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Autism spectrum disorder (ASD) is a neurodevelopmental condition of the central nervous system (CNS) that presents with severe communication problems, impairment of social interactions, and stereotypic behaviours. Emerging studies indicate possible associations between viral infections and neurodegenerative and neurobehavioural conditions including autism. Viral infection during critical periods of early in utero neurodevelopment may lead to increased risk of autism in the offspring. This review is aimed at highlighting the association between viral infections, including viruses similar to COVID-19, and the aetiology of autism. A literature search was conducted using Pubmed, Ovid/Medline, and Google Scholar database. Relevant search terms included "rubella and autism", "cytomegalovirus and autism", "influenza virus and autism", "Zika virus and autism", "COVID-19 and autism". Based on the search terms, a total of 141 articles were obtained and studies on infants or children with congenital or perinatal viral infection and autistic behaviour were evaluated. The possible mechanisms by which viral infections could lead to autism include direct teratogenic effects and indirect effects of inflammation or maternal immune activation on the developing brain. Brain imaging studies have shown that the ensuing immune response from these viral infections could lead to disruption of the development of brain regions and structures. Hence, long-term follow up is necessary for infants whose mothers report an inflammatory event due to viral infection at any time during pregnancy to monitor for signs of autism. Research into the role of viral infection in the development of ASD may be one avenue of improving ASD outcomes in the future. Early screening and diagnosis to detect, and maybe even prevent ASD are essential to reduce the burden of this condition.

Introduction: Children with autism spectrum disorder (ASD) have a variety of co-morbid medical problems, including sleep disturbances. Prevalence of sleep disorders has been reported to be higher in this group as compared to the general population. Identifying sleep problems in children with ASD may help increase awareness and improve the overall quality of care for them. The aim of this study was to determine the prevalence of sleep problems and associated factors in a group of Malaysian children aged 6-16 years, with ASD. Method: This is a cross-sectional study at the Child Development Centre of UKM Medical Centre (UKM MC) on ASD children aged 6-16 years. Demographic data was obtained and the Sleep Disturbances Scale for Children (SDSC) questionnaire was completed by the main caregiver. Logistic regression analysis was used to determine factors related to higher total SDSC scores. Results: A total of 128 patients were recruited (111 boys) with a median age of 8 years 3 months (IQR: 2 years 10 months). Forty-seven (36.7%) of them obtained total SDSC scores in the pathological range with 19 (14.8%) scoring high for overall disturbances and 28 (21.9%) for at least one subtype of sleep disorders: 25 (19.5%) DIMS, 18 (14.1%) SBD, 10 (7.8%) DOES, 5 (3.9%) DOA, 6 (4.7%) SWTD, and 3 (2.3%) SHY. More than half of the children (57.8%) were reported to have sufficient sleep duration of 8-11 h, but longer sleep latency of at least 15 min (82.8%). Half of the ASD children also had co-morbidities in which one-third (34.4%) had attention-deficit hyperactivity disorder (ADHD). Using logistic regression analysis, four factors were significantly associated with higher total SDSC scores; female gender ( p = 0.016), older age group (11-16 years old) ( p = 0.039), shorter sleep length ( p = 0.043), and longer sleep latency ( p < 0.001). Conclusion: The prevalence of sleep disturbances is high among Malaysian children with ASD, especially DIMS. Female gender, older age group, shorter sleep length, and longer sleep latency were found to be associated with the sleep disturbances. Evaluation of sleep problems should form part of the comprehensive care of children with ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Koo, Ismail, Yang and Syed Zakaria.)

The aim of this article is to provide some insights on the osmo-inelastic response under stretching of annulus fibrosus of the intervertebral disc. Circumferentially oriented specimens of square cross section, extracted from different regions of bovine cervical discs (ventral-lateral and dorsal-lateral), are tested under different strain-rates and saline concentrations within normal range of strains. An accurate optical strain measuring technique, based upon digital image correlation, is used in order to determine the full-field displacements in the lamellae and fibers planes of the layered soft tissue. Annulus stress-stretch relationships are measured along with full-field transversal strains in the two planes. The mechanical response is found hysteretic, rate-dependent and osmolarity-dependent with a Poisson's ratio higher than 0.5 in the fibers plane and negative (auxeticity) in the lamellae plane. While the stiffness presents a regional-dependency due to variations in collagen fibers content/orientation, the strain-rate sensitivity of the response is found independent on the region. A significant osmotic effect is found on both the auxetic response in the lamellae plane and the stiffness rate-sensitivity. These local experimental observations will result in more accurate chemo-mechanical modeling of the disc annulus and a clearer multi-scale understanding of the disc intervertebral function.

