Congenital hyperinsulinemia (CHI) is a genetically and clinically heterogenous disorder. In addition to the standard care of management of the proband, genetic counseling regarding the risk of recurrence in the future siblings is an important part in the management of the disorder. The counseling needs identification of accurate etiology and is challenging due to the complexity of the molecular mechanisms of CHI. This case highlights the importance of molecular testing which not only helped in planning the management of the proband with CHI but also helped in providing genetic counseling for which the family had consulted the medical genetics department.B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurological disorders, acting as antigen-presenting cells facilitating antibody production but also as sensors, coordinators, and regulators of the immune response. In particular, B cells can regulate the T cell activation process through their participation in antigen presentation, production of proinflammatory cytokines (bystander activation or suppression), and contribution to ectopic lymphoid aggregates. Such an important interplay between B and T cells makes therapeutic depletion of B cells an attractive treatment strategy. The last decade, anti-B cell therapies using monoclonal antibodies against B cell surface molecules have evolved into a rational approach for successfully treating autoimmune neurological disorders, even when T cells seem to be the main effector cells. The paper summarizes basic aspects of B cell biology, discusses the roles of B cells in neurological autoimmunities, and highlights how the currently available or under development anti-B cell therapeutics exert their action in the wide spectrum and immunologically diverse neurological disorders. The efficacy of the various anti-B cell therapies and practical issues on induction and maintenance therapy is specifically detailed for the treatment of patients with multiple sclerosis, neuromyelitis-spectrum disorders, autoimmune encephalitis and hyperexcitability CNS disorders, autoimmune neuropathies, myasthenia gravis, and inflammatory myopathies. The success of anti-B cell therapies in inducing long-term remission in IgG4 neuroautoimmunities is also highlighted pointing out potential biomarkers for follow-up infusions.Astrocytes are critical regulators of the immune/inflammatory response in several human central nervous system (CNS) diseases. Emerging evidence suggests that dysfunctional astrocytes are crucial players in seizures. The objective of this study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in 4-aminopyridine (4-AP)-induced seizures and the underlying mechanism. We also provide evidence for the role of Yes-associated protein (YAP) in seizures. 4-AP was administered to mice or primary cultured astrocytes. YAP-specific small interfering RNA (siRNA) was administered to primary cultured astrocytes. Mouse brain tissue and surgical specimens from epileptic patient brains were examined, and the results showed that TRPV4 was upregulated, while astrocytes were activated and polarized to the A1 phenotype. The levels of glial fibrillary acidic protein (GFAP), cytokine production, YAP, signal transducer activator of transcription 3 (STAT3), intracellular Ca2+([Ca2+]i) and the third component of complement (C3) were increased in 4-AP-induced mice and astrocytes. Perturbations in the immune microenvironment in the brain were balanced by TRPV4 inhibition or the manipulation of [Ca2+]i in astrocytes. Knocking down YAP with siRNA significantly inhibited 4-AP-induced pathological changes in astrocytes. Our study demonstrated that astrocytic TRPV4 activation promoted neuroinflammation through the TRPV4/Ca2+/YAP/STAT3 signaling pathway in mice with seizures. Astrocyte TRPV4 inhibition attenuated neuroinflammation, reduced neuronal injury, and improved neurobehavioral function. Targeting astrocytic TRPV4 activation may provide a promising therapeutic approach for managing epilepsy.Close relative (consanguineous) marriage is widely practised globally, and it increases the risk of genetic disorders. Mobile apps may increase awareness and education regarding the associated risks in a sensitive, engaging, and accessible manner. This systematic review of patient-facing genetic/genomic mobile apps explores content, function, and quality. We searched the NHS Apps Library and the UK Google Play and Apple App stores for patient-facing genomic/genetic smartphone apps. Descriptive information and information on content was extracted and summarized. Readability was examined using the Flesch-Kincaid metrics. Two raters assessed each app, using the Mobile App Rating Scale (MARS) and the IMS Institute for Healthcare Informatics functionality score. A total of 754 apps were identified, of which 22 met the eligibility criteria. All apps intended to inform/educate users, while 32% analyzed genetic data, and 18% helped to diagnose genetic conditions. Most (68%) were clearly about genetics, but only 14% were affiliated with a medical/health body or charity, and only 36% had a privacy strategy. Mean reading scores were 35 (of 100), with the average reading age being equivalent to US grade 12 (UK year 13). On average, apps had 3.3 of the 11 IMS functionality criteria. The mean MARS quality score was 3.2 ± 0.7. Half met the minimum acceptability score (3 of 5). None had been formally evaluated. It was evident that there are few high-quality genomic/genetic patient-facing apps available in the UK. This demonstrates a need for an accessible, culturally sensitive, evidence-based app to improve genetic literacy within patient populations and specific communities.Myelofibrosis is a chronic hematologic malignancy characterized by constitutional symptoms, bone marrow fibrosis, extramedullary hematopoiesis resulting in splenomegaly and a propensity toward leukemic progression. Given the central role of the JAK-STAT pathway in the pathobiology of myelofibrosis, JAK inhibitors are the mainstay of current pharmacologic management. Although these therapies have produced meaningful improvements in splenomegaly and symptom burden, JAK inhibitors do not significantly impact disease progression. In addition, many patients are ineligible because of disease-related cytopenias, which are exacerbated by JAK inhibitors. Therefore, there is a continued effort to identify targets outside the JAK-STAT pathway. In this review, we discuss novel therapies in development for myelofibrosis. We focus on the preclinical rationale, efficacy and safety data for non-JAK inhibitor therapies that have published or presented clinical data. Specifically, we discuss agents that target epigenetic modification (pelabresib, bomedemstat), apoptosis (navitoclax, navtemdalin), signaling pathways (parsaclisib), bone marrow fibrosis (AVID200, PRM-151), in addition to other targets including telomerase (imetelstat), selective inhibitor of nuclear transport (selinexor), CD123 (tagraxofusp) and erythroid maturation (luspatercept). We end by providing commentary on the ongoing and future therapeutic development in myelofibrosis.

