Photoinduced metal-free trifluoro/perfluoroalkylation of heteroarenes.

A practical and straightforward protocol to access trifluoromethylated/perfluoroalkylated heteroarenes via radical-type nucleophilic substitution rather than typical radical-type electrophilic substitution is described here. The substrate scope was observed to be broad and diverse-covering arenes, heteroarenes (containing N, O, S), bioactive cores, and allylic cores. Mechanistic studies confirmed a radical-mediated reaction pathway.

Biodiversity and Bioactive Potential of Actinomycetes from Unexplored High Altitude Regions of Kargil, India.

The effectiveness of currently available antimicrobials and anticancer medications is steadily declining due to the emergence of drug resistance. Since actinobacteria are important producers of bioactive substances, we have isolated them from the soil samples of exotic North-Western Himalayan terrains. Out of 128 isolates, 39 strains were prioritized based on their bioactive potential. The diversity analysis revealed higher abundance distribution of actinomycetes in the soil of an open field (68.7%), followed by the mountainside (34.9%), from which most of the bioactive strains were obtained. The extract of the strain S26-11 was found to be highly active against Gram-positive Staphylococcus aureus and Bacillus subtilis with a MIC of 0.5 µg/mL and 1 µg/mL respectively. A cytotoxicity assay (sulforhodamine B) was performed on a series of cancer cell lines (PC-3, MCF-7, A-549, and HCT-116). The extract of the strain S26-11 showed cytotoxic activity against all cancer cell lines with an IC50 of 2 µg/mL against PC-3, 1.9 µg/mL against MCF-7, 0.52 µg/mL against A-549, and 0.83 µg/mL against HCT-116. Moreover, the antioxidant activity was assessed using a DPPH-based assay and the results revealed that the S17-8 isolate showed the highest antioxidant activity with IC50 of 114.136 µg/mL. The Response Surface Methodology (RSM) had helped to optimize the physical parameters for scaling up of the bioactive strain S26-11. The unexplored soil niches of Kargil (UT, Ladakh), India, is rich in actinomycetes which are having potential bioactivities, would be worth to explore for the discovery of bioactive compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01133-1.

Comparison of positional artifacts in myocardial perfusion imaging in supine and semi-reclining position using dedicated D-SPECT cardiac camera: validation using CT based attenuation correction.

BACKGROUND: Soft-tissue attenuation remains a major limitation of SPECT-MPI which interferes with the diagnosis of CAD. The current study aims to evaluate the pattern of attenuation artifacts in supine and semi-reclining positions on CZT cardiac camera and their interaction with gender, BMI and stress protocols. METHODS: We prospectively analysed 150 patients acquired in supine and semi-reclining positions on CZT camera. The images were evaluated for severity and extent of defect using 17-segment model. An additional CT scan was acquired to generate AC image in the first 50 patients studied to assist investigator learning for comparison of artifact vs true defects in the two SPECT systems. The defects present in one position or showing change in severity within two positions were considered as positional artifacts and further validated using CTAC supine image. RESULTS: In overall analysis, higher extent and severity of positional artifacts were observed more in semi-reclining position affecting the apex, apico-inferior, inferolateral and inferoseptal segments. Females showed more positional artifacts than males with inferior wall attenuation in the semireclining position and anterior wall attenuation in the supine position. A positive correlation of the extent and severity of positional artifacts was noted with an increasing BMI. In patients with BMI > 30, mid inferior and inferolateral segments were most affected followed by anterior wall segments. Highest correction of artifactual perfusion defects by CTAC was noted in inferior wall followed by inferolateral segments. CONCLUSION: The incidence of positional artifacts was greater in semi-reclining position in females, higher BMI groups and adenosine stress subsets. Knowledge of the pattern of positional artifacts appears to be a reliable alternative of CTAC for correct interpretation of myocardial perfusion images.

Staying and Returning dynamics of young children's attention.

