Maternal first trimester serum levels of free-beta human chorionic gonadotropin and male genital

Are maternal first trimester levels of serum free-beta hCG associated with the development of hypospadias or undescended testis (UDT) in boys? Overall, first trimester maternal levels of serum free-beta hCG are not associated with hypospadias or UDT. However, elevated levels were found in severe phenotypes (proximal hypospadias and bilateral UDT) suggesting an altered pathway of hormonal release in early pregnancy

Association of Early Interventions With Birth Outcomes and Child Linear Growth in Low-Income and Middle-Income Countries:Bayesian Network Meta-analyses of Randomized Clinical Trials

Importance:The first 1000 days of life represent a critical window for child development. Pregnancy, exclusive breastfeeding (EBF) period (0-6 months), and complementary feeding (CF) period (6-24 months) have different growth requirements, so separate considerations for intervention strategies are needed. No synthesis to date has attempted to quantify the associations of interventions under multiple domains of micronutrient and balanced energy protein and food supplements, deworming, maternal education, water sanitation, and hygiene across these 3 life periods with birth and growth outcomes. Objective: To determine the magnitude of association of interventions with birth and growth outcomes based on randomized clinical trials (RCTs) conducted in low-income and middle-income countries (LMICs) using Bayesian network meta-analyses. Data Sources: MEDLINE, Embase, and Cochrane databases were searched from their inception up to August 14, 2018. Study Selection: Included were LMIC-based RCTs of interventions provided to pregnant women, infants (0-6 months), and children (6-24 months). Data Extraction and Synthesis: Two independent reviewers used a standardized data extraction and quality assessment form. Random-effects network meta-analyses were performed for each life period. Effect sizes are reported as odds ratios (ORs) and mean differences (MeanDiffs) for dichotomous and continuous outcomes, with 95% credible intervals (CrIs). This study calculated probabilities of interventions being superior to standard of care by at least a minimal clinically important difference. Main Outcomes and Measures. The study compared ORs on preterm birth and MeanDiffs on birth weight for pregnancy, length for age (LAZ) for EBF, and height for age (HAZ) for CF. Results: Among 302 061 participants in 169 randomized clinical trials, the network meta-analyses found several nutritional interventions that demonstrated greater association with improved birth and growth outcomes compared with standard of care. For instance, compared with standard of care, maternal supplements of multiple micronutrients showed reduced odds for preterm birth (OR, 0.54; 95% CrI, 0.27-0.97) and improved mean birth weight (MeanDiff, 0.08 kg; 95% CrI, 0.00-0.17 kg) but not LAZ during EBF (MeanDiff, −0.02; 95% CrI, −0.18 to 0.14). Supplementing infants and children with multiple micronutrients showed improved LAZ (MeanDiff, 0.20; 95% CrI, 0.03-0.35) and HAZ (MeanDiff, 0.14; 95% CrI, 0.02-0.25). The study found that pregnancy interventions generally had higher probabilities of a minimal clinically importance difference than the interventions for the EBF or CF in the first 1000 days of life. Conclusions and Relevance: These analyses highlight the importance of intervening early for child development, during pregnancy if possible. Results of this study suggest that there is a need to combine interventions from multiple domains and test for their effectiveness as a package

Development neurobiology of the stress response: multilevel regulation of corticotropin-releasing hormone function.

