Craniofrontonasal syndrome in a patient with an inv(X)(p22.2q13.1), separating EFNB1 from its enhancer.

Craniofrontonasal syndrome (CFNS) is an X-linked developmental disorder caused by loss of function variants (LOFVs) in the ephrin B1 (EFNB1) gene located on Xq13.1. In CFNS, unlike in other X-linked disorders, females with heterozygous EFNB1 pathogenic variants (PVs) have a severe phenotype, whereas males carrying hemizygous EFNB1 PVs have a mild phenotype.

Biallelic ATP2B1 variants as a likely cause of a novel neurodevelopmental malformation syndrome with primary hypoparathyroidism.

ATP2B1 encodes plasma membrane calcium-transporting-ATPase1 and plays an essential role in maintaining intracellular calcium homeostasis that regulates diverse signaling pathways. Heterozygous de novo missense and truncating ATP2B1 variants are associated with a neurodevelopmental phenotype of variable expressivity. We describe a proband with distinctive craniofacial gestalt, Pierre-Robin sequence, neurodevelopmental and growth deficit, periventricular heterotopia, brachymesophalangy, cutaneous syndactyly, and persistent hypocalcemia from primary hypoparathyroidism.

The clinician, the lab and the patient: Understanding lab diagnostics to eradicate tuberculosis.

Background: Diagnostic modalities for diagnosing Tuberculosis caused by Mycobacterium group of organisms include mainly AFB smear by Ziehl Neelsen carbol fuchsin smear microscopy, GeneXpert (CB NAAT) molecular method, Line probe assay (Molecular method) and AFB culture (Liquid automated systems and solid media) methods.

Methods: This study was initiated to understand and prioritize TB lab diagnosis, with reference to selection of lab diagnostic tests and its order of preference for MTC and NTM/MOTT closely associating it with the TB irradication program initiated by the Government of India.

Result And Conclusion: The results and discussion bring to light the importance of each test and the purpose of their requisition.

Plexin D1 negatively regulates zebrafish lymphatic development.

Lymphangiogenesis is a dynamic process that involves the directed migration of lymphatic endothelial cells (LECs) to form lymphatic vessels. The molecular mechanisms that underpin lymphatic vessel patterning are not fully elucidated and, to date, no global regulator of lymphatic vessel guidance is known. In this study, we identify the transmembrane cell signalling receptor Plexin D1 (Plxnd1) as a negative regulator of both lymphatic vessel guidance and lymphangiogenesis in zebrafish.

Design and development of essential oil based nanoemulsion for topical application of triclosan for effective skin antisepsis.

The skin acts as a physical barrier to protect the body from the external physical and chemical environment. When skin is infected, the outer epidermal barrier is compromised and colonized with microbial growth. Wound infection presents an immense burden on healthcare costs and decreased the quality of life for patients.

Nanoemulsions for enhanced skin permeation and controlled delivery of chlorohexidine digluconate.

Chlorhexidine digluconate (CHG) is a widely used antiseptic for skin disinfection, as it exhibits poor skin permeability. Therefore, aim of the present study was preparation and evaluation of CHG nanoemulsions (NEs) using high-speed homogenisation (HSH) combined with ultra-probe sonication to improve skin permeability. CHG-NEs were prepared using eucalyptus oil (EO) and olive oil (OO), with a surfactant-to-cosurfactant ratio of 2:1.

Assessment of Arterial Stiffness, Brachial Haemodynamics, and Central Haemodynamics in Diabetic Hypertensives: A Pulse Wave Analysis-Based Case-Control Study from an Urban Area of West India.

Introduction: Hypertension (HTN) and diabetes frequently coexist, imposing significant cardiovascular risk that is normally studied in terms of brachial blood pressure (bBP). Direct and superior parameters like central haemodynamics and arterial stiffness are studied scarcely. Pulse wave analysis (PWA) offers a non-invasive measurement of the same that we studied in diabetic hypertensives.

Impact of diabetic retinopathy on pulse wave analysis-derived arterial stiffness and hemodynamic parameters: A cross-sectional study from Gujarat, India.

Purpose: Type 2 diabetes mellitus (T2DM) is known to produce diabetic retinopathy (DR). Pulse wave analysis (PWA) provides arterial stiffness (AS) and central hemodynamic (CH) parameters. We studied the effect of DR on AS and CH parameters in type 2 diabetics (T2D).

Drug Delivery Approaches for Managing Overactive Bladder (OAB): A Systematic Review.

Overactive bladder syndrome (OAB) is characterised by urgency symptoms, with or without urgency incontinence, usually with frequency and nocturia and severely affects the quality of life. This systematic review evaluates the various drug delivery strategies used in practice to manage OAB. Advanced drug delivery strategies alongside traditional strategies were comprehensively analysed and comparatively evaluated.

Laboratory quality assessment of candidate gene panel testing for acute myeloid leukaemia: a joint ALLG / RCPAQAP initiative.

