Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signaling.

Although Hedgehog (HH) signaling plays a critical role in patterning the ventral midbrain, its role in early midbrain specification is not known. We examined the midbrains of sonic hedgehog (Shh) and smoothened (Smo) mutant mice where HH signaling is respectively attenuated and eliminated. We show that some ventral (Evx1+) cell fates are specified in the Shh-/- mouse in a Ptc1- and Gli1-independent manner. HH-independent ventral midbrain induction was further confirmed by the presence of a Pax7-negative ventral midbrain territory in both Shh-/- and Smo-/- mice at and before embryonic day (E) 8.5. Midbrain signaling centers are severely disrupted in the Shh-/- mutant. Interestingly, dorsal markers are up-regulated (Wnt1, Gdf7, Pax7), down-regulated (Lfng), or otherwise altered (Zic1) in the Shh-/- midbrain. Together with the increased cell death seen specifically in Shh-/- dorsal midbrains (E8.5-E9), our results suggest specific regulation of dorsal patterning by SHH, rather than a simple deregulation due to its absence.     

Disseminated histoplasmosis in an immunocompetent individual--a case report

We report a rare case of disseminated histoplasmosis in a immunocompetent young adult person involving bone marrow, liver, spleen and oral cavity. He presented with oral ulcers, weight loss and pancytopenia. His bone marrow aspiration examination revealed Histoplasma capsulatum.     

Spiracular indices in Anopheles stephensi: a taxonomic tool to identify ecological variants

Thoracic spiracle length and its index was examined for their ability to discriminate two ecological variants, type form and mysorensis, of Anopheles stephensi in the adult stage. The type form is exclusively domestic in all seasons, whereas the mysorensis variant occupies the outdoor niche during monsoon and postmonsoon seasons, with spillover into domestic sites during summer ecological stress periods. A statistically significant co-relation was established between the ridge count of the egg and two adult measurements, the thoracic spiracle length, and the spiracular index. In An. stephensi type form, average spiracle length was 0.11-0.12 mm and average spiracular index was 8.09-9.23, whereas in mysorensis, the corresponding figures were 0.09-0.10 mm and 6.82-7.60. These parameters showed consistent variations in population of mosquitoes that emerged during monsoon and summer season. The thoracic lengths in both variants remained constant, and only spiracular lengths showed fluctuations in three seasonal populations. These measures provide discrimination of adult variants--identifications that are essential in malaria control programs.     

Novel and recurrent mutations in the C-terminal domain of COMP cluster in two distinct regions and result in a spectrum of phenotypes within the pseudoachondroplasia -- multiple epiphyseal dysplasia disease group

Pseudoachondroplasia (PSACH) and some forms of multiple epiphyseal dysplasia (MED) result from mutations in the gene encoding cartilage oligomeric matrix protein (COMP). COMP is a large pentameric glycoprotein found predominantly in the extracellular matrix of cartilage, tendon, and ligament. As a modular protein, it is composed of a coiled-coil domain, four type II (T2) repeats, eight type III (T3) repeats, and a large globular C-terminal domain (CTD). The majority (>85%) of COMP mutations causing PSACH or MED are found in the exons encoding the T3 repeats, and the disease mechanism has been characterised in detail. Much less is known about disease-causing mutations in the CTD; in 10 years only seven mutations have been identified. In this study, we describe eight novel and two recurrent mutations that we have recently identified in patients with PSACH or MED. Interestingly, these mutations result in a spectrum of disease, ranging from mild MED to severe PSACH. Mapping of all known COMP CTD mutations on a three-dimensional model of the C-terminal domain shows that the CTD mutations cluster in two distinct regions. These regions are probably important in stabilising the T3-CTD structure and mediating intra- or intermolecular interactions.     

Psychopathology Symptoms are Associated with Prenatal Health Practices in Pregnant Women with Heavy Smoking Levels

Purpose

Smoking during pregnancy may be linked to other problematic prenatal health behaviors in women. We examined interrelationships among prenatal smoking, prenatal health behaviors and mental health. The objective of this study was to examine factors that may contribute to variations in prenatal health practices among women who smoke during pregnancy.

Methods

Birth mothers from an adoption study (N?=?912) were interviewed about prenatal smoking, health behaviors, and mental health symptoms at 5 months postpartum.

Results

One-quarter of participants (N?=?222) reported smoking 6 or more cigarettes daily for at least 1 trimester. For mothers who smoked more than 6 cigarettes daily, higher levels of antisocial behaviors (β?=????.14, p?=?.03) and depressive symptoms (β?=????.17, p?=?.03) were associated with less frequent prenatal folate use; antisocial behaviors and depressive symptoms were not associated for prenatal folate use among women who did not smoke more than 6 cigarettes daily. For mothers who did not smoke more than 6 cigarettes daily, more depressive symptoms were associated with fewer prenatal care visits (β?=?.12, p?=?.01). Antisocial behaviors and anxiety symptoms were not associated with prenatal care visits in either group of mothers.

Conclusions for Practice

Maternal antisocial behaviors and depressive symptoms during pregnancy may be markers for poorer adherence to recommendations for folate supplementation among women who smoke 6 or more cigarettes daily during pregnancy, independent of adequacy of prenatal care.

     

Extraintestinal Seeding of Salmonella enterica Serotype Typhi,Pakistan

We evaluated Salmonella enterica serotype Typhi strains isolated from all body sites in Pakistan during 2013–2018. Despite an increase in overall number of localized, extensively drug-resistant Salmonella Typhi in organ infections during 2018, there was no increase in the proportion of such isolates in comparison with non–extensively drug-resistant isolates.     

Barriers and Facilitators to Lifestyle Intervention Engagement and Weight Loss in People Living With Spinal Cord Injury

Background: Individuals living with spinal cord injury (SCI) have a high prevalence of obesity and unique barriers to healthy lifestyle. Objective: To examine barriers and facilitators to engagement and weight loss among SCI participants enrolled in the Group Lifestyle Balance Adapted for individuals with Impaired Mobility (GLB-AIM), a 12-month intensive lifestyle intervention. Methods: SCI participants (N = 31) enrolled in a wait-list, randomized controlled trial where all participants received intervention between August 2015 and February 2017. Analyses of pooled data occurred in 2020 to examine cross-sectional and prospective associations of hypothesized barriers and facilitators with (1) intervention engagement, comprised of attendance and self-monitoring, and (2) percent weight change from baseline to 12 months. We performed multivariable linear regression on variables associated with outcomes at p < .05 in bivariate analyses and controlled for intervention group. Results: Participants were middle-aged (mean age, 48.26 ± 11.01 years), equally male (50%) and female, White (80.7%), and unemployed (65.6%). In participants who completed baseline surveys (n = 30), dietary self-efficacy explained 26% of variance in engagement (p < .01); among the 12-month study completers (n = 22, 71.0%), relationship issues explained 23% of variance in engagement (p < .01). Money problems, health issues unrelated to SCI, lack of motivation, and experimental group explained 57% of variance in weight loss (p for model < .01), with lack of motivation uniquely explaining 24% of variance (p < .01). Conclusion: Improving engagement and weight loss for persons with SCI in the GLBAIM program may be achieved by addressing lack of motivation, relationship issues, and nutrition self-efficacy.