Expanding the phenotypic spectrum of MBOAT7‐related intellectual disability

MBOAT7 gene pathogenic variants are a newly discovered and rare cause for intellectual disability, autism spectrum disorder (ASD), seizures, truncal hypotonia, appendicular hypertonia, and below average head sizes (ranging from −1 to −3 standard deviations). There have been only 16 individuals previously reported who have MBOAT7‐related intellectual disability, all of whom were younger than 10 years old and from consanguineous relationships. Thus, there is a lack of phenotypic information for adolescent and adult individuals with this disorder. Medical genetics and psychiatric evaluations in a 14‐year‐old female patient with a history of global developmental delay, intellectual disability, overgrowth with macrocephaly, metrorrhagia, seizures, basal ganglia hyperintensities, nystagmus, strabismus with amblyopia, ASD, anxiety, attention deficit hyperactivity disorder (ADHD), aggressive outbursts, and hyperphagia included a karyotype, methylation polymerase chain reaction for Prader‐Willi/Angelman syndrome, chromosome microarray, and whole exome sequencing (WES), ADOS2, and ADI‐R. WES identified a homozygous, likely pathogenic variant in the MBOAT7 gene (c.855‐2A>G). This is the oldest known patient with MBOAT7‐related intellectual disability, whose unique features compared with previously described individuals include overgrowth with macrocephaly, metrorrhagia, ophthalmological abnormalities, basal ganglia hyperintensities, unspecified anxiety disorder, and ADHD; combined type; and hyperphagia with the absence of appendicular hypertonia and cortical atrophy. More individuals need to be identified in order to delineate the full clinical spectrum of this disorder.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151268/1/ajmgb32749_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151268/2/ajmgb32749.pd

Resolution of Inflammation in Periodontitis: A Comprehensive Review

Inflammation, a natural defence mechanism against injury or infection, can become problematic when it fails to resolve, as observed in conditions like periodontitisThis review explores how inflammation is resolved in periodontitis and seeks potential treatments for this chronic condition, which damages the periodontium, including the gingival tissue, periodontal ligament, and alveolar bone. The pathogenesis of this disease is initiated by the inflammatory response triggered by resident leukocytes and endothelial cells upon exposure to bacterial biofilms, resulting in vasodilation and immune cell recruitment. The review stresses the importance of researching targeted approaches for periodontitis treatment, such as inducing neutrophil apoptosis, shifting from M1 to M2 macrophages, and exploring M2-based tissue engineering. Additionally, investigating lymphangiogenesis and Treg cell recruitment at the inflammation site offers promising avenues. In conclusion, further studies are needed to refine lymphangiogenesis and assess the potential of pro-resolving lipid mediators and anti-inflammatory cytokines in managing periodontitis. Ongoing research aims to uncover the underlying biomolecular mechanisms governing immune cells and resolving mediators, with the ultimate goal of restoring tissue equilibrium and promoting healing

FORMULATION AND CHARACTERIZATION OF METFORMIN HYDROCHLORIDE SUSTAINED RELEASE MATRIX TABLET CONTAINING CASSIA TORA MUCILAGE

All the present investigation an attempt has been made to study the formulation and evaluation of matrix tablet of Metformin HCL using natural mucilage of Cassia tora as a release retardant. The matrix tablet was formulated using different drug polymer ratio. The developed formulation of tablet was evaluated for pre-compression and post–compression method. The result of the pre-compression parameter like Bulk density, tapped density, Carr’s index and Hausner’s ratio were found to be with the limits indicating good flow properties of the granules. Swelling index reveals that with increasing mucilage concentration there is increased swelling showing 61% for F-2 at the end of 5 h whereas for F-3 it was around 89.9 % respectively. In- vitro drug release for F3 formulation was found to be 75% at the end of 10 h. With increases in mucilage concentration the drug release from the matrix tablet got retarded. In- vitro, drug release data obtained were fitted to various release model excess the possible mechanism of the drug release. The results of all these parameters are tabulated and depicted graphically in the result and discussion section. IR spectral studies revealed that the drug, polymer and excipients used were compatible.  Drug release profile of all formulation was plotted in different kinetics. The calculated regression coefficients showed a higher r2 value with higuchi equation (r2= 0.958). Hence the release data of the Tablet obeyed higuchi model and release the drug diffusion. Keywords: Cassia tora, mucilage, granules, drug release, polymerÂ

