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Introduction: As the amyloid precursor protein performs a remarkable part in chronic periodontitis and the progression of Alzheimer's disease growth, discoveryof novelactive inhibitors of this protein can be of great standing in the treatment of periodontitis. Chronic periodontitis is one of the causative factors and metabolic stressor for diabetes control. In chronic periodontitis and Alzheimer's disease, some molecules have been proposed to inhibit proteins in past. Methods: This study was planned to find present potent inhibitors,A library of KDM compounds was obtained from Chem Div Database. Here, all complexes with goodglide score were short listed for analysis of protein-ligand interaction. Calculations were carried out to estimate the interaction of the ligands selected in complex with the beta amyloid protein. Results: Five top hits were found considering Curcuminas reference. Five small molecules have been proposed as possible inhibitors of this protein. Here in this study, we have focused on small molecule lead inhibitors for identification of Chronic Periodontitis and Alzheimer's disease.

Morphea en coup de sabre is a type of linear localized scleroderma, characterized by a sclerotic skin band in the forehaead and frontoparietal scalp area. It can cause cicatricial alopecia, when affecting the scalp. The disease is mostly unilateral and may be associated with neurological complications and eye defects. Herein, we present a case of bilateral morphea en coup de sabre in a young man, which developed following trauma to the head in childhood 10 years earlier. It produced linear bands of alopecia over the scalp and right eyebrow. The lesions progressed over 4 years, then remained quiescent for 6 years and then restarted progressing again. The patient also complained of repeated frontal headaches but the neurological and ocular examination was normal. Dermoscopy and histopathology were used to confirm the diagnosis. The case is unique because of the bilateral manifestation, preceding trauma and recurrence of disease activity.

The mitochondrial manganese superoxide dismutase (MnSOD) enzyme protects lungs against oxidative stress by neutralizing the free radical superoxide produced in the respiratory function. This has relevance to asthma. Therefore, it is of interest to describe the potential effect of MnSOD Ala16Val genetic polymorphism to asthma risk. Known data in this context is inconclusive in nature. The possible link between MnSOD Ala16Val polymorphism and asthma is explored using sequence meta-analysis. Data from the pooled analysis of MnSOD Ala16Val polymorphism using five genetic models i.e., allelic (Val vs. Ala: p=0.846; OR=1.033, 95% CI=0.742 to 1.440) is discussed. Homozygous (Val Val vs. Ala Ala: p=0.517; OR=1.307, 95% CI=0.582 to 2.932) and heterozygous (Val Ala vs. Ala Ala: p=0.307; OR=1.138, 95% CI=0.888 to 1.459) data using the described models are documented. Data from the dominant model (Val Val + Val Ala vs. Ala Ala: p=0.301; OR=1.289, 95% CI=0.797 to 2.085) and the recessive model (Val Val vs. Val Ala + Ala Ala: p=0.761; OR=0.924, 95% CI=0.555 to 1.538) analyses for several ethnic subgroups in this context is reported.

Hutchinson-Gilford progeria syndrome is an extremely rare genetic disorder characterized by premature ageing involving the skin, bones, heart, and blood vessels. The incidence is 1 in several million births. It occurs sporadically and is probably an autosomal dominant syndrome. The diagnosis is essentially clinical and the manifestations become more evident from the first year of life. We report a case of a seven-month- old boy with clinical manifestations characteristic of this syndrome. He had a characteristic “plucked-bird” appearance, prominent eyes and scalp veins, senile look, loss of scalp hair, stunted growth and mottled pigmentation with sclerodermatous changes over the trunk and lower limbs. This interesting case is reported for its rarity.

Background: Vitiligo is a chronic disease of great cosmetic concern presenting with depigmented macules and patches. It is often recalcitrant to medical treatment. Aim: The aim of the study was to study the efficacy and safety of topical 5% 5-fluorouracil with needling versus topical 5% 5-fluorouracil alone in stable vitiligo. Materials and Methods: This interventional prospective study was conducted from July 2018 to June 2019. Total of 60 patients, with stable vitiligo of age older than 10 years, were randomly assigned into two groups of 30 patients each. Group A was treated with needling followed by topical 5% 5-fluorouracil over vitiligo patches. The procedure was performed every 2 weeks for 3 months. Group B was treated with topical 5% 5-fluorouracil alone. Clinical improvement was assessed monthly till 6 months by serial clinical photographs and grading score. Results: Initiation of repigmentation started at 1 month in 76 patches (65%) in Group A, whereas in group B, it was seen in 45 patches (38.7%), which was statistically significant (P = 0.0001). Excellent improvement (>75% repigmentation) was noted in 55 patches (47%) in Group A as compared to 5 patches (4.3%) in group B at the end of 6 months (P = 0.03). Conclusion: Needling with 5% 5-fluorouracil appears to be simple, safe, and effective treatment in vitiligo. It can be used in poor responders to conventional therapy.

DNA repeat expansion sequences cause a myriad of neurological diseases when they expand beyond a critical threshold. Previous electrochemical approaches focused on the detection of trinucleotide repeats (CAG, CGG, and GAA) and relied on labeling of the probe and/or target strands or enzyme-linked assays. However, detection of expanded GC-rich sequences is challenging because they are prone to forming secondary structures such as cruciforms and quadruplexes. Here, we present label- free detection of hexanucleotide GGGGCC repeat sequences, which cause the leading genetic form of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The approach relies on capturing targets by surface-bound oligonucleotide probes with a different number of complementary repeats, which proportionately translates the length of the target strands into charge transfer resistance (R(CT)) signal measured by electrochemical impedance spectroscopy. The probe carrying three tandem repeats transduces the number of repeats into R(CT) with a 3× higher calibration sensitivity and detection limit. Chronocoulometric measurements show a decrease in surface density with increasing repeat length, which is opposite of the impedance trend. This implies that the length of the target itself can contribute to amplification of the impedance signal independent of the surface density. Moreover, the probe can distinguish between a control and patient sequences while remaining insensitive to non-specific Huntington’s disease (CAG) repeats in the presence of a complementary target. This label-free strategy might be applied to detect the length of other neurodegenerative repeat sequences using short probes with a few complementary repeats.

Introduction: The regulation of apoptosis via compounds originated from marine organisms signifies a new wave in the field of drug discovery. Marine organisms produce potent compounds as they hold the phenomenal diversity in chemical structures. The main focus of drug development is anticancer therapy.Methods:Expertise on manifold activities of compounds helps in the discovery of their derivatives for preclinical and clinical experiment that promotes improved activity of compounds for cancer patients.Results:These marine derived compounds stimulate apoptosis in cancer cells by targeting Bcl-2 and Survivin, highlighting the fact that instantaneous targeting of these proteins by novel derivatives results in efficacious and selective killing of cancer cells.Conclusion:Our study reports the identification of Aplysin and Haterumaimide J as Bcl-2 inhibitors and Cortistatin A as an inhibitor of survivin protein, from a sequential virtual screening approach.

