Benzo[a]pyrene exposure causes exonal switch resulting in reduced surface CD5 expression in an AHR-dependent manner.

The function of CD5 protein in T cells is well documented, but regulation of its surface-level expression has yet to be fully understood. However, variation in its surface expression is associated with various immunopathological conditions and haematological malignancies. Briefly, expression of an alternate exon E1B of a human endogenous retroviruses (HERV) origin directly downregulates the conventional transcript variant (E1A), as its expression leads to the retention of the resultant protein at the intracellular level (cCD5). A separate promoter governs the expression of E1B and may be influenced by different transcription factors. Hence, we performed in silico transcription factor binding site (TFBS) analysis of the 3 kb upstream region from TSS of exon E1B and found five putative DREs (Dioxin Response elements) with good similarity scores. Further, we observed the upregulation in E1B expression after the exposure of BaP (a dioxin) and the reduction of E1A expression and their respective protein, i.e. sCD5 and cCD5. The binding of AHR at the predicted DRE sites was confirmed by ChIP qPCR and AHR specific inhibitor and gene silencing studies suggested the involvement of AHR in exonal switch. This study indicates that the polycyclic aromatic hydrocarbon decreases the sCD5 expression by upregulating alternative exon expression, which may adversely affect the overall T cell functions.

Optimization of Newtonian fluid pressure in microcantilever integrated flexible microfluidic channel for healthcare application.

The demand for microfluidic pressure sensors is ever-increasing in various industries due to their crucial role in controlling fluid pressure within microchannels. While syringe pump setups have been traditionally used to regulate fluid pressure in microfluidic devices, they often result in larger setups that increase the cost of the device. To address this challenge and miniaturize the syringe pump setup, the researcher introduced integrated T-microcantilever-based microfluidic devices. In these devices, microcantilevers are incorporated, and their deflections correlate with the microchannel's pressure. When the relative pressure of fluid (plasma) changes, the T-microcantilever deflects, and the extent of this deflection provides information on fluid pressure within the microchannel. In this work, finite element method (FEM) based simulation was carried out to investigate the role of material, and geometric parameters of the cantilever, and the fluid viscosity on the pressure sensing capability of the T-microcantilever integrated microfluidic channel. The T-microcantilever achieves a maximum deflection of 127µm at a 5000µm/s velocity for Young's modulus(E) of 360 kPa of PDMS by employing a hinged structure. On the other hand, a minimum deflection of 4.05 × 10-5µm was attained at 5000µm/s for Young's modulus of 1 TPa for silicon. The maximum deflected angle of the T-cantilever is 20.46° for a 360 kPa Young's modulus while the minimum deflection angle of the T-cantilever is measured at 13.77° for 900 KPa at a fluid velocity of 5000µm s-1. The T-cantilever functions as a built-in microchannel that gauges the fluid pressure within the microchannel. The peak pressure, set at 8.86 Pa on the surface of the cantilever leads to a maximum deflection of 0.096µm (approximately 1µm) in the T-cantilever at a 1:1 velocity ratio. An optimized microfluidic device embedded with microchannels can optimize fluid pressure in a microchannel support cell separation.

Cryptococcosis in kidney transplant recipients: Current understanding and practices.

Cryptococcosis is the third most commonly occurring invasive fungal disease in solid organ transplant recipients (SOT). It is caused by encapsulated yeast, Cryptococcus species, predominantly Cryptococcus neoformans and Cryptococcus gattii. Though kidney transplant recipients are at the lowest risk of cryptococcosis when compared to other solid organ transplant recipients such as lung, liver or heart, still this opportunistic infection causes significant morbidity and mortality in this subset of patients. Mortality rates with cryptococcosis range from 10%-25%, while it can be as high as 50% in SOT recipients with central nervous system involvement. The main aim of diagnosis is to find out if there is any involvement of the central nervous system in disseminated disease or whether there is only localized pulmonary involvement as it has implications for both prognostication and treatment. Detection of cryptococcal antigen (CrAg) in cerebrospinal fluid or plasma is a highly recommended test as it is more sensitive and specific than India ink and fungal cultures. The CrAg lateral flow assay is the single point of care test that can rapidly detect cryptococcal polysaccharide capsule. Treatment of cryptococcosis is challenging in kidney transplant recipients. Apart from the reduction or optimization of immunosuppression, lipid formulations of amphotericin B are preferred as induction antifungal agents. Consolidation and maintenance are done with fluconazole; carefully monitoring its interactions with calcineurin inhibitors. This review further discusses in depth the evolving developments in the epidemiology, pathogenesis, diagnostic assays, and management approach of cryptococcosis in kidney transplant recipients.

An Unusual Effect of Hofmeister Series Salts on the Stability of Toxoplasma gondii Ferredoxin NADP+ Reductase.

BACKGROUND: The ionic interactions play an important role in the stabilization of the native conformation of proteins. Toxoplasma gondii Ferredoxin NADP+ Reductase (TgFNR) remains stable at pH 4.0. However, such modulation of ionic interactions leads to compaction and non-cooperativity in its folding. OBJECTIVE: To gain insights into the role of ionic interactions in the modulation of structure and thermodynamic stability of TgFNR. METHODS: Protein preparations, circular dichroism and fluorescence spectroscopy were used to determine salt-induced changes in the structure and stability of TgFNR. RESULTS: The kosmotropic salts (sodium fluoride and sodium sulphate) appear to induce the biphasic response on the structure and stability of TgFNR. At pH about 4.0, the addition of low concentrations of kosmotropic salts significantly perturbs the existing native-like secondary structure of TgFNR, whereas higher quantities of salt reversed the denaturing impact. This is a one-of-a-kind situation we are unaware of in any other protein. The urea-induced unfolding of TgFNR in the presence of a low dose of salt (100 mM) drastically affected the protein's thermodynamic stability at neutral pH. The increased salt concentrations, on the other hand, reversed the destabilizing effect. CONCLUSION: Our findings imply that electrostatic interactions are exceptionally significant for the TgFNR stability, however, render highly unusual behavior of Hofmeister series salts, indicating a possible crucial role of salt bridges in the stabilization of different conformations of the protein.

Jurkat T Cells are Immunophenotypically Distinct from T-Cell Acute Lymphoblastic Leukemia Cells Due to High-Level Surface Expression of CD5.

Human leukemic T cells show decreased surface CD5 (sCD5) and increased cytoplasmic CD5 (cCD5). When we examined their expressions in the Jurkat T cells, it showed increased sCD5 and decreased cCD5, which is in sharp contrast with the pattern of CD5 expression observed for human leukemic T cells. Furthermore, this opposite pattern was due to the absence of an exonal switch between E1A and E1B. This study suggests that Jurkat cell does not retain all characteristics of T-ALL cells; thus, we should carefully interpret the data obtained using Jurkat T cell as a model cell line of T-ALL.

Contrast Induced Acute Kidney Injury (CI- AKI) - Myths and Realities.

Contrast Induced Acute Kidney Injury (CI-AKI) is one of the most common causes of acute kidney injury in hospitalized patients. These days, contrast agents are widely being used in both cardiology and radiology procedures. Old age, history of diabetes, heart failure, proteinuria and low blood pressure are some important risk factors in the pathogenesis of CI-AKI. Apart from risk stratification and the use of low and iso-osmolar contrast agents, intravenous fluid hydration with crystalloids is the only recommended strategy for the prevention of CI-AKI. Agents like N-acetylcysteine (NAC), atrial natriuretic peptide, ascorbic acid, theophylline, and fenoldopam have failed to show any proven beneficial role in the prevention of CI-AKI. Though hemodialysis is still being perceived by many clinicians as the modality for contrast removal but prophylactic hemodialysis is now not recommended for the prevention of CI-AKI.

Cytodiagnosis of chondroid syringoma-Series of three cases.

Chondroid syringoma is a rare, benign, appendegeal neoplasm. It was initially termed as mixed tumor as it comprises both epithelial cells and chondromyxoid stroma. It usually presents as a slow growing, solitary, painless, subcutaneous, or intracutaneous mass, frequently in the head and neck region. Cytological features usually include the presence of both components, similar to histology but aspiration of only one component or atypical features can pose challenges in diagnosis. According to literature, only a few single case reports describing the cytological features of chondroid syringoma has been published. We report three cases of chondroid syringoma and its differential diagnosis on cytology.

Nephrogenic systemic fibrosis: A frivolous entity.

Gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging are vital in providing enhanced quality images, essential for diagnosis and treatment. Nephrogenic systemic fibrosis (NSF) with GBCAs has been a deterrent for the physician and has led to avoidance of these agents in patients with impaired kidney function. NSF is a progressive debilitating multisystem condition described classically in patients with renal insufficiency exposed to gadolinium contrast media. It is characterized by an induration and hardening of the skin. NSF is described to first involve the extremities and can imperceptibly involve internal organs. Lack of therapeutic interventions to treat NSF makes it more challenging and warrants deep insight into the pathogenesis, risk factors and treatment strategies.

Compromised levels of CD6 and reduced T cell activation in the aged immune system.

The CD6 molecule, a cell surface marker, is involved in immunological synapse formation between T cell and antigen-presenting cell and T lymphocyte activation for adequate immune response. Geriatric individuals fail to mount a satisfactory immunological response against pathogens thus, insights into the functionality of CD6 may provide information for competence building in elderly immune cells. However, limited information is available regarding the status of CD6 in geriatric individuals. In this study, various isoforms of CD6 were analysed in aged mononuclear cells (MNCs) and compared with young individuals. In geriatric individuals, protein and mRNA expressions of CD6 molecule/isoforms were found to be decreased compared to their young counterparts. Furthermore, geriatric MNCs failed to show any change in CD6 levels and its isoforms upon polyclonal activation compared to young MNCs, marked by reduced Ca++ release and IL-2 expression. We suggest an overall decrease in CD6 levels in geriatric MNCs and T cells with suboptimal T cell activation in aged individuals.

COVID-19: Asymptomatic Carrier: An Autopsy Case Report.

The severe acute respiratory syndrome (SARS)-coronavirus- 2 (CoV-2) outbreak in Wuhan, China has now spread to many countries across the world including the India with an increasing death toll. On March 11, 2020, the new clinical condition COVID-19 (Corona-Virus-Disease-19) was declared a pandemic by the World Health Organization (WHO). Owing to its infectivity, high risk of transmission, and limited handling of dead bodies, published data on the course of diseases has been limited. Most patients with COVID-19 have a mild disease course and remain as asymptomatic carrier; however, few patients of older age and with co-morbidites develop severe disease leading on to fatality. If due to COVID-19 infection death occurs, an autopsy is unlikely. However in unnatural deaths the legal duty impels the proper performance of a full autopsy, to find out the cause and manner of death. The detailed autopsy examination along with histo-pathological findings in the organs of asymptomatic patient of COVID-19 and its comparison with microscopic findings in Aluminium Phosphide poisoning are discussed below. This will summarizes the research status for COVID-19 deaths, which will be important for evaluation of cause of death, prevention, control and clinical strategies of COVID-19.

Impact of COVID-19 Pandemic on Neurosurgical Practice in a Tertiary Care Center in India.

Objectives The aim of the study is to determine the magnitude of repercussions of coronavirus disease 2019 (COVID-19) pandemic on neurosurgical specialty and formulate a management approach. Materials and Methods This combined retrospective and prospective study was done in neurosurgical specialty of IMS-BHU, Varanasi, India, a tertiary care center, between January 1, 2020 and May 31, 2020. Analysis of impact on neurosurgical emergency and electives was done over before pandemic, during lockdown 1 and 2 and during lockdown 3 and 4 timelines. Effects of COVID-19 pandemic on psychology of neurosurgical team (50 members) and on patient party (88) were also evaluated. Virtual learning and webinars as a substitute to residential neurosurgical training were analyzed by a questionnaire given to 13 neurosurgeons of our department. Statistical Analysis Ordinary one-way ANOVA (analysis of variance) and unpaired t -test were used according to data analyzed. p < 0.05 was considered statistically significant. GraphPad Prism software was used for this analysis. Results On an average 8.22 admissions per day were done in neurosurgical emergency before pandemic. After lockdown these figures reduced to 3.2 admissions per day during lockdown 1 and 2 and to 5.36 admissions per day during lockdown 3 and 4. There was significant reduction in neurotrauma admission rate during lockdown ( p < 0.0001) at our center. There was 76% reduction in emergency neurosurgical operated cases during pandemic. There was significant reduction in outpatient department (OPD) attendance per day, OPD admissions per day ( p < 0.0001), and total elective surgeries ( p < 0.0001) during lockdown. Of 50 neurosurgical team members (neurosurgeons, nursing, and ground staff) interviewed, 90% of them had the fear of contacting the COVID-19 disease, fear of well-being of family and children, and difficulty in transport. Three out of 13 neurosurgeons (23.1%) agreed on change in practice based on what they learned from virtual teaching and webinars and only two of them (15.4%) accepted improvement of skills based on virtual learning. Conclusion The COVID-19 pandemic is causing a significant impact on health care systems worldwide. For conserving resources elective surgical procedures should be limited. This pandemic has a negative impact on neurosurgical resident training program and psychology of both neurosurgical unit and patients.

Rare, Yet Emerging Cause of Graft Dysfunction-ALECT 2 Amyloidosis.

Amyloidosis is characterized by pathological deposition of abnormal protein aggregates in various tissues, AL protein being the commonest. Amyloidosis derived from leukocyte cell-derived chemotaxin 2 (LECT2) is a recently recognized form of amyloidosis in the United States with predominant involvement of kidney and liver. We present a case of ALECT2 renal amyloid in a transplant recipient who presented with gradual worsening of graft function and subnephrotic proteinuria. To our knowledge, this is first case of LECT2 amyloidosis from Northern India in a transplant recipient. There is no effective therapy for amyloidosis derived from leukocyte cell-derived chemotaxin 2.

Clinical, operative, and outcome analysis of giant extradural hematoma: A retrospective study in tertiary care center.

BACKGROUND: This study is aimed to find a critical volume of operated giant or massive extradural hematoma (EDH) that affects outcome significantly and analyze them with respect to their clinical, surgical, and outcome perspective. METHODS: This retrospective study includes 253 patients operated for EDH in emergency in the Department of Neurosurgery of IMS BHU, Varanasi, India, a tertiary care center, between August 1, 2018, and November 1, 2019. Giant EDH critical volume was evaluated. Twenty-nine patients with giant EDH with clot volume ≥ 80 ml were further analyzed for clinical, surgical, and outcome predictive factors. Statistical analysis was done using Prism GraphPad ver. 8.0.0. P value was taken at 0.05. RESULTS: Dichotomized group analysis with Glasgow Outcome Score (GOS) 4-5 versus GOS 1-3 for testing clot volume revealed significance difference with P < 0.001. Mean volume of GOS 1-3 came out to be 79.68 ml. Hence, we took clot volume >80 ml for further analysis. The most common age group was 20-40 (55.17%). M2 (31.03%) was the most common best motor response in operated giant EDH cases. Most of them were having severe (79.31%) head injury. Glasgow Coma Scale (GCS) at admission (P < 0.0001), pupillary changes (P = 0.0032), and best motor response (P < 0.0001) was significantly (P < 0.05) associated with outcome following surgery for giant EDH. CONCLUSION: Giant EDH with volume ≥ 80 ml is associated with poorer outcome. GCS at admission, pupillary changes, and best motor response is predictors for surgical outcome of giant EDH.

Clinical Profile and Outcome of Brain Abscess in Children from a Tertiary Care Hospital in Eastern Uttar Pradesh.

BACKGROUND AND AIMS: Brain abscess is a serious and dreadful disease presenting at tertiary centre. The objective of this study was to look into the clinical profile, predisposing conditions, microbiology and outcome of children suffering from brain abscess. METHODS: 30 children up to 18 years with clinical and imaging evidence of brain abscess were taken for study. Patients were stabilized as per unit protocol. Necessary investigations were carried out. Neuroimaging (CT or MRI) was used to confirm the diagnosis. All parameters (clinical, investigation, outcome) were recorded in predesigned performa. Neurosurgery consultation was sought in patients with multiple abscesses, posterior fossa abscesses, abscess with air-fluid level and causing midline shift. RESULTS: There were 16 males with 13 patients in age group (5-10 years). Mean duration of stay in hospital was 14.8 days. Most common predisposing factor was chronic suppurative otitis media (n-15). Typically, patients presented with fever, headache and seizures. On examination, motor deficits were the most common followed by signs of meningitis. Computerized tomography confirmed the diagnosis in most cases. Temporal lobe (n-11) was the commonest intracranial site for the abscess. Methicillin resistant staphylococcus and proteus mirabilis were the common pathogen isolated from blood and pus. Blood culture positivity rate was 16.7% and pus culture positivity rate was 25%. All cases were managed with intravenous antibiotics and aspiration (n-10) and excision (n-6). There were 5 deaths. There was complete immediate recovery in 13 cases with residual motor deficit in 12 cases. CONCLUSION: Brain abscess is a rare but serious entity in children. Late diagnosis and improper management leads to poor outcome. Early surgical intervention is helpful. Threshold for diagnosis should be low in children with chronic ear infection and congenital heart diseases.