Background: The role of the axial pre-strain on the torsional response of the intervertebral disc remains largely undefined. Moreover, the chemo-mechanical interactions in disc tissues are still unclear and corresponding data are rare in the literature. The paper deals with an in-vitro study of the pre-strain effect on the chemical sensitivity of the disc torsional response., Methods: Fifteen non-frozen 'motion segments' (two vertebrae and the intervening soft tissues) were extracted from the cervical spines of mature sheep. The motion segments were loaded in torsion at various saline concentrations and axial pre-strain levels in order to modulate the intradiscal pressure. After preconditioning with successive low-strain compressions at a magnitude of 0.1 mm (10 cycles at 0.05 mm/s), the motion segment was subjected to a cyclic torsion until a twisting level of 2 deg. at 0.05 deg./s while a constant axial pre-strain (in compression or in tension) is maintained, the saline concentration of the surrounding fluid bath being changed from hypo-osmotic condition to hyper-osmotic condition., Findings: Analysis of variance shows that the saline concentration influences the torsional response only when the motion segments are pre-compressed (p < .001) with significant differences between hypo-osmotic condition and hyper-osmotic condition., Interpretation: The combination of a compressive pre-strain with twisting amplifies the nucleus hydrostatic pressure on the annulus and the annulus collagen fibers tensions. The proteoglycans density increases with the compressive pre-strain and leads to higher chemical imbalances, which would explain the increase in chemical sensitivity of the disc torsional response., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To study the clinical profile and predictors of outcome in children undergoing decompressive craniectomy (DC) for non-traumatic intracranial hypertension (ICH). Materials and methods: Mixed observational study of children, aged 1 month-12 years, who underwent DC for non-traumatic ICH in a tertiary care pediatric intensive care unit from 2012 to 2017. Data on clinical profile and outcome were retrieved retrospectively and survivors were assessed prospectively. The primary outcome was neurological outcome using Glasgow Outcome Scale-Extended (GOS-E) at minimum 6 months' post-discharge. GOS-E of 1-4 were classified as a poor and 5-8 as a good outcome. Results: Thirty children, median (IQR) age of 6.5 (2, 50) months, underwent DC; of which 26 (86.7%) were boys. Altered sensorium ( n  = 26, 86.7%), seizures ( n  = 25, 83.3%), pallor ( n  = 19, 63.3%) and anisocoria ( n  = 14, 46.7%) were common signs and symptoms. Median (IQR) Glasgow Coma Scale at admission was 9 (6,11). Commonest etiology was intracranial bleed ( n  = 24; 80%). Median (IQR) time to DC was 24 (24,72) h. Eight (26.7%) children died; 2 during PICU stay and 6 during follow-up. Neurological sequelae at discharge ( n  = 28) were seizures ( n  = 25; 89.2%) and hemiparesis ( n  = 16; 57.1%). Twenty-one children were followed-up at median (IQR) duration of 12 (6,54) months. Good neurological outcome was seen in 14/29 (48.2%) and hemiparesis in 10/21 (47.6%) patients. On regression analysis, anisocoria at admission was an independent predictor of poor outcome [OR 7.33; 95%CI: 1.38-38.87; p  = 0.019]. Conclusions: DC is beneficial in children with non-traumatic ICH due to a focal pathology and midline shift. Evidence on indications and timing of DC in NTC is still evolving.

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined, neurodevelopmental disorder that has been modeled as a brain-based disease. The behavioral and cognitive features of ASD are associated with pervasive atypicalities in the central nervous system (CNS). To date, the exact mechanisms underlying the pathophysiology of ASD still remain unknown and there is currently no cure or effective treatment for this disorder. Many publications implicated the association of ASD with inflammation, immune dysregulation, neurotransmission dysfunction, mitochondrial impairment and cell signaling dysregulation. This review attempts to highlight evidence of the major pathophysiology of ASD including abnormalities in the brain structure and function, neuroglial activation and neuroinflammation, glutamatergic neurotransmission, mitochondrial dysfunction and mechanistic target of rapamycin (mTOR) signaling pathway dysregulation. Molecular and cellular factors that contributed to the pathogenesis of ASD and how they may affect the development and function of CNS are compiled in this review. However, findings of published studies have been complicated by the fact that autism is a very heterogeneous disorder; hence, we addressed the limitations that led to discrepancies in the reported findings. This review emphasizes the need for future studies to control study variables such as sample size, gender, age range and intelligence quotient (IQ), all of which that could affect the study measurements. Neuroinflammation or immune dysregulation, microglial activation, genetically linked neurotransmission, mitochondrial dysfunctions and mTOR signaling pathway could be the primary targets for treating and preventing ASD. Further research is required to better understand the molecular causes and how they may contribute to the pathophysiology of ASD.

Background and objective Myocardial infarction (MI) is the leading cause of mortality and morbidity worldwide. Early diagnosis of MI remains the mainstay of prompt treatment. Thus, the shorter the door-to-needle time, the more efficient is the emergency department (ED) to cope with a heart attack emergency. To improve the diagnosis of MI, this study aimed to determine the sensitivity and specificity of (qualitative) troponin I kit against the quantitative lab test for troponin I. Materials and methods Patients of both genders admitted at the Karachi Institute of Heart Diseases with acute coronary syndrome (ACS)/non-ST-elevation myocardial infarction (NSTEMI) were administered a standardized questionnaire. Quantitative analysis of troponin I was carried out by the hospital laboratory. The sample was simultaneously used for qualitative analysis of troponin I using the troponin I test kit. Results We recruited 200 patients comprising 134 (67%) males and 66 (33%) females. In total, 130 (65%) were hypertensive, 64 (32%) had dyslipidemia, 56 (28%) presented with a family history of MI, 60 (30%) had diabetes mellitus, 56 (28%) were smokers, and 24 (12%) presented with a previous history of MI. The kit showed 98% sensitivity and 100% specificity as compared to the quantitative test with a cutoff of 0.30 ng/dl, i.e., the quantitative test showed 128 positive and 72 negative cases, whereas the qualitative test showed 125 positive and 75 negative cases. The differences in test results were on values of 0.39, 0.40, and 0.42 ng/dl, as the qualitative test showed negative results. Conclusion This study showed that the qualitative kit is highly sensitive and specific at higher values of troponin I, i.e., ≥ 0.5 ng/dl. The qualitative test could be very beneficial in cost and time savings for the non-conclusive patients, like NSTEMI and ACS in the ED, and patients coming to the outreach chest pain centres where laboratory services are not adequate and whose Trop I values are not very close to the minimum cutoff values., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2020, Ahmed et al.)