Background and purpose There is evidence that racial and ethnic differences among intracerebral hemorrhage (ICH) patients exist. We sought to establish the occurrence of disparities in hospital utilization in the United States. Methods We identified ICH patients from United States Nationwide Inpatient Sample database for years 2006–2014 using codes (DX1 = 431, 432.0) from the International Classification of Diseases, 9th edition. We compared five race/ethnic categories: White, Black, Hispanic, Asian or Pacific Islander, and Others ( Native American and other) with regard to demographics, comorbidities, disease severity, in-hospital complications, in-hospital procedures, length of stay (LOS), total hospital charges, in-hospital mortality, palliative care, (PC) and do not resuscitate (DNR). We categorized procedures as lifesaving (i.e. ventriculostomy, craniotomy, craniectomy, and ventriculoperitoneal (VP) shunt), life sustaining (i.e. mechanical ventilation, tracheostomy, transfusions, and gastrostomy). White race/ethnicity was set as the reference group. Results Out of 710,293 hospitalized patients with ICH 470,539 (66.2%), 114,821 (16.2%), 66,451 (9.3%), 30,297 (4.3%) and 28,185 (3.9%) were White, Black, Hispanic, Asian or Pacific Islander, and Others, respectively. Minorities (Black, Hispanic, Asian or Pacific Islander, and Others) had a higher rate of in-hospital complications, in-hospital procedures, mean LOS, and hospital charges compared to Whites. In contrast, Whites had a higher rate of in-hospital mortality, PC, and DNR. In multivariable analysis, all minorities had higher rate of MV, tracheostomy, transfusions, and gastrostomy compared to Whites, while Hispanics had higher rate of craniectomy and VP shunt; and Asian or Pacific Islander and Others had higher rate of craniectomy. Whites had a higher rate of in-hospital mortality, palliative care, and DNR compared to minorities. In mediation analysis, in-hospital mortality for whites remained high after adjusting with PC and DNR. Conclusion Minorities had greater utilization of lifesaving and life sustaining procedures, and longer LOS. Whites had greater utilization of palliative care, hospice, and higher in-hospital mortality. These results may reflect differences in culture or access to care and deserve further study.

Background To determine the clinical outcome for intracerebral hemorrhage (ICH) patients with pre-existing renal failure in the United States. Methods We analyzed the data from Nationwide Inpatient Sample (2008-2012) for all ICH patients with or without pre-existing renal failure. Patients were identified using the International Classification of Disease, Ninth Revision, Clinical Modification codes. Baseline characteristics, in-hospital complications, and exposure to invasive procedures were compared between groups. Discharge outcomes (mortality, minimal disability, and moderate-to-severe disability) were compared between the two groups, before and after adjusting for the presence of other medical comorbidities, in-hospital complications, and exposure to invasive procedures. Results Of the 328,728 patients with ICH, 36,067 (11.8%) had pre-existing renal failure as a comorbidity. There were higher rates for in-hospital complications like myocardial infarction (3.5% versus 1.9%, P ≤ .0001), sepsis (5.4% versus 3.0%, P ≤ .0001), pneumonia (7.1% versus 5.3%, P ≤ .0001), deep venous thrombosis (1.6% versus 1.2%, P = .0041), urinary tract infections (16.9% versus 15.1%, P = .0101), and gastrointestinal bleeding (0.4% versus 0.2%, P ≤ .0154), longer hospital stay (9.4 ± 14.4 versus 7.7 ± 11.4; P Conclusions Patients with ICH, who present with pre-existing renal failure, have higher rates of in-hospital mortality but not for disability, the difference remained significant after adjusting for the presence of other medical comorbidities, in-hospital complications or exposure to invasive procedures.

Breast cancer is the leading cause of death among women worldwide. It is a multi-factorial disease caused by genetic and environmental factors. Vitamin D has been hypothesized to lower the risk of breast cancer via the nuclear vitamin D receptor (VDR). Genetic variants of these vitamin D metabolizing genes may alter the bioavailability of vitamin D, and hence modulate the risk of breast cancer. Materials and Methods: The distribution of Fok1 VDR gene (rs2228570) polymorphism and its association with breast cancer was analysed in a case–control study based on 125 breast cancer patients and 125 healthy females from North Indian population, using PCR-RFLP. An In silico exploration of the probable mechanism of increased risk of breast cancer was performed to investigate the role of single nucleotide polymorphisms (SNPs) in cancer susceptibility. Results: The Fok1 ff genotype was significantly associated with an increased risk of breast cancer (p=0.001; χ2=13.09; OR=16.909; %95 CI=2.20 - 130.11). In silico analysis indicated that SNPs may lead to a loss in affinity of VDR to calcitriol, and may also cause the impairment of normal interaction of liganded VDR with its heterodimeric partner, the retinoid X receptor (RXR), at protein level, thereby affecting target gene transcription. Conclusion: Breast cancer risk and pathogenesis in females can be influenced by SNPs. SNPs in VDR may cause alterations in the major molecular actions of VDR, namely ligand binding, heterodimerization and transactivation. VDRE binding and co-activator recruitment by VDR appear to be functionally inseparable events that affect vitamin D-elicited gene transcription. This indicates that breast cancer risk and pathogenesis in females may be influenced by SNPs.

BACKGROUND Seborrheic keratosis is a benign skin tumour. None of the common therapies is satisfactory. This study compared the efficacy of 30% hydrogen peroxide versus 50% trichloroacetic acid in treatment of seborrheic keratoses. METHODS This unblinded, comparative interventional study was conducted on 85 patients of seborrheic keratosis. Lesions were graded using physician's lesion assessment (PLA) scale (0, clear; 1, nearly clear; 2≤1 mm thick; 3≥1 mm thick). Patients were randomly assigned into two groups: A and B. Five target seborrheic keratosis lesions with PLA score of three were selected in each patient. Group A was treated with 30% hydrogen peroxide and group B with 50% trichloroacetic acid. Both groups received treatment every week up to 5 weeks or till complete resolution of lesions. Clinical photographs of all patients were taken every 2 weeks. RESULTS Both the groups were comparable in terms of age and sex. At the end of 6 weeks, lesions were cleared completely in 41.8% of patients in group A and in 23.8% in group B. Mean PLA score decreased significantly in group A from 3 to 1.79 (40.3%) at 2 weeks and to 0.63 (79%) at 6 weeks (P