The ability to respond to adverse environmental cues is present in the neonatal and infant rat, although in an immature form: A number of laboratories have demonstrated stress-induced elevations of plasma glucocorticoids during the first two postnatal weeks. The limbic and hypothalamic mechanisms controlling the hormonal stress-response during this period are not fully understood and are, therefore, the focus of this report. Both hypothalamic corticotropin-releasing hormone (CRH) and vasopressin contribute to the release of ACTH from the pituitary in the adult. The relative roles of these two peptides during the neonatal (first week) and infant (second week) developmental period, are controversial. Evidence is presented that argues strongly for a major role for CRH. Up-regulation of hypothalamic CRH synthesis is a major component in the mature stress response. CRH-mRNA levels in the hypothalamic PVN are increased with cold stress by ninth postnatal day, but not during the first postnatal week. Further, down-regulation of CRH gene expression by glucocorticoids (GC) constitutes a critical "shut-down" mechanism for the hormonal stress response. In vivo and in vitro experiments supporting the "immaturity" of GC feedback on CRH synthesis during the first postnatal week are described. CRH-mediated neurotransmission, in both the endocrine and neuronal effector arms of the response to stress may be modulated via alteration of receptor number. The first member of the CRH receptor family, CRF1, probably mediates the neuroendocrine effects of CRH. The developmental profile of CRF1-mRNA reveals several distinctive spatial and temporal patterns. In the hippocampal CA1, CA2, and CA3a peak (300-600% adult values) CRF1-mRNA is found on postnatal day 6. In the amygdala, CRH receptor mRNA levels are maximal on the ninth postnatal day (at 180% of adult values). In cortex, a steady decline from high postnatal day 2 levels results in adult levels by 12. These findings demonstrate distinct, regional, age-specific control of the synthesis of CRF1. Receptor expression profile may provide important information regarding modulation of the age-specific roles of CRH in different regions. For example, a high ratio of hippocampus/amygdala receptors may preferentially activate negative hippocampal input to the hypothalamus during the neonatal period. Additionally, increased CRH receptor mRNA in the infant compared with the adult provides a mechanism for enhanced excitatory effect of the peptide at this age. In conclusion, increasing evidence exists for multiple control points of the early postnatal response and adaptation to stress. CRH synthesis in hypothalamus and amygdala, its sensitivity to GC feedback, and the abundance and distribution of at least two distinct CRH receptors in the limbic central nervous system and the pituitary are developmentally regulated. All serve as control points permitting an effective endocrine, autonomic, and behavioral response to stressful environmental cues

Characterizing Hydrogen Storage Media: Understanding the Interior Pore Structure of a Cu3BTC2 Metal-Organic Framework Infiltrated with NaAlH4

Preliminary results support the nano-confinement of sodium alanate within the pores of a Cu{sub 3}BTC{sub 2} MOF substrate. Increased {sup 1}H and {sup 27}Al NMR T{sub 1} relaxation rates indicate a close proximity of infiltrated sodium alante to the paramagnetic Cu{sup 2+} ions on the BTC paddlewheel units. This is in support of the theory that an interaction due to the electronegative framework with the sodium alanate facilitates thermodynamically-favorable hydrogen adsorption and desorption. Further studies can elucidate the local electronic environment of the sodium ions, further supporting a charge-transfer mechanism as the driving force for thermodynamically-favorable hydrogen adsorption and desorption

First in vitro isolation of Besnoitia besnoiti from chronically infected cattle in Germany

Besnoitia besnoiti was in vitro isolated during the first recorded outbreak of bovine besnoitiosis in Germany. Molecular characterization of the new isolate, named Bb-GER1, revealed almost 100% identity with other B. besnoiti isolates obtained in Portugal, Spain, Israel or South Africa, when partial sequences of the 18S ribosomal RNA gene, of the internal transcribed spacer 1 and of the 5.8S RNA gene were compared. Cystozoites obtained from skin tissue of one bull were infectious for gamma-interferon knockout (GKO) mice by intraperitoneal (ip) inoculation. Tachyzoites were detected in the peritoneal cavity, spleen, liver and lung of the mice 5 days post-infection. The parasite could be maintained in GKO mice by ip inoculation for at least 5 passages. Peritoneal washings containing tachyzoites were obtained from infected mice and used to infect five cell lines (Vero, MARC-145, NA42/13, BHK21, KH-R). The best growth of tachyzoites was observed in BHK21 cells, but replication occurred to a smaller extent also in MARC-145, NA42/13 and KH-R cells. Subsequent comparative analyses revealed that after direct infection of these cell lines with cystozoites derived from bovine skin, the growth was best in NA42/13 cells. Considerable replication was also observed in the BHK21 and KH-R cell lines. Our observations on the growth characteristics of Bb-GER1 partially contrast those for other isolates. The preferential growth in particular cell lines may be characteristic for particular B. besnoiti isolates. A potential association between growth proper-ties and differences in virulence remains to be established. This is the first in vitro isolation of B. besnoiti from cattle in Germany.Laboratorio de Inmunoparasitologí