A prospective, observational, US-based study (PROVe) used three questionnaires (Pruritus-VAS, Skindex-29, MF/SS-CTCL QoL) to assess quality of life in patients diagnosed with mycosis fungoides cutaneous T-cell lymphoma (MF-CTCL); however, none of these studies was provided with a preference-based algorithm yielding health state utility values (HSUVs).

This study aimed to assess the feasibility of deriving HSUVs from published mapping algorithms by comparing mapped utilities with the HSUVs reported in the MF-CTCL literature.

We searched PubMed, the School of Health and Related Research Health Utility Database (ScHARRHUD), and the Health Economics Research Centre (HERC) database of mapping studies (version 7.0) to identify any studies mapping Pruritus-VAS, Skindex-29, or MF/SS-CTCL QoL to a preference-based instrument (ideally, EQ-5D), and any studies assessing HSUVs in MF-CTCL. Two algorithms from a recent study that mapped Pruritus-VAS onto EQ-5D-3L were applied to the PROVe patient-level data. We perfong algorithms in MF-CTCL.

The HSUVs derived by applying published mapping algorithms to PROVe Pruritus-VAS data appeared largely overestimated if compared with the existing literature. More research is required to understand the applicability of existing mapping algorithms and to develop new mapping algorithms in MF-CTCL.Peri-intraventricular hemorrhage (PIVH) is a serious condition for preterm infants, caused by traumatic or spontaneous rupture of the germinal matrix (GM) capillary network in the cerebral ventricles. It is a common source of morbidity and mortality in neonates, and risk correlates with earlier delivery, low birth weight, maternal-fetal infection, and vital sign derangements, among others. PIVH typically occurs in the first 72 h of life, and symptoms, when present, manifest most commonly within the first week of life. Prevention remains the primary goal in management, predominantly via prolonging of gestation. Current therapy protocols are center-dependent without consistent consensus guidelines, but infant positioning, homeostatic stabilization, and neuroprotection offer potential options. In this update of pharmacologic neuroprotective therapies for PIVH, we highlight commonly utilized therapies and review the investigative literature. Further multi-institutional clinical trials and basic research studies are required.

African Americans (AAs) are disproportionately affected by structural and social determinants of health, resulting in greater risks of exposure to and deaths from COVID-19. Structural and social determinants of health feed vaccine hesitancy and worsen health disparities.

The present study aims to explore vaccine attitudes and intentions among program participants, understand the role of an African American faith-based wellness program in COVID-19 awareness and vaccine uptake, and solicit potential solutions for this deep-rooted public health problem.

Data were collected through 21 in-depth interviews among individuals involved within a community-based wellness program. Sixteen phone and five in-person interviews were conducted with church leaders, lifestyle coaches, and program participants. All interviews were audio-recorded, transcribed verbatim, and inductively and thematically analyzed by three researchers.

Live Well by Faith (LWBF) acted as a trusted information source for COVID-19 resources for uce vaccine hesitancy.

Resource targeting programs such as Live Well by Faith that engage faith and community leaders in co-designed shared and culturally grounded interventions can help restore and strengthen trust in vaccines and governments and reduce vaccine hesitancy.The non-Hispanic Black adult population has notable disparities in mental and physical health compared to several other racial/ethnic groups. Yet, there is a lack of scientific knowledge about psychologically based individual difference factors that may be associated with an exacerbation of common mental and physical health symptoms among non-Hispanic Black persons. The present investigation sought to build on the limited knowledge about anxiety sensitivity among non-Hispanic Black adults by exploring whether this construct was uniquely associated with a range of prevalent mental health and psychosomatic symptoms commonly tied to disparities among this population. Participants included non-Hispanic Black adults (N = 205; Mage = 21.67 years; SDage = 5.39; age range 18-60 years; 82.0% female). Results indicated that anxiety sensitivity was positively related to anxious arousal, general depression, insomnia, fatigue severity, and somatic symptom severity; effects were evident above and beyond the variance explained by a range of covariates, including age, sex, education, subjective social status, and neuroticism.