Efficient Generation of Skin Organoids from Pluripotent Cells via Defined Extracellular Matrix Cues and Morphogen Gradients in a Spindle-Shaped Microfluidic Device.

Pluripotent stem cell-derived skin organoids (PSOs) emerge as a developmental skin model that is self-organized into multiple components, such as hair follicles. Despite their impressive complexity, PSOs are currently generated in the absence of 3D extracellular matrix (ECM) signals and have several major limitations, including an inverted anatomy (e.g., epidermis inside/dermis outside). In this work, a method is established to generate PSOs effectively in a chemically-defined 3D ECM environment. After examining various dermal ECM molecules, it is found that PSOs generated in collagen -type I (COLI) supplemented with laminin 511 (LAM511) exhibit increased growth compared to conventional free-floating conditions, but fail to induce complete skin differentiation due in part to necrosis. This problem is addressed by generating the PSOs in a 3D bioprinted spindle-shaped hydrogel device, which constrains organoid growth longitudinally. This culture system significantly reduces organoid necrosis and leads to a twofold increase in keratinocyte differentiation and an eightfold increase in hair follicle formation. Finally, the system is adapted as a microfluidic device to create asymmetrical gradients of differentiation factors and improves the spatial organization of dermal and epidermal cells. This study highlights the pivotal role of ECM and morphogen gradients in promoting and spatially-controlling skin differentiation in the PSO framework.

Machine Learning Model Based on Insulin Resistance Metagenes Underpins Genetic Basis of Type 2 Diabetes.

Insulin resistance (IR) is considered the precursor and the key pathophysiological mechanism of type 2 diabetes (T2D) and metabolic syndrome (MetS). However, the pathways that IR shares with T2D are not clearly understood. Meta-analysis of multiple DNA microarray datasets could provide a robust set of metagenes identified across multiple studies. These metagenes would likely include a subset of genes (key metagenes) shared by both IR and T2D, and possibly responsible for the transition between them. In this study, we attempted to find these key metagenes using a feature selection method, LASSO, and then used the expression profiles of these genes to train five machine learning models: LASSO, SVM, XGBoost, Random Forest, and ANN. Among them, ANN performed well, with an area under the curve (AUC) > 95%. It also demonstrated fairly good performance in differentiating diabetics from normal glucose tolerant (NGT) persons in the test dataset, with 73% accuracy across 64 human adipose tissue samples. Furthermore, these core metagenes were also enriched in diabetes-associated terms and were found in previous genome-wide association studies of T2D and its associated glycemic traits HOMA-IR and HOMA-B. Therefore, this metagenome deserves further investigation with regard to the cardinal molecular pathological defects/pathways underlying both IR and T2D.

Clinical Profile and Predictors of In-Hospital Mortality in De Novo Convulsive Status Epilepticus in the Elderly Populace.

Background and Purpose: De novo status epilepticus (SE) had worse outcome in comparison to the patients with SE who had previous history of epilepsy. The aim of the present study was to identify clinical features of de novo convulsive status epilepticus (CSE) and the predictors of in-hospital mortality. Methods: Seventy-seven elderly (≥60 years of age) hospitalized patients with de novo CSE were evaluated for clinical profile, aetiologies and predictors of in-hospital mortality. Results: The average age of the participants in the study was 65.96±6.72 years. In de novo CSE, the most common aetiologies were acute symptomatic in 68.8% of cases, followed by remote symptomatic in 24.7%. In-hospital mortality in the de novo CSE in the elderly was 30 (38.9%) in our series. Stroke was the leading cause of death among them (acute stroke in 23 cases and old infarct in 1 case), followed by post-traumatic (n=4) and CNS infection (n=2). On multivariate analysis, it was found that variables significantly related to mortality in de novo CSE were low Glasgow coma scale (GCS) (adjusted odds ratio [AOR], 53.5; 95% confidence interval [CI], 5.17-555.14; p=0.001) and lack of response to first line treatment (AOR, 0.06; 95% CI, 0.01-0.50; p=0.01). Conclusions: In-hospital mortality in de novo CSE patients was linked to a low GCS and a lack of response to first-line therapy. The most efficient strategy to prevent in-hospital mortality in the elderly is to treat de novo CSE promptly and aggressively in the setting of stroke.

Are the labour rooms of primary healthcare facilities capable of providing basic delivery and newborn services? A cross-sectional study.

