (p< 0.001). CONCLUSION Our analysis revealed significant correlation between prolactinoma volume and serum prolactin levels. Patients without remission had greater tumor cellular density than those with remission. The volume-prolactin correlation persisted post-operatively, although surgery reduced tumor density. These results could identify prolactinomas for which surgery could achieve biochemical remission.

Introduction Obstructive sleep apnea (OSA) related growth and developmental deficits were previously described in young children. However, growth and development outcomes of OSA in infants is not as clear. Methods We retrospectively reviewed polysomnography (PSGs) of infants 0–12 months of age done at one tertiary care, urban medical center, between 2012–2019. Indications for the studies were symptoms or high risk for OSA. Diagnosis of OSA was determined when obstructive apnea hypopnea index (oAHI) >1/hr. Demographic information and physician diagnosed developmental and growth delays were collected from medical records. Results A total of 83 infants were included, mean age was 4.4months (6 days-12 months). Mean baseline oAHI was 16.8/hr (1–91.46/hr). 23 patients were noted to have failure to thrive (27.7%), 27 patients had general developmental delay (32.5%), 22 patients had speech delay (26.5%), and 9 patients had motor delay (10.8%). Out of all the patients with any form of delay (N=46), 39.13% were premature, 71.73% had an underlying neurologic abnormality and 39.13% had some other underlying diagnosed syndrome. 2 patients had delay but no associated comorbidity. Patients without any developmental delay showed trend towards likelihood of more severe OSA compared to patients with any delay (p=0.0455). Conclusion Infant OSA is a separate entity from pediatric OSA and requires a better understanding of its association with developmental outcomes. Infants are particularly vulnerable to obstructive sleep-disordered breathing related to their upper airway anatomy, adverse pulmonary mechanics and a REM-predominant sleep state distribution. We describe a cohort of 83 infants undergoing PSGs in their 1st year of life with developmental and growth follow up until 2nd year of life. Most of the infants with moderate to severe OSA had some delay in their development. Infants without diagnosed delay, were less likely to have severe OSA. It remains unclear to what degree OSA is responsible for these findings as opposed to pre-existing comorbidities. Additional prospective, controlled studies with standardized developmental assessments are warranted to assess causality. Support (if any)

Objective Type 2 diabetes (T2D) and Cushing’s syndrome (CS) share clinical characteristics, and several small studies have recorded a high prevalence of hypercortisolism in T2D, which could have therapeutic implications. We aimed to assess the prevalence of endogenous hypercortisolism in T2D patients. Design Systematic review and meta-analysis of the literature. Methods A search was performed in SCOPUS, MEDLINE, and EMBASE for original articles assessing the prevalence of endogenous hypercortisolism and CS in T2D. Data were pooled in a random-effect logistic regression model and reported with 95% confidence intervals (95% CI). Results Fourteen articles were included, with a total of 2827 T2D patients. The pooled prevalence of hypercortisolism and CS was 3.4% (95% CI: 1.5–5.9) and 1.4% (95 CI: 0.4–2.9) respectively. The prevalence did not differ between studies of unselected patients and patients selected based on the presence of metabolic features such as obesity or poor glycemic control (P = 0.41 from meta-regression). Imaging in patients with hypercortisolism (n = 102) revealed adrenal tumors and pituitary tumors in 52 and 14% respectively. Conclusions Endogenous hypercortisolism is a relatively frequent finding in T2D, which may have therapeutic implications.

