Comparison of nasal and face mask ventilation in anaesthetised obese adults: A randomised controlled study.

Background and Aims: The use of a face mask while inducing general anaesthesia (GA) in obese patients is often ineffective in providing adequate ventilation. Although nasal mask ventilation has demonstrated effectiveness for continuous positive airway pressure (CPAP) in obese patients with obstructive sleep apnoea (OSA), it has not yet been applied to the induction of anaesthesia. This study evaluated the efficacy of nasal mask ventilation against standard face mask ventilation in anaesthetised obese patients with body mass index (BMI)>25 kg/m2. Methods: Ninety adult patients with BMI >25 kg/m2 were randomly assigned to receive either facemask (Group FM) or nasal-mask (Group NM) ventilation during induction of GA. Expired tidal volume (VtE), air leak, peak inspiratory pressure (PIP), plateau pressure (PPLAT), oxygen saturation (SpO2), and end-tidal carbon dioxide (EtCO2) were recorded for10 breaths, and their mean was analysed. Results: The mean (standard deviation) VtE measured was not significantly higher in Group NM [455.98 (55.64) versus 436.90 (49.50) mL, P = 0.08, degree of freedom (df):88, mean difference (95% confidence interval [CI]) -19.08 (-41.14, 2.98) mL]. Mean air-leak [16.44 (22.16) versus 31.63 (21.56) mL, P = 0.001, df: 88, mean difference 95%CI: 15.19 (6.03,24.35)], mean PIP [14.79 (1.39) versus 19.94 (3.05) cmH2O, P = 0.001, df: 88, mean difference, 95%CI: 5.15 (4.16, 6.14)], and mean PPLAT [12.04 (1.21) versus 16.66 (2.56) cmH2O, P = 0.001, df: 88, mean difference 95% CI: 4.62 (3.78, 5.45)] were significantly lower in Group NM. EtCO2, SpO2, and haemodynamic measurements were similar between the two groups. Conclusion: Nasal mask ventilation is an effective ventilation method and can be used as an alternative to face mask ventilation in anaesthetised obese adults with BMI>25 kg/m2.

Ratiometric Fluorescent Probe Promotes Trans-differentiation of Human Mesenchymal Stem Cells to Neurons.

Development of multifunctional theranostics is challenging and crucial for deciphering complex biological phenomena and subsequently treating critical disease. In particular, development of theranostics for traumatic brain injury (TBI) and understanding its repair mechanism are challenging and highly complex areas of research. Recently, there have been interesting pieces of research work demonstrated that a small molecule-based neuroregenerative approach using stem cells has potential for future therapeutic lead development for TBI. However, these works demonstrated the application of a mixture of multiple molecules as a "chemical cocktail", which may have serious toxic effects in the differentiated cells. Therefore, development of a single-molecule-based potential differentiating agent for human mesenchymal stem cells (hMSCs) into functional neurons is vital for the upcoming neuro-regenerative therapeutics. This lead could be further extraploted for the design of theranostics for TBI. In this study, we have developed a multifunctional single-molecule-based fluorescent probe, which can image the transdifferentiated neurons as well as promote the differentiation process. We demonstrated a promising class of fluorescent probes (CP-4) that can be employed to convert hMSCs into neurons in the presence of fibroblast growth factor (FGF). This fluorescent probe was used in cellular imaging as its fluorescence intensity remained unaltered for up to 7 days of trans-differentiation. We envision that this imaging probe can have an important application in the study of neuropathological and neurodegenerative studies.

High-Affinity Fluorescent Probes for the Detection of Soluble and Insoluble Aß Deposits in Alzheimer's Disease.