How to cite this article : Ismail J, Bansal A. Passive Leg Raising for Fluid Responsiveness in Children: Is it Reliable? Indian J Crit Care Med 2020;24(5):291-292., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.)

Background Various indicators of socioeconomic position (SEP) may have opposing effects on the risk of hypertension in disadvantaged settings. For example, high income may reflect sedentary employment, whereas greater education may promote healthy lifestyle choices. We assessed whether education modifies the association between income and hypertension in 3 regions of South India at different stages of epidemiological transition. Methods and Results Using a cross-sectional design, we randomly selected villages within each of rural Trivandrum, West Godavari, and Rishi Valley. Sampling was stratified by age group and sex. We measured blood pressure and anthropometry and administered a questionnaire to identify lifestyle factors and SEP, including education, literacy, and income. Logistic regression was used to assess associations between various components of SEP and hypertension, and interaction analyses were used to determine whether educational attainment modified the association between income and hypertension. Trivandrum, the region of highest SEP, had the greatest prevalence of hypertension, whereas Rishi Valley, the lowest SEP region, had the least. Overall, greater income was associated with greater risk of hypertension. In interaction analyses, there was no evidence that educational attainment modified the association between income and hypertension. Conclusions Education is widely considered to ameliorate the risk of hypertension in high-income countries. Why this effect is absent in rural India merits investigation.

Objective: This study aims to evaluate the magnetic resonance imaging (MRI) brain patterns among hypoxic-ischemic encephalopathy (HIE) babies who underwent post-cooling MRI brain as well as to correlate the post-cooling brain scoring with patient's neurodevelopmental outcome at 2 years., Subjects and Methods: It was a retrospective cross sectional study carried out at a tertiary university hospital. Record of patients diagnosed with neonatal HIE from 2007 until 2016 who completed 72 h of cooling therapy and had MRI brain within 2 weeks of life were included in this study. A new scoring system by Trivedi et al . that emphasizes on subcortical deep gray matter and posterior limb internal capsule injury were utilized upon MRI assessment, using TW, T2W, and diffusion-weighted imaging (DWI) sequences. Cumulative MRI brain score was obtained and graded as none, mild, moderate, and severe brain injury. The MRI brain scoring was then correlated with patient's 2 years neurodevelopmental outcome using Fisher's Exact Test., Results: A total of 23 patients were eligible of which 19 term neonates were included. 13% of these neonates ( n = 3) had mild MRI brain injury grading with 52.2% ( n = 12) moderate and 34.8% ( n = 8) severe. There was no significant correlation seen between MRI brain grading and developmental outcome at 2 years old ( P > 0.05)., Conclusion: There was no significant correlation between neonatal MRI brain injury grading and 2 years neurodevelopmental outcome. Nevertheless, the new MRI brain scoring by Trivedi et al . is reproducible and comprehensive as it involves various important brain structures, assessed from different MRI sequences., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Radiology and Imaging.)

Objectives: Energy needs in critically ill children are dynamic and variable. Data on energy balance in children with severe sepsis using indirect calorimetry (IC) is lacking. Thus, we planned to study the energy needs and balance of this cohort., Methods: Prospective observational study conducted in ventilated children aged 5 to 12 years, admitted in pediatric intensive care unit with severe sepsis from May 2016 to June 2017. Measured resting energy expenditure (mREE) was measured with IC (Quark RMR, COSMED) till 7 days or pediatric intensive care unit discharge. Predicted energy expenditure (pREE) was estimated using Schofield, Harris and Benedict, and FAO/WHO/UNU equations. Primary outcome was to study the daily energy balance. Secondary outcome was to determine nitrogen balance and agreement of mREE with pREE., Results: Forty children (24 boys) with median age of 7 (5.2, 10) years were enrolled. All received enteral nutrition; 35 (87.5%) received inotropic support. Median ventilation-free days were 19 days and 4 children died (10%). A total of 176 IC measurements were obtained with an average of 4 per patient. The mean mREE was 51 ± 17 kcal/kg and mean respiratory quotient was 0.77 ± 0.07. There was persistent negative energy balance from days 1 to 7 and negative nitrogen balance from days 1 to 5. There was poor agreement of pREE with mREE using Bland Altman plots. None of severity of illness scores (PRISM III, daily Sequential Organ Function Assessment, daily Vasoactive Inotropic Score) showed correlation with mREE., Conclusions: Persistent negative energy and nitrogen balance exist during acute phase of severe sepsis. Predictive equations are inaccurate compared with IC as the criterion standard.

Objectives:: To evaluate the association of severe vitamin D deficiency with clinically important outcomes in children with septic shock., Methods:: We enrolled children ≤17 years with septic shock prospectively over a period of 6 months. We estimated 25-hydroxyvitamin D [25 (OH) D] levels at admission and 72 hours. Severe deficiency was defined as serum 25 (OH) <10 ng/mL. We performed univariate and multivariate analysis to evaluate association with clinically important outcomes., Results:: Forty-three children were enrolled in the study. The prevalence of severe vitamin D deficiency was 72% and 69% at admission and 72 hours, respectively. On univariate analysis, severe vitamin D deficiency at admission was associated with lower rates of shock reversal, 74% (23) versus 25% (3); relative risk (95% confidence interval [CI]): 2.9 (1.09-8.08), at 24 hours and greater need for fluid boluses (75 vs 59 mL/kg). On multivariate analysis, nonresolution of shock at 24 hours was significantly associated with severe vitamin D deficiency after adjusting for other key baseline and clinical variables, adjusted odds ratio (95% CI): 12 (2.01-87.01); 0.01., Conclusion:: The prevalence of severe vitamin D deficiency is high in children with septic shock admitted to pediatric intensive care unit. Severe vitamin D deficiency at admission seems to be associated with lower rates of shock reversal at 24 hours of ICU stay. Our study provides preliminary data for planning interventional studies in children with septic shock and severe vitamin D deficiency.