Summary Background Schnitzler syndrome (SchS) is an acquired autoinflammatory disease characterized by chronic urticarial rash in association with monoclonal gammopathy. Patients may progress to lymphoproliferative disorders, but the associated factors and exact risk of progression are still not well defined. Aim To characterize the clinical findings, laboratory abnormalities and histopathology of patients with SchS and their respective outcomes. Methods We retrospectively reviewed the clinical files and the histological specimens of patients with SchS diagnosed from 1988 to 2015. Results Nine patients (two women, seven men) were diagnosed with SchS. Mean age at diagnosis was 61.1 years (range 29–80), with a mean time to diagnosis of 3.7 years and a mean follow-up period of 10.1 years (range 3–25). Four patients displayed an association of fever and arthralgia, and all nine patients consistently showed laboratory markers of inflammation. Serum values of the monoclonal component, IgMκ in eight patients and IgGλ in one patient, progressively increased over time. During follow-up, carried out in association with the haematology department five patients progressed to lymphoproliferative disease, namely, lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinaemia (n = 4) and diffuse large B-cell lymphoma (n = 1). Conclusions SchS is a rare chronic inflammatory disease with a substantial impact on quality of life. Our study highlights the importance of lifelong follow-up for individuals with SchS, owing to the risk of progression to a lymphoproliferative disorder.

As concerns about bed bug sightings began to increase and schools began to report bed bug introductions, an expert group convened by the Environmental Protection Agency recommended development of curricula to teach young students about bed bug biology and management. The Bed Bugs and Book Bags curriculum is our response to this recommendation. This third- through fifth-grade curriculum was developed using a six-step process, and has been implemented by health educators, teachers, and the pest management industry within and outside of the United States. The curriculum consists of 10 lessons correlated with state health educational standards and is specifically designed to educate teachers and students about bed bugs. In pilot testing of various groups including teachers, students, custodial staff at rescue missions, and pest management professionals, teacher and student groups had the highest increase in knowledge gain after being introduced to the curriculum. The curriculum is available online at http://duval.ifas.uf.edu/Bed_Bugs.shtml. Based on self-reporting, it has a potential impact of reaching approximately 40,000 people across the United States, Canada, and Saudi Arabia. The Bed Bugs and Book Bags curriculum placed first as a learning module with the Florida Association for …

Context and objective: GH insensitivity with immune dysfunction caused by STAT5B mutations is an autosomal recessivecondition. Heterozygous mutations in other genes involved in growth regulation were previously associated with a mildheight reduction. Our objective was to assess for the first time the phenotype of heterozygous STAT5B mutations.Methods: We genotyped and performed clinical and laboratory evaluations in 52 relatives of two previously describedBrazilian brothers with homozygous STAT5B c.424_427del mutation (21 heterozygous). Additionally, we obtained heightdata and genotype from 1104 adult control individuals from the same region in Brazil and identified five additional familiesharboring the same mutation (18 individuals, 11 heterozygous). Furthermore, we gathered the available height data fromfirst-degree relatives of patients with homozygous STAT5B mutations (17 individuals from seven families). Data fromheterozygous individuals and non-carriers were compared.Results: Individuals carrying heterozygous STAT5B c.424_427del mutation were 0.6 SDS shorter than their non-carrierrelatives (PZ0.009). Heterozygous subjects also had significantly lower SDS for serum concentrations of IGF1 (PZ0.028) andIGFBP3 (PZ0.02) than their non-carrier relatives. The 17 heterozygous first-degree relatives of patients carrying homozygousSTAT5B mutations had an average height SDS of K1.4G0.8 when compared with population-matched controls (P! 0.001).Conclusions: STAT5B mutations in the heterozygous state have a significant negative impact on height (w3.9 cm). This effectis milder than the effect seen in the homozygous state, with height usually within the normal range. Our results support thehypothesis that heterozygosity of rare pathogenic variants contributes to normal height heritability. Fil: Scalco, Renata C.. Universidade de Sao Paulo; Brasil Fil: Hwa, Vivian. Cincinnati Center for Growth Disorders; Estados Unidos Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina Fil: Jasper, Hector Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina Fil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Marino, Roxana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Pereira, Alberto M.. Leiden University Medical Center; Países Bajos Fil: Tonelli, Carlos A.. Universidade do Extremo Sul Catarinense; Brasil Fil: Wit, Jan M.. Leiden University Medical Center; Países Bajos Fil: Rosenfeld, Ron G.. Oregon Health and Science University; Estados Unidos Fil: Jorge, Alexander A. L. . Universidade de Sao Paulo; Brasil