The overproduction and deposition of the amyloid-ß (Aß) aggregates are accountable for the genesis and development of the neurologic disorder Alzheimer's disease (AD). Effective medications and detection agents for AD are still deficient. General challenges for the diagnosis of Aß aggregates in the AD brain are (i) crossing the blood-brain barrier (BBB) and (ii) selectivity to Aß species with (iii) emission maxima in the 500-750 nm region. Thioflavin-T (ThT) is the most used fluorescent probe for imaging Aß fibril aggregates. However, because of the poor BBB crossing (log P = -0.14) and short emission wavelength (482 nm) after binding with Aß fibrils, ThT can be limited to in vitro use only. Herein, we have developed Aß deposit-recognizing fluorescent probes (ARs) with a D-π-A architecture and a longer emission wavelength after binding with Aß species. Among the newly designed probes, AR-14 showed an admirable fluorescence emission (>600 nm) change after binding with soluble Aß oligomers (2.3-fold) and insoluble Aß fibril aggregates (4.5-fold) with high affinities Kd = 24.25 ± 4.10 nM; Ka = (4.123 ± 0.69) × 107 M-1 for fibrils; Kd = 32.58 ± 4.89 nM; and Ka = (3.069 ± 0.46) × 107 M-1 for oligomers with high quantum yield, molecular weight of <500 Da, reasonable log P = 1.77, stability in serum, and nontoxicity, and it can cross the BBB efficiently. The binding affinity of AR-14 toward Aß species is proved by fluorescence binding studies and fluorescent staining of 18-month-old triple-transgenic (3xTg) mouse brain sections. In summary, the fluorescent probe AR-14 is efficient and has an admirable quality for the detection of soluble and insoluble Aß deposits in vitro and in vivo.

Vanillin Benzothiazole Derivative Reduces Cellular Reactive Oxygen Species and Detects Amyloid Fibrillar Aggregates in Alzheimer's Disease Brain.

The misfolding of amyloid beta (Aß) peptides into Aß fibrillary aggregates is a major hallmark of Alzheimer's disease (AD), which responsible for the excess production of hydrogen peroxide (H2O2), a prominent reactive oxygen species (ROS) from the molecular oxygen (O2) by the reduction of the Aß-Cu(I) complex. The excessive production of H2O2 causes oxidative stress and inflammation in the AD brain. Here, we have designed and developed a dual functionalized molecule VBD by using π-conjugation (C═C) in the backbone structure. In the presence of H2O2, the VBD can turn into fluorescent probe VBD-1 by cleaving of the selective boronate ester group. The fluorescent probe VBD-1 can undergo intramolecular charge transfer transition (ICT) by a π-conjugative system, and as a result, its emission increases from the yellow (532 nm) to red (590 nm) region. The fluorescence intensity of VBD-1 increases by 3.5-fold upon binding with Aß fibrillary aggregates with a high affinity (Kd = 143 ± 12 nM). Finally, the VBD reduces the cellular toxic H2O2 as proven by the CCA assay and DCFDA assay and the binding affinity of VBD-1 was confirmed by using in vitro histological staining in 8- and 18-month-old triple transgenic AD (3xTg-AD) mice brain slices.

Covid-19 and Mucormycosis Superinfection: Prospective, Obsevational Study in a Single Center.

Background: Mucormycosis (MCR) has been increasingly described in patients with coronavirus disease 2019 (COVID-19), but the epidemiological factors, neurological presentation, and outcome of such patients are not well described. Aims: To study the patient demographics, presenting symptoms and signs, the role of co-morbidities, medications used to treat COVID-19, and the outcomes of management and to study the spectrum of neuraxis involvement and its outcome. Methods: It was a prospective, observational, cross-sectional hospital-based single center cohort study. Confirmed MCR cases with and without COVID-19 were collected. The study was carried out over a period of 3 months from May to July 2021, followed by 3-month follow-up. Information on epidemiological factors, neurological findings, treatment (including medical and surgical treatment), and outcome was recorded. Results: A total of 141 patients were diagnosed with MCR, out of which 98 were COVID-associated MCR (CAM). The CAM incidence was 0.39% among COVID-19-positive patients. The MCR case fatality rate at 90 days was 43.9% but was higher for CAM than for non-CAM patients. Older ages (>50 years), diabetes mellitus, multiple risk factors, diabetic ketoacidosis on admission, brain involvement, and history of COVID-19 pneumonitis were associated with a higher risk for death. Conclusions: Possibly because of improper usage of corticosteroids, zinc, oxygen, and tocilizumab, there was sudden surge of cases of MCR in the COVID-19 pandemic. Therefore, treating physicians should use the COVID-19 pneumonia regimen judiciously. Neurological involvement itself is a poor prognostic sign, but combined surgical and medical management exhibited better outcome.

Facile Method of Tubulin Purification from Goat Brain for Reconstitution of Microtubule-Associated Intracellular Function.

