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About half of the neurons in the parabrachial nucleus (PB) that are activated by CO2 are located in the external lateral (el) subnucleus, express calcitonin gene-related peptide (CGRP), and cause forebrain arousal. We report here, in male mice, that most of the remaining CO2-responsive neurons in the adjacent central lateral (PBcl) and Kölliker-Fuse (KF) PB subnuclei express the transcription factor FoxP2 and many of these neurons project to respiratory sites in the medulla. PBclFoxP2 neurons show increased intracellular calcium during wakefulness and REM sleep and in response to elevated CO2 during NREM sleep. Photo-activation of the PBclFoxP2 neurons increases respiration, whereas either photo-inhibition of PBclFoxP2 or genetic deletion of PB/KFFoxP2 neurons reduces the respiratory response to CO2 stimulation without preventing awakening. Thus, augmenting the PBcl/KFFoxP2 response to CO2 in patients with sleep apnea in combination with inhibition of the PBelCGRP neurons may avoid hypoventilation and minimize EEG arousals.The parabrachial nucleus contains separate populations of neurons that respond to elevated CO2 with EEG arousal and increased breathing. Here we report that the parabrachial respiratory neurons express FoxP2 and are required for respiratory responses to elevated CO2. [ABSTRACT FROM AUTHOR]

Seasonality was shown to have an effect on food availability and accessibility, increasing the risk of food insecurity and causing poor diet quality and malnutrition. Therefore, this study aimed to determine seasonal effects on household food security status, diet quality, and nutritional status of urban poor adolescents in Malaysia. A cohort study was conducted among 164 adolescents aged 10–17 from 12 People Housing Programme in Kuala Lumpur, Malaysia during the Northeast (November 2021 till March 2022) and Southwest (June 2022 till September 2022) monsoon. Household food security status was measured using the 18-item USDA Household Food Security Survey Module. Dietary intake was determined using a two-days 24-h dietary recall and translated into Standardized Malaysian Healthy Eating Index (S-MHEI). Anthropometric and haemoglobin level measurements were performed to determine nutritional status. Seasonality was found to have a significant effect on overall diet quality (p = 0.021), food groups such as fish (p < 0.001), meat/poultry/eggs (p = 0.003), and legumes/nuts (p < 0.001), and fat nutrient (p = 0.037) as well as anaemia status (p = 0.020) after controlling the confounders. Although food security did not vary with seasons, seasonality affected the consumption of certain food groups as well as anaemia status for urban poor adolescents. Seasonally sensitive nutrition initiatives should be developed to ensure diet adherence to recommendations, ultimately enhancing the diet quality of urban poor adolescents. [ABSTRACT FROM AUTHOR]