Electrophysiological correlates of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism

The brain-derived neurotrophic factor (BDNF) protein is essential for neuronal development. Val66Met (rs6265) is a functional polymorphism at codon 66 of the BDNF gene that affects neuroplasticity and has been associated with cognition, brain structure and function. The aim of this study was to clarify the relationship between BDNF Val66Met polymorphism and neuronal oscillatory activity, using the electroencephalogram (EEG), in a normative cohort. Neurotypical (N = 92) young adults were genotyped for the BDNF Val66Met polymorphism and had eyes open resting-state EEG recorded for four minutes. Focal increases in right fronto-parietal delta, and decreases in alpha-1 and right hemispheric alpha-2 amplitudes were observed for the Met/Met genotype group compared to Val/Val and Val/Met groups. Stronger frontal topographies were demonstrated for beta-1 and beta-2 in the Val/Met group versus the Val/Val group. Findings highlight BDNF Val66Met genotypic differences in EEG spectral amplitudes, with increased cortical excitability implications for Met allele carriers

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

"Mother-weights" and lost fathers: parents in South Asian American literature

That parent-child relationships should play a significant role within South Asian American literature is perhaps no surprise, since this is crucial material for any writer. But the particular forms they so often take – a dysfunctional mother-daughter dynamic, leading to the search for maternal surrogates; and the figure of the prematurely deceased father – are more perplexing. Why do families adhere to these patterns in so many South Asian American texts and what does that tell us about this œuvre? More precisely, why are mothers subjected to a harsher critique than fathers and what purpose does this critique serve? How might we interpret the trope of the untimely paternal death? In this article I will seek to answer these questions – arguably key to an understanding of this growing body of writing – by considering works produced between the 1990s and the early twenty-first century by a range of South Asian American writers

RGS4 inhibits angiotensin II signaling and macrophage localization during renal reperfusion injury independent of vasospasm

Vascular inflammation is a major contributor to the severity of acute kidney injury. In the context of vasospasm-independent reperfusion injury we studied the potential anti-inflammatory role of the Gα-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 minute injury, although post-ischemic renal arteriolar diameter was equal to the wild type early after injury. A 10 minute unilateral injury was performed to study reperfusion without vasospasm. Eighteen hours after injury blood flow was decreased in the inner cortex of wild type mice with preservation of tubular architecture. Angiotensin II levels in the kidneys of wild type and transgenic mice were elevated in a sub-vasoconstrictive range 12 and 18 hours after injury. Angiotensin II stimulated pre-glomerular vascular smooth muscle cells (VSMC) to secrete the macrophage chemoattractant, RANTES; a process decreased by angiotensin II R2 (AT2) inhibition. However, RANTES increased when RGS4 expression was suppressed implicating Gα protein activation in an AT2-RGS4-dependent pathway. RGS4 function, specific to VSMC, was tested in a conditional VSMC-specific RGS4 knockout showing high macrophage density by T2 MRI compared to transgenic and non-transgenic mice after the 10 minute injury. Arteriolar diameter of this knockout was unchanged at successive time points after injury. Thus, RGS4 expression, specific to renal VSMC, inhibits angiotensin II-mediated cytokine signaling and macrophage recruitment during reperfusion, distinct from vasomotor regulation

Language of Lullabies: The Russification and De-Russification of the Baltic States

This article argues that the laws for promotion of the national languages are a legitimate means for the Baltic states to establish their cultural independence from Russia and the former Soviet Union