Dysregulated alveolar epithelial cell progenitor function and identity in Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) is a genetic disorder of endosomal protein trafficking associated with pulmonary fibrosis in specific subtypes, including HPS-1 and HPS-2. Single mutant HPS1 and HPS2 mice display increased fibrotic sensitivity while double mutant HPS1/2 mice exhibit spontaneous fibrosis with aging, which has been attributed to HPS mutations in alveolar epithelial type II (AT2) cells. We utilized HPS mouse models and human lung tissue to investigate mechanisms of AT2 cell dysfunction driving fibrotic remodeling in HPS.

c.1155-3A>G is a pathogenic variant that causes aberrant splicing, disrupted parafibromin expression, and hyperparathyroidism-jaw tumor syndrome.

Germline and somatic pathogenic variants in the gene, encoding the nuclear protein parafibromin, increase the risk for parathyroid carcinoma and cause hereditary primary hyperparathyroidism (PHPT) syndromes known as familial isolated hyperparathyroidism (FIHP) and hyperparathyroidism-jaw tumor syndrome (HPT-JT). The identification of pathogenic germline variants in PHPT-susceptibility genes can influence surgical planning for parathyroidectomy, guide screening for potential syndromic manifestations, and identify/exonerate at-risk family members. Numerous types of pathogenic germline variants have been described for -related conditions, including deletion, truncating, missense, and splice site mutations.

SP-101, A Novel Adeno-Associated Virus Gene Therapy for the Treatment of Cystic Fibrosis, Mediates Functional Correction of Primary Human Airway Epithelia From Donors with Cystic Fibrosis.

Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. Although CF affects multiple organs, lung disease is the main cause of morbidity and mortality, and gene therapy is expected to provide a mutation-agnostic option for treatment. SP-101 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a human minigene, , and is being investigated as an inhalation treatment for people with CF.

Consensus Statement of the IAP - Neurodevelopmental Chapter On Neurodevelopmental Disorders Habilitation Process: Strategic Plan for Prevention, Early Detection and Early Intervention.

Justification: Neurodevelopmental disorders, as per DSM-V, are described as a group of conditions with onset in the development period of childhood. There is a need to distinguish the process of habilitation and rehabilitation, especially in a developing country like India, and define the roles of all stakeholders to reduce the burden of neurodevelopmental disorders.

Process: Subject experts and members of Indian Academy of Pediatrics (IAP) Chapter of Neurodevelopmental Pediatrics, who reviewed the literature on the topic, developed key questions and prepared the first draft on guidelines.

Therapeutic Role of Pharmacological Chaperones in Lysosomal Storage Disorders: A Review of the Evidence and Informed Approach to Reclassification.

The treatment landscape for lysosomal storage disorders (LSDs) is rapidly evolving. An increase in the number of preclinical and clinical studies in the last decade has demonstrated that pharmacological chaperones are a feasible alternative to enzyme replacement therapy (ERT) for individuals with LSDs. A systematic search was performed to retrieve and critically assess the evidence from preclinical and clinical applications of pharmacological chaperones in the treatment of LSDs and to elucidate the mechanisms by which they could be effective in clinical practice.

Restoring Ciliary Function: Gene Therapeutics for Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by defects in motile cilia, which play an important role in several organ systems. Lung disease is a hallmark of PCD, given the essential role of cilia in airway surface defense. Diagnosis of PCD is complicated due to its reliance on complex tests that are not utilized by every clinic and also its phenotypic overlap with several other respiratory diseases.

Additively manufactured flexible on-package phased array antennas for 5G/mmWave wearable and conformal digital twin and massive MIMO applications.

This paper thoroughly investigates material characterization, reliability evaluation, fabrication, and assembly processes of additively manufactured flexible packaging and reconfigurable on-package antenna arrays for next-generation 5G/mmWave wearable and conformal applications. The objective is to bridge the technology gap in current Flexible Hybrid Electronics (FHE) designs at mmWave frequencies and address the challenges of establishing future design standards for additively manufactured flexible packages and System-on-Package (SoP) integrated modules. Multiple 3D printed flexible materials have been characterized for their electrical and mechanical properties over the 5G/mmW frequency band (26-40 GHz), and the inkjet printed interconnects on 3D printed Polypropylene (PP) substrates demonstrated excellent electrical and mechanical performance during a 10,000-time cyclic bending test over typical wearable flexible radii down to 1 inch.

Fibrillary Glomerulonephritis, DNAJB9, and the Unfolded Protein Response.

Background: Fibrillary glomerulonephritis (FGN) is found in approximately 1% of native kidney biopsies and was traditionally defined by glomerular deposition of fibrils larger than amyloid (12-24 nm diameter) composed of polyclonal IgG. Recent identification of DNAJB9 as a sensitive and specific marker of FGN has revolutionized FGN diagnosis and opened new avenues to studying FGN pathogenesis. In this review, we synthesize recent literature to provide an updated appraisal of the clinical and pathologic features of FGN, discuss diagnostic challenges and pitfalls, and propose molecular models of disease in light of DNAJB9.

Increased breastfeeding; an educational exchange program between India and Norway improving newborn health in a low- and middle-income hospital population.

Background: The purpose of the project was to improve newborn health in neonatal care units in a low resource area with high neonatal mortality, predominantly by better nutrition and educational exchange of health care workers.

Method: A fourfold program to make human milk production and distribution feasible and desirable. 1 Education to enlighten health care workers and parents to the excellence of human milk.

Association of telomere length with diabetes mellitus and idiopathic dilated cardiomyopathy in a South Indian population: A pilot study.

Telomere shortening has been associated with ageing and with many age-related diseases including cancer, coronary artery disease, heart failure and diabetes. We sought to investigate the link between telomere shortening and age-related diseases like type 2 diabetes mellitus (DM) (without any complications: DM; with neuropathic complication: DN) and idiopathic dilated cardiomyopathy (IDCM) in south Indian population. We compared telomere lengths of blood lymphocytes taken from patients with associated age-related diseases, namely DM (n = 47), DN (n = 52) and IDCM (n = 34) and controls (n = 46).

A monster of a disease.

When compulsions and obsessive thoughts took over her world, a graduate student found strength in her identity as a scientist.

Preclinical MRI to Quantify Pulmonary Disease Severity and Trajectories in Poorly Characterized Mouse Models: A Pedagogical Example Using Data from Novel Transgenic Models of Lung Fibrosis.

Structural remodeling in lung disease is progressive and heterogeneous, making temporally and spatially explicit information necessary to understand disease initiation and progression. While mouse models are essential to elucidate mechanistic pathways underlying disease, the experimental tools commonly available to quantify lung disease burden are typically invasive (, histology). This necessitates large cross-sectional studies with terminal endpoints, which increases experimental complexity and expense.