The intervertebral disc exhibits a complex inelastic response characterized by relaxation, hysteresis during cyclic loading and rate dependency. All these inelastic phenomena depend on osmotic interactions between disc tissues and their surrounding chemical environment. Coupling between osmotic and inelastic effects is not fully understood, so this article aimed to study the influence of chemical conditions on the inelastic behaviour of the intervertebral disc in response to different modes of loading. A total of 18 non-frozen 'motion segments' (two vertebrae and the intervening soft tissues) were dissected from the cervical spines of mature sheep. The motion segments were loaded in tension, compression and torsion at various loading rates and saline concentrations. Analysis of variance showed that saline concentration significantly influenced inelastic effects in tension and especially in compression (p < 0.05), but not in torsion. Opposite effects were seen in tension and compression. An interpretation of the underlying osmo-inelastic mechanisms is proposed in which two sources of inelastic effects are identified, that is, extracellular matrix rearrangements and fluid exchange created by osmosis.

Introduction: Prevalence of obesity in Autism Spectrum Disorder (ASD) has been reported to be higher than in the general population. Determining prevalence may help increase awareness of obesity in ASD and potentially lead to initiatives to reduce obesity. In order to understand obesity in ASD children, common risk factors were assessed including physical activity, feeding problems and sleep disturbances. Methods: This is a cross-sectional study performed at the Child Development Center at Universiti Kebangsaan Malaysia Medical Center on 151 ASD children aged 2-18 years. Anthropometric and demographic information were obtained and parents completed three questionnaires; Children Sleep Habits Questionnaire (CSHQ), Physical Activity for Older Children Questionnaire (PAQ-C) and Brief Autism Mealtime Behavior Questionnaire (BAMBI). Results: For ASD children in our sample, the prevalence of overweight (BMI ≥85th to <95th percentiles) was 11.3% and the prevalence of obesity (BMI ≥95th percentile) was 21.9%. The overweight/obese ASD children's median age was higher at 8.5 years (IQR 5.81-10.13) compared to the normal/underweight group of 6.33 years (IQR 4.75-7.7) with a p -value of 0.001. The two groups also differed significantly for maternal BMI and paternal age. The median maternal BMI in the overweight/obese group was 26.05 (IQR 23.35-32.25), statistically significantly higher ( p = 0.003) than in the non-overweight/obese group, 24.7 (IQR 21-27.9). The median paternal age of 40 years (IQR 37-44) was statistically significantly higher ( p = 0.039) in the overweight/obese group, compared to the median paternal age in the non-overweight/obese group of 38 (IQR 35-42). The male overweight/obese children had median PAQ-C score of 2.44 (IQR 2.00-3.00) vs. 2.89 (IQR 2.35-3.53) in the counterpart group with a p -value of 0.01. Using the multiple linear regression stepwise method, three predictors associated with BMI percentiles reached a statistical level of significance; PAQ-C score in males ( p < 0.001), the BAMBI domains of Food Refusal ( p = 0.001) and Limited Variety of Food ( p = 0.001). Conclusions: The prevalence of obesity and overweight is high among Malaysian ASD children and adolescents. Older child age, high maternal BMI, older paternal age, low physical activity, low likelihood of food refusal and high likelihood of food selectivity were found to be risk factors for high BMI in these children.

Disseminated cryptococcosis is infrequent in immunocompetent children. Pulmonary and central nervous system are the commonly involved sites of infection in an immunocompromised host. We report a fatal case of disseminated cryptococcosis in an immunocompetent host presenting as fever of unknown origin with miliary shadows on chest radiograph, mimicking tuberculosis. In countries with the heavy burden of tuberculosis, a high index of suspicion is needed for early diagnosis of its close mimics like disseminated cryptococcosis.

Septic shock in children is associated with high mortality, especially in developing countries. Management includes early recognition, timely antibiotics, aggressive fluid resuscitation, and appropriate vasoactive therapy, to achieve the therapeutic end points. The evidence at each step in management has evolved over the past decade with a paradigm shift in emphasis from a 'protocolized care' to an 'individualized physiology-based care'. This shift mirrors the general trend one observes in critical care with respect to various treatment modalities i.e. moving away from a liberal to a more conservative approach be it fluids, ventilation, transfusion, antibiotics or insulin. The age-old questions of how much fluid to give, what inotropes to start, when to administer antibiotics, are steroids indicated and when to consider extracorporeal therapies in refractory shock are finding new answers from the recent spate of evidence. It is therefore imperative for all of us to be aware of the recent changes in management, to enable us to adopt an evidenced based approach while managing children with septic shock. In this review, we have tried to summarize the key changes in evidence that have occurred over the past decade at various steps in the management of pediatric septic shock.

In this data article, we provide energy dispersive X-ray spectroscopy (EDX) spectra of the electrospun composite (SnO 2 -TiO 2 ) nanowires with the elemental values measured in atomic and weight%. The linear sweep voltammetry data of composite and its component nanofibers are provided. The data collected in this article is directly related to our research article "Synergistic combination of electronic and electrical properties of SnO 2 and TiO 2 in a single SnO 2 -TiO 2 composite nanowire for dye-sensitized solar cells" [1].