In this paper, we decompose selective sustained attending behavior into components of continuous attention maintenance and attentional transitions and study how each of these components develops in young children. Our results in two experiments suggest that changes in children's ability to return attention to a target locus after distraction ("Returning") play a crucial role in the development of selective sustained attention between the ages of 3.5-6 years, perhaps to a greater extent than changes in the ability to continuously maintain attention on the target ("Staying"). We further distinguish Returning from the behavior of transitioning attention away from task (i.e., becoming distracted) and investigate the relative contributions of bottom-up and top-down factors on these different types of attentional transitions. Overall, these results (a) suggest the importance of understanding the cognitive process of transitioning attention for understanding selective sustained attention and its development, (b) provide an empirical paradigm within which to study this process, and (c) begin to characterize basic features of this process, namely its development and its relative dependence on top-down and bottom-up influences on attention. RESEARCH HIGHLIGHTS: Young children exhibited an endogenously ability, Returning, to preferentially transition attention to task-relevant information over task-irrelevant information. Selective sustained attention and its development were decomposed into Returning and Staying, or task-selective attention maintenance, using novel eye-tracking-based measures. Returning improved between the ages of 3.5-6 years, to a greater extent than Staying. Improvements in Returning supported improvements in selective sustained attention between these ages.

Divergent Signaling Pathways May Lead to Convergence in Cancer Therapy - A Review.

Cancer is a chaos of uncontrolled cell proliferation that has consistently invented new circuitry programs to operate inside the cell machinery. Globally, cancer statistics account for 65% of mortality worldwide, mainly due to the adoption of lifestyle behaviours. In 2020, FDA approved 40 new drugs, out of which 16 (40%) were approved as cancer drugs. Overall, the risk of dying from cancer decreased, but further reductions in cancer death rates can be accelerated by applying existing cancer control knowledge across all the population segments, emphasising those in the lowest socio-economic and other disadvantaged population. Various therapeutic regimes, including low-molecular-weight inhibitors, targeting oncogenic signaling pathways are under development. However, the pitfall of targeted therapies is the quick emergence of acquired drug resistance encumbered with toxic side effects. Several FDA acclaimed therapeutic legacies or biosimilars earmarked signaling pathways of rare diseases (cystic fibrosis, erythropoietic protoporphyria, neuromyelitis optica spectrum disorder, tenosynovial giant cell tumor, sickle cell disease, systemic sclerosis-associated interstitial lung disease, muscular dystrophy), neurological and psychiatric disorders, infectious diseases, heart, lung, circulatory, endocrine diseases, autoimmune conditions, cancers and blood disorders. When cancer progresses, these signals develop specific characteristics that can be targeted for anti-cancer therapy. The designer inhibitors have emerged as novel pharmaceutical interventions that aim to block the pathways in an effort to reverse the abnormal phenotype of the cancer cells. Numerous cell-signaling channels have evolved and invigorated to make off three-dimensional feedback networks. The magnitude of accessible information by pathways occupies curated information as a consortium. To fully appreciate the pivotal roles that signaling cascades play in tumor development, it is necessary to understand the involved signaling cascades in the interaction between cancer cells. The prime endeavour is to canonically curate all signaling pathways involving cell cycle, EGFR, MAPK, GPCR, PI3K/ AKT/mTOR, immune checkpoints, nuclear receptors, janus kinase, transcription activators etc., involving the manipulation of genetic and nuclear receptors. Here, we will summarize the vast amount of information describing the signals that mediate crosstalk between cancer cells and the targets related to this crosstalk.

Visible-light-induced alkylation of 2-iminochromene.

A metal-free, photochemical protocol for C-4 alkylation of 2-iminochromene has been developed by employing the naturally abundant feedstock carboxylic acid. Selective C-4 alkylation under photoredox conditions to access C-4 alkylated 2-iminochromene in up to 81% yield was achieved. In addition, biologically relevant chromophores can be easily incorporated under this protocol.

Redox activated amines in the organophotoinduced alkylation of coumarins.

The coumarin core represents the quintessential scaffold of many natural products. While C-3 alkylation is easily achievable, effective greener strategies for C-4 alkylation have been less forthcoming. Herein, we report a metal-free photoinduced deaminative strategy for C-4 alkylation of coumarins using redox activated secondary and benzylic amine derived Katritzky pyridinium salts.