Background Human Cytomegalovirus (CMV), because of its ability to extensively manipulate host immunity during active infection, has been suggested to be involved in autoimmunity. However, its influence on T-cells and cytokines in systemic autoimmune diseases like systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is indistinct. Methods We investigated the in-vitro response of T lymphocytes from SLE and SSc patients to CMV antigen. Functional activity of T lymphocytes was determined by estimating Th1 (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines. Results We observed that CMV antigen stimulation in-vitro resulted in significant increase in CD4:CD8 T-cell ratio in peripheral blood mononuclear cells (PBMCs) from SLE and SSc patients; response dominated by CD4+ than CD8+ memory T-cells. SSc T-cell response was differentiated by aberrant increase in CD4+CD25+ T-cells. CMV antigen caused elevation in IL-4 and IFN-γ production in both patient PBMCs, whereas IL-2 was also raised in SLE PBMCs. The development of large pool of memory T-cells and overproduction of IFN-γ may result in flare-up of autoimmunity in these patients. Conclusion Our study provides an insight into the immunopathological potential of CMV-reactive immune cells to develop new potential strategies for targeted therapeutic intervention.

Background: Genetic changes in p53 gene contribute to breast cancer susceptibility. Objective and Methods: A case-control study and a meta-analysis were performed to investigate the role of p53 codon72 SNP with breast cancer susceptibility in Indian women. Results: p53 heterozygous arginine variant was associated with decreased risk of breast cancer in total cohort. In meta-analysis, Allelic and GG vs. CC genetic comparison model were found to be associated with breast cancer risk. Moreover, recessive comparison model indicated a protective correlation with breast cancer occurrence. Conclusion: The findings of our case-control study and meta-analysis suggest a significant association between p53 Arg72Pro polymorphism and an increased risk of breast cancer in Indian population.

The current study investigates the role of circulating free DNA (cfDNA) as a liquid biopsy in diagnosis gall bladder carcinoma (GBC) utilizing levels of long DNA fragments (ALU247) derived from tumor necrosis, short apoptotic fragments (ALU115) denoting total cfDNA and cfDNA integrity denoting ratio of ALU247 and ALU115. The global methylation status of cfDNA was also estimated with the hypothesis that these parameters provide a diagnostic distinction between cancer and non-cancer subjects, with higher or altered values favoring presence of malignancy. Study group included 60 cases of GBC and 36 controls including diseased controls (cholecystitis) and healthy subjects. Median levels of ALU115, ALU247 and cfDNA integrity were significantly different in GBC at 1790.88, 673.75, 0.4718 vs. controls at 840.73, 165.03, 0.1989 ng/ml respectively. Global DNA methylation was not significantly different between GBC at 0.679% and controls at 0.695%. The sensitivity and specificity of ALU 247 in discriminating GBC from controls was highest with a sensitivity, specificity and diagnostic accuracy of 80.0%, 86.1% and 82.2% respectively. Global DNA methylation showed lowest sensitivity of 55.0% and specificity of 50.0%. Clinico-pathological parameters showing significant association with cfDNA integrity, on ROC curve analysis, showed significant diagnostic discrimination of the tumor stage, lymphovascular invasion, disease stage and grade histology. This is a first time analysis of ALU115, ALU247 and cfDNA integrity in the diagnosis of GBC and confirms that the combination of ALU247 and cfDNA integrity provides good sensitivity, specificity and diagnostic accuracy in discriminating GBC from controls as well correlates with aggressive disease parameters.

The macrophage migration inhibitory factor (MIF) is a cytokine that plays an important role in inhibiting the growth of pathogenic Mycobacterium tuberculosis (M.tb) and regulates immune responses against M.tb pathogen. MIF -173 G > C gene polymorphism may affect immunity in an individual and leads to susceptibility to tuberculosis (TB). A large number of studies have investigated the relevance of this polymorphism with TB risk, but their results were inconclusive. To obtain a precise conclusion, a meta-analysis was performed by retrieving six eligible studies from Google Scholar, PubMed (Medline), and EMBASE online databases. Overall combined analysis suggested increased TB risk between MIF -173 G > C polymorphism and overall risk in four genetic models, i.e., allelic (C vs. G: p = 0.001; OR = 1.517, 95% CI = 1.312 to 1.753), homozygous (CC vs. GG: p = 0.026; OR = 1.874, 95% CI = 1.079 to 3.257), heterozygous (GC vs. GG: p = 0.001; OR = 1.542, 95% CI = 1.273 to 1.868) and dominant model (CC + GC vs. GG: p = 0.001; OR = 1.631, 95% CI = 1.362 to 1.955). Similarly, increased TB risk was observed in subgroup analysis of Asian ethnicity. No publication bias was observed. These results suggested that MIF -173 G > C variant is a significant risk factor for TB in overall and in Asian populations, and can be used as prognostic marker for TB susceptibility.

The emergence of multi-drug resistant strains and co-occurrence of tuberculosis with HIV creates a major burden to the human health globally. Failure of primary antibacterial therapy necessitates the identification of new mycobacterial drugs. In this study, a comprehensive analysis involving bottom-up systems biology approach was applied wherein we have identified potential therapeutic targets of Mycobacterium tuberculosis infections. Our study prioritized M. tuberculosis therapeutic targets [aspartate-β-semialdeyhde dehydrogenase (ASD), dihydrodipicolinate reductase and diaminopimelate decarboxylase] based on flux and elementary mode analysis using direct mathematical modeling of the relevant metabolic pathways. Molecular docking and simulation studies of the priority target (i.e., ASD) revealed the therapeutic potential of the selected natural products (Huperzine A, Rosmarinic acid and Curcumin) based ASD inhibitors. The study highlights the crucial role of systems biology in conjunction with molecular interaction (docking) for probing novel leads against an increasingly resistant pathogen, M. tuberculousis. This article is protected by copyright. All rights reserved

