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Cancer is the second leading cause of death worldwide responsible for about 10 million deaths per year. To date several approaches have been developed to treat this deadly disease including surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy, and synthetic lethality. The targeted therapy refers to targeting only specific proteins or enzymes that are dysregulated in cancer rather than killing all rapidly dividing cells, has gained much attention in the recent past. Kinase inhibition is one of the most successful approaches in targeted therapy. As of 30 March 2021, FDA has approved 65 small molecule protein kinase inhibitors and most of them are for cancer therapy. Interestingly, several kinase inhibitors contain one or more fused heterocycles as part of their structures. Pyrrolo[2,1-f][1,2,4]triazine is one the most interesting fused heterocycle that is an integral part of several kinase inhibitors and nucleoside drugs viz. avapritinib and remdesivir. This review articles focus on the recent advances made in the development of kinase inhibitors containing pyrrolo[2,1-f][1,2,4]triazine scaffold.

Coronavirus disease knocked in Wuhan city of China in December 2019 which spread quickly across the world and infected millions of people within a short span of time. COVID-19 is a fast-spreading contagious disease which is caused by SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2). Accurate time series forecasting modeling is the need of the hour to monitor and control the universality of COVID-19 effectively, which will help to take preventive measures to break the ongoing chain of infection. India is the second highly populated country in the world and in summer the temperature rises up to 50°, nowadays in many states have more than 40° temperatures. The present study deals with the development of the autoregressive integrated moving average (ARIMA) model to predict the trend of the number of COVID-19 infected people in most affected states of India and the effect of a rise in temperature on COVID-19 cases. Cumulative data of COVID-19 confirmed cases are taken for study which consists of 77 sample points ranging from 1st March 2020 to 16th May 2020 from six states of India namely Delhi (Capital of India), Madya Pradesh, Maharashtra, Punjab, Rajasthan, and Uttar Pradesh. The developed ARIMA model is further used to make 1-month ahead out of sample predictions for COVID-19. The performance of ARIMA models is estimated by comparing measures of errors for these six states which will help in understanding future trends of COVID-19 outbreak. Temperature rise shows slightly negatively correlated with the rise in daily cases. This study is noble to analyse the variation of COVID-19 cases with respect to temperature and make aware of the state governments and take precautionary measures to flatten the growth curve of confirmed cases of COVID-19 infections in other states of India, nearby countries as well.

Despite advances in research and improved neurological intensive care in recent years, the clinical outcome of severely head injured patients is still poor. Primary insult is followed by a complex cascade of molecular and biochemical events that lead to neuroinflammation, brain edema, and delayed neuronal death. No specific pharmacological therapy is currently available which prevents the development of secondary brain injuries, and most therapeutic strategies have failed in translation from bench to bedside. There are limitations of clinical and radiological methods in delineating the exact severity and prognosis of traumatic brain injury (TBI). A myriad complex biochemical markers are under investigation to delineate the extent of brain tissue damage and to independently predict the outcome, but a search for simple biomarker still eludes the research. Progesterone, a gonadal hormone and a neurosteroid, although controversial as a neuroprotective agent, may hold promise as a simple biochemical marker of the outcome in severe TBI.

Background Head injury is a major health hazard throughout the world. Overall, the mortality/morbidity has not changed much in the last few decades. In developing nations, the situation is worse. Methods The study was conducted for a period of 1 year. The data collected include demographic profile, mode, circumstances and timing of the injury, neurological assessment using Glasgow Coma Scale (GCS) scoring, computed tomography (CT) scan findings, type of management, and outcome. Results Transport-related injuries and falls were the common cause of head injury, with more severe injuries seen in patients without wearing helmets and seat belts. The youth is at high risk of receiving head injuries. The summer season showed a maximum incidence of head injuries. The most common lesions on CT scan were linear fracture of the skull and brain contusion. Mortality rate was 26% and it correlated with the GCS at presentation. Conclusion Head injury mostly affects young people and males outnumber females. Road traffic accident is the major cause. People not abiding by the traffic rules, such as wearing helmets and seat belts, were at high risk of developing head injury and poor outcome.

The conventional centrifugal casting of Ni-Cr (N)-based alloys is commercially established process for the preparation of partial/complete dentures. But hitherto little has been reported on the mul...

Objective To analyze role of phosphodiesterase 5 (PDE5) inhibitors on urodynamic parameters in patients with suprasacral spinal cord injury. Materials and Methods This was a prospective observational hospital-based study conducted on a cohort of patients, aged between 18 and 65 years with suprasacral spinal cord injury, who were registered in Department of Neurosurgery/Urology. Cutoff period since injury was 2 years. After taking consent, baseline urodynamic study was performed, which was repeated 2 hours after taking single oral dose of 20 mg tadalafil. Urodynamic parameters such as maximum detrusor filling/voiding pressures, maximum bladder capacity, and bladder compliance before and after taking drug were compared for final results and conclusion. Results Following administration of 20 mg of tadalafil, maximum bladder capacity in mL showed statistically significant improvement from 268.39 ± 130.0 to 298.55 ± 112.0.(p < 0.05). Bladder compliance improved from 18.68 ± 6.4 to 20.25 ± 7.5 mL/cm H2O (p > 0.05). Maximum detrusor filling pressure improved from 36.03 ± 20.54 to 32.90 ± 16.47 cm H2O (p > 0.05). Maximum detrusor voiding pressure improved from 64.65 ± 33.19 to 58.13 ± 20.7 cm H2O (0 > 0.05). In patients with injury above D6 spinal cord level, statistically significant improvement was seen in maximum bladder capacity and bladder compliance after 2 hours of single oral dose of tadalafil (p < 0.05). Conclusion Our study suggests a positive role of PDE inhibitors in improving urodynamic parameters in patients with suprasacral spinal cord injury with improvement in parameters such as bladder capacity, detrusor pressures, and bladder compliance. Because this is a small study group, more studies such as this are required to reach to final conclusion.