The damage and crack resistance improvement of bioactive glass is of prime importance, particularly when applied to the repair of load-bearing bones. The present contribution is focused on the prediction of damage mechanisms and crack resistance under uniaxial compression of bioactive glass matrix composites reinforced with a particulate phase. In order to characterize the effects of voids and particles on the damage mechanisms and the macro-response, a two-step homogenization is performed by considering the two phases existing at two different scales: micro/meso through the homogenization of the porous matrix and then meso/macro through the periodic micro-field approach. The damage in the bioactive glass matrix is computed via an anisotropic stress-based damage model, implemented into a finite element program. Failure resulting of excessive damage accumulation in the bioactive glass matrix is predicted by a critical damage criterion combined with a vanishing element technique. The implication of particles in the toughening mechanism as well as the damage and crack resistance improvement in this class of porous biomaterials is highlighted via a parametric study using the proposed numerical model., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To compare the effect of administration of 40-60 mL/kg of fluids as fluid boluses in aliquots of 20 mL/kg each over 15-20 minutes with that over 5-10 minutes each on the composite outcome of need for mechanical ventilation and/or impaired oxygenation-increase in oxygenation index by 5 from baseline in the initial 6 and 24 hours in children with septic shock., Design: Randomized controlled trial., Setting: Pediatric emergency and ICU of a tertiary care institute., Patients: Children (< 18 yr old) with septic shock., Interventions: We randomly assigned participants to 15-20 minutes bolus (study group) or 5-10 minutes bolus groups (control group)., Measurements and Main Results: We assessed the composite outcomes in the initial 6 and 24 hours after fluid resuscitation in both groups. We performed logistic regression to evaluate factors associated with need for ventilation in the first hour. Data were analyzed using Stata 11.5. Of the 96 children, 45 were randomly assigned to "15-20 minutes group" and 51 to "5-10 minutes group." Key baseline characteristics were not different between the groups. When compared with 5-10 minutes group, fewer children in 15-20 minutes group needed mechanical ventilation or had an increase in oxygenation index in the first 6 hours (36% vs 57%; relative risk, 0.62; 95% CI, 0.39-0.99) and 24 hours (43% vs 68%; relative risk, 0.63; 95% CI, 0.42-0.93) after fluid resuscitation. We did not find any difference in secondary outcomes such as death (1.2; 0.70-2.03), length of stay (mean difference: 0.52; -1.72 to 2.7), or resolution of shock (0.98; 0.63-1.53)., Conclusion: Children receiving fluid boluses over 5-10 minutes each had a higher risk of intubation than those receiving boluses over 15-20 minutes each. Notwithstanding the lack of difference in risk of mortality and the possibility that a lower threshold of intubation and mechanical ventilation was used in the presence of fluid overload, our results raise concerns on the current recommendation of administering boluses over 5-10 minutes each in children with septic shock.

Excessive crying is a common complaint in young infants, especially in those less than 3 mo of age. Altered circadian rhythm, immaturity of central nervous system and alteration of intestinal microbiota are some of the proposed mechanisms for this problem. Although it is commonly benign, crying can be the only clinical manifestation of many serious underlying illnesses, thus warranting careful clinical examination for ruling out organic causes. Urgent care clinics are best suited for evaluation and treatment of benign etiologies and promptly referring children with red flags to an emergency department. Routine investigations are not indicated in an afebrile infant with no signs of illness on history and physical examination. Excessive crying due to colic often results in parental stress and exhaustion. Treatment in such cases revolves more on reassuring the parents and avoiding drugs with uncertain action and potential side-effects.

Hypoparathyroidism leading to status dystonicus is rarely reported in literature. The authors present an 8-y-old girl with idiopathic familial hypoparathyroidism who presented with status dystonicus. She was managed successfully with midazolam infusion, calcium and vitamin D supplementation, and oral anti-dystonia drugs.

Potocki-Lupski syndrome (PTLS), also known as duplication 17p11.2 syndrome, trisomy 17p11.2 or dup(17)(p11.2p11.2) syndrome, is a developmental disorder and a rare contiguous gene syndrome affecting 1 in 20,000 live births. Among the key features of such patients are autism spectrum disorder, learning disabilities, developmental delay, attention-deficit disorder, infantile hypotonia and cardiovascular abnormalities. Previous studies using microarray identified variations in the size and extent of the duplicated region of chromosome 17p11.2. However, there are a few genes which are considered as candidates for PTLS which include RAI1, SREBF1, DRG2, LLGL1, SHMT1 and ZFP179. In this report, we investigated a case of a 3-year-old girl who has developmental delay. Her chromosome analysis showed a normal karyotype (46,XX). Analysis using array CGH (4X44 K, Agilent USA) identified an ~4.2 Mb de novo duplication in chromosome 17p11.2. The result was confirmed by fluorescence in situ hybridization (FISH) using probes in the critical PTLS region. This report demonstrates the importance of microarray and FISH in the diagnosis of PTLS.

A one-dimensional morphology comprising nanograins of two metal oxides, one with higher electrical conductivity (CuO) and the other with higher charge storability (Co 3 O 4 ), is developed by electrospinning technique. The CuO-Co 3 O 4 nanocomposite nanowires thus formed show high specific capacitance, high rate capability, and high cycling stability compared to their single-component nanowire counterparts when used as a supercapacitor electrode. Practical symmetric (SSCs) and asymmetric (ASCs) supercapacitors are fabricated using commercial activated carbon, CuO, Co 3 O 4 , and CuO-Co 3 O 4 composite nanowires, and their properties are compared. A high energy density of ∼44 Wh kg -1 at a power density of 14 kW kg -1 is achieved in CuO-Co 3 O 4 ASCs employing aqueous alkaline electrolytes, enabling them to store high energy at a faster rate. The current methodology of hybrid nanowires of various functional materials could be applied to extend the performance limit of diverse electrical and electrochemical devices.

