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The fibrous scaffolds for bone tissue engineering that mimic the extracellular matrix with bioactive and bactericidal properties could provide adequate conditions for regeneration of damaged bone. Electrospun ultrathin fiber covered with nano-hydroxyapatite is a favorable fibrous scaffold design. We developed a fast and reproducible strategy to produce polyvinylidene fluoride (PVDF)/nano-hydroxyapatite (nHAp) nanofibrous scaffolds with bactericidal and bioactive properties. Fibrous PVDF scaffolds were obtained first by the electrospinning method. Then, their surfaces were modified using oxygen plasma treatment followed by electrodeposition of nHAp. This process formed nanofibrous and superhydrophilic PVDF fibers (133.6 nm, fiber average diameter) covered with homogeneous nHAp (202.6 nm, average particle diameter) crystals. Energy-dispersive X-ray spectrometry demonstrated the presence of calcium phosphate, indicating a Ca/P molar ratio of approximately 1.64. X-ray diffraction, Fourier transform infrared spectroscopy, and Raman spectroscopy spectra identified β-phase of nHAp. Thermal analysis indicated a slight reduction in stability after nHAp electrodeposition. Bactericidal assays showed that nHAp exhibited 99.8% efficiency against Pseudomonas aeruginosa bacteria. The PVDF/Plasma and PVDF/nHAp groups had the highest cell viability, total protein, and alkaline phosphatase activity by 7 days after exposure of the scaffolds to MG63 cell culture. Therefore, the developed scaffolds are an exciting alternative for application in bone regeneration.
The production of beef cattle in the Atlantic Forest biome mostly takes place in pastoral production systems. There are millions of hectares covered with pastures in this biome, including degraded pasture (DP), and only small area of the original Atlantic Forest has been preserved in tropics, implying that actions must be taken by the livestock sector to improve sustainability. Intensification makes it possible to produce the same amount, or more beef, in a smaller area; however, the environmental impacts must be assessed. Regarding climate change, the C dynamics is essential to define which beef cattle systems are sustainable. The objectives of this study were to investigate the C balance (t CO2e./ha per year), the intensity of C emission (kg CO2e./kg BW or carcass) and the C footprint (t CO2e./ha per year) of pasture-based beef cattle production systems, inside the farm gate and considering the inputs. The results were used to calculate the number of trees to be planted in beef cattle production systems to mitigate greenhouse gas (GHG) emissions. The GHG emission and C balance, for 2 years, were calculated based on the global warming potential (GWP) of AR4 and GWP of AR5. Forty-eight steers were allotted to four grazing systems: DP, irrigated high stocking rate pasture (IHS), rainfed high stocking rate pasture (RHS) and rainfed medium stocking rate pasture (RMS). The rainfed systems (RHS and RMS) presented the lowest C footprints (−1.22 and 0.45 t CO2e./ha per year, respectively), with C credits to RMS when using the GWP of AR4. The IHS system showed less favorable results for C footprint (−15.71 t CO2e./ha per year), but results were better when emissions were expressed in relation to the annual BW gain (−10.21 kg CO2e./kg BW) because of its higher yield. Although the DP system had an intermediate result for C footprint (−6.23 t CO2e./ha per year), the result was the worst (−30.21 CO2e./kg BW) when the index was expressed in relation to the annual BW gain, because in addition to GHG emissions from the animals in the system there were also losses in the annual rate of C sequestration. Notably, the intensification in pasture management had a land-saving effect (3.63 ha for IHS, 1.90 for RHS and 1.19 for RMS), contributing to the preservation of the tropical forest.
Accurate estimates of methane (CH4) production by cattle in different contexts are essential to developing mitigation strategies in different regions. We aimed to: (i) compile a database of CH4 emissions from Brazilian cattle studies, (ii) evaluate prediction precision and accuracy of extant proposed equations for cattle and (iii) develop specialized equations for predicting CH4 emissions from cattle in tropical conditions. Data of nutrient intake, diet composition and CH4 emissions were compiled from in vivo studies using open-circuit respiratory chambers, SF6 technique or the GreenFeed® system. A final dataset containing intake, diet composition, digestibility and CH4 emissions (677 individual animal observations, 40 treatment means) obtained from 38 studies conducted in Brazil was used. The dataset was divided into three groups: all animals (GEN), lactating dairy cows (LAC) and growing cattle and non-lactating dairy cows (GCNL). A total of 54 prediction equations available in the literature were evaluated. A total of 96 multiple linear models were developed for predicting CH4 production (MJ/day). The predictor variables were DM intake (DMI), gross energy (GE) intake, BW, DMI as proportion of BW, NDF concentration, ether extract (EE) concentration, dietary proportion of concentrate and GE digestibility. Model selection criteria were significance (P < 0.05) and variance inflation factor lower than three for all predictors. Each model performance was evaluated by leave-one-out cross-validation. The Intergovernmental Panel on Climate Change (2006) Tier 2 method performed better for GEN and GCNL than LAC and overpredicted CH4 production for all datasets. Increasing complexity of the newly developed models resulted in greater performance. The GCNL had a greater number of equations with expanded possibilities to correct for diet characteristics such as EE and NDF concentrations and dietary proportion of concentrate. For the LAC dataset, equations based on intake and animal characteristics were developed. The equations developed in the present study can be useful for accurate and precise estimation of CH4 emissions from cattle in tropical conditions. These equations could improve accuracy of greenhouse gas inventories for tropical countries. The results provide a better understanding of the dietary and animal characteristics that influence the production of enteric CH4 in tropical production systems.
The authors intend to characterize the population of foreign patients admitted to Department L of Centro Hospitalar Psiquiátrico de Lisboa, Portuguese biggest Psychiatric hospital, and compare it with published data on the subject.
The authors identified all foreigner patients hospitalized in the Inpatient Clinic from 01/01/2010 to 30/06/2011. Clinical information was obtained from the case notes and statistically treated. Relevant literature collected from PubMed was reviewed.
A great heterogeneity of nationalities was found including 21 countries, the majority of which are a part of CPLP (Community of Portuguese Language Countries). Nearly all of the patients (91%) were in Portugal as immigrants, most being single and unemployed. Housing conditions are unstable. Psychiatric diagnoses show that schizophrenia is the pathology with more expression (27%), followed by major depression (16%) and bipolar disorder (15%). A significant number of patients have disorders due to psychoactive substance use (19%). After discharged from the hospital 77% where referred to outpatient services, but only half of those are still being followed-up.
Social and familial stability is an important factor influencing mental health. Most patients covered by this study experience familiar, professional and housing instability, making them a risk group. Schizophrenia and affective disorders are the most prevalent pathologies, which agrees with the prevailing idea that social distress is a risk factor to them.
Further studies should be held in order to characterise foreigner populations admitted to psychiatric clinics so that better therapeutic and follow-up measures can be carried out.
The full etiology of transsexualism is still unknown. However many factors, like biological and environmental, are being suggested as possible explanations to the cause of this entity.
We intend to revisit the major etiological theories of transsexuality, based on the description of two cases occurring in first-degree relatives.
A mother and her daughter both diagnosed with Gender Identity Disorder are followed at Multidisciplinary Clinical Sexology Group in our facilities since 2011.
This case is related to a young girl who in her childhood felt and behaved himself as a boy by adopting male gender stereotypes. She has lived with distress during the development of female secondary sexual characteristics, and the age of 17, after identifying his problem decided to tell his mother. However our patient founded that her mother, with 38 years old, was already resigned by living with a sex gender that didn't recognize as her own. In the end they decided to confront the social and family environment, joining both in the process of sexual reassignment.
The transsexualism is a complex phenomenon. The occurrence of two cases of transsexualism in a mother and daughter highlights the importance of consider and extend the knowledge about the biological aspects of gender identity disorder.
It is relevant to communicate the cases occurring within the same family to contribute to the etiology investigation in this area. In the literature the rare cases described of family transsexuals are among brothers, which makes this case between mother and daughter special.
