Notes

Mutation array regarding autosomal recessive non-syndromic hearing difficulties in key Iran.
Focusing on antibiotics as a main pillar of intervention is likely to engender antimicrobial resistance, eventually hindering the appreciable gains LMICs have achieved in neonatal health outcomes.Introduction Neuropathic pain is a chronic condition that significantly affects the quality of life of millions of people globally. Most of the pharmacologic treatments currently in use demonstrate modest efficacy and over half of all patients do not respond to medical management. Hence, there is a need for new, efficacious drugs. Evidence points toward voltage-gated sodium channels as a key target for novel analgesics.Area covered The role of voltage-gated sodium channels in pain pathophysiology is illuminated and the preclinical and clinical data for new sodium channel blockers and toxin-derived lead compounds are examined. The expansion of approved sodium channel blockers is discussed along with the limitations of current research, trends in drug development, and the potential of personalized medicine.Expert opinion The transition from preclinical to clinical studies can be difficult because of the inherent inability of animal models to express the complexities of pain states. Pain pathways are notoriously intricate and may be pharmacologically modulated at a variety of targets; it is unlikely that action at a single target could completely abolish a pain response because pain is rarely unifactorial. Combination therapy may be necessary and this could further confound the discovery of novel agents.The aim of this narrative review was to demonstrate how the notion of allostatic load (AL) relates directly to the mental health disparities observed between Indigenous and non-Indigenous Australians. We also endeavored to synthesize the results of the limited number of studies examining stress and AL in Indigenous Australians in order to explore the potential public health benefits of the AL concept. A range of literature examining health inequalities, psychosocial determinants of mental illness and AL was explored to demonstrate the applicability of stress biology to the significant mental health burden faced by Indigenous Australians. Furthermore, all original studies indexed in MEDLINE that provided quantitative data on primary stress biomarkers in Indigenous Australians were selected for review. Evidence of hypothalamic-pituitary-adrenal axis dysregulation and increased AL is apparent even in the handful of studies examining stress biomarkers in Indigenous Australians. Urinary, salivary, hair and fingernail cortisol, hair cortisone, urinary epinephrine, heart rate variability and the cortisol awakening response are all AL parameters which have been shown to be dysregulated in Indigenous Australian cohorts. Furthermore, associations between some of these biomarkers, self-perceived discrimination, exposure to stressful life events and symptoms of psychiatric disorders in Indigenous Australians have also been demonstrated. The continued assessment of AL biomarkers and their relationship with past traumas, lifetime stressors and socio-economic factors amongst Indigenous Australians is important to addressing the mental health this population. Measurement of AL biomarkers in a culturally appropriate manner may lead to more targeted preventative measures, interventions and policies, which mitigate the effects of stress at both the individual and societal level.Introduction Pulmonary arterial hypertension (PAH) is a progressive disease characterized by remodeling of small pulmonary arteries leading to increased pulmonary arterial pressure. Existing treatments acts to normalize vascular tone via three signaling pathways the prostacyclin, the endothelin-1, and the nitric oxide. Although over the past 20 years, there has been considerable progress in terms of treatments for PAH, the disease still remains incurable with a disappointing prognosis.Areas covered This review summarizes the pathophysiology of PAH, the advantages and disadvantages of the inhalation route, and assess the relative advantages various inhaled therapies for PAH. The recent studies concerning the development of controlled-release drug delivery systems loaded with available anti-PAH drugs have also been summarized.Expert opinion The main obstacles of current pharmacotherapies of PAH are their short half-life, stability, and formulations, resulting in reducing the efficacy and increasing systemic side effects and unknown pathogenesis of PAH. The pulmonary route has been proposed for delivering anti-PAH drugs to overcome the shortcomings. However, the application of approved inhaled anti-PAH drugs is limited. Inhalational delivery of controlled-release nanoformulations can overcome these restrictions. Extensive studies are required to develop safe and effective drug delivery systems for PAH patients.Introduction Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system affecting primarily the spinal cord and optic nerves. Most NMOSD patients are seropositive for immunoglobulin G autoantibodies against astrocyte water channel aquaporin-4, called AQP4-IgG, which cause astrocyte injury leading to demyelination and neurological impairment. Current therapy for AQP4-IgG seropositive NMOSD includes immunosuppression, B cell depletion, and plasma exchange. https://www.selleckchem.com/products/epz015666.html Newer therapies target complement, CD19 and IL-6 receptors.Areas covered This review covers early-stage pre-clinical therapeutic approaches for seropositive NMOSD. Targets include pathogenic AQP4-IgG autoantibodies and their binding to AQP4, complement-dependent and cell-mediated cytotoxicity, blood-brain barrier, remyelination and immune effector and regulatory cells, with treatment modalities including small molecules, biologics, and cells.Expert opinion Though newer NMOSD therapies appear to have increased efficacy in reducing relapse rate and neurological deficit, increasingly targeted therapies could benefit NMOSD patients with ongoing relapses and could potentially be superior in efficacy and safety. Of the various early-stage therapeutic approaches, IgG inactivating enzymes, aquaporumab blocking antibodies, drugs targeting early components of the classical complement system, complement regulator-targeted drugs, and Fc-based multimers are of interest. Curative strategies, perhaps involving AQP4 tolerization, remain intriguing future possibilities.
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