Tubulin/microtubule plays crucial role in eukaryotic cell division. Polymerization of αß-tubulin heterodimers forms the microtubules, which is essential for the segregation of chromosomes during cell division and organelle positioning. Our method of tubulin purification from the goat brain includes isolation of goat brain, multiple cycles of polymerization (warming at 37 °C)-depolymerization (cooling at 4 °C) followed by centrifugation process. The purified tubulin from goat brain is highly functional and successfully used in different applications including reconstitution of cell like environments and understanding molecular mechanisms. Toward the end of the chapter, we have discussed, how this purified tubulin can be used for reconstitution of intracellular microtubule-associated events or function. To enable our reconstitution approach, we have developed various micropatterned-based platform and their fabrication methodology with single ligand and dual-ligand functionalizations, which are also demonstrated. These chemically functionalized micropatterned platforms are extremely useful for immobilization of tubulin/microtubule onto the localized defined area, which will be helpful in mimicking cellular phenomena like kinesin-driven transport, microtubule dynamics, etc.

A Comparative Time Matched Hospital Based Study of First Ever Stroke Patients Admitted to Stroke Unit during Pre-Covid 19 vs Covid 19 Pandemic Era.

SARS CoV- 2 infection may lead to wide range of neurological complications, which range from anosmia to stroke. An observation shows a fall in the number of first-time stroke admissions, but that these admissions are more severe. Therefore, to gain an insight into it, a retrospective comparison of first ever stroke characteristics in pre-COVID 19 era and COVID 19 pandemic era at GMC, Kota, Rajasthan. MATERIAL: The study was conducted at GMC Kota, a tertiary care hospital in Rajasthan. All patients having their first ever stroke and admitted to our stroke unit during the pre-COVID 19 period (April 2019-May 2019) and the COVID 19 period (April 2020-May 2020) were considered. The characteristics of stroke, the severity, the number of admissions per day, and demographic characteristics as well as the short-term outcomes were studied. OBSERVATION: Of the 108 patients included, 44 (40.7%) presented during the COVID-19 period. There was a 36% reduction in first-ever stroke diagnoses from (1.05/day) to (0.72/day) (p<0.0001). The admitted patients were five years older and in much worse health than in the pre-COVID 19 era (p<0.0001). There was a statistically significant reduction in MRI use by 27% (p=0.055). CONCLUSION: The observation suggests an overall reduced number of stroke admissions per day. Patients admitted were older and more severely ill. In COVID 19 era patients, mortality and mRS at admission and discharge were higher, along with a longer hospital stay. An overall reduction in the utilization of MRI was observed due to COVID protocol.

Discovery of imidazole-based GSK-3ß inhibitors for transdifferentiation of human mesenchymal stem cells to neurons: A potential single-molecule neurotherapeutic foresight.

The transdifferentiation of human mesenchymal stem cells (hMSC) to functional neurons is crucial for the development of future neuro-regenerative therapeutics. Currently, transdifferentiation of hMSCs to neurons requires a "chemical cocktail" along with neural growth factors. The role of the individual molecules present in a "chemical cocktail" is poorly understood and may cause unwanted toxicity or adverse effects. Toward, this goal, we have showcased the discovery of an imidazole-based "single-molecule" transdifferentiation initiator SG-145C. This discovery was achieved via screening of a small molecule library through extensive in silico studies to shortlist the best-fitting molecules. This discovery evolved through a careful selection to target Glycogen synthase kinase-3ß (GSK-3ß), which is one of the important proteins responsible for neurogenesis. Rigorous computational experiments, as well as extensive biological assays, confirmed that SG-145C has significant potential to transdifferentiate hMSCs to neurons. Interestingly, our results suggest that SG-145C can inhibit the proteasomal degradation of phosphorylated ß-catenin, in turn promoting transdifferentiation of hMSCs into neurons via the Wnt pathway.

Cell-Derived Exosome Therapy: A Novel Approach to Treat Post-traumatic Brain Injury Mediated Neural Injury.

Traumatic brain injury (TBI) causes serious neuronal injury that often leads to death. To date there is no clinically successful treatment strategy that has been reported which offers repair of the brain injury or neural injury. Significant attempts have been made to develop effective therapies for TBI, and one of the most promising approaches is a stem cell based therapeutic approach with mesenchymal stem cells (MSCs). This approach is regarded as having the most potential in regenerative medicine. Toward this venture, the generation and release of exosomes can be attributed to the therapeutic effects of MSCs. Exosomes are nanosized vesicles, carry proteins, lipids, mRNA, and miRNA, and assist in cell-cell communication. Exosomes can interact with brain parenchyma cells and with the neurogenic niche, which can help in neurogenesis and brain remodeling. Exosomes derived from MSCs and human-induced pluripotent stem cells (hiPSCs) can be a promising approach in neuronal injury healing. In this Viewpoint, we discussed the most recent knowledge for exosome therapies for neural injuries and highlighted the major advantages of this therapy.