Deregulated Fbxo7 expression is associated with many pathologies, including anaemia, male sterility, cancer, and Parkinson’s disease, demonstrating its critical role in a variety of cell types. Although Fbxo7 is an F-box protein that recruits substrates for SCF-type E3 ubiquitin ligases, it also promotes the formation of cyclin D/Cdk6/p27 complexes in an E3-ligase independent fashion. We discovered PFKP, the major gatekeeper of glycolysis, in a screen for Fbxo7 substrates. PFKP has been previously shown to be a critical substrate of Cdk6 for the viability of T-ALL cells. We investigated the molecular relationships between Fbxo7, Cdk6 and PFKP, and the functional effect Fbxo7 has on T cell metabolism, viability, and activation. Fbxo7 promotes Cdk6-independent ubiquitination and Cdk6-dependent phosphorylation of PFKP. Importantly Fbxo7-deficient cells have reduced Cdk6 activity, and haematopoietic and lymphocytic cell lines show a significant dependency on Fbxo7. Compared to WT cells, CD4+ T cells with reduced Fbxo7 expression show increased glycolysis, despite lower cell viability and activation levels. Metabolomic studies of activated CD4+ T cells confirm increased glycolytic flux in Fbxo7-deficient cells, as well as altered nucleotide biosynthesis and arginine metabolism. We show Fbxo7 expression is glucose-responsive at the mRNA and protein level, and we propose Fbxo7 inhibits PFKP and glycolysis via its activation of Cdk6.

BACKGROUND Students undergoing MBBS course are all the time very busy in their studies, they hardly get any time for exercise. Sedentary habits and shift to western lifestyle and fast food culture has led to overweight and obesity. This study was done to determine the prevalence of overweight and obesity among the first year MBBS students of batch 2016-17. METHODS The present study was carried from June to August 2017 among 200 first year MBBS students of Govt. Medical College, Amritsar of Punjab. RESULTS Prevalence of overweight and obesity was 22.5% and 15.5% respectively. Boys are more overweight 24.51% and obese 25.49% than girls 20.41% and 5.10% respectively. CONCLUSIONS The present study concluded that obesity is prevalent in first year MBBS students and causes are faulty eating habits and lack of regular exercise.

Diabetes mellitus, commonly referred to as diabetes, is the 8th leading cause of death worldwide. As of 2015, approximately 415 million people were estimated to be diabetic worldwide, type 2 diabetes being the most common accounting for approximately 90-95% of all diagnosed cases with increasing prevalence. Fructose-1,6-bisphosphatase is one of the important therapeutic targets recently discovered to treat this chronic disease. In this focused review, we have highlighted recent advances and structure-activity relationship studies in the discovery and development of different fructose-1,6-bisphosphatase inhibitors reported since the year 2000.

Genetic models validated Inhibitor of nuclear factor (NF) kappa B kinase beta (IKKβ) as a therapeutic target for KRAS mutation associated pancreatic cancer. Phosphorylation of the activation loop serine residue (S(177), S(181)) IKKβ is a key event that drives tumor necrosis factor (TNF) α induced NF-κB mediated gene expression. Here we conducted structure activity relationship (SAR) study to improve potency and oral bioavailability of a quinoxaline analog 13–197 that was previously reported as an NFκB inhibitor for pancreatic cancer therapy. The SAR led to the identification of a novel quinoxaline urea analog 84 that reduced the levels of p-IKKβ in dose- and time-dependent studies. When compared to 13–197, analog 84 was ~2.5-fold more potent in TNFα-induced NFκB inhibition and ~4-fold more potent in inhibiting pancreatic cancer cell growth. Analog 84 exhibited ~4.3-fold greater exposure (AUC(0−)∞) resulting in ~5.7-fold increase in oral bioavailability (%F) when compared to 13–197. Importantly, oral administration of 84 by itself and in combination of gemcitabine reduced p-IKKβ levels and inhibited pancreatic tumor growth in a xenograft model.

Highlights • The study is about the prediction of COVID-19 cases in major countries around the globe. Its Noble study. • It will help the different countries to make the decision on this virus. • ARIMA and LSSVM are the machine learning models, which computes accurate prediction with the least error. • The model provides the 99% approximate accuracy. • This manuscript will also help to all governments for preparing isolation wards, availability of medical staff, medicines requirement, the decision on lock down, economic plans, etc., Discussions about the recently identified deadly coronavirus disease (COVID-19) which originated in Wuhan, China in December 2019 are common around the globe now. This is an infectious and even life-threatening disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has rapidly spread to other countries from its originating place infecting millions of people globally. To understand future phenomena, strong mathematical models are required with the least prediction errors. In the present study, autoregressive integrated moving average (ARIMA) and least square support vector machine (LS-SVM) models are applied to the data consisting of daily confirmed cases of SARS-CoV-2 in the most affected five countries of the world for modeling and predicting one-month confirmed cases of this disease. To validate these models, the prediction results were tested by comparing it with testing data. The results revealed better accuracy of the LS-SVM model over the ARIMA model and also suggested a rapid rise of SARS-CoV-2 confirmed cases in all the countries under study. This analysis would help governments to take necessary actions in advance associated with the preparation of isolation wards, availability of medicines and medical staff, a decision on lockdown, training of volunteers, and economic plans.