Electronic Structure of the Complex Hydride NaAlH4

Density functional calculations of the electronic structure of the complex hydride NaAlH4 and the reference systems NaH and AlH3 are reported. We find a substantially ionic electronic structure for NaAlH4, which emphasizes the importance of solid state effects in this material. The relaxed hydrogen positions in NaAlH4 are in good agreement with recent experiment. The electronic structure of AlH3 is also ionic. Implications for the binding of complex hydrides are discussed.Comment: 4 pages, 5 figure

First in vitro isolation of Besnoitia besnoiti from chronically infected cattle in Germany

Besnoitia besnoiti was in vitro isolated during the first recorded outbreak of bovine besnoitiosis in Germany. Molecular characterization of the new isolate, named Bb-GER1, revealed almost 100% identity with other B. besnoiti isolates obtained in Portugal, Spain, Israel or South Africa, when partial sequences of the 18S ribosomal RNA gene, of the internal transcribed spacer 1 and of the 5.8S RNA gene were compared. Cystozoites obtained from skin tissue of one bull were infectious for g-interferon knockout (GKO) mice by intraperitoneal (ip) inoculation. Tachyzoites were detected in the peritoneal cavity, spleen, liver and lung of the mice 5 days post-infection. The parasite could be maintained in GKO mice by ip inoculation for at least 5 passages. Peritoneal washings containing tachyzoites were obtained from infected mice and used to infect five cell lines (Vero, MARC-145, NA42/13, BHK21, KH-R). The best growth of tachyzoites was observed in BHK21 cells, but replication occurred to a smaller extent also in MARC-145, NA42/13 and KH-R cells. Subsequent comparative analyses revealed that after direct infection of these cell lines with cystozoites derived from bovine skin, the growth was best in NA42/13 cells. Considerable replication was also observed in the BHK21 and KH-R cell lines. Our observations on the growth characteristics of Bb-GER1 partially contrast those for other isolates. The preferential growth in particular cell linesmay be characteristic for particular B. besnoiti isolates. A potential association between growth properties and differences in virulence remains to be established. This is the first in vitro isolation of B. besnoiti from cattle in Germany

Effect of redo varicocelectomy on semen parameters and pregnancy outcome: An original report and meta-analysis

Recurrence following varicocelectomy is an important cause of treatment failure and persistence of subnormal semen parameters. This original study was combined with a systemic review and meta-analysis aiming to evaluate the efficacy of redo varicocelectomy on male fertility potential and pregnancy outcome. The retrospective study included 32 patients who underwent microsurgical subinguinal varicocelectomy for patients with recurrent varicocele. Changes in semen parameters and hormone profiles before and after surgery were compared. The literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and included seven articles in addition to our original report. Results of the original study revealed statistically significant improvements in sperm concentration, progressive motility, total motile sperm count and normal morphology following redo varicocelectomy. The meta-analysis results echoed those reported in our original study and depicted significant improvements in sperm concentration (mean difference [MD] = +20.281 million/ml, p < 0.001), total motility (MD = +9.659%, p = 0.001), total motile sperm count (MD = +23.258 million sperm, p < 0.001) and normal morphology (MD = +4.460%, p < 0.001). Overall pregnancy outcome was reported in seven studies with a rate of 34.6%. No significant changes were noted in any of the collected hormone results both in this original report and in the meta-analysis. In conclusion, redo varicocelectomy has a beneficial role on male fertility potential and can be offered for men with recurrent varicocele as directed by their individual clinical condition

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY challenge

Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups