Water, sanitation, and hygiene vulnerability in child stunting in developing countries: a systematic review with meta-analysis.

OBJECTIVES: This study aimed to perform a systematic review and meta-analysis to assess the scientific evidence of the relationship between vulnerability to access to safe drinking water, sanitation, and hygiene (WASH) practices on stunting in children aged <5 years in developing countries. STUDY DESIGN: This is a systematic review and meta-analysis article to assess the relationship between under-five stunting and WASH vulnerability in developing countries. METHODS: The systematic review with meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol methodology. The following databases were used: LILACS, MEDLINE (via PubMed), SciELO, Web of Science, ScienceDirect, SCOPUS, and Embase. All original studies identified that related WASH vulnerability to stunting in children aged <5 years in developing countries was included. Three authors performed independently the selection and extraction of data from the articles. The statistical software STATA version 11 was used. Cochran's Q test and Chi-square test (I2) with 95% significance were used to assess the heterogeneity of the studies. RESULTS: The search resulted in the initial identification of 2047 articles; after reading the abstracts, followed by the full articles, 14 articles were included in the systematic review and eight articles were included in the meta-analysis. The studies selected for the systematic review were published between the years 1992 and 2021 and conducted in eight countries, namely, Ethiopia, India, Indonesia, Bangladesh, Tanzania, Peru, China, and Lesotho. The studies assessed vulnerability to access to WASH on the growth of children aged <5 years. There was a significant difference when relating WASH vulnerability to children's height. The meta-analysis of this study showed that the impact of WASH on child stunting is significant when it comes to lack of sanitation in 72% of the studies. CONCLUSIONS: The study found that WASH vulnerability contributes to stunting in children aged <5 years in developing countries. Based on our findings, we recommend incorporating WASH strategies, especially sanitation, into the formulation of interventions integrating with health promotion policies for healthy early childhood development.

Abdominal TRPV1 channel desensitization enhances stress-induced hyperthermia during social stress in rats.

AIMS: In rats, stress-induced hyperthermia caused by social interaction depends on brown adipose tissue (BAT) thermogenesis and peripheral vasoconstriction. However, the peripheral mechanisms responsible for regulating the level of hyperthermia during social stress are still unknown. The transient receptor potential vanilloid 1 (TRPV1) subfamily, expressed in sensory and visceral neurons, can serve as a thermoreceptor. Here, we tested the hypothesis that the abdominal TRPV1 is essential in regulating stress-induced hyperthermia during social stress. MAIN METHODS: Male Wistar rats received an intraperitoneal injection of Resiniferatoxin (RTX) - an ultra-potent capsaicin analog, (i.e., to desensitize the TRPV1 channels) or vehicle. Seven days later, we evaluated the effects of abdominal TRPV1 channels desensitization on core body temperature (CBT), brown adipose tissue (BAT) temperature, tail skin temperature, and heart rate (HR) of rats subjected to a social stress protocol. KEY FINDINGS: We found abdominal TRPV1 desensitization increased CBT and BAT temperature but did not change tail skin temperature and HR during rest. However, under social stress, we found that abdominal TRPV1 desensitization heightened the increase in CBT and BAT caused by stress. Also, it abolished the increase in tail skin temperature that occurs during and after social stress. TRPV1 desensitization also delayed the HR recovery after the exposure to the social stress. SIGNIFICANCE: These results show that abdominal TRPV1 channels desensitization heightens stress-induced hyperthermia, causing heat dissipation during and after social stress, enabling optimal thermal control during social encounters.

Panic results in unique molecular and network changes in the amygdala that facilitate fear responses.

Recurrent panic attacks (PAs) are a common feature of panic disorder (PD) and post-traumatic stress disorder (PTSD). Several distinct brain regions are involved in the regulation of panic responses, such as perifornical hypothalamus (PeF), periaqueductal gray, amygdala and frontal cortex. We have previously shown that inhibition of GABA synthesis in the PeF produces panic-vulnerable rats. Here, we investigate the mechanisms by which a panic-vulnerable state could lead to persistent fear. We first show that optogenetic activation of glutamatergic terminals from the PeF to the basolateral amygdala (BLA) enhanced the acquisition, delayed the extinction and induced the persistence of fear responses 3 weeks later, confirming a functional PeF-amygdala pathway involved in fear learning. Similar to optogenetic activation of PeF, panic-prone rats also exhibited delayed extinction. Next, we demonstrate that panic-prone rats had altered inhibitory and enhanced excitatory synaptic transmission of the principal neurons, and reduced protein levels of metabotropic glutamate type 2 receptor (mGluR2) in the BLA. Application of an mGluR2-positive allosteric modulator (PAM) reduced glutamate neurotransmission in the BLA slices from panic-prone rats. Treating panic-prone rats with mGluR2 PAM blocked sodium lactate (NaLac)-induced panic responses and normalized fear extinction deficits. Finally, in a subset of patients with comorbid PD, treatment with mGluR2 PAM resulted in complete remission of panic symptoms. These data demonstrate that a panic-prone state leads to specific reduction in mGluR2 function within the amygdala network and facilitates fear, and mGluR2 PAMs could be a targeted treatment for panic symptoms in PD and PTSD patients.

Association of high-fat diet with neuroinflammation, anxiety-like defensive behavioral responses, and altered thermoregulatory responses in male rats.

Overweight and obesity are a worldwide pandemic affecting billions of people. These conditions have been associated with a chronic low-grade inflammatory state that is recognized as a risk factor for a range of somatic diseases as well as neurodevelopmental disorders, anxiety disorders, trauma- and stressor-related disorders, and affective disorders. We previously reported that the ingestion of a high-fat diet (HFD; 45% fat kcal/g) for nine weeks was capable of inducing obesity in rats in association with increased reactivity to stress and increased anxiety-related defensive behavior. In this study, we conducted a nine-week diet protocol to induce obesity in rats, followed by investigation of anxiety-related defensive behavioral responses using the elevated T-maze (ETM), numbers of FOS-immunoreactive cells after exposure of rats to the avoidance or escape task of the ETM, and neuroinflammatory cytokine expression in hypothalamic and amygdaloid nuclei. In addition, we investigated stress-induced cutaneous thermoregulatory responses during exposure to an open-field (OF). Here we demonstrated that nine weeks of HFD intake induced obesity, in association with increased abdominal fat pad weight, increased anxiety-related defensive behavioral responses, and increased proinflammatory cytokines in hypothalamic and amygdaloid nuclei. In addition, HFD exposure altered avoidance- or escape task-induced FOS-immunoreactivity within brain structures involved in control of neuroendocrine, autonomic, and behavioral responses to aversive stimuli, including the basolateral amygdala (BLA) and dorsomedial (DMH), paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei. Furthermore, rats exposed to HFD, relative to control diet-fed rats, responded with increased tail skin temperature at baseline and throughout exposure to an open-field apparatus. These data are consistent with the hypothesis that HFD induces neuroinflammation, alters excitability of brain nuclei controlling neuroendocrine, autonomic, and behavioral responses to stressful stimuli, and enhances stress reactivity and anxiety-like defensive behavioral responses.

PSD95 and nNOS interaction as a novel molecular target to modulate conditioned fear: relevance to PTSD.

Stimulation of N-methyl-D-aspartic acid receptors (NMDARs) and the resulting increase of nitric oxide (NO) production are critical for fear memory formation. Following NMDAR activation, efficient production of NO requires linking the 95 kDa postsynaptic density protein (PSD95), a scaffolding protein to neuronal nitric oxide synthase (nNOS). A variety of previously studied NMDAR antagonists and NOS inhibitors can disrupt fear conditioning, but they also affect many other CNS functions such as motor activity, anxiety, and learning. We hypothesized that disrupting nNOS and PSD95 interaction in the amygdala, a critical site for fear memory formation, will reduce conditioned fear. Our results show that systemic treatment with ZL006, a compound that disrupts PSD95/nNOS binding, attenuates fear memory compared to its inactive isomer ZL007. Co-immunoprecipitation after fear conditioning showed a robust increase in the amygdala PSD95/nNOS binding, which was blocked by systemic pre-administration of ZL006. Treatment of amygdala slices with ZL006 also impaired long-term potentiation (LTP), a cellular signature of synaptic plasticity. Direct intra-amygdala infusion of ZL006 also attenuated conditioned fear. Finally, unlike NMDAR antagonist MK-801, ZL006 does not affect locomotion, social interaction, object recognition memory, and spatial memory. These findings support the hypothesis that disrupting the PSD95/nNOS interaction downstream of NMDARs selectively reduces fear memory, and highlights PSD95/nNOS interaction as a novel target for fear-related disorders, such as posttraumatic stress disorder.

Efeitos da granulometria e da forma física da ração sobre o desempenho de frangos de corte / Effects of particle size and physical form of diets on broiler performance

Foram utilizados 936 pintos de corte machos e 1008 fêmeas da linhagem Cobb(r) criados no período de um a 45 dias. Os tratamentos foram compostos por duas formas físicas da ração (farelada e peletizada) e duas granulometrias do milho (3,8mm e 7,0mm). O delineamento experimental foi inteiramente ao acaso, em arranjo fatorial 2 x 2 (duas granulometrias x duas formas físicas), com seis repetições de 39 aves cada para os machos e seis repetições de 42 aves cada para as fêmeas. A ração peletizada produzida com moagem 3,8mm apresentou melhor PDI (P≤0,05). Aves fêmeas alimentadas com ração peletizada apresentaram maior consumo de ração, ganho de peso e melhor conversão alimentar que aquelas que receberam ração farelada. Não foi observada diferença significativa (P>0,05) entre os tratamentos para as variáveis ganho de peso, conversão alimentar e consumo de ração dos machos. Não houve influência da forma física e da granulometria sobre a viabilidade das aves em nenhuma fase de criação (P>0,05).

A total of 936 male chickens and 1008 female Cobb(r) were used from 1 to 45 days old. Treatments consisted of two physical forms (mash and pelleted diets) and two particle sizes ( corn ground through 3.8mm and 7.0mm sieves). The experimental design was completely randomized in a 2 x 2 factorial design (two particle sizes x two physical forms), with six replicates of 39 birds each for males and six replicates of 42 birds each for females. PDI from the pelleted physical form that was produced with 3.8mm grinding showed better results (P≤0.05). Female birds fed pelleted diets had greater feed intake, weight gain and better feed conversion than those fed mash diet. No significant difference (P>0.05) was observed between the treatments for male feed intake, weight gain and feed conversion from 1 to 45 days of age. There was no influence of the physical form and particle size on the feasibility of birds in any phase (P>0.05).

Amygdalar neuronal activity mediates the cardiovascular responses evoked from the dorsolateral periaqueductal gray in conscious rats.

There is ample evidence that both lateral/dorsolateral periaqueductal gray (l/dlPAG) and basolateral amygdala (BLA) are essential for the regulation of the autonomic responses evoked during innate reactions to threatening stimuli. However, it is not well established to what extent the BLA regulates the upstream functional connection from the l/dlPAG. Here we evaluated the role of the BLA and its glutamatergic receptors in the cardiovascular responses induced by l/dlPAG stimulation in rats. We examined the influence of acute inhibition of the BLA, unilaterally, by injecting muscimol on the cardiovascular responses evoked by the injection of N-methyl D-aspartate (NMDA) into the l/dlPAG. We also evaluated the role of BLA ionotropic glutamate receptors in these responses by injecting antagonists of NMDA and AMPA/kainate receptor subtypes into the BLA. Our results show that the microinjection of NMDA in the BLA increased the mean arterial pressure (MAP) and heart rate (HR). Injection of NMDA into the l/dlPAG caused similar increases in these variables, which was prevented by the prior injection of muscimol, a GABAA agonist, into the BLA. Moreover, injection of glutamatergic antagonists (2-amino-5-phosphonopentanoate (AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)) into the BLA reduced the increase in MAP and HR induced by l/dlPAG activation. Finally, the inhibition of the central amygdala neurons failed to reduce the cardiovascular changes induced by l/dlPAG activation. These results indicate that physiological responses elicited by l/dlPAG activation require the neuronal activity in the BLA. This ascending excitatory pathway from the l/dlPAG to the BLA might ensure the expression of the autonomic component of the defense reaction.

Blunted GABA-mediated inhibition within the dorsomedial hypothalamus potentiates the cardiovascular response to emotional stress in rats fed a high-fat diet.

Rats fed a high-fat diet (HFD) present an exaggerated endocrine response to stress conditions, which, like obesity, show a high correlation with cardiovascular diseases. Meanwhile the GABAergic neurotransmission within the dorsomedial hypothalamus (DMH) is involved in the regulation of the physiological responses during emotional stress. Here we evaluated the influence of obesity, induced by a HFD, on the cardiovascular responses induced by air jet stress in rats, and the role of the GABAergic tonus within the DMH in these changes. Our results showed that consumption of a HFD (45% w/w fat) for 9 weeks induced obesity and increases in baseline mean arterial pressure (MAP) and heart rate (HR). Moreover, obesity potentiated stress responsiveness, evidenced by the greater changes in MAP and HR induced by stress in obese rats. The injection of muscimol into the DMH reduced the maximal increases in HR and MAP induced by stress in both groups; however, the reduction in the maximal increases in MAP in the HFD group was less pronounced. Moreover, the injection of muscimol into the DMH of obese rats was less effective in reducing the stress-induced tachycardia, since the HR attained the same levels at the end of the stress paradigm as after the vehicle injection. Injection of bicuculline into DMH induced increases in MAP and HR in both groups. Nevertheless, obesity shortened the tachycardic response to bicuculline injection. These data show that obesity potentiates the cardiovascular response to stress in rats due to an inefficient GABAA-mediated inhibition within the DMH.