Targeting Chondroitin Sulfate Proteoglycans: An Emerging Therapeutic Strategy to Treat CNS Injury.

Chondroitin sulfate proteoglycans (CSPGs) are the most abundant components of glial scar formed after severe traumatic brain injury as well as spinal cord injury and play a crucial inhibitory role in axonal regeneration by selective contraction of filopodia of the growth cone of sprouting neurites. Healing of central nervous system (CNS) injury requires degradation of the glycosamine glycan backbone of CSPGs in order to reduce the inhibitory effect of the CSPG layer. The key focus of this Viewpoint is to address a few important regenerative approaches useful for overcoming the inhibitory barrier caused by chondroitin sulfate proteoglycans.

An overview of key potential therapeutic strategies for combat in the COVID-19 battle.

The sudden ravaging outbreak of a novel coronavirus, or SARS-CoV-2, in terms of virulence, severity, and casualties has already overtaken previous versions of coronaviruses, like SARS CoV and MERS CoV. Originating from its epicenter in Wuhan, China, this mutated version of the influenza virus with its associated pandemic effects has engulfed the whole world with awful speed. In the midst of this bewildering situation, medical and scientific communities are on their toes to produce the potential vaccine-mediated eradication of this virus. Though the chances are really high, to date no such panacea has been reported. The time requirements for the onerous procedures of human trials for the successful clinical translation of any vaccine or potential therapeutics are also a major concern. In order to build some resistance against this massive pandemic, the repurposing of some earlier antiviral drugs has been done, along with the refurbishment of some immune-responsive alternative avenues, like monoclonal antibody mediated neutralization, interferon treatment, and plasma therapy. New drugs developed from the RBD domain of the virus spike protein and drugs targeting viral proteases are also undergoing further research and have shown potential from preliminary results. The sole purpose of this review article is to provide a brief collective overview of the recent status of therapeutics advances and approaches, and their current state of implementation for the management of COVID-19.

Three-Dimensional Microfluidic Platform with Neural Organoids: Model System for Unraveling Synapses.

Unraveling the large number of various signals in the brain under the influence of physical and chemical cues that govern the formation of individual neurons, axons, dendrites, and their functional synapses during the development of neural network is a challenging task. To understand this task, microfluidic devices equipped with microchannels for reconstitution of cell/tissue-culture environments have been studied. Microfluidic devices are emerging as powerful tools in neurobiology, since they are capable of controlling and manipulating the microenvironment of the brain in a precise manner. They can enhance the physiological relevance of three-dimensional (3D) cell culture by allowing spatial control over fluids in micrometer-sized channels. Recent technological advancement in designing microfluidic platforms for studying neural communication, disease progression, and detection of neurotransmitters enhance our fundamental knowledge and understanding. However, more such advanced and innovative interventions are required. This Viewpoint focuses on highlighting a few of them with future scope of further advancement in this field.

Conductance Photoswitching of Metal-Organic Frameworks with Embedded Spiropyran.

Conductive metal-organic frameworks (MOFs) as well as smart, stimuli-responsive MOF materials have attracted considerable attention with respect to advanced applications in energy harvesting and storage as well as in signal processing. Here, the conductance of MOF films of type UiO-67 with embedded photoswitchable nitro-substituted spiropyrans was investigated. Under UV irradiation, the spiropyran (SP) reversibly isomerizes to the open merocyanine (MC) form, a zwitterionic molecule with an extended conjugated π-system. The light-induced SP-MC isomerization allows for remote control over the conductance of the SP@UiO-67 MOF film, and the conductance can be increased by one order of magnitude. This research has the potential to contribute to the development of a new generation of photoelectronic devices based on smart hybrid materials.

Extracapsular excision of hepatic hemangioma: A single centre experience.