Purpose: To study the significance of filling cystometry with pressure flow studies and bladder electromyography (EMG) in assessment and management of neurogenic bladder with myelopathies and evaluated neurological recovery in the follow-up period. Methods: The study was a 3-year prospective urodynamic study in 63 patients, with traumatic and nontraumatic myelopathy. Bladder management was advised based on the cystometric findings. Neurological recovery and mode of bladder management were evaluated during follow-up after a minimum of 6 months. Results: Mean age was 44.6 years (range 10–80 years). Thoracolumbar area was most commonly involved. Cystometry revealed overactive detrusor in 46 patients, (17 had detrusor sphincter dyssynergia [DSD], 29 without DSD) and areflexic/underactive detrusor in 9 patients. Postvoid residual (>15% of voided urine) was significant in 27 patients. Neurological recovery was seen in 60.3%, whereas 22.2% showed no improvement (partial improvement in 4.8%) and 12.6% had normal bladder function both initially and at follow-up. Correlation between neurological recovery and bladder management was found to be insignificant (P > 0.05) using spearman's correlation coefficient. Conclusion: Filling cystometry with pressure flow studies and EMG study is valuable for the assessment and management of neurogenic bladder in patients with myelopathy. In neurogenic bladder management and follow-up, pressure flow studies help to prevent complications and upper urinary tract complications.

BACKGROUND The Waist-Hip Ratio (WHR) and Waist Circumference (WC) were used to identify people at health risk both from being overweight and having visceral fat distribution. The aim of this study was to determine the association of WHR and WC in measuring the abdominal obesity, cardiovascular risk and weight management. MATERIALS AND METHODS The study involved 200 medical students (102 boys and 98 girls) in the age group of 18-23 years (mean age 20.43 ± 8.9 years) of Government Medical College, Amritsar, Punjab. WHR was divided into three groups in females- ≤0.80, 0.81-0.85 and >0.86 and males- ≤0.90, 0.90-1.0 and >1.0. WC was also divided into three groups in females- 88 cm and males- 102 cm. RESULTS The results of measurement of Waist-Hip Ratio (WHR) of females were ≤0.80 (2%), 0.81-85 (10%) and >0.86 (88%) and males ≤90 (82%), 0.90-1.0 (15%) and >1.0 (3%). Waist Circumference (WC) of females was 88 cm (19%) and males 102 cm (4%). CONCLUSION WHR is a better predictor of Cardiovascular Diseases (CVD) than WC. WHR and WC are measures of abdominal obesity and should be incorporated in weight management. WHR 0.81-0.86 in girls and 0.90-1.0 in males have moderate health risk, while >0.86 in females and >1.0 in males have high health risk. Men with WC ≥94 cm and women ≥80 cm should gain no further weight while men with WC ≥102 cm and women with ≥88cm should reduce their weight to avoid cardiovascular risks. Waist circumference is another alternative.

BACKGROUND Fingerprints are one of the most reliable tool of identification. As fingerprints never change from birth till death, therefore fingerprint evidence is by far the most effective and reliable evidence in court of law. The aim of the study is to find the incidence of patterns of left and right thumb impressions and blood groups of males and females, respectively. MATERIALS AND METHODS The present study was conducted on 150 medical students including 76 males and 74 females in the age group of 18-23 years in the Department of Physiology, Government Medical College, Amritsar, Punjab. RESULTS The distribution of loops were higher on thumbs of both sexes. In males, the frequency of loops on left thumb were found higher 48 (63.16), followed by whorls 21 (27.63%) and arches 7 (9.21%). In females, the frequency of loops on right thumb were found higher 45 (60.81), followed by whorls 23 (31.08) and arches 6 (8.11). CONCLUSION The frequency of loops were higher followed by whorls and arches on thumbs of both sexes. The blood group B was dominant followed by O, A and AB blood groups.