Abrasive Wear Behavior of Cryogenically Treated Boron Steel (30MnCrB4) Used for Rotavator Blades.

Rotavator blades are prone to significant wear because of the abrasive nature of sand particles. The aim of this research work is to investigate the effect of cryogenic treatment and post tempering on abrasive wear behavior, in the presence of angular quartz sand (grain size of 212-425 µm), of rotavator blade material of boron steel (30MnCrB4). Cryogenic treatment has caused an improvement in the abrasive wear resistance and microhardness of 30MnCrB4 by 60% and 260.73%, respectively, compared to untreated material due to enhancement in hardness, the conversion of retained austenite into martensite, and the precipitation of secondary carbides in boron steel after exposure to cryogenic temperature. Economic analysis justifies the additional cost of cryogenic treatment.

Epidemiological and Clinico-radiological Evaluation of Head Injury in Pediatric Population.

BACKGROUND: Head injury in infancy and childhood has been documented as the single most common cause of death. In India, children aged <15 years constitute 35% of the total population and contribute to 20-30% of all head injuries. In this study, we attempted to analyze the epidemiological factors, management, and outcome of traumatic brain injury (TBI). The objective of this study were to find the causes of head injury in children and its pattern of distribution in this population and to analyze the efforts required to prevent the injury and management focusing on limiting the progression of primary brain injury and minimizing secondary brain insult. RESULTS: A total of 2714 patients with head injury were admitted at our hospital during the study period and, out of them, 508 (18.17%) were pediatric patients with age less than 18 years. Of the 508 patients, only 497 patients were included in this study. In the present study, 357 (71.83%) were males and 140 (28.16%) were females. In total, 351 cases were managed conservatively whereas surgical intervention was conducted in 146 cases (P < 0.001). In this study, the most common mode of injury was a road traffic accident (RTA) (46.88%; n=233), followed by fall from height (34.8%; n=173) (P < 0.001). It was also seen that epidural hematoma and fracture hematoma were the most common computed tomography findings in pediatric patients with head injury followed by parenchymal contusion or contusion with or without fracture followed by diffuse axonal injury. A total of 344 cases out of 497 cases were discharged with Glasgow outcome score (GOS)-5 whereas nine cases remained in a persistent vegetative state (GOS-2). CONCLUSION: Early intervention aimed at the primary lesion in TBI in children generally carries a good outcome, and limits as much as possible the ongoing biomechanical, physiological, and pathological sequelae post-TBI. In teenagers, the importance of proper self-care along with adequate safety gears while doing any TBI-prone activity should be emphasized.

MEMS impedance flow cytometry designs for effective manipulation of micro entities in health care applications.

Efficient manipulation of micro biological cells has always been a very important task in healthcare sector for which a Micro Electro Mechanical System (MEMS) based impedance flow cytometry has been proven to be a promising technique. This technique utilise the advantage of dielectrophoresis (DEP) force which is generated by non-uniform electric field in a microfluidic channel using an appropriate external AC supply at certain frequency range. The DEP forces generated in micro-channel depend upon various biological and physical parameters of cell and suspending medium. Apart from that design parameters of microfluidic channel and dimension of electrodes used for generating DEP action also plays major role in micro cell/bead manipulation. This article give remarks on the operating parameters which affects the cell manipulation and interrogates the currently accepted various electrode orientations in microfluidic MEMS flow cytometer technologies for effective manipulation of micro entities like healthy human cells (T-lymphocytes, B- lymphocytes, Monocytes, Leukocytes erythrocytes and human kidney cells HEK293), animal cells (neuroblastoma N115 and sheep red blood cells), cancer cells (MCF-7, MDA-435 and CD34+), yeast cells (saccharomyces cerevisiae, listeria innocua and E. coli) and micro particles (polystyrene beads) based on their dielectric properties using DEP action. Article focuses on the key electrode orientations for generation of non-uniform electric field in microfluidic flow cytometer like tapered electrodes, trapezoidal electrode arrays, Interdigitated electrodes, curved microelectrode and 3D electrode orientations and give remarks on their advantages and limitations. The cell manipulation with current MEMS impedance flow cytometry orientations targeting possibilities of implementation of the lab-on-chip devices has been discussed.