The major breakthroughs in our knowledge of how biology plays a role in Parkinson's disease (PD) have opened up fresh avenues designed to know the pathogenesis of disease and identify possible therapeutic targets. Mitochondrial abnormal functioning is a key cellular feature in the pathogenesis of PD. An enzyme, leucine-rich repeat kinase 2 (LRRK2), involved in both the idiopathic and familial PD risk, is a therapeutic target. LRRK2 has a link to the endolysosomal activity. Enhanced activity of the LRRK2 kinase, endolysosomal abnormalities and aggregation of autophagic vesicles with imperfectly depleted substrates, such as α-synuclein, are all seen in the substantia nigra dopaminergic neurons in PD. Despite the fact that LRRK2 is involved in endolysosomal and autophagic activity, it is undefined if inhibiting LRRK2 kinase activity will prevent endolysosomal dysfunction or minimise the degeneration of dopaminergic neurons. The inhibitor's capability of LRRK2 kinase to inhibit endolysosomal and neuropathological alterations in human PD indicates that LRRK2 inhibitors could have significant therapeutic usefulness in PD. G2019S is perhaps the maximum common mutation in PD subjects. Even though LRRK2's well-defined structure has still not been established, numerous LRRK2 inhibitors have been discovered. This review summarises the role of LRRK2 kinase in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Alcoholic neuropathy emerges following the persistent alcohol imbibing, and triggers nerve damage through de-escalating the receptors situated in the central nervous system (CNS), which consecutively evolves into debilitating neuropathic state and further precipitates hyperalgesia, allodynia, dysesthesia, ataxia, numbness, immobility, and decline in certain body functions. Existing pharmacotherapy, such as anticonvulsants (gabapentin and topiramate), and antidepressant drugs (duloxetine, and venlafaxine) render short-lasting benefits; however, their continual use is not favoured nowadays because of their detrimental outcomes and habit-forming behaviour. Consequently, the research is being shifted towards exploring novel propitious targets which entirely assist in the cessation of the disease. This review discloses the multitudinous pathways implicated in the pathogenesis of alcoholic neuropathy, with special emphasis on purinergic and orexinergic receptors. Moreover, the review focuses on targeting purinergic (P2X3, P2X2/3, P2X4, P2X7, and P2Y12), and orexinergic (OX1 and OX2) receptors associated with the evolution of alcoholic neuropathy, and to incentivize further investigation to attain novel propitious strategy in alcoholic neuropathy treatment. The mechanisms implicated in the progression of alcoholic neuropathy comprises malnourishment (B vitamins scarcity), direct pernicious outcomes of alcohol, increased oxidative-nitrosative stress, protein kinase C epsilon (PKCε), and extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) functioning, abnormalities in the axonal transport and cytoskeleton system, activation of nuclear factor-kappa B (NF-κB) and caspase pathway, stimulation of the sympathoadrenal and hypothalamo–pituitary–adrenal (HPA) axis, and microglial cells of spinal column. The purinergic receptor antagonists, orexins/orexinergic receptor antagonists eliminate/modulate hyperalgesia, allodynia, inflammatory pain, liberation of inflammatory mediators, NF-κB signalling pathway, ROS formation, nerve cell deterioration, and craving for alcohol consumption, thereby ceasing the evolution of alcoholic neuropathy. The authors focus to highlight the importance of this alternative strategy as a novel target in alcoholic neuropathy, and to incentivize researchers to scrutinize the possible benefits of purinergic and orexins/orexinergic receptors in the therapy of alcoholic neuropathy. [ABSTRACT FROM AUTHOR]

During obstructive sleep apnea, elevation of CO2 during apneas contributes to awakening and restoring airway patency. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) containing calcitonin gene related peptide (PBelCGRP neurons) are critical for causing arousal during hypercapnia. However, others found that genetic deletion of serotonin (5HT) neurons in the brainstem also prevented arousal from hypercapnia. To examine interactions between the two systems, we showed that dorsal raphe (DR) 5HT neurons selectively targeted the PBel. Either genetically directed deletion or acute optogenetic silencing of DRSert neurons dramatically increased the latency of mice to arouse during hypercapnia, as did silencing DRSert terminals in the PBel. This effect was mediated by 5HT2a receptors which are expressed by PBelCGRP neurons. Our results indicate that the serotonergic input from the DR to the PBel via 5HT2a receptors is critical for modulating the sensitivity of the PBelCGRP neurons that cause arousal to rising levels of blood CO2. Dorsal raphe 5HT(DRSert) neurons regulate arousal from hypercapnia by their projections to the neurons in the external lateral parabrachial nucleus (PBel) that are glutamatergic and also express calcitonin gene related peptide (PBelCGRP). The DRSert input to the PBel modulates the arousal system to rising levels of blood CO2, and may be mediated by 5HT2a receptors on the PBelCGRP neurons. [ABSTRACT FROM AUTHOR]

Aim: Children's psychosocial factors related to healthy meal preparation are important for sustainable healthy dietary behaviour. At present, there is no valid and reliable tool to measure children's psychosocial factors related to healthy meal preparation. Hence, this study aimed to develop, validate and determine the reliability of a questionnaire designed to measure psychosocial factors related to healthy meal preparation among Malaysian children. Subjects and methods: This cross-sectional study included 250 children aged 9–11 years. The questionnaire developed was tested for face and content validity. Item analysis was conducted for the knowledge domain. Construct validity of attitude, practice and self-efficacy domains was assessed using exploratory factor analysis with principle axis factoring extraction and direct oblimin rotation. Cronbach's alpha coefficient and Kuder-Richardson Formula 20 assessed internal consistency. The intraclass correlation coefficient determined test-retest reliability. Results: All experts rated the questionnaire with a > 0.75 validity index. The knowledge domain had the optimal level of difficulty and could discriminate children with top and lower scores. Three-factor solutions emerged for the attitude domain and two-factor solutions emerged for the practice and self-efficacy domains, with appropriate factor loadings (> 0.40). Internal consistency ranged from 0.63–0.75 for the respective domains and an overall internal consistency of 0.82 for the whole questionnaire. Intraclass correlation coefficients ranged from 0.85–0.89 for the respective domains. Conclusion: Outcomes demonstrated that the questionnaire is a reliable and valid evaluation tool and can be adapted by countries to use in hands-on healthy meal preparation interventions to advocate healthy dietary behaviours among children. [ABSTRACT FROM AUTHOR]