Introduction: Chronic lymphocytic leukemia (CLL) is an incurable, heterogenetic disease dependent on B cell receptor (BCR) signaling with subsequent nuclear factor-kappa B (NF-κB) activation resulting in the evasion of apoptosis and enhanced malignant B cell growth. Targeted therapies such as ibrutinib (IBR; BTK inhibitor) and venetoclax (VEN; BCL2 antagonist) have revolutionized the management of CLL, however ~20% of patients relapse, signifying the urgent need for novel therapeutics for CLL patients especially those with refractory/relapse (ref/rel) disease. Additionally, various tumor microenvironment (TME) stimuli fuel CLL growth and contribute to drug resistance through the activation of numerous signaling pathways (BCR, CD40R, TLR, BAFFR) and consequential sustained NF-κB activation. Currently, there are no FDA approved drugs that effectively target the NF-κB protein family. Herein we introduce 36-286 (N3), a novel spirocyclic dimer which displays NF-κB inhibitory activity and elicits potent anti-leukemic properties. N3 is a dimer of a spirocyclic α-methylene-γ-butyrolactone analog that covalently binds to surface exposed cysteine residues on NF-κB proteins (IKKβ and P65) (Rana S et al, 2016). Our study aims to investigate N3's mode of action (MOA) and to establish its anti-leukemic effects in CLL including drug-resistant disease, thereby introducing a novel therapeutic option for rel/ref disease. Methods: Cell growth via MTS proliferation assay was determined following treatment with N3 (0.125 - 2 μM) in a panel of malignant B cell lines [CLL (HG3, MEC1, OSUCLL), diffuse large B cell lymphoma (Pfeiffer, RC, RIVA), mantle cell lymphoma (Jeko1)], and in patient derived CLL cells stimulated with CpG ODN 2006 (CpG; 3.2 μM). Viability testing of normal B cells isolated from healthy donors was conducted following N3 treatment. Anti-tumor properties of N3 (1 - 2 μM; 4h) in the HG3 and OSUCLL cell lines were further confirmed under conditions mimicking different TME stimuli such as α-IgM (10 μg/mL), CD40L (100 ng/mL), BAFF (50 ng/mL) or CpG (3.2 μM). Protein expression of oncogenic MYC, select NF-κB pathway proteins (IKKα, IKKβ, P65, IκBα, RelB) and the anti-apoptotic protein MCL1 was determined following treatment with N3 (0.25 - 2 μM; 4h) by immunoblot (IB). Next, we induced IBR resistance in HG3 cells by prolonged exposure to increasing IBR concentrations (~10-15 fold its IC 50 in parental cells). Cell proliferation via MTS was determined following treatment with N3 on these resistant cells. To gain insight on the potential MOA of N3 in CLL, we adapted a proteomics-based approach (TMT labeled mass spectrometry) and conducted RNA-seq in OSUCLL cells treated with N3 (1 - 2 μM) for up to 24 h. Subsequent pathway analysis was performed to identify the top factors modulated by N3. Results: N3 showed remarkable efficacy (IC 50 < 0.6 μM) across all the malignant B cell lines evaluated while sparing normal B cells. In CpG stimulated primary CLL, N3 resulted in marked anti-leukemic effects (0.125 μM) comparable to IBR (1 μM). N3 induced cell apoptosis in CLL cell lines in a dose-dependent manner with marked PARP cleavage. Furthermore, our IB analyses of N3 treated CLL cell lines showed reduced levels of NF-κB pathway proteins, MYC and MCL1. Notably, N3 was effective in reducing levels of the above-mentioned proteins in the presence of the various TME stimuli. Strikingly, N3 maintained its cytotoxic effects in ibrutinib resistant HG3 cells. Studies to confirm N3's cytotoxicity in VEN resistant CLL cells are ongoing. Top ten pathways from both proteomics and RNA-seq analyses revealed an upregulation of the unfolded protein response (UPR) and inhibition of cap-dependent protein translation. IB analyses of select factors related to UPR (CHOP, XBP1, PERK, IRE1) and protein translation (eIF2α, 4E-BP1, PDCD4) in N3 treated CLL cells validated our omics' findings. Efforts to identify the proteome wide direct targets of N3 in CLL cells are currently underway. Conclusion: N3 is a novel pre-therapeutic lead that targets multiple survival and proliferation pathways through the inhibition of NF-κB activity and upregulation of UPR. We show that its highly cytotoxic in tumor B cells while sparing normal B cells. Moreover, N3 sustained its anti-tumor properties under different TME stimuli and in IBR resistant cells, indicating the potential use of this compound in rel/ref patients following evaluation in murine CLL models. Disclosures No relevant conflicts of interest to declare.

BACKGROUND ABO blood groups are associated with some important chronic diseases, obesity being the major risk factor is rising rapidly globally. The present study seeks to determine if there is any association between ABO blood groups and body mass index. MATERIALS AND METHODS The present study involve 200 medical students, 102 boys and 98 girls in the age group of 18-23 years in the Government Medical College, Amritsar. Weight, height for BMI and blood groups were determined in order to find any association between ABO blood group and BMI. RESULTS Overweight and obesity was found more prevalent in boys than girls, 22.5% students were overweight and 15.5% were obese. The prevalence of overweight was (24.52% boys and 20.40% girls) and prevalence of obesity was (25.49% boys and 5.10% girls). Blood group B was reported the most common blood groups (37.5%) followed by blood group O (32.0%), while blood groups A and AB were found 19.5% and 11% of participants, respectively. The prevalence of overweight (BMI 25-29.9) among participants based on blood group O, A, AB and B was 29.69%, 25.64%, 18.18%, 16.00%, while obesity (BMI >30) among participants based on blood groups B, O, A and AB was 24.00%, 10.94%, 10.26% and 9.09%. CONCLUSION Prevalence of overweight and obesity was more in blood group O and B respectively and was more in males than females