Nutrient requirements in cattle are dependent on physiological stage, breed and environmental conditions. In Holstein × Gyr crossbred dairy heifers, the lack of data remains a limiting factor for estimating energy and protein requirements. Thus, we aimed to estimate the energy and protein requirements of Holstein × Gyr crossbred heifers raised under tropical conditions. Twenty-two crossbred (½ Holstein × ½ Gyr) heifers with an average initial BW of 102.2 ± 3.4 kg and 3 to 4 months of age were used. To estimate requirements, the comparative slaughter technique was used: four animals were assigned to the reference group, slaughtered at the beginning of the experiment to estimate the initial empty BW (EBW) and composition of the animals that remained in the experiment. The remaining animals were randomized into three treatments based on targeted rates of BW gain: high (1.0 kg/day), low (0.5 kg/day) and close to maintenance (0.1 kg/day). At the end of the experiment, all animals were slaughtered to determine EBW, empty body gain (EBG) and body energy and protein contents. The linear regression parameters were estimated using PROC MIXED of SAS (version 9.4). Estimates of the parameters of non-linear regressions were adjusted through PROC NLIN of SAS using the Gauss–Newton method for parameter fit. The net requirements of energy for maintenance (NEm) and metabolizable energy for maintenance (MEm) were 0.303 and 0.469 MJ/EBW0.75 per day, respectively. The efficiency of use of MEm was 64.5%. The estimated equation to predict the net energy requirement for gain (NEg) was: NEg (MJ/day) = 0.299 × EBW0.75 × EBG0.601. The efficiency of use of ME for gain (kg) was 30.7%. The requirement of metabolizable protein for maintenance was 3.52 g/EBW0.75 per day. The equation to predict net protein requirement for gain (NPg) was: NPg (g/day) = 243.65 × EBW−0.091 × EBG. The efficiency of use of metabolizable protein for gain (k) was 50.8%. We observed noteworthy differences when comparing to ME and protein requirements of Holstein × Gyr crossbred heifers with other systems. In addition, we also observed differences in estimates for NEm, NEg, NPg, kg and k. Therefore, we propose that the equations generated in the present study should be used to estimate energy and protein requirements for Holstein × Gyr crossbred dairy heifers raised in tropical conditions in the post-weaning phase up to 185 kg of BW.
Bipolar disorder (BD), along with schizophrenia, is one of the most severe psychiatric conditions and is correlated with attentional deficits and emotion dysregulation. Bipolar patients appear to be highly sensitive to the presence of emotional distractors. Yet, no study has investigated whether perceptual load modulates the interference of emotionally distracting information. Our main goal was to test whether bipolar patients are more sensitive to task-irrelevant emotional stimulus, even when the task demands a high amount of attentional resources.
Fourteen participants with BD I or BD II and 14 controls, age- and gender-matched, performed a target-letter discrimination task with emotional task-irrelevant stimulus (angry, happy and neutral facial expressions). Target-letters were presented among five distractor-letters, which could be the same (low perceptual load) or different (high perceptual load). Participants should discriminate the target-letter and ignore the facial expression. Response time and accuracy rate were analyzed.
showed a greater interference of facial stimuli at high load than low load, confirming the effectiveness of perceptual load manipulation. More importantly, patients tarried significantly longer at high load. This is consistent with deficits in control of attention, showing that bipolar patients are more prone to distraction by task-irrelevant stimulus only when the task is more demanding. Moreover, for bipolar patients neutral and angry faces resulted in a higher interference with the task (longer response time), compared to controls, suggesting an attentional bias for neutral and threating social cues. Nevertheless, a more detailed investigation regarding the attentional impairments in social context in BD is needed.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Sensory processing is the individual's ability to receive, process and integrate sensory information from the environment and body movement in the central nervous system, in order to produce adaptive responses. Sensory processing disorders (SPD) are associated to difficulties in regulating emotions and behaviours as well as motor abilities in response to sensory stimulation that lead to impairment in development and functioning. It is estimated that SPD affect 5–16% of school-aged children. Although these diseases constitute a primary diagnostic category in the Diagnostic Classification of Mental Health and Development Disorders of Infancy and Early Childhood: DC0-3, they have not yet been validated by the Diagnostic and Statistical Manual of Mental Disorders-DSM. In the latest edition of DSM, SPD were only included as one of the diagnostic criteria of autism-spectrum disorders. However, several studies have suggested that SPD may present themselves solely or coexist with other clinical conditions.
The aim of this study was to review systematically the relationship between SPD and psychopathology.