Botulism is a rare potentially fatal and treatable disorder caused by a bacteria-produced toxin that affects the presynaptic synaptic membrane resulting in a characteristic neuromuscular dysfunction. It is caused by either the ingestion of the toxin or the bacteria, inhalation, or wound infection. We present our observations with a descriptive case series of wound botulism secondary to black tar heroin (BTH) injection. We report a retrospective single-center case series of 15 consecutive cases of wound botulism presenting to University Medical Center of El Paso. Medical records where reviewed to obtain demographic information, clinical presentation, treatment, and outcome. We identified fifteen patients with mean age of 47 years: twelve men, and three women. All had administered BTH through skin popping and had abscesses in the administration areas. By history, the most common symptoms were dysphagia (66%), proximal muscle weakness of upper and lower extremity (60%), neck flexor muscle weakness (33%), ophthalmoplegia (53%), bilateral ptosis (46%), dysarthria (53%), double vision (40%), blurred vision (33%), and dry mouth (20%). During the examination, the most common features noted were: proximal muscle weakness of upper and lower extremities (73%), ophthalmoplegia (53%), ptosis (46%). In patients with documented wound botulism, the pupils were reactive in 46%. All patients required mechanical ventilation and were treated with the trivalent antitoxin. Eleven patients (73.3%) were discharged home, two were transferred to a skill nursing facility, and two were transferred to long-term acute care facility. In our patients, BTH injection, involving the action of injecting under the skin acetylated morphine derivatives (mostly 6-monoacetylmorphine and 3-monoacetylmorphine), was associated with the development of botulism. The availability of BTH at the US–Mexican border is not surprising since it is frequently produced in Latin America. Its association with the development of botulism should be recognized early to allow a prompt diagnosis and treatment with the antitoxin. A clinical feature worth noting is the presence of normal pupillary light reflex in nearly half of patients. Therefore, the presence of a normal pupillary response does not exclude the presence of wound botulism.

To determine whether there is any differential benefit of albumin administration within 2 h of onset of ischemia and in settings (severe ischemia with reperfusion in cardioembolic strokes with National Institutes of Health Stroke Scale [NIHSS] ≥15), most representative of experimental models of cerebral ischemia in which albumin was effective in reducing neurological injury. High-dose intravenous (IV) albumin treatment for acute ischemic stroke (ALIAS) trial did not show overall clinical benefit in ischemic stroke patients in contrast to preclinical studies; however, models of preclinical studies were not completely followed. A total of 1275 patients combined from ALIAS trials I and II were included in our analysis. We analyzed preclinical studies and selected patients with large ischemic stroke (NIHSS ≥15) related to cardioembolic etiology (n = 189). Outcomes were then studied including time from onset to IV albumin administration. The odds of excellent outcome (mRS 0–1) at 3 months was not different with high-dose IV albumin infusion (n = 100) compared with placebo (n = 89) ((odds ratio [OR]) 1.632 [0.719–3.708], p value 0.2419). When we further classified these subjects according to time of IV albumin administration, we observed significantly higher odds of excellent outcome at 3 months when patients received IV albumin within 2 h, OR 9.369 (CI 1.040–84.405), p value 0.0461, after adjusting for age, gender, baseline NIHSS score, and any therapeutic procedure. A trend for benefit is noted in ischemic stroke patients with large cardioembolic stroke (NIHSS ≥15) when high-dose albumin was initiated within 2 h, suggesting that certain ischemic stroke subgroups of patients most representative of preclinical settings may benefit from such a treatment. Additional clinical trials maybe needed to stratify subjects and treatment assignments according to NIHSS severity and timely randomization to evaluate this concept further.

The incidences of melanomas are increasing by leaps and bounds across the globe despite early detection and intervention. The numbers of patients dying from metastatic melanoma have been continually increased over the past thirty years. It has been considered as one of the most therapy-resistant malignancies due to the cross-resistant mechanism developed by the metastatic cells. With time, many new therapies came and they failed miserably. Ipilimumab, a monoclonal antibody that works to activate the immune system by targeting CTLA-4 proved to be a boon for advance melanoma very recently. But it could not stand firmly against the resistant metastatic skin cancer cells. Now, the new skin cancer drug named pembrolizumab proved as a new miraculous molecule. It's a humanized monoclonal antibody that blocks a biological pathway called programmed cell death-1 (PD-1), which melanoma cells activate to suppress the immune system. This antibody has surpassed ipilimumab at all the stages of clinical trials because of its non-cross resistant mechanism to malignant cells. The present review critically analyses the reasons of efficacy success of pembrolizumab over ipilizumab shown at various stages of clinical trials.

Nowadays, most of the people are suffering from the attack of chronic diseases because of their lifestyle, food habits, and reduction in physical activities. Diabetes is one of the most common chronic diseases being suffered by the people of all ages. As a result, the healthcare sector is generating extensive data containing huge volume, enormous velocity, and a vast variety of heterogeneous sources. In such scenario, scientific solutions offer to harness these massive, heterogeneous and complex datasets to obtain more meaningful information. Moreover, machine learning algorithms can play a tremendous part in creating a statistical prediction-based model. The aim of this paper is to identify the prevalence of diabetes related to long-term complications among patients with type-2 diabetes mellitus. The processing and statistical analysis require machine learning environment known as Scikit-Learn, Pandas for Python, and R-Studio for R. In this work, machine learning approaches such as decision tree, random forest for developing classification system-based prediction model to assess type-2 diabetes mellitus chronic diseases have been studied. Additionally, we have proposed an algorithm which is solely based on random forest and tried to detect the complicated areas of type-2 diabetes patients.

Background and objectives: Myasthenia gravis (MG) and Guillain&ndash, Barr&eacute, Syndrome (GBS) are autoimmune neuromuscular disorders that may present as neuromuscular emergencies requiring mechanical ventilation and critical care. Comparative outcomes of these disease processes, once severe enough to require mechanical ventilation, are not known. In this study, we compared the patients requiring mechanical ventilation in terms of in-hospital complications, length of stay, disability, and mortality between these two disease entities at a national level. Materials and Methods: Mechanically ventilated patients with primary diagnosis of MG (n = 6684) and GBS (n = 5834) were identified through retrospective analysis of Nationwide Inpatient Sample (NIS) database for the years 2006 to 2014. Results: Even though mechanically ventilated MG patients were older (61.0 &plusmn, 19.1 versus 54.9 &plusmn, 20.1 years) and presented with more medical comorbidities, they had lower disease severity on admission, as well as lower in-hospital complications sepsis, pneumonia, and urinary tract infections as compared with GBS patients. In the multivariate analysis, after adjusting for confounders including treatment, GBS patients had significantly higher disability (odds ratio (OR) 15.6, 95% confidence interval (CI) 10.9&ndash, 22.2) and a longer length of stay (OR 3.48, 95% CI 2.22&ndash, 5.48). There was no significant difference in mortality between the groups (8.45% MG vs. 10.0% GBS, p = 0.16). Conclusion: Mechanically ventilated GBS patients have higher disease severity at admission along with more in-hospital complications, length of stay, and disability compared with MG patients. Potential explanations for these findings include delay in the diagnosis, poor response to immunotherapy particularly in patients with axonal GBS variant, or longer recovery time after nerve damage.

Cancer is the second deadliest disease listed by the WHO. One of the major causes of cancer disease is tobacco and consumption possibly due to its main component, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A plethora of studies have been conducted in the past aiming to decipher the association of NNK with other diseases. However, it is strongly linked with cancer development. Despite these studies, a clear molecular mechanism and the impact of NNK on various system-level networks is not known. In the present study, system biology tools were employed to understand the key regulatory mechanisms and the perturbations that will happen in the cellular processes due to NNK. To investigate the system level influence of the carcinogen, NNK rewired protein&ndash, protein interaction network (PPIN) was generated from 544&nbsp, reported proteins drawn out from 1317 articles retrieved from PubMed. The noise was removed from PPIN by the method of modulation. Gene ontology (GO) enrichment was performed on the seed proteins extracted from various modules to find the most affected pathways by the genes/proteins. For the modulation, Molecular COmplex DEtection (MCODE) was used to generate 19 modules containing 115 seed proteins. Further, scrutiny of the targeted biomolecules was done by the graph theory and molecular docking. GO enrichment analysis revealed that mostly cell cycle regulatory proteins were affected by NNK.

One of the most prominent and metabolically the most active organ of human body is liver, whose formation is built upon subtle organic compounds and responsible for storing the energy of a living body. Damaging this organ could lead to liver failure and possibly imply to a gruesome death. An early detection of primary causes of liver failure could revoke the adverse effect of liver diseases. Several metabolic compounds of human body such as Bilirubin, Total Proteins, Albumin, Alkaline, Alamine, Asparatate and outer factors such as gender, age etc. are considered as vital elements to find possible liver disease patient. In this paper, we have attempted to analyze the causal factors behind liver disease statistically and bring out the most significant factors. Again, we have introduced a reduced model based on the significance of logistic regression analysis, where we successfully eliminated highly co-related variables to get rid of multi co-linearity. A comparison has been conducted on the basis of the performance of the various machine learning and deep learning algorithms.

In today’s era, most of the people are suffering with chronic diseases because of their lifestyle, food habits and reduction in physical activities. Diabetes; is one of the most common chronic diseases which is happened to the people of all ages. Diabetes complication arises in human body due to increase of blood glucose (sugar) level than the normal level. Type-2 diabetes is considered as one of the most prevalent endocrine disorders. Type-2 diabetes is considered one of the most prevalent endocrine disorders. In this circumstance, we have tried to apply Machine learning algorithm to create the statistical prediction based model that people having diabetes can aware of their prevalence. The aim of this paper is to detect the prevalence of diabetes relevant complications among patients with type-2 diabetes mellitus. The processing and statistical analysis we used Scikit-Learn, Pandas for Python. We also have used unsupervised Machine Learning approaches known as Artificial Neural Network (ANN) and K-means Clustering for developing classification system based prediction model to judge type-2 diabetes mellitus chronic diseases.

The association of interleukin-6 (IL-6)-174G C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association. A total of 13 studies, including the current one, involving 3291 RA cases and 3812 controls were analyzed. Out of the 13 studies, 6 were from Asian, 6 from Caucasian and 1 from a mixed population. Our case-control study showed significant association of IL-6-174G C SNP with increased RA risk: allelic (OR = 3.750, 95% CI = 1.800-7.813, p 0.001); dominant (OR = 2.800, 95% CI = 1.167-6.721, p = 0.021); and recessive (OR = 36.72, 95% CI = 2.004-672.7, p = 0.015). The meta-analysis revealed the increased RA risk associated with IL-6-174G C SNP in overall population: allelic (OR = 1.650, 95% CI = 1.169-2.329, p = 0.004); homozygous (OR = 1.380, 95% CI = 0.906-2.101, p = 0.133); heterozygous (OR = 1.559, 95% CI = 1.001-2.428, p = 0.049); dominant (OR = 1.663, 95% CI = 1.078-2.567, p = 0.022); and recessive (OR = 1.366, 95% CI = 0.964-1.935, p = 0.079). Subgroup analysis also showed this polymorphism to be associated with increased RA risk in Asian population: allelic (OR = 3.724, 95% CI = 1.361-10.190, p = 0.010); dominant (OR = 3.823, 95% CI = 1.320-11.074, p = 0.013); and recessive (OR = 4.357, 95% CI = 1.634-11.623, p = 0.003), but not in Caucasian population. This meta-analysis shows that IL-6-174G C SNP is significantly associated with increased RA risk in overall, and specifically in Asian population.

Gall bladder Carcinoma (GBC) is the fifth most common cancer of the digestive tract and frequently diagnosed in late stage of disease. Estimation of circulating free DNA (cfDNA) in serum has been applied as a "liquid biopsy" in several deep seated malignancies. Its value in diagnosis of gall bladder carcinoma has not been studied. The present study was designed to assess the role of cfDNA in the diagnosis of GBC and correlate levels with the TNM stage. Serum was collected from 34 patients with GBC and 39 age and sex matched controls including 22 cholecystitis and 17 healthy individuals. Serum cfDNA levels were measured through quantitative polymerase chain reaction (qPCR) by amplification of β-globin gene. Performance of the assay was calculated through the receiver operating characteristic (ROC) curve. The cfDNA level was significantly lower in healthy controls and cholecystitis (89.32 ± 59.76 ng/ml, 174.21 ± 99.93 ng/ml) compared to GBC (1245.91 ± 892.46 ng/ml, p =

Expression of various cytochrome P450s (CYPs) in mammalian brain cells is well documented. However, such studies are hampered in neural/glial cells of human origin due to nonavailability of human brain cells. To address this issue, we investigated the expression and inducibility of CYP2C8 and CYP3A4 and their responsiveness against cyclophosphamide (CPA) and organophosphorus pesticide monocrotophos (MCP), a known developmental neurotoxicant in human neural (SH-SY5Y) and glial (U373-MG) cell lines. CPA induced significant expression of CYP2C8 and CYP3A4 in both types of cells in a time-dependent manner. Neural cell line exhibited relatively higher constitutive and inducible expression of CYPs than the glial cell line. MCP exposure alone could not induce the significant expression of CYPs, whereas the cells preexposed to CPA showed a significant response to MCP. Similar to the case of CPA induced expressions, neural cells were found to be more vulnerable than glial cells. Our data indicate differential expressions of CYPs in cultured human neural and glial cell lines. The findings were synchronized with protein ligand docking studies, which showed a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR and PXR. Similarly, the known CYP inducer CPA has also shown significant high docking scores with the two studied CYP regulators. We also observed a significant induction in reactive oxygen species (ROS), lipid peroxides (LPO), micronucleus (MN), chromosomal aberration (CA), and reduction in reduced glutathione (GSH) and catalase following the exposure of MCP. Moreover, the expressions of apoptotic markers such as caspase-3, caspase-9, Bax, and p53 were significantly upregulated, whereas the levels of antiapoptotic marker, Bcl2, was downregulated after the exposure of MCP in both cell lines. These findings confirm the involvement of ROS-mediated oxidative stress, which subsequently triggers apoptosis pathways in both human neural (SH-SY5Y) and glial (U373-MG) cell lines following the exposure of MCP.

Hepatotoxicity is a severe problem generally faced by tuberculosis (TB) patients. It is a well-known adverse reaction due to anti-TB drugs in TB patients undergoing long-term treatment. The studies published previously have explored the connection of N-acetyltransferase 2 (NAT2) gene polymorphisms with isoniazid-induced hepatotoxicity, but the results obtained were inconsistent and inconclusive. A comprehensive trial sequence meta-analysis was conducted employing 12 studies comprising 3613 controls and 933 confirmed TB cases using the databases namely, EMBASE, PubMed (Medline) and Google Scholar till December 2017. A significant association was observed with individuals carrying variant allele at position 481C>T (T vs. C: P = 0.001; OR = 1.278, 95% CI = 1.1100–1.484), at position 590G>A (A vs. G: P = 0.002; OR = 1.421, 95% CI = 1.137–1.776) and at position 857G>A (A vs. G: P = 0.0022; OR = 1.411, 95% CI = 1.052–1.894) to higher risk of hepatotoxicity vis-à-vis wild-type allele. Likewise, the other genetic models of NAT2 gene polymorphisms have also shown increased risk of hepatotoxicity. No evidence of publication bias was observed. These results suggest that genetic variants of NAT2 gene have significant role in isoniazid induced hepatotoxicity. Thus, NAT2 genotyping has the potential to improve the understanding of the drug–enzyme metabolic capacity and help in early predisposition of isoniazid-induced hepatotoxicity.

Angiotensin-converting enzyme (ACE) gene is indispensable for endothelial control and vascular tone regulatory systems, usually affected in Systemic Lupus Erythematosus (SLE). ACE insertion/deletion (I/D) polymorphism may influence the progress of SLE. Earlier studies have investigated this association without any consistency in results. We performed this meta-analysis to evaluate the precise association between ACE I/D polymorphism and SLE susceptibility. The relevant studies were searched until December, 2017 using Medline (PubMed), Google-Scholar and EMBASE search engines. Twenty-five published studies involving 3,308 cases and 4,235 controls were included in this meta-analysis. Statistically significant increased risk was found for allelic (D vs. I: p = 0.007; OR = 1.202, 95% CI = 1.052–1.374), homozygous (DD vs. II: p = 0.025; OR = 1.347, 95% CI = 1.038–1.748), dominant (DD+ID vs. II: p = 0.002; OR = 1.195, 95% CI = 1.070–1.334), and recessive (DD vs. ID+II: p = 0.023; OR = 1.338, 95% CI = 1.042–1.718) genetic models. Subgroup analysis stratified by Asian ethnicity revealed significant risk of SLE in allelic (D vs. I: p = 0.045; OR = 1.238, 95% CI = 1.005–1.525) and marginal risk in dominant (DD+ID vs. II: p = 0.056; OR = 1.192, 95% CI = 0.995–1.428) models; whereas, no association was observed for Caucasian and African population. Publication bias was absent. In conclusion, ACE I/D polymorphism has significant role in overall SLE risk and it can be exploited as a prognostic marker for early SLE predisposition.

N-acetylcysteine is a mucolytic drug which is commonly used as an antidote for acetaminophen toxicity. It is a thiol compound, which acts as a donor of cysteine, leading to replenishment of glutathione and thus acts as an antioxidant. It also has anti-inflammatory effects, alters the levels of neurotransmitters, inhibits proliferation of fibroblasts and keratinocytes and causes vasodilatation. Due to these actions, n-acetylcysteine has found use in several dermatologic conditions in systemic and topical form. The drug has been used as an adjuvant in the management of conditions such as toxic epidermal necrolysis, drug hypersensitivity syndrome, trichotillomania, skin picking disorders and onychotillomania, ichthyoses, contact dermatitis, atopic dermatitis, melasma, pseudoporphyria, connective tissue diseases, wound healing and alopecia. It also has a role in protection from radiation-induced skin damage including photo-ageing, photocarcinogenesis and radiation dermatitis. Most indications in dermatology are supported by case reports, small case series and small trials. Higher quality of evidence is needed for its wider use. The drug is cheap and is generally safe with few adverse effects. Thus a greater role is possible for use of n-acetylcysteine in various skin conditions. This review explores the various uses of n-acetylcysteine in the field of dermatology, the evidence supporting the same, the possible mechanisms of action and the adverse effects of the drug.

Lupus vulgaris, the commonest form of tuberculosis of the skin, presents with a plaque that enlarges slowly with advancing edges while showing atrophy at other areas. It may be acquired by the blood stream, via lymph, by contiguous spread or from external inoculation. We describe a case of lupus vulgaris with a large erythematous-scaly plaque of 44 × 26 cm over the back and a similar 7 × 5 cm plaque over the right thigh. The plaque over the back was gradually progressive for the previous ten years and showed scarring and atrophy at places. Histopathology of the area showed caseating granulomas with Langhans giant cells, epitheloid cells and lymphocytes. A diagnosis of lupus vulgaris was made. This case is being presented owing to the large size of the lesion.

Dopamine (DA) is a classical neurotransmitter and dysfunction in its synaptic handling underlies many neurological disorders, including addiction, depression, and neurodegeneration. A key to understanding DA dysfunction is the accurate measurement of dopamine uptake by dopaminergic neurons. Current methods that allow for the analysis of dopamine uptake rely on standard multiwell-plate based ELISA, or on carbon-fibre microelectrodes used in in vivo recording techniques. The former suffers from challenges associated with automation and analyte degradation, while the latter has low throughput and is not ideal for laboratory screening. In response to these challenges, we introduce a digital microfluidic platform to evaluate dopamine homeostasis in in vitro neuron culture. The method features voltammetric dopamine sensors with limit of detection of 30 nM integrated with cell culture sites for multi-day neuron culture and differentiation. We demonstrate the utility of the new technique for DA uptake assays featuring in-line culture and analysis, with a determination of uptake of approximately ∼32 fmol in 10 min per virtual microwell (each containing ∼200 differentiated SH-SY5Y cells). We propose that future generations of this technique will be useful for drug discovery for neurodegenerative disease as well as for a wide range of applications that would benefit from integrated cell culture and electroanalysis.

Background: Despite the frequent occurrence of brain death in intensive care unit, the prevalence rate of brain death in ischemic stroke (IS), intracranial hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is not known at national level. In addition the prevalence of cardiac arrest in these patients is not established. Methods: From 2012, ICD-9-CM includes a specific code for brain death (348.82). Brain death patients were identified from the nationwide in-patient sample database for the years 2012 to 2014. Associated in-hospital cardiac arrest patients were also identified under each category. Demographics, medical comorbidities, in-hospital complications, procedures, length of stay and hospital charges were compared. Results: Rate of brain death was highest in SAH related mortality (22%, 3255 brain deaths/ 14620 in-hospital mortality), followed by ICH, (12.5%, 5760 brain deaths/ 45945 in-hospital mortality) and ischemic stroke (3%, 1840 brain death/62285 in-hospital mortality). Majority of the patients had brain death secondary to neurological insult (ICH n=5260, 91.3%; SAH n= 2625 (80.6%) and IS n=1640, 89.1%) without any secondary diagnosis of in-hospital cardiac arrest. Length of stay was shorter in patients with SAH and ICH (mean 2.92±4.13 days and 2.53±3.56 days respectively) compared to IS patients (mean 4.93 ± 10.2 days, p < 0.001) suggesting brain death is an early event in hemorrhagic stroke. Conclusion: Brain death in the majority of cerebrovascular patients occurs as a result of primary neurological insult without associated cardiac arrest. It occurs much earlier in hemorrhagic stroke compared to ischemic stroke.

Caspase-3 has been identified as a key mediator of neuronal apoptosis. The present study identifies caspase-3 as a common player involved in the regulation of multineurodegenerative disorders, namely, Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). The protein interaction network prepared using STRING database provides a strong evidence of caspase-3 interactions with the metabolic cascade of the said multineurodegenerative disorders, thus characterizing it as a potential therapeutic target for multiple neurodegenerative disorders.In silicomolecular docking of selected nonpeptidyl natural compounds against caspase-3 exposed potent leads against this common therapeutic target. Rosmarinic acid and curcumin proved to be the most promising ligands (leads) mimicking the inhibitory action of peptidyl inhibitors with the highest Gold fitness scores 57.38 and 53.51, respectively. These results were in close agreement with the fitness score predicted using X-score, a consensus based scoring function to calculate the binding affinity. Nonpeptidyl inhibitors of caspase-3 identified in the present study expeditiously mimic the inhibitory action of the previously identified peptidyl inhibitors. Since, nonpeptidyl inhibitors are preferred drug candidates, hence, discovery of natural compounds as nonpeptidyl inhibitors is a significant transition towards feasible drug development for neurodegenerative disorders.

Human aldose reductase (hAR) is the key enzyme in sorbitol pathway of glucose utilization and is implicated in the etiology of secondary complications of diabetes, such as, cardiovascular complications, neuropathy, nephropathy, retinopathy, and cataract genesis. It reduces glucose to sorbitol in the presence of NADPH and the major cause of diabetes complications could be the change in the osmotic pressure due to the accumulation of sorbitol. An activated form of hAR (activated hAR or ahAR) poses a potential obstacle in the development of diabetes drugs as hAR-inhibitors are ineffective against ahAR. The therapeutic efficacy of such drugs is compromised when a large fraction of the enzyme (hAR) undergoes conversion to the activated ahAR form as has been observed in the diabetic tissues. In the present study, attempts have been made to employ systems biology strategies to identify the elementary nodes of human polyol metabolic pathway, responsible for normal metabolic states, followed by the identification of natural potent inhibitors of the activated form of hAR represented by the mutant C298S for possible antidiabetic applications. Quantum Mechanical Molecular Mechanical docking strategy was used to determine the probable inhibitors of ahAR. Rosmarinic acid was found as the most potent natural ahAR inhibitor and warrants for experimental validation in the near future.

Key Clinical Message Wound botulism is a potentially lethal condition that can cause paralysis. Its association with black tar heroin is a well‐established fact. It is essential to alert clinicians in recognizing the patients with history of injection drug abuse presenting with clinical features of botulism early on admission for prompt diagnosis and treatment.

Metastatic melanoma is a least common form of cancer as it accounts only for 1% of all cancer cases. But, it is most deadly in nature and is haunting mankind for long emotionally as well as economically. The sites for the onset of the disease are pigment-producing cells of the skin, mucosa, eye etc. It has the potential to spread other sites like subcutaneous tissue, lymph nodes, lungs, liver, bone and brain. The United States Food & Drug Administration has approved various drug molecules from time to time. The molecules (Dabrafenib-BRAF inhibitor and Trametinib-MEK inhibitor) have proved their credentials alone and in combination as well. These molecules have demonstrated good results for various end points like median progression free survival, overall survival, objective response etc. The median progression free survival for patients using dabrafenib and trametinib were 5.1 and 4.8 months, respectively (administered singly). It has increased to 11.4 months in the combination treatment “dabrafenib + trametinib”, which is approximately 104% and 138% greater than dabrafenib and trametinib treated groups alone. Similarly, the overall survival rate and objective response rate for the patients administered with “dabrafenib + trametinib” have been increased by 72% 64%, respectively. All these increments in these parameters were for a short period of time as the molecules were unable to withstand the pressure of resistance developed in the patients. So, the current review suggests the use of BRAF and MEK inhibitors as intermittent therapy along with heat shock protein 90 (HSP90) molecules.

Purpose: Earlier studies have shown that tumor necrosis factor (TNF) -308 G>A (rs1800629) gene polymorphism is implicated in the susceptibility to leprosy, but results were inconsistent. Methods: A meta-analysis of 14 studies involving 3327 leprosy cases and 3203 controls was performed to appraise the association of TNF -308 G>A polymorphism with leprosy using MEDLINE (PUBMED), EMBASE, and Google Scholar web databases. Results: Overall, no significant association was observed in allelic (A vs. G: P=0.068; OR = 0.836, 95% CI = 0.689–1.013), homozygous (AA vs. GG: P=0.394; OR = 0.810, 95% CI = 0.499–1.315), heterozygous (GA vs. GG: P=0.059; OR = 0.780, 95% CI = 0.603–1.010), dominant (AA + GA vs. GG: P=0.067; OR = 0.797, 95% CI = 0.625–1.016), and recessive (AA vs. GG + GA: P=0.594; OR = 0.877, 95% CI = 0.542– 1.420) genetic models. Subgroup analysis showed no association in Asians. Whereas, reduced risk was found in allelic contrast (A vs. G: P=0.014; OR = 0.832, 95% CI = 0.718–0.963) and dominant models (AA + GA vs. GG: P=0.004; OR = 0.790, 95% CI = 0.673–0.928) of the mixed population. Conclusions: TNF -308 G>A polymorphism is not associated with leprosy risk in the overall population. However, subgroup analysis demonstrated protective effect of the said polymorphism in leprosy risk in the Latin American population, but showed no association in the Asians.