Synthesis of 3-N-/O-/S-methyl-imidazo[1,2-a] pyridine derivatives for caspase-3 mediated apoptosis induced anticancer activity.

A library of 49 analogs of imidazo[1,2-a]pyridine with 2-halo, aryl, styryl and phenylethynyl-substitution at C-2 position and N-/O-/S-methyl linkage at C-3 position, have been synthesized and evaluated for their anti-proliferative activity against breast (MCF-7, MDA-MB-231), pancreatic (MiaPaca-2), lung (A549), prostate (PC-3) and colon (HCT-116) cancer cell lines and normal cells (HEK-293). Among the screened compounds, 5b exhibited best anticancer potential in all tested cancer cells with IC50 ranging from 3.5 to 61.1 µM and no toxicity in normal cells. Further, mechanistic study of 5b revealed concentration dependent increased generation of ROS, reduced mitochondrial membrane potential (MMP), surface and nuclear morphological alterations and inhibition of colony formation in HCT-116 cells. Western blot results had shown that the cell death in HCT-116 colon cancer cells was achieved through the induction of apoptosis via upregulation of the PTEN gene and downregulation of AKT pathway. Similarly, 5b treatment induced caspase-3 cleavage which is a hallmark of apoptosis. Molecular docking and binding energy (ΔG) studies of hit 5b with respect to three important cancer targets (EGFR, mTOR and PI3Kα) revealed strong binding of inhibitor with PI3Kα (docking score -6.932 and ΔG -56.297).

Enhanced Algal Biomass Production in a Novel Electromagnetic Photobioreactor (E-PBR).

Enhancement in algal biomass production is a crucial parameter for generating value-added chemicals from renewable carbon sources. This study aimed to fabricate a novel photobioreactor with integrated and innovative electromagnets to assess microalgae's growth under the magnetic field's effect. The present study observed the effect of magnetic field exposure on the microalgae Chlorella sorokiniana cultivation and estimated the change in pigments with growth. In addition, the carbohydrate content of Chlorella sorokiniana was also evaluated. Chlorella sorokiniana culture, when exposed to a magnetic field strength of 10 mT d-1 resulted in a greater biomass concentration and productivity of about 12% and 8%, respectively, higher than the control culture. A positive effect of magnetic field exposure was also observed in the microalga's pigments concentration and carbohydrate content. The chlorophyll-a content increased twofold exponentially with the growth and the carbohydrate content of the microalgae cells also increased by 15% compared to the control culture. Therefore, the novel Electromagnetic Photobioreactor (E-PBR) can be used to produce enhanced biomass and other value-added products.

Antimicrobial and Cytotoxic Potential of Helminthosporin from Rumex abyssiniscus Jacq. Discovered as a Novel Source of Syringic Acid and Bis(2-ethyloctyl) Phthalate.

Rumex abyssinicus Jacq. is a perennial medicinal herb widely used in traditional medicine to treat many diseases. Phytochemicals of the plant were isolated using column chromatography and thin layer chromatography techniques. Extract, fractions and pure compounds were screened for antimicrobial activity against sensitive and multi-drug resistant microbes and their cytotoxicity was performed on different cancer cell lines. The mechanism of action of purified helminthosporin as well as the potent fraction containing a mixture of two compounds was assessed. Fraction R7C3 was the most potent antibacterial with the lowest MIC value of 0.12 µg/mL. Helminthosporin was the most potent compound with the lowest MIC value of 1.95 µg/mL. The compound was more potent than the antibiotic chloramphenicol against multi-drug resistant (MDR) bacteria with MIC equal to 16 µg/mL. The fraction and helminthosporin were shown to destroy the cell wall of the yeast and bacteria, and DNA fragmentation effect on the genome of Candida albicans and Bacillus cereus. Helminthosporin was the most cytotoxic compound with IC50 ˂ 10 µM. Fraction R7C3 showed the most potent cytotoxic effects on all cancer cell lines, with IC50 ranging from ˂1 to 4.35 ng/mL. Our study is the first report on the mechanism of action of helminthosporin, a potent candidate in the development of new drugs against multi-resistant bacteria and cancer cells. In addition, this study uncovered Rumex abyssinicus as a new source of syringic acid and bis(2-ethyloctyl) phthalate.