Articles indexed in the Pubmed database were analyzed.
Although sensory processing problems are well known to occur in association with autism, their relationship with other mental disorders is not a well studied area. Some studies have related them with ADHD, behavioural disorders and learning disorders. Some studies also comproved that SPD are a valid diagnosis and that there are individuals with SPD who do not meet the criteria for other known disorder. One study found an abnormal white matter microstructure in children with SPD. Despite these findings SPD need to be further studied.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Yukon Territory (YT) is a remote region in northern Canada with ongoing spread of tuberculosis (TB). To explore the utility of whole genome sequencing (WGS) for TB surveillance and monitoring in a setting with detailed contact tracing and interview data, we used a mixed-methods approach. Our analysis included all culture-confirmed cases in YT (2005–2014) and incorporated data from 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping, WGS and contact tracing. We compared field-based (contact investigation (CI) data + MIRU-VNTR) and genomic-based (WGS + MIRU-VNTR + basic case data) investigations to identify the most likely source of each person's TB and assessed the knowledge, attitudes and practices of programme personnel around genotyping and genomics using online, multiple-choice surveys (n = 4) and an in-person group interview (n = 5). Field- and genomics-based approaches agreed for 26 of 32 (81%) cases on likely location of TB acquisition. There was less agreement in the identification of specific source cases (13/22 or 59% of cases). Single-locus MIRU-VNTR variants and limited genetic diversity complicated the analysis. Qualitative data indicated that participants viewed genomic epidemiology as a useful tool to streamline investigations, particularly in differentiating latent TB reactivation from the recent transmission. Based on this, genomic data could be used to enhance CIs, focus resources, target interventions and aid in TB programme evaluation.
The Rio Grande Cone is a major fanlike depositional feature in the continental slope of the Pelotas Basin, Southern Brazil. Two representative sediment cores collected in the Cone area were retrieved using a piston core device. In this work, the organic matter (OM) in the sediments was characterized for a continental vs. marine origin using chemical proxies to help constrain the origin of gas in hydrates. The main contribution of OM was from marine organic carbon based on the stable carbon isotope (δ13C-org) and total organic carbon/total nitrogen ratio (TOC:TN) analyses. In addition, the 14C data showed important information about the origin of the OM and we suggest some factors that could modify the original organic matter and therefore mask the “real” 14C ages: (1) biological activity that could modify the carbon isotopic composition of bulk terrestrial organic matter values, (2) the existence of younger sediments from mass wasting deposits unconformably overlying older sediments, and (3) the deep-sediment-sourced methane contribution due to the input of “old” (>50 ka) organic compounds from migrating fluids.
Few studies have used genomic epidemiology to understand tuberculosis (TB) transmission in rural and remote settings – regions often unique in history, geography and demographics. To improve our understanding of TB transmission dynamics in Yukon Territory (YT), a circumpolar Canadian territory, we conducted a retrospective analysis in which we combined epidemiological data collected through routine contact investigations with clinical and laboratory results. Mycobacterium tuberculosis isolates from all culture-confirmed TB cases in YT (2005–2014) were genotyped using 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) and compared to each other and to those from the neighbouring province of British Columbia (BC). Whole genome sequencing (WGS) of genotypically clustered isolates revealed three sustained transmission networks within YT, two of which also involved BC isolates. While each network had distinct characteristics, all had at least one individual acting as the probable source of three or more culture-positive cases. Overall, WGS revealed that TB transmission dynamics in YT are distinct from patterns of spread in other, more remote Northern Canadian regions, and that the combination of WGS and epidemiological data can provide actionable information to local public health teams.