In 1984, nearly 500,000 inhabitants of Bhopal city, India, were exposed to toxic gases that leaked from a nearby pesticide manufacturing plant. In 1985, four cohorts were established to assess the long-term health impact of exposure, namely, mild, moderate, severely exposed and unexposed groups. The self-reported morbidity data of these cohorts were collected by follow-up cross-sectional surveys at regular intervals over the last 35 years. The present study aimed to analyse the long-term trend of chronic (duration of symptoms3 months) respiratory morbidity in the four cohorts, stratified by age groups.The design of this study is a longitudinal analysis of cross-sectional respiratory morbidity data.Chronic respiratory morbidity data within the cohorts were analysed at 5-year intervals (first recorded data from 1986). Based on age at the time of exposure, subjects were stratified into four age groups: children (aged10 years), teenagers (aged ≥10 to20 years), younger adults (aged ≥20 to40 years) and older adults (aged ≥40 years).During the first decade, after exposure to the toxic gases, chronic respiratory morbidity in children and teenagers was high (up to 9.1%), which declined thereafter. Progressively increasing chronic respiratory morbidity was observed in both the younger and older adult age groups within all cohorts during the initial 5-10 years after exposure. Respiratory morbidity in both the younger and older adult age groups remained high for 15-20 years and thereafter recorded a declining trend. The highest respiratory morbidity observed during this study in the younger and older adult age groups was 38.6% and 59.5%, respectively; these values were both recorded in the severely exposed cohort.Exposure to toxic gases released during the Bhopal gas disaster has resulted in chronic respiratory morbidity of the exposed population; this morbidity has continued over decades. The age of the individuals at the time of exposure and exposure severity were crucial determinants of the long-term trend of respiratory morbidity.

We investigated effects of the ryanodine receptor (RyR) modulator caffeine on Na+ current (INa) activation and inactivation in intact loose-patch clamped murine skeletal muscle fibres subject to a double pulse procedure. INa activation was examined using 10-ms depolarising, V1, steps to varying voltages 0–80 mV positive to resting membrane potential. The dependence of the subsequent, INa inactivation on V1 was examined by superimposed, V2, steps to a fixed depolarising voltage. Current-voltage activation and inactivation curves indicated that adding 0.5 and 2 mM caffeine prior to establishing the patch seal respectively produced decreased (within 1 min) and increased (after ~2 min) peak INa followed by its recovery to pretreatment levels (after ~40 and ~30 min respectively). These changes accompanied negative shifts in the voltage dependence of INa inactivation (within 10 min) and subsequent superimposed positive activation and inactivation shifts, following 0.5 mM caffeine challenge. In contrast, 2 mM caffeine elicited delayed negative shifts in both activation and inactivation. These effects were abrogated if caffeine was added after establishing the patch seal or with RyR block by 10 μM dantrolene. These effects precisely paralleled previous reports of persistently (~10 min) increased cytosolic [Ca2+] with 0.5 mM, and an early peak rapidly succeeded by persistently reduced [Ca2+] likely reflecting gradual RyR inactivation with ≥1.0 mM caffeine. The latter findings suggested inhibitory effects of even resting cytosolic [Ca2+] on INa. They suggest potentially physiologically significant negative feedback regulation of RyR activity on Nav1.4 properties through increased or decreased local cytosolic [Ca2+], Ca2+-calmodulin and FKBP12.

This research work focuses on preparation of partial dentures (as functional prototypes) by additive manufacturing (AM)-assisted centrifugal casting (CC). The master pattern for partial dentures was prepared on fused deposition modelling (FDM) set-up (established by AM technique at low cost). The final dentures as functional prototypes were prepared with a nickel–chromium (Ni–Cr)-based alloy by varying different proportions of Ni% (N) by weight %. The other input parameters were powder to water P/W ratio (W) and pH value (H) of water used for mixing the investment. The samples prepared were ascertained for dimensional deviation (Δd), surface finish (Ra) and micro-hardness (HV) as output parameters. Finally, multifactor optimization has been applied on output parameters of functional prototypes prepared. This study highlights that partial denture prepared with W-100/15, H-7 and N-61% gives overall better results from mechanical properties and dimensional accuracy viewpoint. The results are also supported by photo-micrographic analysis.

Introduction: Endoscopoic third ventriculostomy (ETV) is currently considered the best alternative to cerebrospinal fluid (CSF) shunt systems in the treatment of obstructive hydrocephalus. The aim of ETV is to communicate the third ventricle with the interpendicular cistern and create CSF flow which bypasses an obstruction to the circulation of the CSF. Aims and Objectives: The purpose of this study was to elucidate the indications, efficacy, safety and outcome Of ETV pediatric patients of noncommunicating hydrocephalus. Material and Methods: This study is a 3 year prospective study from June 2012 to May 2015. Records were kept for age, gender, etilogical factors, symptoms, signs, previous use of shunt or external ventricular device, imaging findings, and surgical complications (intraoperative and postoperative). Only those patients with age between 6months and 18 years with symptoms of intracranial hypertension and radiographic evidence of noncommunicating hydrocephalus were included in the study. Results: A total of 53 patients were studied, out of these 29 were boys and 24 were girls. The mean age of the patients was 6.6 years. Overall a total of 50 successful ETVs were done in 53 patients. The success rate is estimated to be 94%. There was no mortality. The average postoperative hospital stay was 4 days. The followup ranged from 6 to 16 months (mean, 12 months). Conclusion: ETV in children is a safe, simple and effective treatment and a logical alternative to shunting procedure for patients of noncommunicating hydrocephalus.