The objective of this study was to determine the net requirements of minerals for the growth and maintenance of intact male F1 Boer × Saanen goat kids in the initial phase of growth. The following 2 experiments were performed: Exp. 1 was performed to determine the net growth requirements for Ca, P, Mg, Na, and K by F1 Boer × Saanen goat kids from 5 to 25 kg of BW and Exp. 2 was performed to determine the maintenance requirements of F1 Boer × Saanen goats from 15 to 25 kg BW. In Exp. 1, 32 intact male goat kids were distributed in a completely randomized design and mineral body composition was fit to an allometric equation in the form of a nonlinear model. To determine the mineral requirements for maintenance in Exp. 2, 21 intact male goat kids were distributed in a randomized block design, where the goat kids were subjected to 3 levels of feed restriction (0, 30, and 60% feed restriction). At the onset of Exp. 2, 7 goat kids were harvested and used to estimate the initial body composition (15 kg BW). Initial body composition was used to calculate the retention of minerals. The maintenance requirements were estimated by regressions obtained from the retention of minerals in the empty body and the intake of the mineral. The concentration of Ca, P, Na, and K in the empty BW decreased by 11, 13, 26, and 23% with the increase in BW from 5 to 25 kg (P < 0.01). As a consequence, our results showed that net requirements of Ca, P, Mg, Na, and K for weight gain decreased by 27.5, 27.8, 4.25, 43.2, and 39.7%, respectively, with the increase in BW from 5 to 25 kg (P < 0.01). The net requirements (g/kg of ADG) decreased from 9.7 to 7.0 for Ca, 6.5 to 4.7 for P, 0.38 to 0.36 for Mg, 0.88 to 0.50 for Na, and 1.9 to 1.2 for K when BW increased from 5 to 25 kg. The daily net requirements for maintenance per kilogram of BW were 38 mg of Ca, 42 mg of P, 1.6 mg of Mg, 5.0 mg of Na, and 19 mg of K. These results for the nutritional requirements of minerals may help to formulate more balanced diets for F1 Boer × Saanen goat kids in the initial growth phase.

Diaphania hyalinata L. (Lepidoptera: Crambidae) is a key pest of plants in the family Cucurbitaceae, defoliating and reducing photosynthetic area and yield. Trichospilus diatraeae Margabandhu & Cherian, 1942 (Hymenoptera: Eulophidae) parasitizes the pupae of this pest, but its biological and reproductive parameters with this host are unknown. The objective of our study was to characterize the reproduction of T. diatraeae in D. hyalinata pupae with different densities of this parasitoid. Individual D. hyalinata pupae (48 h old) were exposed to different densities of T. diatraeae (1:1, 4:1, 8:1, 12:1, 16:1, 20:1, and 24:1). The parasitoid density did not affect the parasitism and emergence rate of this natural enemy. The progeny, sex ratio, longevity, and head capsule width of T. diatraeae males and females decreased with increasing density, and its life cycle was proportional to density increase of T. diatraeae. Densities of up to eight T. diatraeae individuals per D. hyalinata pupae are favorable for the development of this parasitoid.

This study, conducted at São Paulo State University feedlot, Dracena campus, Brazil, was designed to evaluate the effects of either nutritional restriction or intake of concentrate feedstuffs prior to the adaptation period on rumen morphometrics of Nellore cattle. The experiment was designed as a completely randomized block, replicated 8 times (4 animals/pen), in which 96 22-mo-old yearling Nellore bulls (365.5 ± 39.2 kg) were fed in 24 pens according to the treatments: Restriction (Tifton hay fed at 1.4% BW + supplement); Control (Tifton hay fed ad libitum + supplement) and Concentrate (Tifton hay fed ad libitum + 0.5% BW of concentrate and supplement). This study lasted 144-d, divided into 2 periods: 32-d of pre-adaptation, when cattle were submitted to the treatments previously described, and 112-d of feeding high-concentrate diets, where cattle were fed same diets. At the end of pre-adaptation period, one animal per pen (n=24) was slaughtered for rumen evaluations. The remaining 72 animals were harvested after 112-d of feeding high-concentrate diets. A 1-cm(2) fragment of each rumen was collect from ventral sac. Histological measurements were performed in 4 papillae per animal using computer-aided light microscope for image analysis. No treatment or harvesting date main effect (P>0.10) was observed for papillae width and papillae area. However, cattle consuming concentrate prior to adaptation had shorter (Pab, Control: 3.54(a), Concentrate: 3.17(b)) than cattle on control group. A significant interaction was observed for keratinized layer thickness (P=0.04) and mitotic index (P=0.08), where no differences were observed prior to adaptation period, but cattle consuming concentrate during pre-adaptation period had thinner keratinized layer in µm (Restriction: 14.18(a), Control: 13.90(a), Concentrate: 12.76(b)) and greater mitotic index in % (Restriction: 7.95(b), Control: 8.23(b), Concentrate: 8.74(a)) after 144-d on feed. The feeding of concentrate prior to adaptation period impacted rumen tissue histology.