Expression of estrus near timed artificial insemination (TAI) is associated with greater fertility, and estrus detection could improve TAI fertility or direct TAI management, although accurate estrus detection can be difficult and time-consuming using traditional methods. The aim of this study is to evaluate influence of estrus on pregnancy (artificial insemination pregnancy rates (P/AI)) and to validate an alternative method to classify estrus/heat expression using tail chalking (HEATSC) in postpartum Bos indicus cows subjected to TAI in progesterone–estrogen-based protocols. In experiment 1 (Exp. 1), cows (5491) were subjected to visual observation of estrus after progesterone device removal, before TAI, and P/AI was evaluated according to estrus and body condition score (BCS). Cows received a progesterone device and 2 mg estradiol benzoate (EB). After 8 days, the device was removed and 150 μg of d-cloprostenol and 300 IU equine chorionic gonadotrophin was given. Later, animals in Exp. 1 received 1 mg EB and TAI 44 to 48 h. In the Exp. 2 – 3830 cows using similar protocol, received different ovulation inducers: 1 mg EB (n=1624) or 1 mg estradiol cypionate (EC; n=2206) on day 8 (D8). Cows were then marked with chalk, and HEATSC evaluated at TAI on D10 (HEATSC1 – no chalk removal=no estrus expression; HEATSC2 – partial chalk removal=low estrus expression; HEATSC3 – near complete/complete chalk removal=high estrus expression). In Exp. 1, cows showing estrus presented greater P/AI (48.4% v. 40.2%, P<0.05). In Exp. 2, P/AI (HEATSC1 – 40.0%; HEATSC2 – 49.7%; HEATSC3 – 60.9%; P<0.001), and larger follicle timed artificial insemination (LFTAI) (<0.001) varied according to HEATSC. There was no difference in P/AI (P=0.41) or LFTAI (P=0.33) according to ovulation inducer. Cows with greater BCS showed greater P/AI in both experiments (P<0.05). Estrus presence and greater HEATSC improved P/AI, and EC v. EB used promoted differential estrus manifestation (cows showing HEATSC2 and HEATSC3: 79.5% with EB v. 69.98% with EC use, P<0.001), however, with similar P/AI. The use of HEATSC in B. indicus cows subjected to TAI is useful to identify cows with greater estrus expression and consequently improved pregnancy rates in TAI, allowing the cows with low HEATSC to be targeted for additional treatments aimed at improving P/AI.
The use of tail chalk and estrus/heat expression scores (HEATSC) evaluation is instrumental in identifying cows with greater estrus expression and greater artificial insemination pregnancy rates (P/AI) in cows submitted to timed artificial insemination (TAI), and cows with low or no estrus expression present lower P/AI. It was intended in this study to improve the pregnancy rates in TAI for Bos indicus beef cows, and gonadotrophin-releasing hormone (GnRH) injection was hypothesized to increase pregnancy rates in a TAI program for cows submitted to progesterone–estradiol-based protocols with low or no estrus expression, evaluated by HEATSC. Cows (n= 2284) received a progesterone device and 2 mg estradiol benzoate, after 8 days the device was removed and 1 mg estradiol cypionate, 150 μg of d-cloprostenol and 300 IU equine chorionic gonadotropin was administered. All cows were marked with chalk and HEATSC evaluated (scales 1 to 3) at TAI performed on day 10. Animals with HEATSC1 and HEATSC2 (n= 937) received 100 μg de gonadorelin (GNRH group; n= 470), or 1 ml saline (Control group; n= 467), and cows with HEATSC3 (named HEAT group; n= 1347) received no additional treatment. The larger dominant follicle, evaluated on day 8and at TAI (day 10), was greater in HEAT group (P= 0.0145 and P <0.001, respectively). Corpus luteum (CL) area and progesterone concentration was evaluated on day 17, and CL area was larger in HEAT group, intermediary in Control and lower in GnRH group (Control= 2.68 cm2, GnRH= 2.37 cm2, HEAT group= 3.07 cm2, P <0.001). Greater progesterone concentrations were found in HEAT group than in Control and GnRH groups (Control= 4.74 ng/ml, GnRH= 4.29 ng/ml, HEAT group= 6.08 ng/ml, P<0.001). There was a difference in ovulation rate, greater in HEAT group than GnRH and Control groups (Control= 72.5%; GnRH= 81.25%; HEAT group= 90.71%; P= 0.0024). Artificial insemination pregnancy rates was greater in HEAT group (57.09% (769/1347) than in Control and GNRH groups, with positive effect of GnRH injection at the time of TAI in P/AI (Control= 36.18% (169/467), GnRH= 45.95% (216/470); P<0.0001). In conclusion, GnRH application in cows with low HEATSC (1 and 2) is a simple strategy, requiring no changes in TAI management to increase pregnancy rates in postpartum beef cows submitted to progesterone–estradiol-based TAI protocols, without reaching, however, the pregnancy rates of cows that demonstrate high estrus expression at the TAI.