The induction heating loss mechanism in nanofluids prepared using synthesized β-NaFeO2 nanoparticles has been discussed concerning optimization of magnetic relaxation (Neel and Brownian) losses, specific absorption rate (SAR), intrinsic loss power (ILP)as well as the concentration of nanoparticles. The highest value of SAR for β-NaFeO2 nanoparticles is 705.86 W/g at 335.2 Oe field and 267 kHz frequency. The value of Brownian and total relaxation time has been calculated theoretically and found to be τ B = 6.126 × 10−4 sand τ = 2.668 × 10−7 s, respectively. For Hyperthermia treatment, 2 to 5 mg/mL is the best suitable lowest concentration to achieve high SAR and ILP under applied field. The maximum value of ILP observed is 1.49 nHm2/kg. The calculated theoretical and experimental parameters of induction heating make synthesized β-NaFeO2 nanoparticles suitable for the treatment of cancer via Hyperthermia.

Introduction: Craniosynostosis is the premature fusion of one or more of the cranial sutures and can occur as part of a syndrome or as an isolated defect. Pansynostosis is a rare form of craniosynostosis that involves premature fusion of all the cranial sutures (coronal, sagittal, metopic, and occipital). Particularly in cases of late presentation, there are heightened clinical concerns, both functional and aesthetic. In untreated cases of pansynostosis and increased intracranial pressure, optic nerve damage progresses to optic atrophy and then blindness. Objectives: Cranial vault reconstruction is the standard surgical treatment. We attempt to highlight the importance of modifying the osteotomies and reshaping of the cranial vault based on individual requirements in order to achieve the best possible result and to prevent catastrophic blood loss. Method and Results: We present a case of modified pi with triple-bonnet flap and fronto-orbital advancement, an individual modification of the techniques of cranial vault reconstruction, in a patient with pansynostosis with optic atrophy. Conclusion: The technical variation can be applied to any case of pansynostosis requiring cranial vault reconstruction.

IL-6 is a major causative factor of inflammatory disease. Although IL-6 and its signaling pathways are promising targets, orally available small-molecule drugs specific for IL-6 have not been developed. To discover IL-6 antagonists, we screened our in-house chemical library and identified LMT-28, a novel synthetic compound, as a candidate IL-6 blocker. The activity, mechanism of action, and direct molecular target of LMT-28 were investigated. A reporter gene assay showed that LMT-28 suppressed activation of STAT3 induced by IL-6, but not activation induced by leukemia inhibitory factor. In addition, LMT-28 downregulated IL-6–stimulated phosphorylation of STAT3, gp130, and JAK2 protein and substantially inhibited IL-6–dependent TF-1 cell proliferation. LMT-28 antagonized IL-6–induced TNF-α production in vivo. In pathologic models, oral administration of LMT-28 alleviated collagen-induced arthritis and acute pancreatitis in mice. Based on the observation of upstream IL-6 signal inhibition by LMT-28, we hypothesized IL-6, IL-6Rα, or gp130 to be putative molecular targets. We subsequently demonstrated direct interaction of LMT-28 with gp130 and specific reduction of IL-6/IL-6Rα complex binding to gp130 in the presence of LMT-28, which was measured by surface plasmon resonance analysis. Taken together, our data suggest that LMT-28 is a novel synthetic IL-6 inhibitor that functions through direct binding to gp130.

Background Intracranial schwannomas not related to cranial nerves are very rare. Young age, no known history of neurofibromatosis, and seizure as initial symptom have been reported to be associated with intraparenchymal schwannoma. Case description We report a case of supratentorial parasagittal schwannoma in the right frontal region presenting with seizure episode in a 70-year-old man. Computed tomography and magnetic resonance imaging showed a right frontal solid, enhancing extra-axial lesion based on anterior and middle third junction of superior sagittal sinus. The preoperative diagnosis was right parasagittal meningioma, however, the microscopic examination of the mass showed the characteristic pattern of cellular Antony A pattern. Immunohistocemically, the tumor stained positive for S-100 protein but negatively for epithelial membrane antigen and glial fibrillary acidic protein. These findings are consistent with schwannoma. Cysts, calcification, and peritumoral edema are common in intracerebral schwannoma, which were not seen in our case. Conclusion On the basis of clinical presentation and radiological appearances, schwannoma in unusual sites can easily be mistaken for meningiomas; immunochemistry plays an important role in differentiating them. Till date, to the best of our knowledge, this is the second reported case of schwannoma mimicking meningioma in parasagittal location.

This study aimed to examine the influence of prebiotics on growth and activity of Lactobacillus plantarum and their effect on adherence of anaerobic pathogens to Caco-2 and HT-29 intestinal cell lines. The specific growth rate of indigenous L. plantarum in lactulose (0.51/hr) was found to be maximum followed by fructooligosaccharide (0.34/hr) and inulin (0.18/hr) which was statistically at par with reference strain. Shortest mean doubling time of indigenous strain was observed with lactulose (1 hr 35 min) followed by fructooligosaccharide (2 hr 3 min), and inulin (3 hr 85 min). Lactic and short-chain fatty acids namely, acetic, propionic, and butyric were the principle metabolites observed after fermentation of prebiotics as detected by ultra-performance liquid chromatography analysis. No significant change in growth and pH of anaerobic pathogens was observed in medium supplemented with different prebiotics. Presence of lactulose showed maximum inhibition in adherence of anaerobic pathogens namely, Peptostreptococcus anaerobius (39 and 37%), Clostridium perfringens (36 and 34%), and Bacteroides fragilis (18 and16%), to Caco-2 and HT-29 intestinal cell lines. Practical applications The ability of certain bacteria to ferment prebiotics selectively is an important probiotic characteristic. According to the results of this study, lactulose was found to be the promising ingredient in combination with indigenous strain that not only supported the growth of lactobacillus strain, but also inhibited the adherence of anaerobic pathogens to intestinal cell lines. The metabolites produced on fermentation of prebiotic such as lactate, acetate, propionate, and butyrate have many reported health benefits in boosting the gut immunity of the host. Negligible growth of anaerobic pathogens in lactulose indicating its safe use without any ill effect to the host. Thus, the lactulose might have a potential for practical use in food industry for the development of future functional and dietary foods to impart health benefits at both colonic and systemic levels.