Mangroves support diverse macroalgal assemblages as epibionts on their roots and tree trunks. These algae provide nutrients to the primary consumers in the aquatic food web and have been reported to be substantial contributors to marine ecosystems. The species diversity, biomass, and habitat characteristics of mangrove macroalgae were investigated at three stations in the Sibuti mangrove estuary, Sarawak, Malaysia, from November 2012 to October 2013. Three groups of macroalgae were recorded and were found to be growing on mangrove prop roots, namely Rhodophyta ( Caloglossa ogasawaraensis , Caloglossa adhaerens , Caloglossa stipitata , Bostrychia anomala, and Hypnea sp.), Chlorophyta ( Chaetomorpha minima and Chaetomorpha sp.), and Phaeophyta ( Dictyota sp.). The biomass of macroalgae was not influenced ( p >0.05) by the season in this mangrove forest habitat. The macroalgal species Hypnea sp. contributed the highest biomass at both Station 1 (210.56 mg/cm 2 ) and Station 2 (141.72 mg/cm 2 ), while the highest biomass was contributed by B. anomala (185.89 mg/cm 2 ) at Station 3. This study shows that the species distribution and assemblages of mangrove macroalgae were influenced by environmental parameters such as water nutrients, dissolved solids, and salinity in the estuarine mangrove habitats of Sibuti, Sarawak.

This article addresses the heat capacity of quantum dots (QDs) using density functional theory (DFT). By analyzing the evolution of phonon density of states and heat capacity as CdSe clusters grow from a molecular cluster into larger quantum confined solids, we have shown that their heat capacity does not fit very well with the Debye T 3 model. We observed that the number of phonon modes, which is discrete, increases as the particles grow, and the dispersion relation shows a quadratic behavior in contrast to the bulk solids whose dispersion relation is linear and equal to the sound velocity. The phonon density of states showed a square root variation with respect to frequency whereas that of the bulk is a quadratic variation of frequency. From the observed variation in the phonon density of states and holding the fact that the atomic vibrations in solids are elastically coupled, we have re-derived the expression for total energy of the QDs and arrive at a T 3/2 model of heat capacity, which fits very well to the observed heat capacity data. These results give promising directions in the understanding of the evolution of the thermophysical properties of solids.

Background: Due to the limited data available in the pediatric population and lack of interventional studies to show that administration of vitamin D indeed improves clinical outcomes, opinion is still divided as to whether it is just an innocent bystander or a marker of severe disease. Our objective was therefore to estimate the prevalence of vitamin D deficiency in children admitted to intensive care unit (ICU) and to examine its association with duration of ICU stay and other key clinical outcomes., Methods: We prospectively enrolled children aged 1 month-17 years admitted to the ICU over a period of 8 months (n = 101). The primary objectives were to estimate the prevalence of vitamin D deficiency (serum 25 (OH) <20 ng/mL) at 'admission' and to examine its association with length of ICU stay., Results: The prevalence of vitamin D deficiency was 74 % (95 % CI: 65-88). The median (IQR) duration of ICU stay was significantly longer in 'vitamin D deficient' children (7 days; 2-12) than in those with 'no vitamin D deficiency' (3 days; 2-5; p = 0.006). On multivariable analysis, the association between length of ICU stay and vitamin D deficiency remained significant, even after adjusting for key baseline variables, diagnosis, illness severity (PIM-2), PELOD, and need for fluid boluses, ventilation, inotropes and mortality [adjusted mean difference (95 % CI): 3.5 days (0.50-6.53); p = 0.024]., Conclusions: We observed a high prevalence of vitamin D deficiency in critically ill children in our study population. Vitamin D deficient children had a longer duration of ICU stay as compared to others.

We previously disclosed the discovery of rationally designed N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1 (GlyT-1), represented by analogues 10 and 11. We describe herein further structure-activity relationship exploration of this series via an optimization strategy that primarily focused on the sulfonamide and benzamide appendages of the scaffold. These efforts led to the identification of advanced leads possessing a desirable balance of excellent in vitro GlyT-1 potency and selectivity, favorable ADME and in vitro pharmacological profiles, and suitable pharmacokinetic and safety characteristics. Representative analogue (+)-67 exhibited robust in vivo activity in the cerebral spinal fluid glycine biomarker model in both rodents and nonhuman primates. Furthermore, rodent microdialysis experiments also demonstrated that oral administration of (+)-67 significantly elevated extracellular glycine levels within the medial prefrontal cortex (mPFC).