ObjectivePatients with long-term remission of Cushing's disease (CD) have persistent psychological and cognitive impairments. It is unknown whether, and to what extent, these impairments are accompanied by structural abnormalities in the brain. We aim to investigate structural changes in the brain in patients with predominantly long-term remission of CD and to examine whether these changes are associated with psychological and cognitive dysfunction and clinical severity.DesignA cross-sectional, case–control study.MethodsIn 25 patients with predominantly long-term remission of CD and 25 matched healthy controls, grey matter volumes in the regions of interest (hippocampus, amygdala, and anterior cingulate cortex (ACC)) and in the whole brain were examined, using 3T magnetic resonance imaging and a voxel-based morphometry approach. Psychological and cognitive functioning were assessed using validated questionnaires and clinical severity was assessed using the Cushing's syndrome severity index.ResultsCompared with controls, patients had smaller grey matter volumes of areas in the ACC (on average 14%, PPP=0.005), more anxiety (P=0.003), more social phobia (P=0.034), more apathy (P=0.002), and more cognitive failure (P=0.023) compared with controls, but the differences in grey matter volumes were not associated with psychological or cognitive measures, nor with clinical severity.ConclusionPatients with predominantly long-term remission of CD showed specific structural brain abnormalities, in the presence of psychological dysfunction. Our data form a basis for future work aimed at elucidating the relation of the structural brain abnormalities and the sustained psychological deficits after long-term exposure to high cortisol levels.

BackgroundThe beneficial effects of recombinant human GH (rhGH) therapy in GH deficient (GHD) adults are well-established in the short term. However, data documenting the effects during prolonged follow-up are relatively scarce.ObjectiveTo evaluate the reported effects of rhGH replacement (≥5 years) in GHD adults on biochemical and anthropometric parameters, quality of life (QoL), bone metabolism, muscle strength, serious adverse events and mortality.MethodsWe conducted a systematic literature search. Quality assessment of retrieved papers was performed using a quality assessment based on the modified STROBE statement.ResultsWe included 23 prospective studies with a rhGH treatment duration ranging from 5 to 15 years. Overall, beneficial effects were reported on QoL, body composition, lipid profile, carotid intima media thickness and bone mineral density. In contrast, the prevalence of the metabolic syndrome, glucose levels, BMI and muscle strength were not, or negatively, influenced. Most of the studies were uncontrolled, lacked the presence of a control group (of non-treated GHD patients), and reported no data on lipid-lowering and anti-diabetic medication. Overall mortality was not increased.ConclusionrhGH treatment in adult GHD patients is well-tolerated and positively affects QoL in the long term. However, the metabolic and cardiovascular effects during long-term treatment are variable. The low numbers of long-term studies and studied patients and lack of control data hamper definite statements on the efficacy of prolonged treatment. Therefore continuous monitoring of the effects of rhGH replacement to enable an adequate risk-benefit analysis that may justify prolonged, potentially life-long, treatment is advisable.

ObjectiveCushing's disease (CD) is a rare endocrine disorder characterized by excess secretion of ACTH due to a pituitary adenoma. Current treatment options are limited and may pose additional risks. A literature review was conducted to assess the holistic burden of CD.DesignStudies published in English were evaluated to address questions regarding the epidemiology of CD, time to diagnosis, health-related quality of life (HRQoL), treatment outcomes, mortality, prevalence of comorbidities at diagnosis, and reversibility of comorbidities following the treatment.MethodsA two-stage literature search was performed in Medline, EMBASE, and Science Citation Index, using keywords related to the epidemiology, treatment, and outcomes of CD: i) articles published from 2000 to 2012 were identified and ii) an additional hand search (all years) was conducted on the basis of bibliography of identified articles.ResultsAt the time of diagnosis, 58–85% of patients have hypertension, 32–41% are obese, 20–47% have diabetes mellitus, 50–81% have major depression, 31–50% have osteoporosis, and 38–71% have dyslipidemia. Remission rates following transsphenoidal surgery (TSS) are high when performed by expert pituitary surgeons (rates of 65–90%), but the potential for relapse remains (rates of 5–36%). Although some complications can be partially reversed, time to reversal can take years. The HRQoL of patients with CD also remains severely compromised after remission.ConclusionsThese findings highlight the significant burden associated with CD. As current treatment options may not fully reverse the burden of chronic hypercortisolism, there is a need for both improved diagnostic tools to reduce the time to diagnosis and effective therapy, particularly a targeted medical therapy.

Numerical simulations of minor mergers, typically having mass ratios greater than 3:1, predict little enhancement in the global star formation activity. However, these models also predict that the satellite galaxy is more susceptible to the effects of the interaction than the primary. We use optical integral field spectroscopy and deep optical imaging to study the NGC7771+NGC7770 interacting system (~10:1 stellar mass ratio) to test these predictions. We find that the satellite galaxy NGC7770 is currently experiencing a galaxy-wide starburst with most of the optical light being from young and post-starburst stellar populations(

Although progressive supranuclear palsy is defined by its akinetic rigidity, vertical supranuclear gaze palsy and falls, cognitive impairments are an important determinant of patients’ and carers’ quality of life. Here, we investigate whether there is a broad deficit of modality-independent social cognition in progressive supranuclear palsy and explore the neural correlates for these. We recruited 23 patients with progressive supranuclear palsy (using clinical diagnostic criteria, nine with subsequent pathological confirmation) and 22 age- and education-matched controls. Participants performed an auditory (voice) emotion recognition test, and a visual and auditory theory of mind test. Twenty-two patients and 20 controls underwent structural magnetic resonance imaging to analyse neural correlates of social cognition deficits using voxel-based morphometry. Patients were impaired on the voice emotion recognition and theory of mind tests but not auditory and visual control conditions. Grey matter atrophy in patients correlated with both voice emotion recognition and theory of mind deficits in the right inferior frontal gyrus, a region associated with prosodic auditory emotion recognition. Theory of mind deficits also correlated with atrophy of the anterior rostral medial frontal cortex, a region associated with theory of mind in health. We conclude that patients with progressive supranuclear palsy have a multimodal deficit in social cognition. This deficit is due, in part, to progressive atrophy in a network of frontal cortical regions linked to the integration of socially relevant stimuli and interpretation of their social meaning. This impairment of social cognition is important to consider for those managing and caring for patients with progressive supranuclear palsy.

Mrk938 is a luminous infrared galaxy in the local Universe believed to be the remnant of a galaxy merger. It shows a Seyfert 2 nucleus and intense star formation according to optical spectroscopic observations. We have studied this galaxy using new Herschel far-IR imaging data in addition to archival X-ray, UV, optical, near-IR and mid-IR data. Mid- and far-IR data are crucial to characterise the starburst contribution, allowing us to shed new light on its nature and to study the coexistence of AGN and starburst activity in the local Universe. The decomposition of the mid-IR Spitzer spectrum shows that the AGN bolometric contribution to the mid-IR and total infrared luminosity is small (Lbol(AGN)/LIR~0.02), which agrees with previous estimations. We have characterised the physical nature of its strong infrared emission and constrained it to a relatively compact emitting region of