Accurate classification of acute myeloid leukaemia (AML) has become increasingly reliant on molecular characterisation of this blood cancer. Throughout Australia and New Zealand massively parallel sequencing (MPS) is being adopted by diagnostic laboratories for the routine evaluation of patients with AML. This technology enables the surveying of many genes simultaneously, with many technical advantages over single gene testing approaches.

Functional CRISPR and shRNA Screens Identify Involvement of Mitochondrial Electron Transport in the Activation of Evofosfamide.

Evofosfamide (TH-302) is a hypoxia-activated DNA-crosslinking prodrug currently in clinical development for cancer therapy. Oxygen-sensitive activation of evofosfamide depends on one-electron reduction, yet the reductases that catalyze this process in tumors are unknown. We used RNA sequencing, whole-genome CRISPR knockout, and reductase-focused short hairpin RNA screens to interrogate modifiers of evofosfamide activation in cancer cell lines.

Solid lipid nanoparticles for targeted delivery of triclosan into skin for infection prevention.

Healthcare-associated infections (HAIs) are a concern for health service providers, exacerbated by poor delivery of antimicrobials to target sites within the skin. The dermal route is attractive for local and systemic delivery of drugs, however; permeation, penetration, and access to deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). Solid lipid nanoparticles present several benefits for topical delivery for therapeutic applications, especially via the follicular route.

Derivation of Breast Cancer Cell Lines Under Physiological (5%) Oxygen Concentrations.

Most human breast cancer cell lines currently in use were developed and are cultured under ambient (21%) oxygen conditions. While this is convenient in practical terms, higher ambient oxygen could increase oxygen radical production, potentially modulating signaling pathways. We have derived and grown a series of four human breast cancer cell lines under 5% oxygen, and have compared their properties to those of established breast cancer lines growing under ambient oxygen.

Efficient identification of somatic mutations in acute myeloid leukaemia using whole exome sequencing of fingernail derived DNA as germline control.

Recent advances in next-generation sequencing have made it possible to perform genome wide identification of somatic mutation in cancers. Most studies focus on identifying somatic mutations in the protein coding portion of the genome using whole exome sequencing (WES). Every human genome has around 4 million single nucleotide polymorphisms (SNPs).

Evofosfamide for the treatment of human papillomavirus-negative head and neck squamous cell carcinoma.

Evofosfamide (TH-302) is a clinical-stage hypoxia-activated prodrug of a DNA-crosslinking nitrogen mustard that has potential utility for human papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC), in which tumor hypoxia limits treatment outcome. We report the preclinical efficacy, target engagement, preliminary predictive biomarkers and initial clinical activity of evofosfamide for HPV-negative HNSCC. Evofosfamide was assessed in 22 genomically characterized cell lines and 7 cell line-derived xenograft (CDX), patient-derived xenograft (PDX), orthotopic, and syngeneic tumor models.

A fluorescence in situ hybridization-based screen allows rapid detection of adverse cytogenetic alterations in patients with acute myeloid leukemia.

In adult acute myeloid leukemia (AML), the karyotype of the leukemic cell is among the strongest prognostic factors. The Medical Research Council (MRC) and the European LeukemiaNet (ELN) classifications distinguish between favorable, intermediate and adverse cytogenetic risk patients who differ in their treatment response and overall survival. Conventional cytogenetic analyses are a mandatory component of AML diagnostics but they are time-consuming; therefore, therapeutic decisions in elderly patients are often delayed.

An ETV6-ABL1 fusion in a patient with chronic myeloproliferative neoplasm: Initial response to Imatinib followed by rapid transformation into ALL.

We report the case of a 26 year-old patient presenting with a persistent leukocytosis and CML-like marrow but no evidence of a BCR/ABL1 fusion. Molecular cytogenetics revealed that a portion of the ETV6 locus was inserted into the ABL1 locus. An ETV6/ABL1 fusion transcript could subsequently be confirmed.

DNA Repair and Chromosomal Translocations.

The balance between DNA damage, especially double strand breaks, and DNA damage repair is a critical determinant of chromosomal translocation frequency. The non-homologous end-joining repair (NHEJ) pathways seem to play the major role in the generation of chromosomal translocations. The "landscape" of chromosomal translocation identified in malignancies is largely due to selection processes which operate on the growth advantages conveyed to the cells by the functional consequences of chromosomal translocations (i.

Lipid nanoparticles for dermal drug delivery.

Lipid based drug delivery systems have been widely studied and reported over the past decade and offer a useful alternative to other colloidal drug delivery systems. Skin is a popular route of drug delivery for locally and systemically acting drugs and nanoparticles are reported as a potential formulation strategy for dermal delivery. Although the skin acts as a natural physical barrier against penetration of foreign materials, including particulates, opportunities exist for the delivery of therapeutic nanoparticles, especially in diseased and damaged skin and via appendageal routes such as the openings of hair follicles.

Mutations in SEC24D, encoding a component of the COPII machinery, cause a syndromic form of osteogenesis imperfecta.

As a result of a whole-exome sequencing study, we report three mutant alleles in SEC24D, a gene encoding a component of the COPII complex involved in protein export from the ER: the truncating mutation c.613C>T (p.Gln205(∗)) and the missense mutations c.