OBJECTIVES: The study aimed to assess the functionality of labour rooms by evaluating the labour room infrastructure with reference to the standard guidelines, the status of the availability of human resources, the availability of essential equipment and consumables in the labour room and by documenting the knowledge of the healthcare provider in terms of labour room practices. The study also explored the facility parameters associated with its delivery load taking the facility as a unit of analysis. DESIGN: A cross-sectional analytical study. SETTING: India has realised the importance of improving the quality of care in public health facilities, and steps are being taken to make healthcare more responsive to women's needs. With an increase in the proportion of institutional deliveries in India, the outcome of the delivery process can be improved by optimising the health facility components. PARTICIPANTS: The study was conducted in 52 health facilities and healthcare providers involved in the delivery process in the selected facilities. RESULTS: The infrastructure of the facilities was found to be the best for medical college followed by district hospitals, Community Health Centres (CHCs), Primary Health Centres (PHCs) and subcentres. Similar findings were observed in terms of the availability of equipment and consumables. Lack of healthcare providers was observed as only 20% of the posts for health personnel were fulfilled in CHCs followed by PHCs, subcentres and district hospitals where 43, 50 and 79% of the available vacancies were fulfilled. The level of knowledge of healthcare providers in terms of partograph, active management of the third stage of labour and post-partum haemorrhage ranged as per their designation. The specialists were the most knowledgeable while the Auxiliary Nurse Midwife (AMNs) were the least. All the components of structural capacity, i.e. infrastructure (r 2 = 0.377, P value < 0.001), equipment and consumable (r 2 = 0.606, P value < 0.001) and knowledge of healthcare providers (r 2 = 0.456, P value < 0.001) along with the overall facility score were positively correlated with the average delivery load of the health facility. The results from multivariate linear regression depict significant relation between the delivery load and availability of equipment and consumables (t = 4.015, P < 0.01) and with the knowledge of healthcare providers (t = 2.129, P = 0.039). CONCLUSIONS: The higher facilities were better equipped to provide delivery and newborn care. A higher delivery load was found at high-level facilities which can be attributed to better infrastructure, adequate supply of equipment and consumables and availability of trained human resources.

Aortic dissection in a young male with isolated interrupted aortic arch: an unusual association.

Interruption of the aortic arch (IAA) is a rare congenital anomaly which has been infrequently documented in the adult population. Aortic dissection (AD) is an emergency often presenting as acute chest pain and warranting urgent intervention. A 32-year-old male presented to Emergency Department with acute chest pain. Clinical examination revealed feeble pulses in bilateral lower limbs with a blood pressure difference between upper and lower limbs. Two-dimensional Echocardiography was suggestive of IAA with AD in the descending thoracic aorta. This was confirmed on computed tomography scan of the aorta which revealed complete interruption of the aortic arch distal to left subclavian artery along with the presence of an intimo-medial flap in descending thoracic aorta. A diagnosis of IAA with AD was made. The patient underwent an urgent aortic repair surgery following which he has been largely asymptomatic. A suspicion of AD should always be made in any patient presenting with acute onset chest pain radiating to the back along with accelerated hypertension/feeble pulses in extremity. Occurrence of AD in an adult with IAA is a distinct rarity and has been documented only thrice.

Breast Cancer Image Classification: A Review.

BACKGROUND: Breast cancer represents uncontrolled breast cell growth. Breast cancer is the most diagnosed cancer in women worldwide. Early detection of breast cancer improves the chances of survival and increases treatment options. There are various methods for screening breast cancer, such as mammogram, ultrasound, computed tomography and Magnetic Resonance Imaging (MRI). MRI is gaining prominence as an alternative screening tool for early detection and breast cancer diagnosis. Nevertheless, MRI can hardly be examined without the use of a Computer-Aided Diagnosis (CAD) framework, due to the vast amount of data. OBJECTIVE: This paper aims to cover the approaches used in the CAD system for the detection of breast cancer. METHODS: In this paper, the methods used in CAD systems are categories into two classes: the conventional approach and artificial intelligence (AI) approach. RESULTS: The conventional approach covers the basic steps of image processing, such as preprocessing, segmentation, feature extraction and classification. The AI approach covers the various convolutional and deep learning networks used for diagnosis. CONCLUSION: This review discusses some of the core concepts used in breast cancer and presents a comprehensive review of efforts in the past to address this problem.

Central retinal artery occlusion as the presenting manifestation of invasive rhino-orbital-cerebral mucormycosis.

Rhino-orbital-cerebral mucormycosis (ROCM) is a rare but devastating fungal infection caused by filamentous fungi of the family Mucoraceae. We report a rare case of unilateral ROCM in a diabetic patient where central retinal artery occlusion (CRAO) was the first manifestation of the disease. Magnetic resonance imaging scan revealed orbital and intracranial spread of the disease. Definitive diagnosis was established by culture of the biopsy specimen which showed Rhizopus oryzae on Sabouraud's dextrose agar. The patient was successfully treated with extensive debridement of sinuses and intravenous liposomal amphotericin B; however, the left eye remained blind following the CRAO.

CHA2DS2-VASc score as a novel predictor for contrast-induced nephropathy after percutaneous coronary intervention in acute coronary syndrome.

BACKGROUND: CHA2DS2-VASc score, used for atrial fibrillation to assess the risk of embolic complications, have shown to predict adverse clinical outcomes in acute coronary syndrome (ACS), irrespective of atrial fibrillation. This study envisaged to assess the predictive role of CHA2DS2-VASc score for contrast-induced nephropathy (CIN) in patients with ACS undergoing percutaneous coronary intervention (PCI). METHODS: A total of 300 consecutive patients with ACS undergoing PCI were enrolled in this study. CHA2DS2-VASc score was calculated for each patient. These patients were divided into two groups as Group 1 (with CIN) and Group 2 (without CIN). CIN was defined as increase in serum creatinine level ≥0.5 mg/dL or ≥25% increase from baseline within 48 h after PCI. After receiver operating characteristic curve analysis, the study population was again classified into two groups: CHA2DS2-VASc score ≤3 group (Group A) and score ≥4 group (Group B). RESULTS: CIN was reported in 41 patients (13.6%). Patients with CIN had a higher frequency of hypertension, diabetes mellitus, and had a lower left ventricular ejection fraction and baseline estimated glomerular filtration rate. Receiver operating characteristic curve analysis showed good predictive value of CHA2DS2-VASc score for CIN (area under the curve 0.81, 95% CI 0.73-0.90). Patients with a CHA2DS2-VASc score of ≥4 had a higher frequency of CIN as compared with patients with score ≤3 (56.8% vs 4.8%; p = 0.0001) with multivariate analysis demonstrating CHA2DS2-VASc score of ≥4 to be an independent predictor of CIN. CONCLUSION: In patients with ACS undergoing PCI, CHA2DS2-VASc score can be used as a novel, simple, and a sensitive diagnostic tool for the prediction of CIN.

Superior vena cava syndrome due to pacemaker leads: an Indian report with a review of management practices.

Superior vena cava [SVC] syndrome due to pacemaker leads is a distinct diagnostic rarity. It is diagnosed clinically based on constellation of signs and symptoms supported by imaging evidence of SVC obstruction. A 70-year-old male, an ex-smoker, presented with facial and upper limb swelling along with exertional dyspnea. He had undergone transvenous dual chamber rate modulated [DDDR] pacemaker implantation four years back for symptomatic sinus node dysfunction. Imaging demonstrated a hypodense-filling defect in the SVC causing 70-80% luminal narrowing along with presence of collaterals. Patient was managed on anticoagulants and planned for SVC stenting with epicardial pacing which failed. Patient refused to undergo further any further treatment and was subsequently lost to follow-up. To the best of our knowledge, this is the first detailed description of SVC syndrome due to pacemaker leads from India, which was managed medically.

An unusual occurrence of stromal keratitis in dengue fever.

Dengue is a mosquito-borne infection endemic in the tropical and subtropical regions of the world. Classic dengue fever is a self-limiting, influenza-like illness transmitted by Aedes aegypti mosquito. Ophthalmic manifestations though rare can involve both the anterior and posterior segments and are usually associated with the thrombocytopenic state. However, ophthalmic complications such as anterior uveitis and vasculitis suggest immune-mediated pathogenesis. Herein, we report a rare case of stromal keratitis and an unusual occurrence of simultaneous bilateral blindness following dengue fever in a young girl.

An Alternate Vista in Rehabilitation of Cranial Defects: Combining Digital and Manual Techniques to Fabricate a Hybrid Cranioplast.

The desired features of a cranioplast include providing an acceptable contour, continuity with the remaining skull (marginal adaptation), improvising the aesthetic outcome, providing a strengthened prosthesis to avoid fracture in case of repeat trauma, and protecting the remaining neurological structures. Combining digital and manual techniques to fabricate a hybrid polymethylmethacrylate cranioplast during the rehabilitation of a pediatric patient with cranial defect has been described. Utilization of digital techniques (rapid prototyping to obtain skull analog) and manual (hand) sculpting of the prosthesis strengthened with glass fiber enabled the authors to fabricate a hybrid cranioplast. Satisfactory outcome was achieved.

Hypoxia-induced activation of p38 mitogen-activated protein kinase and phosphatidylinositol 3'-kinase signaling pathways contributes to expression of interleukin 8 in human ovarian carcinoma cells.

PURPOSE: Overexpression of interleukin 8 (IL-8) is associated with disease progression in human ovarian cancer. Hypoxia, a common feature in solid tumors, induces IL-8 expression in human ovarian carcinoma cells through activation of nuclear factor-kappa B and activating protein-1. Here we show the upstream components of these signal transduction pathways that lead to IL-8 expression under hypoxia. EXPERIMENTAL DESIGN: We incubated Hey-A8 human ovarian carcinoma cells under hypoxic condition (1% O(2)) and determined hypoxia regulation of phosphatidylinositol 3'-kinase (PI3K)/Akt pathway, mitogen-activated protein kinases (MAPKs), and effects of ras and vascular endothelial growth factor by Western and Northern blots, the use of specific inhibitors, in vitro kinase assays, luciferase reporter genes, and ELISA. RESULTS: While investigating the upstream signaling pathways, we found that Akt kinase and p38 MAPK are activated by hypoxia. Both hypoxia-induced Akt and p38 MAPK functional activity, and IL-8 mRNA and protein expression were reduced with the inhibition of PI3K and p38 MAPK. Oncogenic ras overexpression resulted in an increase in the hypoxia-induced IL-8 expression, whereas the inhibition of ras by transfection of dominant-negative ras inhibited the hypoxia-induced IL-8 expression. CONCLUSIONS: These results show that hypoxia activates ras, PI3K/Akt pathway, and p38 MAPK pathway to enhance IL-8 gene transcription under hypoxia, and suggest these signaling pathways as potential targets for controlling IL-8 expression and angiogenesis by human ovarian carcinoma cells.