Background Spinal epidural abscess, although an uncommon disease, often correlates with a high morbidity owing to significant delay in diagnosis. Methods In a prospective 5-year study, the clinical and magnetic resonance (MR) findings, treatment protocols, microbiology, and neurological outcomes were analyzed for 27 patients with spinal epidural abscess. Results Patients were typically middle-aged with underlying diabetes and presented with lumbar abscesses. Those undergoing surgical intervention >36 h after the onset of symptoms had poor neurological outcomes. Conclusion Early recognition and timely evacuation of spinal abscesses minimized neurological morbidity and potential mortality.

A 42-day study was conducted to evaluate the effect of ground full-fat flaxseed supplementation on growth performance, carcass characteristics, α-linolenic acid (ALA), linoleic acid (LA) and organoleptic characteristics of broiler meat. A total of 200 one-day-old broiler chicks were randomly allocated to five experimental groups and were fed isoenergetic and isonitrogenous diets containing flaxseed at 0%, 2.5%, 5.0%, 7.5% and 10%. Flaxseed supplementation did not affect the weekly body weight of broiler chicks during the first three weeks, but thereafter it reduced significantly with increasing levels of flaxseed in the diets. Birds fed on 10% flaxseed showed a reduction of 10.08% in body weight as compared to the control group. Diets containing 5.0–7.5% flaxseed resulted in significantly lower weight gain, higher feed conversion ratio, energy efficiency ratio and lower protein efficiency ratio as compared to control and 2.5% flaxseed diets. The carcass characteristics data indicated a little variation in...

BACTEC 460 has now been phased out, so the search for an alternative is imperative. We have determined the activity of standard anti-tuberculosis drugs against intramacrophage Mycobacterium tuberculosis, in vitro, by using BACTEC 460 and MGIT 960 methods. The minimum inhibitory concentrations of isoniazid, rifampicin, ethambutol and streptomycin against intracellular M. tuberculosis H37Rv were found to be 0.2, 0.8, 8.0, and 5.0 μg/mL, respectively, by both methods. These results show a significant (p

Background: Laryngoscopy is associated with a sympathetic response that results in a rapid increase in blood pressure and heart rate in these patients. The mechanisms underlying these hemodynamic changes are incompletely understood. They may be caused by a reflex sympathetic discharge due to stimulation of the upper respiratory tract. It has been observed that hemodynamic responses to tracheal intubation are associated with an increase in plasma catecholamine concentrations and are attenuated by β-adrenergic blockade. These hemodynamic changes may be undesirable particularly in neurosurgical patients. Aim of the study is the present study was prospective, randomized, double-blind conducted to evaluate the efficacy of dexmdetomidine and fentanyl in attenuation of pressor responses to laryngoscopy and intubation in neurosurgical patients undergoing lumbar spine surgeries.Methods: A total of 60 patients of 18–65 years, American Society of Anaesthesiologists Class I/II of undergoing elective neurosurgical procedures were included in the study. The patients were divided into two groups of 30 patients each. Group D received dexmedetomidine and Group F received Fentanyl. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MAP) were recorded preoperatively (baseline), at 5 and 8 minutes after infusion of study drug, before induction, 1 minute after induction, 2 minute after intubation, 5 minute after intubation, 10 minute after intubation and 15 minute after intubation.Results: There was a better control of Heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure in Group D when compared to Group F during laryngoscopy and after intubation.Conclusions: The present study shows that dexmedetomidine suppresses hemodynamic responses effectively than fentanyl.

Background: Central venous cannulation is a commonly performed procedure in neurosurgical patients to maintain the hemodynamic stability in the intraoperative period. It is used for infusion of intravenous fluids, vasopressors central venous pressure monitoring and detection of air embolism. Subclavian vein is commonly performed as there are minimal effects of positioning on it. Supraclavicular approach to subclavian vein cannulation is not as frequently employed as the infraclavicular approach. The purpose of this study was to compare the supraclavicular approach versus the infraclavicular approach in terms of number of attempts, success rate of catheterization and complications associated with the procedure.Methods: About 150 patients undergoing various neurosurgical procedures were enrolled in the study. They were divided into two groups. 75 patients underwent right supraclavicular catheterization of subclavian vein while as 75 patients underwent right infraclavicular catheterisation of the subclavian vein. The number of attempts for cannulation, success or failure of catheterization and any complications associated with the procedure or in the postoperative period were noted in each group. The data was compared between the two groups by using Chi-square test and Student’s Independent Samples T-test.Results: The right supraclavicular vein was successfully cannulated in 90.66% while as the right infraclaviclar vein was successfully cannulated in 96% of the patients (p >0.05). Malpositioning of catheter (threaded in contralateral subclavian) was noted in 4 patients in Group S and ipsilateral internal jugular vein in 2 patients. Pneumothorax was encountered in 1 patient in the group S undergoing supraclavicular subclavian vein cannulations while as subclavian arterial puncture was seen in 4 patients who underwent infraclavicular arterial puncture.Conclusions: There was no difference in successive cannulations between right the supraclavicular and right infraclaviclar veins. The rate of complications between the two approaches was comparable.