Alternative splicing (AS) defects that adversely affect gene expression and function have been identified in diabetic hearts; however, the mechanisms responsible are largely unknown. Here, we show that the RNA-binding protein RBFOX2 contributes to transcriptome changes under diabetic conditions. RBFOX2 controls AS of genes with important roles in heart function relevant to diabetic cardiomyopathy. RBFOX2 protein levels are elevated in diabetic hearts despite low RBFOX2 AS activity. A dominant-negative (DN) isoform of RBFOX2 that blocks RBFOX2-mediated AS is generated in diabetic hearts. DN RBFOX2 interacts with wild-type (WT) RBFOX2, and ectopic expression of DN RBFOX2 inhibits AS of RBFOX2 targets. Notably, DN RBFOX2 expression is specific to diabetes and occurs at early stages before cardiomyopathy symptoms appear. Importantly, DN RBFOX2 expression impairs intracellular calcium release in cardiomyocytes. Our results demonstrate that RBFOX2 dysregulation by DN RBFOX2 is an early pathogenic event in diabetic hearts., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Traumatic brain injuries (TBIs) present a chief public health threat affecting nations worldwide. As numbers of patients afflicted by TBI are expected to rise, the necessity to increase our understanding of the pathophysiological mechanism(s) as a result of TBI mounts. TBI is known to augment the risk of developing a number of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD). Hence, it is rational to assume that a common mechanistic ground links the pathophysiology of NDs to that of TBIs. Through this review, we aim to identify the protein-protein interactions, differential proteins expression, and PTMs, mainly glycosylation, that are involved in the pathogenesis of both ND and TBI. OVID and PubMed have been rigorously searched to identify studies that utilized advanced proteomic platforms (MS based) and systems biology tools to unfold the mechanism(s) behind ND in an attempt to unveil the mysterious biological processes that occur postinjury. Various PTMs have been found to be common between TBI and AD, whereas no similarities have been found between TBI and PD. Phosphorylated tau protein, glycosylated amyloid precursor protein, and many other modifications appear to be common in both TBI and AD. PTMs, differential protein profiles, and altered biological pathways appear to have critical roles in ND processes by interfering with their pathological condition in a manner similar to TBI. Advancement in glycoproteomic studies pertaining to ND and TBI is urgently needed in order to develop better diagnostic tools, therapies, and more favorable prognoses., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The Fritillaria imperialis is an ornamental flower that can be found in various parts of the world including Iraq, Afghanistan, Pakistan, and the Himalayas. The use of this plant as traditional remedy is widely known. This study aims to unveil the anti-cancer potentials of Isopimara-7,15-Dien-19-Oic Acid, extracted from the bulbs of F. imperialis in cervical cancer cell line, HeLa cells. Flow cytometry analysis of cell death, gene expression analysis via cDNA microarray and protein array were performed. Based on the results, Isopimara-7,15-Dien-19-Oic acid simultaneously induced cell death and promoted cell survival. The execution of apoptosis was apparent based on the flow cytometry results and regulation of both pro and anti-apoptotic genes. Additionally, the regulation of anti-oxidant genes were up-regulated especially thioredoxin, glutathione and superoxide dismutase- related genes. Moreover, the treatment also induced the activation of pro-survival heat shock proteins. Collectively, Isopimara-7,15-Dien-19-Oic Acid managed to induce cellular stress in HeLa cells and activate several anti- and pro survival pathways.

Background: The kava-kava plant (Piper methysticum) is traditionally consumed by the pacific islanders and has been linked to be involved in several biological activities. Flavokawain B is a unique chalcone, which can be found in the roots of the kava-kava plant. In this study, the operational mechanism of the anti-cancer activity of a synthetic Flavokawain B (FKB) on two breast cancer cell lines, MCF-7 and MDA-MB231 was investigated., Method: Several in vitro assays were attempted such as MTT, flow cytometry of cell cycle analysis, annexin V analysis, and JC-1 analysis to detect apoptosis. Moreover, in vitro metastasis assays were also performed such as transwell migration assay, invasion assay, rat aorta ring and HUVEC tube formation. Molecular analysis of related genes and proteins were conducted using real-time PCR and proteome profiler analysis., Results: Based on our results, apoptosis was induced when both MCF-7 and MDA-MB231 were treated with FKB. A significant G2/M arrest was seen in MDA-MB231 cells. Additionally, FKB also inhibited the in vitro migration and invasion in MDA-MB231 cells in a dose dependent manner. Moreover, FKB can be a potential inhibitor in angiogenesis as it suppressed the formation of vessels in HUVEC cells as well as in the ex-vivo rat aortic ring assay., Conclusion: Our findings suggested that FKB also regulated several receptor tyrosine kinases. Overall, FKB is not only a potential candidate to be an anti-cancer agent, but as an anti-metastatic agent as well.

Objective: To find out the long term outcome of deformity correction by hemivertebra resection in congenital thoracolumbar spinal deformities by a single posterior approach., Methods: This is a retrospective study carried out at the Department of Spine Surgery, Combined Military Hospital, Rawalpindi, Pakistan from April 2006 to April 2013. All operated patients having single level hemivertebrae of thoracolumbar spine with at least two years follow up were included. Data was analyzed using SPSS ver. 17., Results: There were 24 patients with mean age of 17 years (SD=8.41). Male to female ratio was 9(37.5%): 15(62.5%). Mean operation time was 4.23 hours (SD=1.2). Mean blood loss was 787 ml (SD=479). Mean follow up was for 5 years and 7 months (SD=30 months). Mean pre-op scoliosis was 51 degrees (SD=22), which improved to 20 degrees (SD=15) on last follow up (61% improvement). Mean pre-op kyphosis was 42 degrees (SD=35), which improved to 13 degrees (SD=15) on last follow up (69% improvement). Mean pre-op sagittal shift was 22mm (SD=24.9), which improved to 6mm (SD=9.37) on last follow up (73% improvement). Mean pre-op coronal shift was 34mm (SD=27.1), which improved to 8mm (SD=8.58) on last follow up (76% improvement). Five patients had complications. One proximal junctional kyphosis, one implant failure, one transient deficit and two wound infections., Conclusions: Posterior resection of hemivertebrae for congenital thoracolumbar deformities gives excellent correction of deformity in experienced hands and has acceptable complication rate.