Prenatal exposure to ethanol leads to a myriad of developmental disorders known as fetal alcohol spectrum disorder, often characterized by growth and mental retardation, central nervous system damage, and specific craniofacial dysmorphic features. The mechanisms of ethanol toxicity are not fully understood, but exposure during development affects the expression of several genes involved in cell cycle control, apoptosis, and transcriptional regulation. MicroRNAs (miRNAs) are implicated in some of these processes, however, it is not yet clear if they are involved in ethanol-induced toxicity. In order to clarify this question, we have exposed zebrafish embryos to ethanol and evaluated whether a miRNA deregulation signature could be obtained. Zebrafish embryos were exposed to 1 and 1.5% of ethanol from 4 h postfertilization (hpf) to 24 hpf. The miRNA expression profiles obtained reveal significant miRNA deregulation and show that both ethanol concentrations upregulate miR-153a, miR-725, miR-30d, let-7k, miR-100, miR-738, and miR-732. Putative gene targets of deregulated miRNAs are involved in cell cycle control, apoptosis, and transcription, which are the main processes affected by ethanol toxicity. The conservation of affected mechanisms among vertebrates leads us to postulate that similar miRNA deregulation occurs in humans, highlighting a relevant role of miRNAs in ethanol toxicology. published

ObjectiveActive Cushing's syndrome (CS) is associated with cardiomyopathy, characterized by myocardial structural, and ultrastructural abnormalities. The extent of myocardial fibrosis in patients with CS has not been previously evaluated. Therefore, the objective of this study was to assess myocardial fibrosis in CS patients, its relationship with left ventricular (LV) hypertrophy and function, and its reversibility after surgical treatment.Design and methodsFifteen consecutive CS patients (41±12 years) were studied together with 30 hypertensive (HT) patients (matched for LV hypertrophy) and 30 healthy subjects. Echocardiography was performed in all patients including i) LV systolic function assessment by conventional measures and by speckle tracking-derived global longitudinal strain, ii) LV diastolic function assessment using E/E′, and iii) myocardial fibrosis assessment using calibrated integrated backscatter (IBS). Echocardiography was repeated after normalization of cortisol secretion (14±3 months).ResultsCS patients showed the highest value of calibrated IBS (−15.1±2.5 dB) compared with HT patients (−20.0±2.6 dB,PPr=0.79,Pr=0.60,P=0.02). After successful surgical treatment, calibrated IBS normalized (−21.0±3.8 vs −15.1±2.5 dB,PConclusionsPatients with CS have increased myocardial fibrosis, which is related to LV systolic and diastolic dysfunction. Successful treatment of CS normalizes the extent of myocardial fibrosis. Therefore, myocardial fibrosis appears to be an important factor in the development and potential regression of CS cardiomyopathy.

The female reproductive ability is crucial to the efficiency of swine production, but genetic progress is limited by its low heritability and sex-limited expression. Thus, the objective of this study was to understand the relationship between testis size in boars and reproductive traits in sows. In this study, Yorkshire and Landrace boars (161) and sows (420) were analyzed for testis (boars) width (TW) and area (TA) and reproductive traits (sows): total born (TB), number born alive (NBA), alive 48h (alive48), total born dead (TBD), stillborn, and mummies. Genetic analyses were performed including the fixed effects of age, breed, contemporary group, and parity (for sow traits only), and a random animal effect in the models. The 420 sows were daughters of 13 of the 161 boars. For the phenotypic analysis, we performed a Poisson regression of the reproductive traits of the 420 daughters on the testis size of their 13 sires, with parity and breed of the sow as fixed effect and sow as random effect, and TW or TA as fixed covariates (linear and quadratic). The heritability estimates of TA and TW were 0.69 ± 0.22 and 0.66 ± 0.21, respectively, and the reproductive traits ranged from 0.01 ± 0.01 (TBD) to 0.09 ± 0.04 (NBA). The phenotypic analysis showed quadratic (P < 0.05) and linear (P < 0.05) relationships between reproductive traits in sows with TA and TW, respectively. The optimum TA ranged from 17.09cm2 to 18.55cm2 associated with higher number of TB, NBA, and alive48 (P < 0.05), which did not overlap with the range related to higher number of TBD, mummies, and stillborn (16.0cm2 to 16.57cm2; P < 0.05). Also, increasing the testis width is associated with an increase in TB, NBA, and alive48 (P < 0.05) but not TBD, mummies, and stillborn (P>0.05). Phenotypic assessment of testis size of sires may be a useful tool to select/cull animals for breeding, improving female performance.

BackgroundSubclinical hyperthyroidism is associated with cardiovascular morbidity. Recent advances in echocardiography imaging have allowed sophisticated evaluation of myocardial tissue properties.ObjectiveTo investigate the myocardial effects of long-term exogenous subclinical hyperthyroidism using two-dimensional speckle tracking echocardiography imaging (2D-STE).DesignProspective, single-blinded, placebo-controlled randomized trial of 6 months duration with two parallel groups.Patients and methodsTotally 25 patients with a history of differentiated thyroid carcinoma on long-term TSH-suppressive levothyroxine (l-T4) substitution were randomized to persistent TSH-suppressive l-T4 substitution (low-TSH group) or restoration of euthyroidism. Additionally 40 euthyroid controls were studied.Results (proposal)At baseline, the group of patients showed normal left ventricular (LV) systolic function but impaired diastolic function as assessed with conventional echocardiographic parameters. Importantly, 2D-STE analysis demonstrated the presence of subclinical LV systolic and diastolic dysfunction with impaired circumferential and longitudinal strain and strain rate at the isovolumic relaxation time. After restoration of euthyroidism, a significant improvement in LV systolic and diastolic function as assessed with 2D-STE strain was observed.ConclusionProlonged subclinical hyperthyroidism leads to systolic and diastolic dysfunction, which is reversible after restoration of euthyroidism. 2D-STE is a more sensitive technique to evaluate subtle changes in LV performance of these patients.

Staphylococcus lugdunensis are unusually virulent coagulase-negative staphylococci associated with skin infections and endocarditis. We developed an accurate and simple PCR assay to identify S. lugdunensis isolates based on detection of the fbl gene, which encodes a fibrinogen-binding protein involved in pathogen adhesion. The PCR assay was established using 16 reference strains of different Staphylococcus species and further validated with a collection of 63 clinical staphylococcal isolates that were also phenotypically characterized. Reliable results for the detection of S. lugdunensis isolates were obtained for 100% of the strains evaluated, indicating that this PCR assay can be used in the routine of microbiology laboratories as one more tool for correct species differentiation.

Vapor toxicities of two prototype formate esters, ethylene glycol di-formate (EGDF) and heptyl formate, and the prototype heterobicyclic menthofuran were determined against laboratory-reared adult house flies, Musca domestica L. (Diptera: Muscidae). Toxicities were compared between house flies and other dipteran species tested previously. The organophosphate fumigant insecticide dichlorvos (DDVP) was used as a positive control. Although less toxic than DDVP, all three prototype compounds were toxic to house flies. Most toxic was menthofuran (LC50 = 3.70 mg/liter air), followed by EGDF (LC50 = 9.27 mg/liter air) and heptyl formate (LC50 = 32.62 mg/liter air). The toxicity of menthofuran when applied after piperonyl butoxide increased 1.5-fold. The toxicities of heptyl formate and EGDF when applied after S,S,S-tributyl phosphorotrithioate decreased by 1.5- and 2-folds, respectively. These results are slightly different from results obtained for other dipterans, further supporting previous hypotheses that toxicity may have some species specificity. Ceramic porous rods impregnated with heptyl formate were used to evaluate the effectiveness of controlled vapor release for a single dose of heptyl formate against house flies. Controlled vapor release ofheptyl formate can be used successfully to provide prolonged house fly mortality. Even though the prototype compounds did not exhibit toxicity as high as that of DDVP, their toxicities to dipterans, along with their reduced mammalian toxicities relative to DDVP, make them potential DDVP replacement candidates.