Spinal hydatid cysts, mainly in the form of osseous and epidural involvement, account for 1% of all cases of hydatid disease. Primary spinal intradural extramedullary (IDEM) hydatid cysts are extremely rare, with only 49 cases reported in the literature to date. IDEM hydatid cysts, a diagnostic challenge, should be suspected in cases of spinal cord compression, especially in previously treated systemic hydatidosis, or in endemic areas, or if the patient has migrated from or visited an endemic area. It should also be included in the differential diagnosis of IDEM cystic lesions seen on magnetic resonance imagining. Imaging modalities like magnetic resonance imagining have greatly improved the ability to diagnose the hydatid cyst of the spine. Surgical cyst extirpation followed by antihelminthic treatment with albendazole is the treatment of choice. From the review of literature, it seems that, in terms of intradural location and recurrence, intradural hydatid disease behaves differently from osseous and extradural disease.

Laparoscopic cholecystectomy is a very commonly performed procedure. Position of epigastric port is prefered by some surgeons from left side of the falciform ligament, whereas others prefer from right side of ligament. In this study we have compared the ergonomics and results of two approaches by conducting the procedure upon 100 patients. The advantages and disadvantages of each technique are discussed in this report.

Skull fractures are traditionally classified into linear, comminuted or depressed which can either be simple or compound. A skull fracture where the bone fragment is elevated above the intact skull known as elevated skull fracture has been reported infrequently in literature. We report a unique case of simple elevated vertex fracture in a 3-month-old child where the vertex had separated from the calvarium and was elevated above the level of outer table in a patient with delayed neurological deterioration. Cerebrospinal fluid leak into tight subgaleal space and gradual thrombosis of superior sagittal sinus could have led to late clinical deterioration. Prolonged monitoring, probably early repair of dural tear and aggressive management of raised ICP, is required. Reduction of fracture with careful manipulation of SSS should weigh the risk of exsanguination. No such case of an elevated vertex fracture has been reported so far in the literature.

Sellar and suprasellar tuberculomas are rare. Patients with these lesions usually experience headache, vomiting, and hypofunction of pituitary gland; imaging reveals an enhancing sellar-suprasellar mass. We report 2 rare cases of sellar-suprasellar tuberculomas in children aged 8 and 6 years. One child presented with features of headache and vomiting, and the other presented with posterior pituitary dysfunction. In both cases, imaging revealed sellar-suprasellar masses. Both cases were multidrug-resistant tuberculomas. We discuss sellar-suprasellar tuberculomas, a rare form of neurotuberculosis in the background of an overall increase in multidrug-resistant tuberculosis, especially in children.

In clinical practice dermatological reactions are common but comprehensive information regarding their incidence, severity is often not available as many cases go unreported. The objective of this study was to evaluate the types of dermatological adverse drug reactions (ADRs) in a tertiary care hospital and determine their causal relationship with the offending drug. This prospective, observational study was conducted at GSVM medical college Kanpur, Northern India for one year. Patients of all age and either sex were included. Dermatological adverse drug reactions were reported by the physicians of various department of the hospital and their causality assessments were performed as per World health organization (WHO) Uppsala monitoring centre (UMC), Expanded Rawlins and Thompson’s classification was used for determining type of ADRs, outcome and seriousness of ADR were assessed as per WHO. Descriptive statistics were used for data analysis. A total of 105 dermatological adverse drug reactions were reported from various departments of this tertiary care hospital. Most of the adverse drug reactions were observed in the age group of 0–20 year. Rash (35 ADRs) was commonly reported reaction. Anticancer drugs lead to 48 ADRs (mainly with Paclitaxel+Carboplatin-11, Adriamycin+Cyclophosphamide-7), followed by Antibacterial with 28 ADRs (mainly with Vancomycin-6, Cefixime-4 and Amoxicillin-4). A total of 8 ADRs were of serious type mainly with Vancomycin-Red man syndrome-6, Carbamazepine-toxic epidermal necrolysis-1 and Nimesulide-Steven Johnson Syndrome-1. Most of the adverse drug reactions on causality assessment were possible (77, 73.33%) and Probable (28, 26.67%) in nature. Type -B ADRs account for 2/3rd of the total dermatological ADRs. It’s highly emphasized for careful monitoring for ADRs associated with high risk drugs and more awareness should be created.

A total of 450 experimental runs were performed at three speed levels, i.e., 5.6, 7.4 and 9.3 m/s as well as three sitting postures, i.e., lean forwards (LF), vertical erect with no back rest (VE-NB) and lean with back rest (L-WB). Majority of vibration levels were exceeding ISO 2631-1 1997 exposure action value. Vibration transmission was highest for posture LF followed by VE-NB and L-WB at 7.4 and 9.3 m/s, whereas VE-NB at 5.6 m/s followed by LF and L-WB. Subjective comfort responses are significant at 5% level for neck, shoulder and lower back with mean daily exposure levels. 1/3rd octave band showed dominant frequencies of 3.15 and 4 Hz that could affect health and safety of drivers due to existing natural frequencies of various body parts. It is recommended that tractors need more design efforts to damp vibration transmission along z axis so as to enhance ride comfort level.