There are only limited reports on Punjabi’s health status in Malaysia. This cross-sectional study assessed the prevalence of metabolic syndrome (Mets) and its risk factors among 277 subjects recruited from the Malaysian Punjabi community. Overall prevalence of Mets was 43%, but 61% among females. Subjects classified with Mets had significantly (p < 0.05) higher body mass index, visceral fat and percentage of body fat. Daily carbohydrate and glycemic index (GI) were also higher among Mets subjects (p < 0.05). Logistics regression analysis showed that primary level of education (OR 5.57, CI 1.29-23.97, p = 0.021) was a factor associated with Mets, followed by middle household income (OR 2.30, CI 1.01-5.20, p = 0.046), GI (OR 1.03, CI 1.00-1.06, p = 0.026), and age (OR 1.03, CI 1.00-1.05, p = 0.023). Mets shows high prevalence among the studied Punjabi population, prompting the consideration of adequate preventive measures, primarily among lower socioeconomic groups. [ABSTRACT FROM AUTHOR]

Medical therapy has limited value in managing symptoms of progressive familial intrahepatic cholestasis (PFIC). Liver transplantation (LT) is the only definite therapy for progressive liver failure and intractable pruritis. In recent years, biliary diversion (BD) has also shown therapeutic promise. This study was designed to review the experience of management and outcome of seven PFIC patients. Two children each had type II and III and three had type I/II PFIC, respectively. Medical treatment was successful in only one. Decompensated cirrhosis had already set in four children. They underwent a living related LT. There was one post transplant mortality. Remaining all children had a normal graft function at a mean follow-up of 50 months. One patient of PFIC type I/II received internal and another of PFIC type II received external BD. Both patients were asymptomatic at follow-up of 19 and 23 months respectively. Nontransplant surgical options should be offered to noncirrhotic children with PFIC. [ABSTRACT FROM AUTHOR]

This case-series analyzed the outcome of live donor liver transplantation (LT) performed in children <7.5kg from January 2008 to June 2009 at our center. Five patients (3 males, 2 females, mean age, 8.2 ± .4 months; mean weight 6.8 ± 0.4 kg) underwent LT. The indications of LT included biliary atresia (3) and idiopathic neonatal hepatitis (2). Postoperative complications included acute rejection (1), portal venous thrombosis (1), bile leak (1), severe hypertension (1) and bacterial sepsis (4). There were no donor related complications. The median follow-up duration is 11 months with patient and graft survival rates of 100% each, respectively. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) often leads to severe lower limb (LL) deformities due to recurrent fractures that significantly hamper ambulation. We describe our management experience of correction of LL deformities in four children with OI. Medical management consisted of peri and postoperative pamidronate therapy, calcium supplementation and rehabilitative care. Deformities were corrected with multiple osteotomies and intramedullary fixation by titanium elastic nails. At a mean follow-up of 30 months, all children have significantly reduced fracture incidence and have no evidence of recurrence of deformities with improved ambulatory status. We emphasize the importance of combined medical and surgical therapy for these patients. [ABSTRACT FROM AUTHOR]

We report and discuss a unique case of hemophagocytosis associated with hepatitis A and E coinfection in a young child which has never been reported earlier in children. Its varied presentation is emphasized and possible management options and outcome are discussed. [ABSTRACT FROM AUTHOR]

A letter to the editor on the case of an infant with facial palsy and Kawasaki disease is presented.

Four case records of patients with Seckel Syndrome (SS) were retrieved. Typical of bird headed dwarfism was seen in all. Chromosome 18 deletion was seen in one child with SS. MRI abnormalities were detected in 3 patients. Cytogenetic studies and neuroimaging is likely to provide important diagnostic and prognostic information. [ABSTRACT FROM AUTHOR]

Acrodermatitis Enteropathica (AE) is an important nutritional disorder of children affecting both innate and cell mediated immunity. It predisposes to secondary bacterial and candida superinfections. We describe an infant with typical features of AE who had candida infection with a fulminant course. Need of early recognition and prompt initiation of therapy for fungal infection in AE is emphasized. [ABSTRACT FROM AUTHOR]

A letter to the editor about the promotion of pediatric cadaver organ donation (PCOD) programme in India is presented.