Objectives: To document the outcome of spinal surgery in patients of cervical spondylotic myelopathy., Methods: The quasi-experimental study was conducted at the Department of Spine Surgery at Combined Military in a tertiary care hospital in Rawalpindi from 2006 to 2013. A pre-designed proforma was used for each patient and records were kept a custom-built computer database. Neurik grading was used to assess neurological status preoperatively, at 6 months, 1 year and 2 years., Results: There were 120 patients with a mean age of 60.08 years (range 26-82, standard deviation 13.13). Of them 108 (90%) were males and 12 (10%) females. The preoperative neurologic status was Nurick\'s grade 0 in 6 (5%) patients There were 120, I in 9 (7.5%), II in 23 (19.16%), III in 28 (23.33%) and IV in 19 (15.83%) and V in 35 (28.16%). The spine was approached anteriorly in 48 (40%) patients and posteriorly in 72 (60%). Single level was involved in 23 (19.16), two in 30 (25%), three in 22 (18.33%) and four in 45 (37.5%) cases. Anterior cervical disc excision and fusion was done in 26 (21.67%), anterior corpectomy and fusion with bone graft or a cage in 21(17.5%) cases, laminoplasty in 9 (7.5%), laminectomy with lateral mass screw fixation with reconstruction titanium plate in 37 (30.83%) or with rod 24 (20%). In 3 (2.5%) cases only decompressive laminectomy was done. At 6 months Nurick 0 was in 26 %21.67%), I in 14 (11.67), II in 17 (14.16), III in 21 (17.5), IV in 29 (24.16%) and V in 13 (10.83). At one year Nurick grade was 0 in 38 (32.67%, I in 16 (13.33%), II in 14 (11.67), III in 15 (12.5%), IV in 23 (19.16) and V in 14 (11.67%). At the end of 2 years Neurik grade was 0 in 40 (33.33%), I in 15 (12.5%), II in 13 (10.83%), III in 16 (13.33%), IV in 22 (18.33% and V in 14 (11.67%)., Conclusions: Single, double and triple levels with predominantly anterior cervical spondylotic myelopathy pathology can be operated anteriorly while multi-level disease with lordotic spine should be approached posteriorly.

Objective: To assess the outcome of surgical treatment in spondylolisthesis of lumbosacral region using Oswestry disability Index., Methods: The quasi-experimental study was conducted at the Combined Military Hospital, Rawalpindi from 2006 to 2013 and comprised surgically treated patients with spondylolisthesis. The patients with degenerative and isthmic types with follow-up of at least two years were included. A performa was designed for each patient and records were kept in a custom-built database. Oswestry disability index was used as the assessment tool and assessment was done pre-operatively, at 1, 3 and 6 months and then at 1 year and 2 years., Results: There were 96 patients with mean pre-op Oswestry disability index score of 81.06% (range 42.22-100, SD ±11.99). L5-S1 was affected in 44 (45.83%) patients, L4-L5 in 30 (31.25%), L4-5-S1 in 7 (7.29%) and multi or high level was found in the rest of the cases. One level was involved in 77 (80.2%), 2 in 11 (11.45%), 3 in 7 (7.29%) and 4 in 1 (1.04%). The slip grade as per Meyerding grades was 1 in 31 (32.29%), II in 39 (40.62%), III in 19 (19.79%), IV in 5 (5.2%) and 2 (2.08%) had spondyloptosis. Mean follow-up was 42 months (range 24-63). Mean Oswestry disability score at 1 month was 38.51% (range 11- 62.22%, SD ±11.75); at 6 months 10.02% (range 0-40%, SD ±6.99); at 1 year 4.62% (range 0-24%, SD ±5.36) and at 2 years 4.21% (range 0-15%, SD ±4.2)., Conclusions: Surgical treatment of spondylolisthesis gives excellent long-term result in most patients.

Bronchobiliary fistula (BBF) is a rare condition, defined by the presence of abnormal communication between biliary tract and bronchial tree. We describe a 3½-year-old child who developed BBF after rupture of liver abscess. She underwent exploratory laparotomy and peritoneal wash for ruptured liver abscess. Seven months later she presented with fever and cough with yellow-colored expectoration (bilioptysis). An abnormal communication between right branch of the hepatic duct and a branch of right main bronchus was identified. Child underwent right lateral thoracotomy and right lower lobectomy with surgical excision of sinus tract. On follow-up child was asymptomatic and doing well.

Perovskite solar cells employing CH3NH3PbI3-xClx active layers show power conversion efficiency (PCE) as high as 20% in single cells and 13% in large area modules. However, their operational stability has often been limited due to degradation of the CH3NH3PbI3-xClx active layer. Here, we report a perovskite solar module (PSM, best and av. PCE 10.5 and 8.1%), employing solution-grown TiO2 nanorods (NRs) as the electron transport layer, which showed an increase in performance (∼5%) even after shelf-life investigation for 2500 h. A crucial issue on the module fabrication was the patterning of the TiO2 NRs, which was solved by interfacial engineering during the growth process and using an optimized laser pulse for patterning. A shelf-life comparison with PSMs built on TiO2 nanoparticles (NPs, best and av. PCE 7.9 and 5.5%) of similar thickness and on a compact TiO2 layer (CL, best and av. PCE 5.8 and 4.9%) shows, in contrast to that observed for NR PSMs, that PCE in NPs and CL PSMs dropped by ∼50 and ∼90%, respectively. This is due to the fact that the CH3NH3PbI3-xClx active layer shows superior phase stability when incorporated in devices with TiO2 NR scaffolds.

Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography and computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using in vitro ADME profiling data, 9t was identified as possessing favorable permeability and a low potential for efflux, but it was rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by high plasma clearance. Brain exposure at a level expected to support modulation of a pharmacodynamic marker in mouse was achieved when the compound was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole.