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Biliary Atresia (BA) is a progressive inflammatory liver disease and the most frequent indication for pediatric liver transplant. There is a strong association between BA in adulthood and reduced cognitive abilities, however, data on neurodevelopmental outcomes at an early age are scarce, with small participant numbers. Hence, the neurodevelopmental difficulties in BA are poorly understood in childhood even though the brain development and maturation occur in parallel with the time-course of BA. This study aimed to characterize the cognitive and behavioral phenotype within BA infants from the age of 14 months to 4 years and investigate the extent to which this group deviates from children of typical development.
Methods
42 infants with BA that were diagnosed and treated at Kings College Hospital were recruited into this study. These infants ranged from 14 months to 4 years (mean age = 3 Years, 1 month). Out of the 42 infants, 19 had received a liver transplant, 22 were stable on their native liver, and 1 was on the transplant waiting list. 36 Mullens Scale of Early Learning assessments and 42 Vineland Adaptive Behavior Scale Interviews were collected. 42 typically developing infants (TD) were also recruited into the study, matched for age and gender to the BA population. First, we compared the whole group with BA to TD; then we compared children with BA on their native liver to those with a transplant.
Results
Across the cohort with BA, infants scored significantly lower on the Vineland Summary T-Score compared to age-matched TD control children (t(82) = −5.05, p < .001) and across all domains of the Vineland. They also scored significantly lower than TD children on the Mullens Development Assessment (t(66) = −6.52, p < .001), and this was also across all domains. BA children on their native liver scored lower on both instruments than children who had received a liver transplant, however, this difference did not reach significance.
Conclusion
Individuals with Biliary Atresia, regardless of their transplant status, show lower levels of development across all aspects, suggesting a global delay. These findings suggest that all of these young children remain at significant risk for neurodevelopmental difficulties. These findings emphasize that special attention to neurodevelopment needs to be given as part of a holistic approach to care in a serious life-long illness. Work is ongoing to understand the trajectory of brain maturation in these children to ensure neurodevelopmental needs are addressed alongside physical health.
A conjecture of Alon, Krivelevich and Sudakov states that, for any graph
$F$
, there is a constant
$c_F \gt 0$
such that if
$G$
is an
$F$
-free graph of maximum degree
$\Delta$
, then
$\chi\!(G) \leqslant c_F \Delta/ \log\!\Delta$
. Alon, Krivelevich and Sudakov verified this conjecture for a class of graphs
$F$
that includes all bipartite graphs. Moreover, it follows from recent work by Davies, Kang, Pirot and Sereni that if
$G$
is
$K_{t,t}$
-free, then
$\chi\!(G) \leqslant (t + o(1)) \Delta/ \log\!\Delta$
as
$\Delta \to \infty$
. We improve this bound to
$(1+o(1)) \Delta/\log\!\Delta$
, making the constant factor independent of
$t$
. We further extend our result to the DP-colouring setting (also known as correspondence colouring), introduced by Dvořák and Postle.
Opioid dependent individuals frequently complain of sleep problems in withdrawal and during abstinence.
Objectives
The objectives were to assess the subjective sleep parameters among buprenorphine-maintained opioid-dependent patients and to correlate it with socio-demographics, concomitant drug use and treatment related variables
Methods
Using a cross-sectional study design, 106 hundred six opioid-dependent patients maintained on buprenorphine for at least six months and on same dose in past month were interviewed. Sleep was assessed by Pittsburgh sleep quality index (PSQI) and Epworth sleepiness scale. Association between subjective sleep parameters, socio-demographics, concomitant drug use and treatment related variables was also studied.
Results
All participants were males. Their mean age was 41.1 years (SD:14.3). The mean duration of illicit opioid use was 10 years (IQR: 5,22). About 63.2% (n=67) had PSQI scores more than 5 denoting sleep problem. The scores obtained in Epworth Sleeping Scale were in normal range. Mean subjective total sleep time of the sample was 403.5 (SD 94.8) minutes and median sleep latency was 35 (IQR 18.8, 62.5) minutes. Subjective total sleep time was significantly higher in participants who had use tobacco in the past three months (p value=0.03) and who were in moderate ASSIST risk category (p value=0.04). Subjective sleep latency was significantly higher (p value=0.04) in participants who had used opioids in last three months. It was observed that age was a significant predictor of subjective total sleep time and OST compliance was a significant predictor of sleep latency.
Conclusions
A sizeable proportion of opioid dependent patients on buprenorphine have sleep problems
Spermatozoa, one of the two most pivotal cells of biological existence, are responsible for mediating the transfer of genetic information to subsequent generations. Mammalian fertilization and subsequent embryonic development depend in part on the inherent integrity of sperm genome. Different fertility societies around the globe and the World Health Organization (WHO) estimate that infertility is present in between 7 and 15 percent of couples of reproductive age [1].
Unfolded protein response (UPR) is an evolutionarily conserved pathway triggered during perturbation of endoplasmic reticulum (ER) homeostasis in response to the accumulation of unfolded/misfolded proteins under various stress conditions like viral infection, diseased states etc. It is an adaptive signalling cascade with the main purpose of relieving the stress from the ER, which may otherwise lead to the initiation of cell death via apoptosis. ER stress if prolonged, contribute to the aetiology of various diseases like cancer, type II diabetes, neurodegenerative diseases, viral infections etc. Understanding the role of UPR in disease progression will help design pharmacological drugs targeting the sensors of signalling cascade acting as potential therapeutic agents against various diseases. The current review aims at highlighting the relevance of different pathways of UPR in disease progression and control, including the available pharmaceutical interventions responsible for ameliorating diseased state via modulating UPR pathways.
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.
Background: Linezolid an oxazolidinone drug available in both parenteral and oral formulations has emerged as a novel alternative to vancomycin and other second-generation drugs for the treatment of infections from gram-positive cocci. Clinical isolates of linezolid-resistant staphylococci and enterococci were reported. Since then, linezolid-resistant strains have become an increasing problem worldwide. The most frequently reported mechanisms of linezolid resistance include the mutation in 23S ribosomal nucleic acid and presence of cfr gene. Methicillin-resistant coagulase-negative staphylococci (MR-CoNS) and vancomycin-resistant Enterococcus (VRE) have become a worrisome clinical problem. Objective: Therefore, we aimed to determine the distribution of linezolid-resistant strains in an inpatient setting of a tertiary-care hospital in India and to evaluate the resistance mechanisms among these isolates. In addition, the clonal diversity of the isolates was determined by pulsed-field gel electrophoresis (PFGE). Methods: The distribution, clonal diversity, and resistance mechanism of linezolid resistant-Staphylococcus haemolyticus (LRSH) strains were determined. The isolates were identified by MALDI-TOF. The mechanism of resistance was determined by sequence analysis of the domain V of 23SrRNA and screening for cfr gene. Clonal relatedness was defined by PFGE. Results: In total, 13 LRSH isolates were recovered from pus specimens. The 13 LRSH strains isolated had an linezolid MIC of 256 g/mL. Sequencing results revealed G2576T mutations in 7 (53.8%), G2447U in 4 (30.7%) and C2534U in 1 (7.6%) isolate of S. haemolyticus. One isolate of S. haemolyticus showed 2 simultaneous mutations (G2576T and G2447U) in the domain V region of 23Sr RNA gene. PFGE of the LR-SH isolates revealed the presence of 11 clones. Of the 11 clones, clones I and II had 2 isolates each. Isolates of clone I exhibited a band pattern identical with the previous isolates of LRSH isolated from the orthopedic unit. Similarly, isolates of clone II also shared the same band pattern with the previous LRSH isolates from the dermatology unit of our center. Conclusions: This study highlights the importance of continuous monitoring of vigilance of linezolid resistance in staphylococci. Rationalizing the use of linezolid and implementing methods to control the spread of hospital clones is of paramount importance to prevent further dissemination of these strains.
The prevalence of substance use is among adolescents is on rise. In India, inhalant is one of the common drugs of use and acts as a gateway for illicit substance use. The mainstay of treatment for inhalant use among this population is psychosocial interventions. In India, we largely rely on western models to guide intervention programs, however, there is a need to develop and test the psychosocial interventions which are culturally relevant and effective.