This qualitative study explores the experiences of older adults participating in a creative visual arts program at a residential care facility in Victoria, British Columbia. A narrative inquiry approach was used to conduct face-to-face interviews with 10 residents and three program staff in addition to the systematic observations of program activities and an arts exhibit. The findings reveal the program fostered a sense of community among participants and enhanced their sense of self-worth as artists. A public art exhibition at a community centre underlined the value of residents’ artwork and gave meaning and purpose to their involvement in the program. Findings show the importance of arts programs in fostering creativity in later life and illustrate how people living in institutions can experience multiple dimensions of the self through artistic forms of expression. This study highlights the need to increase access to arts programs for individuals living in residential care.
Sugarcane is an important forage source for dairy cows in tropical countries. However, it provides limited digestible fiber and energy intake, and fat supplementation can be a way to increase energy density and decrease dietary, non-fiber carbohydrates concentrations. We aimed to evaluate the performance, digestion and metabolism of dairy cows in early lactation fed different concentrations of soybean oil (SBO) in sugarcane-based diets. Fourteen primiparous (545±17.2 kg of BW) and eight multiparous (629±26.7 kg BW) Holstein dairy cows were used according to a randomized block design. After calving, diets were randomly assigned to cows within the two parity groups. Diets were formulated with increasing concentrations of SBO (g/kg dry matter (DM)): control (0), low (LSBO; 15.7), medium (MSBO; 44.3) and high (HSBO; 73.4). The study was performed from calving until 84 days in milk, divided into three periods of 28 days each. Dry matter intake (DMI) was affected quadratically in response to SBO addition with the greatest and lowest values of 19.0 and 16.0 kg/day for LSBO and HSBO diets, respectively. The digestibility of potentially digestible NDF was quadratically affected by SBO with the greatest value of 623 g/kg for LSBO diet. Both milk and energy-corrected milk (ECM) production were quadratically affected by SBO inclusion, with greatest ECM values of 27.9 and 27.3 for LSBO and MSBO, respectively. Soybean oil inclusion linearly decreased milk fat concentration by 13.2% from control to HSBO. The CLA t10,c12-18:2 was observed in milk fat only for MSBO and HSBO diets. Soybean oil inclusion did not affect plasma glucose or serum concentrations of total proteins, globulins, albumin, urea nitrogen, beta-hydroxybutyrate, non-esterified fatty acids or insulin. Serum concentrations of total cholesterol, triglycerides and low-density lipoprotein increased with SBO supplementation. Soybean oil inclusion in sugarcane-based diets for early lactation dairy cows from 15.7 to 44.3 g/kg DM can improve energy intake and performance; however, at 44.3 g/kg DM milk fat concentration and ECM decreased. Soybean oil inclusion at 73.4 g/kg DM adversely affected energy intake, fiber digestion and performance of early lactation dairy cows and is not recommended.
The present review will present the recent published results and discuss the main effects of nutrients, mainly fatty acids, on the expression of genes involved in lipid metabolism. In this sense, the review focuses in two phases: prenatal life and finishing phase, showing how nutrients can modulate gene expression affecting marbling and fatty acid profile in meat from ruminants. Adiposity in ruminants starts to be affected by nutrients during prenatal life when maternal nutrition affects the differentiation and proliferation of adipose cells enhancing the marbling potential. Therefore, several fetal programming studies were carried out in the last two decades in order to better understand how nutrients affect long-term expression of genes involved in adipogenesis and lipogenesis. In addition, during the finishing phase, marbling becomes largely dependent on starch digestion and glucose metabolism, being important to create alternatives to increase these metabolic processes, and modulates gene expression. Different lipid sources and their fatty acids may also influence the expression of genes responsible to encode enzymes involved in fat tissue deposition, influencing meat quality. In conclusion, the knowledge shows that gene expression is a metabolic factor affecting marbling and fatty acid profile in ruminant meat and diets and their nutrients have direct effect on how these genes are expressed.