Background: Currently, endovascular treatment is advocated for middle cerebral artery (MCA) occlusions, however not much is known about the natural history of an M1 compared to an M2 occlusion. Objective: To compare the clinical outcome in endovascularly treated patients with proximal vessel occlusion (M1) versus a more distal occlusion (M2) among patients with ischemic stokes in a negative trial. Methods: Data from Interventional Management of Stroke trial (IMS-III) for patients with acute ischemic stroke with distal MCA (mainly M2 and beyond) occlusions diagnosed by either computed tomographic angiography (CTA) or catheter angiography were analyzed. NIHSS at admission, baseline characteristics, infarct volume at baseline and outcome at 90 days (mRS score) were compared between the two groups. Favorable outcome was defined by discharge modified Rankin scale (mRS) score of 0-2, at 3 months. Multivariate logistical regression was performed to compare the outcomes after adjusting for potential confounders. Results: Of the 434 from the endovascular therapy group, 215 (49.5%) and 98 (22.5%) patients had M1 and M2 occlusion respectively. Patients with M1 occlusion had higher mean NIHSS at admission (18.76± 4.94 versus 17.37± 5.72, P-value = 0.029) and higher infarct volume (105.92 ± 113.23 versus 49.67 ± 63.42, P-value = 0.000) . Rate of favorable outcome defined by mRS at discharge was lower among patients with M1 (31.53%vs.46.67%p-value = 0.0128) . After adjusting for age, sex, total NIHSS score at admission, hepato-biliary disorders, anticoagulants, antiplatelet, NSAIDS, patients with M1 occlusion had higher rates of poor outcomes; odds ratio (OR) 1.819 (confidence interval [CI] 1.032- 3.205, P=0.03860). Conclusions: In patients enrolled in IMS-III trial, an M1 occlusion demonstrated a larger tissue infarct size and a lower rate of favorable outcome than an M2 occlusion, given the negative results of the trial, these findings reflect the natural history of these two occlusion sites.

Objective: The middle cerebral artery (MCA) occlusion is the most commonly treated vessel with mechanical thrombectomy. The MCA is defined in segments. The M1 segment is classically defined as the horizontal segment extending from the internal carotid artery bifurcation to the Sylvian fissure. It is assumed that the MCA bifurcation occurs in the M1-2 junction, and terms M2 occlusion and division occlusion are used indistinctly, however it is not known how often the MCA bifurcation occurs within the M1 segment. Methodology: Consecutive patients undergoing cerebral angiograms were selected between 2011 and 2015. The anatomy of the MCA was classified as classical, when the bifurcation occurs at the M1-2 junction and non-classical when the bifurcation occurs within the M1 segment, having the M1 segment a pre-bifurcation (main trunk) and a post-bifurcation (division) occlusion. Demographics and vascular risk factors were also collected. Results: A total of 500 patients underwent a cerebral angiogram and were studied. The classical pattern was found in 47.5% patients on the left and 53.5% patients on the right. There were no differences between the classical and non-classical anatomical pattern when demographics or vascular risk factors were compared. Conclusion: In our series of patients the non-classical pattern was found in almost 50.0% of the patients undergoing a cerebral angiogram. In the endovascular treatment of acute ischemic stroke, it is necessary to develop a new classification as an M1 occlusion could relate to a post-bifurcation (division) or a pre-bifurcation (main trunk) occlusion and comparison of these groups may lead to confounding results.

Background: Clinical characteristics and outcomes for patients with intracerebral hemorrhage and underlying chronic kidney disease (CKD) are not well determined. We hypothesized rate adverse events and in-hospital mortality is higher in patients with intracerebral hemorrhage and underlying renal disease. Objective: To determine the Outcomes for intracerebral hemorrhage stroke patients with renal failure as comorbidity in the United States Methods: We analyzed the data from Nationwide Inpatient Sample (2009-2011) for all intracerebral hemorrhage stroke patients with or without renal failure as comorbidity. Patients were identified using the International Classification of Disease, Ninth Revision. Baseline characteristics, in-hospital complications including myocardial infarction), sepsis, pneumonia, deep venous thrombosis, urinary tract infections, and discharge outcomes (mortality, minimal disability, and moderate-to-severe disability) were compared between the two groups. All in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis. Results: Of the 33521 patients with intracerebral hemorrhage stroke, 3899 (11.6%) had renal failure as comorbidity. Patients with underlying renal disease were higher rates for in hospital complications like myocardial infarction (3.64% versus 2.03%, P≤.0001) , sepsis (5.82% versus 3.14%, P≤.0001) , pneumonia (6.92% versus 5.18%, P≤.0001) , deep venous thrombosis (1.67 % versus 1.17%, P≤ .0.0078) , urinary tract infections (16.41% versus 15.08%, P≤ 0.0293) and hypernatremia (8.62% versus 4.98%, P≤ In multivariate analysis adjusted for baseline cormorbitdities and in hospital complications, intracerebral hemorrhage patients with underlying renal disease had higher in hospital mortality (OR 1.146 (95% confidence interval (CI) 1.058- 1.240p-value=0.0008) , while there is no statistically significant difference for minimal/moderate disability between two groups ( OR = 0.980 (95% CI 0.896- 1.072 p-value=0.6571). Conclusions: Intracerebral hemorrhage patients with underlying renal disease have higher rate of in hospital complications and mortality. Future prospective studies are indicated to study this finding.

Lipoid proteinosis (LP) is a rare progressive autosomal recessive disorder caused by mutations in the extracellular matrix protein 1 gene present on chromosome 1q21. It is characterized by infiltration of hyaline material into the skin, mucosae, and internal organs. Patients present with a classical history of repeated blistering, skin scarring, beaded eyelid papules, waxy papules over the body, and laryngeal and tongue infiltration leading to hoarseness of voice and restricted tongue movement. A variety of ocular manifestations have been described in association with LP. We report a case of a 10-year-old female child with typical features suggestive of LP associated with unilateral esotropia. The case is reported here for its rarity and uncommon association with esotropia hitherto not documented. Dermoscopic findings of the case are also discussed.

Key Clinical Message In our patient with Steele–Richardson–Olszewski syndrome presenting with apraxia of eyelid opening, there is a possibility to be readily confused with conditions presenting in similar pattern such as blepharospasm and eyelid ptosis. Therefore, it is essential to correlate the clinical findings with electromyographic recordings and dopamine transporter scan (DaT).