Objective
The present study aims to highlight the culture specific psychopathological factors associated with inhalant use among adolescents. The paper aims at studying the effectiveness of a psychosocial intervention in reducing the frequency and quantity of inhalant use among adolescent clinic population.
Methodology
Four adolescents reporting to the Adolescent Clinic at the National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi were recruited for the study. A single-case design was adopted. The pre-, and post- intervention assessment were carried out.
Results and Discussion
There was a significant reduction in frequency and quantity of inhalant use in the cases. The findings of the study are discussed in the light of available research work, implications, limitations of the study and suggestions for future research. The psychpathological factors and challenges to intervention are discussed.
Exposure to adverse events is prevalent among youths and robustly associated with risk for depression, particularly during adolescence. The Dimensional Model of Adversity and Psychopathology (DMAP) distinguishes between adverse events that expose youths to deprivation versus threat, positing unique mechanisms of risk (cognitive functioning deficits for deprivation, and altered fear and emotion learning for threat) that may require different approaches to intervention. We examined whether deprivation and threat were distinctly associated with behavioral measures of cognitive processes and autonomic nervous system function in relation to depression symptom severity in a community sample of early adolescents (n = 117; mean age 12.73 years; 54.7% male). Consistent with DMAP, associations between threat and depression symptoms, and between economic deprivation and depression symptoms, were distinctly moderated by physiological and cognitive functions, respectively, at baseline but not follow-up. Under conditions of greater cognitive inhibition, less exposure to deprivation was associated with lower symptom severity. Under conditions of blunted resting-state autonomic response (electrodermal activity and respiratory sinus arrhythmia), greater exposure to threat was associated with higher symptom severity. Our findings support the view that understanding risk for youth depression requires parsing adversity: examining distinct roles played by deprivation and threat, and the associated cognitive and biological processes.
A computational study based on molecular dynamics simulation technique has been used to predict the mechanical and thermal behavior of carbon nanotube (CNT) reinforced natural rubber (NR) composites. A single-walled 5,5 armchair type CNT has been used for this purpose. In this study, a comparison has been made between pristine and functionalized CNTs. The functionalization groups used in this study were carboxylic (COOH), ester (COOCH3) and hydroxyl (OH). The studies show the improvement in elastic properties of developed composites in the presence of functionalization group. In addition, the effect of volume fraction and 1-25% addition of functionalization group has been studied. The obtained simulation results show the better load-transfer capacity in developed polymer system and improved elastic modulus. Thermal properties of developed composite systems were studied by non-equilibrium molecular dynamics method (NEMD). The addition of functionalized CNTs shows enhanced mechanical and thermal properties.
Design and fabrication of a microstrip feedline-based Vivaldi antenna in the frequency range of 6.0–8.0 GHz have been presented. The Vivaldi antenna is a planar antenna, fabricated at the microstrip feedline by having an exponentially tapered slot profile on it. An optimized computer-aided design has been developed and simulated for the desired radiation parameters like voltage standing wave ratio, bandwidth, directionality, beam-width, etc. The optimized design has been fabricated and tested. Wherever the results are not found as desired; problem has been comprehensively investigated and analyzed. This is found associated with a discontinuity at feed line, fabrication tolerance constraints and parasitic capacitance at the edges or the bent of the microstrip feedline which introduce the parasitic reactance in antenna design. Here, the presented work explores a generalized theoretical procedure for the compensation of associated problem by incorporating the reactive patch on the feedline. The developed theory is applied in fabrication and tested for the desired results.
Defenders of the Enlightenment highlight the long neglected anticolonial writings of thinkers like Immanuel Kant, which serve as a corrective to the misrepresentation of the Enlightenment's epistemological investment in imperialism. One of the most pervasive repercussions of the claim that the Enlightenment was always already anti‐imperial is that postcolonial critique is rendered redundant, and the project of decolonizing European philosophy becomes unnecessary. Contesting the exoneration of Enlightenment philosophers of racism and sexism, this article debunks the claim that Kantian cosmopolitanism was an antidote to colonialism. Addressing the ambivalent legacies of the European Enlightenment for the postcolonial world, with special focus on the “Syrian refugee crisis,” the article examines the enduring normative violence exerted by Enlightenment principles of cosmopolitanism and outlines the contested terrains that inflect current geopolitics of knowledge‐production. Given that the normative idea of philosophy, as defined during the Enlightenment, continues to delegitimize non‐European perspectives, the integration of previously marginalized knowledges into the philosophical canon is insufficient; rather, in order to desubalternize non‐Western epistemologies, it is imperative to undo the uneven distribution of epistemic agency globally. Drawing on Gayatri Spivak's ideas of transnational literacy and planetary ethics, the article concludes by underscoring the contribution of postcolonial‐feminist critique in imagining postimperial philosophy in a global age.
Two-hundred MRSA strains from inpatients with healthcare-associated (HA) and 100 MRSA strains from outpatients with community-associated (CA) skin and soft tissue infections (SSTIs) were tested for antimicrobial susceptibility, staphylococcal cassette chromosome mec (SCCmec) typing, Panton–Valentine leucocidin (PVL) toxin, seh and arcA genes. Based on SCCmec typing, HA-MRSA isolates were further divided into HA-SCCmec I/II/III MRSA and HA-SCCmec IV/V MRSA, and CA-MRSA isolates into CA-SCCmec I/II/III MRSA and CA-SCCmec IV/V MRSA. SCCmec types were further characterized by pulsed-field gel electrophoresis, spa typing and multi-locus sequence typing. Seventy-five (37·5%) HA-MRSA isolates and 83/100 CA-MRSA isolates were SCCmec IV/V genotype. HA-SCCmec IV/V MRSA was associated with malignancy (P = 0·03) and bone fractures (P = 0·02) compared to CA-SCCmec IV/V MRSA. HA-SCCmec IV/V MRSA was associated with PVL gene carriage compared to HA-SCCmec I/II/III MRSA (P < 0·001). ST22-MRSA-IV (EMRSA-15), ST772-MRSA-V, and ST36-MRSA-IV and ST239:EMRSA-I:III were the major clones identified. Our study documents the emergence of SCCmec IV and SCCmec V MRSA clones in an Indian hospital.
Patients who are refractory to medical management can be candidates for surgical treatment such as anatomical or functional hemispherectomy. This chapter presents a case study of a 10-month-old male with left-sided hemiparesis. The patient subsequently developed seizures refractory to medical treatment and presented for a right functional hemispherectomy. Postoperatively, antithrombin III (ATIII) levels were checked twice daily and infusions of thrombate III were dosed accordingly. Early surgery for intractable epilepsy is recommended as it has been shown to improve functional outcomes. Anatomic hemispherectomy consists of the resection of the frontal, parietal and occipital cortices, complete temporal lobectomy and insular resection. Perioperative complications associated with this procedure include significant changes in systemic and pulmonary vascular resistance, arrhythmias, cardiac arrest, neurogenic pulmonary edema, seizures, cerebral edema, massive blood loss, and coagulopathy. Patients undergoing hemispherectomy are usually on chronic anticonvulsant therapy.
Relationships between the X-ray and radio behavior of black hole X-ray binaries during outbursts have established a fundamental coupling between the accretion disks and radio jets in these systems. I begin by reviewing the prevailing paradigm for this disk-jet coupling, also highlighting what we know about similarities and differences with neutron star and white dwarf binaries. Until recently, this paradigm had not been directly tested with dedicated high-angular resolution radio imaging over entire outbursts. Moreover, such high-resolution monitoring campaigns had not previously targetted outbursts in which the compact object was either a neutron star or a white dwarf. To address this issue, we have embarked on the Jet Acceleration and Collimation Probe Of Transient X-Ray Binaries (JACPOT XRB) project, which aims to use high angular resolution observations to compare disk-jet coupling across the stellar mass scale, with the goal of probing the importance of the depth of the gravitational potential well, the stellar surface and the stellar magnetic field, on jet formation. Our team has recently concluded its first monitoring series, including (E)VLA, VLBA, X-ray, optical, and near-infrared observations of entire outbursts of the black hole candidate H 1743-322, the neutron star system Aquila X-1, and the white dwarf system SS Cyg. Here I present preliminary results from this work, largely confirming the current paradigm, but highlighting some intriguing new behavior, and suggesting a possible difference in the jet formation process between neutron star and black hole systems.