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Multilocus disease-causing genomic variations (MGVs) and multiple genetic diagnoses (MGDs) are increasingly being recognised in individuals and families with Mendelian disorders. This can be mainly attributed to the widespread use of genomic tests for the evaluation of these disorders. We conducted a retrospective study of families evaluated over the last 6 years at our centre to identify families with MGVs and MGDs. MGVs were observed in fourteen families. We observed five different consequences: (i) individuals with MGVs presenting as blended phenotypes (ii) individuals with MGVs presenting with distinct phenotypes (iii) individuals with MGVs with age-dependent penetrance (iv) individuals with MGVs with one phenotype obscured by another more predominant phenotype (v) two distinct phenotypes in different individuals in families with MGVs. Consanguinity was present in eight (8/14, 57.1%) of them. Thirteen families had two Mendelian disorders and one had three Mendelian disorders. The risk of recurrence of one or more conditions in these families ranged from 25% to 75%. Our findings underline the importance of the role of a clinical geneticist in systematic phenotyping, challenges in genetic counselling and risk estimation in families with MGVs and MGDs, especially in highly inbred populations.

This article presents a power- and area-efficient multistandard serial link transceiver designed for application rates of up to 112 Gb/s, such as OIF CEI-112G and IEEE 802.3ck 400GBASE. The receiver features a continuous time linear equalizer, a programmable gain amplifier (PGA), a three-tap sampling-based feed-forward equalizer, and an 18-tap decision feedback equalizer. The transmitter uses a half-rate 2:1 multiplexer (MUX) with a duty cycle distortion corrected clock and a 7-bit digital to analog converter (DAC)-based driver with a six-tap feed-forward equalizer. The shared phase-locked loop (PLL) has a tuning range of 40–60 GHz with 0.12-ps rms jitter in integer mode and 0.16-ps jitter in fractional- ${N}$ mode measured at 56 GHz. The transmitter shows an eye with an RLM of 0.999. The transceiver can compensate for up to 43.9-dB insertion loss (IL) channel at 112 Gb/s. It consumes 690-mW per receiver (RX)/transmitter (TX). It is fabricated in 7-nm FinFET technology and occupies 0.63-mm2 per RX/TX.

The contribution of de novo variants as a cause of intellectual disability (ID) is well established in several cohorts reported from the developed world. However, the genetic landscape as well as the appropriate testing strategies for identification of de novo variants of these disorders remain largely unknown in low-and middle-income countries like India. In this study, we delineate the clinical and genotypic spectrum of 54 families (55 individuals) with syndromic ID harboring rare de novo variants. We also emphasize on the effectiveness of singleton exome sequencing as a valuable tool for diagnosing these disorders in resource limited settings. Overall, 46 distinct disorders were identified encompassing 46 genes with 51 single-nucleotide variants and/or indels and two copy-number variants. Pathogenic variants were identified in CREBBP, TSC2, KMT2D, MECP2, IDS, NIPBL, NSD1, RIT1, SOX10, BRWD3, FOXG1, BCL11A, KDM6B, KDM5C, SETD5, QRICH1, DCX, SMARCD1, ASXL1, ASXL3, AKT3, FBN2, TCF12, WASF1, BRAF, SMARCA4, SMARCA2, TUBG1, KMT2A, CTNNB1, DLG4, MEIS2, GATAD2B, FBXW7, ANKRD11, ARID1B, DYNC1H1, HIVEP2, NEXMIF, ZBTB18, SETD1B, DYRK1A, SRCAP, CASK, L1CAM, and KRAS. Twenty-four of these monogenic disorders have not been previously reported in the Indian population. Notably, 39 out of 53 (74%) disease-causing variants are novel. These variants were identified in the genes mainly encoding transcriptional and chromatin regulators, serine threonine kinases, lysosomal enzymes, molecular motors, synaptic proteins, neuronal migration machinery, adhesion molecules, structural proteins and signaling molecules.

ABSTRACTObjectives:Curcuma amadaRoxb. (Mango ginger) was evaluated for anti-obesity, anti-amnesic and neuroprotection using high-fat and high-sugar diet (HFHS)-induced obesity and cognitive impairment in rats.Methods:Animals were exposed to HFHS diet to evaluate lipid parameters and subjected to Y maze test and Pole climbing test to evaluate the memory. In addition, oxidative stress parameters, acetyl cholinesterase activity (AChE), neurochemicals and histopathology were assessed in the brain.Results:HFHS diet led to increased body weight and lipid parameters (total cholesterol, low-density lipoprotein [LDL], and very low-density lipoprotein [VLDL], triglycerides [TG]) but not high-density lipoprotein (HDL). Elevated serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT), oxidative biomarker, decreased enzymatic and non-enzymatic antioxidants, Acetylcholinesterase (AChE) activity and reduced percentage of spontaneous alternation behaviour (% SAB in Y-maze test) as well as reduced serotonin and dopamine levels and neurodegeneration were observed in HFHS diet-fed rats. Curcuma amada(CAAE1, 100 mg/kg and CAAE2, 300 mg/kg) treatment to HFHS diet-fed rats (21 days after HFHS diet feeding alone) showed dose-dependent activity and ameliorated the HFHS diet-induced alterations in lipid parameters related to obesity, hepatological parameters, memory, oxidative stress, neurochemicals and neurodegeneration. Furthermore, 300 mg/kg of C. amada(CAAE2) augmented the memory by inhibiting acetylcholinesterase (AChE) activity; it also ameliorated the effect of antioxidants such as glutathione, superoxide dismutase (SOD), and total thiol and mitigated the effect of malondialdehyde (MDA). CAAE2 also controlled the level of dopamine and serotonin and reduced the neurodegeneration in the hippocampus CA1 region.Discussion:The results of the present study indicated that treatment with C. amada300 mg/kg (CAAE2) attenuated the HFHS diet-induced obesity, memory loss, oxidative stress, and neurodegeneration. These study results indicated that the administration of C. amadaoffers a potential treatment option for obesity and memory loss, and it requires further preclinical and clinical evaluations.

Inflammatory immune response to atherogenic self-antigens plays an important role in the development of atherosclerosis. We evaluated the role of oral tolerance to three peptides in controlling atherosclerosis in New Zealand white rabbits.

Presently, great importance has been given to Low Level Laser Therapy (LLLT) with the intent of promoting wound healing process. The present study was aimed to investigate the promotive effect of LLLT on full thickness excision wounds in Swiss albino mice using optical fiber probe based light device. Circular wounds of diameter 15 mm were illuminated with single exposure of various laser doses 1, 2, 3, 4, 6, 8 and 10 J/cm2along with appropriate controls. Further, an optimal dose of 2 J/cm2was applied to excision wounds at different post-wounding treatment schedules (0, 24 h and 48 h) to explicate the relations between treatment schedule and its tissue regeneration potential. Wound area, mean wound healing time along with hydroxyproline and glucosamine levels from wound ground tissue was assessed to evaluate the resultant photobiostimulatory outcome. Histological analysis was performed on day 10 of post-wounding. A significant increase in hydroxyproline (P< 0.001) and glucosamine levels (P< 0.01) were observed in 2 J/cm2irradiation group, which was also substantiated by histological findings. In conclusion, the present study demonstrated that the immediate irradiation of 2 J/cm2dose following wounding hasten the healing process compared to the unilluminated control.

We report on a 16monthold girl with multiple swellings on her skull due to massive osteolysis, growth retardation, facial anomalies, and wrinkly skin with mosaic hypopigmentation. She also had severe hypercalcemia, which gradually returned to normal levels. The condition likely represents Gorham syndrome with systemic manifestations. © 2010 WileyLiss, Inc.

To establish the risk associated with mutations in the coding region of GDF9gene in Indian women with ovarian failure.

Micro-Raman spectra of formalin-fixed oral squamous normal and carcinoma tissues, stored at room temperature for 2 months, have been recorded. Spectra were recorded both in the epithelial and subepithelial regions of the tissues. No noticeable spectral contamination due to formalin was observed. Very significant differences between spectra of normal epithelial and malignant epithelial samples were found. No such differences in spectra of subepithelial malignant and subepithelial normal samples could be observed. This study shows that spectra from the epithelial region changes drastically because of malignancy-induced biochemical changes in this region. Major differences between normal and malignant spectra seem to arise from the protein composition, conformational/structural changes, and possible increase in protein content in malignant epithelia. The differences between normal epithelial and subepithelial spectra, as expected, arise mainly from the collagen in subepithelial tissue. Principal component analysis of the combined sets of spectra—epithelial and subepithelial, normal and malignant— showed that very good discrimination can be achieved by Raman microspectroscopy. This study thus validates the suitability of formalin-fixed tissues for optical pathology in oral malignancy.