BACKGROUNDS/AIMS: Hepatic hemangioma is a common non-epithelial neoplasm of the liver. Presence of symptoms and uncertainty in diagnosis are the most common indications for surgery. METHODS: Eighteen patients with hepatic hemangioma, operated on from January 2011 to December 2016 at the Hepato-pancreato-biliary surgical unit of Tata Memorial Hospital, were retrospectively analyzed. RESULTS: Main indications for operation were presence of symptoms, the most common being pain and diagnostic uncertainty. The median size of hemangioma was 9.9 cm (range 3.2 to 24 cm). All patients underwent extra-capsular excision of hemangioma. The median operating time was 180 minutes (range 75 to 460 minutes) and median blood loss was 950 ml (range 100 to 3,500 ml). Median post-operative stay was 5.5 days (range 3 to 10 days). One (5.6%) patient required re-exploration for post-operative hemorrhage, Clavien Dindo (CD) grade IIIb, and one (5.6%) had postoperative purulent intra-abdominal collection requiring percutaneous cutaneous drainage CD grade IIIa. There was no postoperative mortality. Postoperative day 3 liver function tests were within normal limits. Size of the tumor did not correlate significantly with postoperative complications (p=0.135). CONCLUSIONS: Surgical treatment of hemangioma should be guided by presence of symptoms or by the presence of diagnostic uncertainty, not by size alone. The size had no correlation with perioperative complications. The technique of extra-capsular excision is safe and technically feasible in most of the hemangiomas. This technique preserves maximum liver parenchyma, resulting in early postoperative recovery with minimal morbidity.

Aurora kinase-induced phosphorylation excludes transcription factor RUNX from the chromatin to facilitate proper mitotic progression.

The Runt-related transcription factors (RUNX) are master regulators of development and major players in tumorigenesis. Interestingly, unlike most transcription factors, RUNX proteins are detected on the mitotic chromatin and apparatus, suggesting that they are functionally active in mitosis. Here, we identify key sites of RUNX phosphorylation in mitosis. We show that the phosphorylation of threonine 173 (T173) residue within the Runt domain of RUNX3 disrupts RUNX DNA binding activity during mitotic entry to facilitate the recruitment of RUNX proteins to mitotic structures. Moreover, knockdown of RUNX3 delays mitotic entry. RUNX3 phosphorylation is therefore a regulatory mechanism for mitotic entry. Cancer-associated mutations of RUNX3 T173 and its equivalent in RUNX1 further corroborate the role of RUNX phosphorylation in regulating proper mitotic progression and genomic integrity.

Standard imaging techniques for assessment of portal venous system and its tributaries by linear endoscopic ultrasound: a pictorial essay.

Linear Endosonography has been used to image the Portal Venous System but no established standard guidelines exist. This article presents techniques to visualize the portal venous system and its tributaries by linear endosonography. Attempt has been made to show most of the first order tributaries and some second order tributaries of splenic vein, superior mesenteric vein and portal vein.

Portal venous system and its tributaries: a radial endosonographic assessment.

The use of Color Doppler in endosonography has enabled detailed real-time assessment of the abdominal vasculature. Standard stations are used during the routine evaluation on endosonography. However, the imaging techniques do not describe the vascular imaging of the portal venous system and its tributaries, in detail. This article demonstrates the normal findings on the portal venous system and its tributaries using radial endosonography.

Calculating prevalence of hepatitis B in India: using population weights to look for publication bias in conventional meta-analysis.

Publication bias can result from the propensity of researchers to document what is unusual. This can distort the inferences drawn in systematic reviews. To measure the distortion, it has been suggested that a second analysis be done; using weights proportional to the size of the population from which the samples are drawn. We re-evaluate data from a published meta-analysis on prevalence of hepatitis B in India, to see how this approach alters the results. Prevalence of hepatitis B among tribal and non-tribal populations in different States was analyzed. Weights were then assigned according to population of the State. The overall country prevalence was then calculated. Using population-weights it is estimated that the point-prevalence of hepatitis B among non-tribal populations is 3.07% [95% CI: 2.5-3.64]. Among tribal populations it is 11.85% (CI 10.76-12.93). Overall prevalence was 3.70 (CI: 3.17-4.24) (corresponding to a chronic carrier rate of 2.96%). The present analysis using population-weights has resulted in the estimated prevalence among non tribal populations increasing by 24% and that among tribal populations decreasing by 25.5% when compared to figures of the meta-analysis published earlier. The advantages and drawbacks of this procedure are discussed.