Animal evidence has suggested that maternal emotional and nutritional stress during pregnancy is associated with behavioral outcomes in offspring. The nature of the stresses applied may differ, but it is often assumed that the mother’s hippocampus–hypothalamic–pituitary–adrenal (HHPA) axis response releases higher levels of glucocorticoid hormones. The bed nucleus of the stria terminalis (BNST) is in a pivotal position to regulate the HHPA axis and the stress response, and it has been implicated in anxiety behavior. In the current study, to search whether BNST structural changes and neurochemical alterations are associated with anxiety-related behavior in adult gestational protein-restricted offspring relative to an age-matched normal protein diet (NP) rats, we conduct behavioral tests and, BNST dendritic tree analysis by Sholl analysis, associated to immunoblotting–protein quantification [11β-HSD2, GR, MR, AT1R, 5HT1A and 5HT2A, corticotrophin-releasing factor (CRH) and CRH1]. Dams were maintained either on isocaloric standard rodent chow [with NP content, 17% casein or low protein content (LP), 6% casein] chow throughout their entire pregnancy. Here, in rats subjected to gestational protein restriction, we found: (a) a significant reduction in dendritic length and impoverished dendritic arborization in BNST neurons; (b) an elevated plasmatic corticosterone levels; and (c) associated with enhanced anxiety-like behavior when compared with age-matched NP offspring. Moreover, altered protein (11β-HSD2, GR, MR and type 1 CRH receptors) expressions may underlie the increase in anxiety-like behavior in LP offspring. This work represents the first demonstration that BNST developmental plasticity by maternal protein restriction, resulting in fine structural changes and neurochemical alterations that are associated with modified behavioral states.
Globally, the prevalence of tuberculosis (TB) disease is higher in males. This study examined the effect of sex and age on Mycobacterium tuberculosis (Mtb) infection. Demographic and exposure data were collected on household contacts of sputum smear-positive pulmonary TB patients in Brazil. Contacts with tuberculin skin test induration ⩾10 mm at baseline or 12 weeks were considered Mtb infected. The study enrolled 917 household contacts from 160 households; 508 (55.4%) were female, median age was 21.0 years (range 0.30–87.0) and 609 (66.4%) had Mtb infection. The proportion infected increased with age from 63.3% in girls <5 years to 75.4% in women ⩾40 years and from 44.9% in boys <5 years to 73.6% in men ⩾40 years. Multivariable modelling showed the odds of infection increased between age 5 and 14 years among female contacts (OR 1.5 per 5-year age increase; 95% CI 1.1–2.2; P = 0.02) and between ages 0–4 and 15–39 years among male contacts (OR 2.7, 95% CI 0.83–8.9 and 1.1, 95% CI 0.99–1.3 per 5-year age increase; P = 0.10, 0.07, respectively). The study suggests that the age at which Mtb infection increases most is different in females compared with males. Studies are needed to explore whether these findings are due to differences in host susceptibility, exposure outside the household or other factors.
Background: Heterozygous loss-of-function mutations in the synaptic scaffolding gene SHANK2 are strongly associated with autism spectrum disorder (ASD). However, their impact on the function of human neurons is unknown. Derivation of induced pluripotent stem cells (iPSC) from affected individuals permits generation of live neurons to answer this question. Methods: We generated iPSCs by reprogramming dermal fibroblasts of neurotypic and ASD-affected donors. To isolate the effect of SHANK2, we used CRISPR/Cas9 to knock out SHANK2 in control iPSCs and correct a heterozygous nonsense mutation in ASD-affected donor iPSCs. We then derived cortical neurons from SOX1+ neural precursor cells differentiated from these iPSCs. Using a novel assay that overcomes line-to-line variability, we compared neuronal morphology, total synapse number, and electrophysiological properties between SHANK2 mutants and controls. Results: Relative to controls, SHANK2 mutant neurons have increased dendrite complexity, dendrite length, total synapse number (1.5-2-fold), and spontaneous excitatory postsynaptic current (sEPSC) frequency (3-7.6-fold). Conclusions: ASD-associated heterozygous loss-of-function mutations in SHANK2 increase synaptic connectivity among human neurons by increasing synapse number and sEPSC frequency. This is partially supported by increased dendrite length and complexity, providing evidence that SHANK2 functions as a suppressor of dendrite branching during neurodevelopment.