Adjustment in tumbling rates improves bacterial chemotaxis on obstacle-laden terrains.

The mechanisms of bacterial chemotaxis have been extensively studied for several decades, but how the physical environment influences the collective migration of bacterial cells remains less understood. Previous models of bacterial chemotaxis have suggested that the movement of migrating bacteria across obstacle-laden terrains may be slower compared with terrains without them. Here, we show experimentally that the size or density of evenly spaced obstacles do not alter the average exit rate of Escherichia coli cells from microchambers in response to external attractants, a function that is dependent on intact cell-cell communication. We also show, both by analyzing a revised theoretical model and by experimentally following single cells, that the reduced exit time in the presence of obstacles is a consequence of reduced tumbling frequency that is adjusted by the E. coli cells in response to the topology of their environment. These findings imply operational short-term memory of bacteria while moving through complex environments in response to chemotactic stimuli and motivate improved algorithms for self-autonomous robotic swarms.

Synthesis, Biological Activity and Molecular Docking Studies of Heterocyclic Chalcones.

Nineteen heterocyclic chalcones were synthesized from 4-acetyl-5-methylquinolylpyrazole and heteroaryl (imidazole, pyrazole, thiophene, indole and triazole) aldehydes and were screened in vitro using four tumor cell lines for their cytotoxic capability and for antimicrobial activity. The chalcone 5b exhibited the highest activity with IC50 values 2.14 µM against colon (HCT-116) and 5.0 µM, against prostate (PC-3) cancer cell lines and also displayed good activity against fungal strain (A. niger) with MIC value 9.1 µM. The chalcones 5q and 5p displayed good activity against bacterial strains (S. aureus) having MIC value 2.6 µM and fungal strain (C. albicans) having MIC value 5.4 µM, respectively. The molecular docking outcome revealed that the synthesized heterocyclic chalcones demonstrated hydrogen bond, hydrophobic and electrostatic interactions with their respective biochemical targets.

n-Player Stochastic Duel Game Model with Applied Deep Learning and Its Modern Implications.

This paper provides a conceptual foundation for stochastic duels and contains a further study of the game models based on the theory of stochastic duels. Some other combat assessment techniques are looked upon briefly; a modern outlook on the applications of the theory through video games is provided; and the possibility of usage of data generated by popular shooter-type video games is discussed. Impactful works to date are carefully chosen; a timeline of the developments in the theory of stochastic duels is provided; and a brief literature review for the same is conducted, enabling readers to have a broad outlook at the theory of stochastic duels. A new evaluation model is introduced in order to match realistic scenarios. Improvements are suggested and, additionally, a trust mechanism is introduced to identify the intent of a player in order to make the model a better fit for realistic modern problems. The concept of teaming of players is also considered in the proposed mode. A deep-learning model is developed and trained on data generated by video games to support the results of the proposed model. The proposed model is compared to previously published models in a brief comparison study. Contrary to the conventional stochastic duel game combat model, this new proposed model deals with pair-wise duels throughout the game duration. This model is explained in detail, and practical applications of it in the context of the real world are also discussed. The approach toward solving modern-day problems through the use of game theory is presented in this paper, and hence, this paper acts as a foundation for researchers looking forward to an innovation with game theory.

Empagliflozin containing chitosan-alginate nanoparticles in orodispersible film: preparation, characterization, pharmacokinetic evaluation and its in-vitro anticancer activity.

OBJECTIVE: The main objective of this study was to develop the orodispersity film containing chitosan-alginate nanoparticles to improve dissolution profile, therapeutic effect with improved bioavailability of empagliflozin through oral route noninvasively for further cytotoxicity study. METHODS: The nanoparticles were developed through two-step mechanisms ionotropic pre-gelation and polyelectrolyte complexation methods. The prepared nanoparticles were added to a polymer matrix containing hypromellose, polyvinyl alcohol, and maltodextrin and cast to rapidly dissolving thin film by solvent casting method. RESULTS: The physicochemical characteristics of empagliflozin in the orodispersible film were most favorable for further studies. This formulation has achieved a higher permeability (7.2-fold) as compared to the reference drug product (Jardiance) after 45 min. In vivo pharmacokinetic studies in Wistar rats have revealed that chitosan-alginate empagliflozin nanoparticles in the orodispersible film were 1.18-fold more bioavailable in comparison to free empagliflozin in orodispersible film. The Cmax observed for the empagliflozin-loaded orodispersible film was 15.42 ± 5.13 µg/mL in comparison to 18.21 ± 5.53 µg/mL for empagliflozin nanoparticle-containing orodispersible film and 12.19 ± 6.71 µg/mL for freed rug suspension. The t1/2and AUC0-t values for chitosan-alginate nanoparticles of empagliflozin in the orodispersible film were found1.4-fold more than empagliflozin loaded orodispersible film (without nanoparticles). The cytotoxicity study has shown that chitosan-alginate nanoparticles of empagliflozin in orodispersible film achieved a 2.5-fold higher cytotoxic effect than free empagliflozin in orodispersible film in A549lung cancer cells. CONCLUSIONS: This study provides evidence that chitosan-alginate nanoparticles of empagliflozin in orodispersible film can be an effective drug carrier system to improve sustained effect with better bioavailability of poorly water-soluble drug.

Anticancer Activity of Cordia dichotoma against a Panel of Human Cancer Cell Lines and Their Phytochemical Profiling via HPLC and GCMS.

The current study was conducted to examine the in vitro anticancer potential of Cordia dichotoma (bark, leaves, pulp and seed). The plant material was collected from UT of J&K and methodical bioassays were carried out on ten human cancer cell lines (Michigan Cancer Foundation-7 (MCF-7), M.D. Anderson-Metastatic Breast (MDA-MB-231), Neuroblastoma-2a (N2A), SH-SY5Y, U-251, HCT-116, SW-620, A-549, MIA PaCa-2, Panc-1) from five different origins (breast, CNS, colon, lung, pancreas) respectively. Methanolic extracts were produced and fractions were then obtained from the extracts and evaluated for cytotoxicity. Mechanistic assays, HPLC, and GCMS profiling were performed on the highest active fraction. The Sulforhodamine B (SRB) assay determined the in vitro cytotoxicity. The findings revealed that the bark portion had in vitro cytotoxicity against the A-549 human lung cancer cell line. To our knowledge, this is the first study to show that the plant's bark has anticancer properties and induced chromatin condensation, confirmed cell death via ROS generation, and significantly decreased colony formation in A-549 cell line from lung origin in a dose-dependent manner. Furthermore, HPLC and GCMS investigations indicated the presence of a number of bioactive molecules such as gallic acid (144,969.86) uV*sec, caffeic acid (104.26) uV*sec, ferulic acid (472.87) uV*sec, vanillic acid (13,775.39) uV*sec, palmitic acid (18.34%), cis vaccenic acid (28.81%), etc. and one of the compounds was reported for the first time from the bark. As a result of its promising efficacy, it may become an essential cancer chemopreventive or chemotherapeutic medication for patients with lung carcinoma.

Lactate enhanced-quick Sequential Organ Failure Assessment 2 (LqSOFA2): A new score for bedside prognostication of patients with sepsis.

Background & objectives: Early diagnosis and prompt treatment remain a challenge in sepsis. To study the role of quick Sequential Organ Failure Assessment (qSOFA), blood lactate levels and a new score Lactate - Enhanced-qSOFA 2 (LqSOFA2) in predicting outcome in patients with sepsis and their association with established severity scores. Methods: This was a prospective, observational study in patients admitted to ICU of a tertiary care hospital in north India. qSOFA, Acute Physiology and Chronic Health Evaluation II (APACHE II), SOFA score and LqSOFA2 were calculated in 150 patients with sepsis. Measurements of lactate and SOFA score was done on days one, three and seven. Results: The mean arterial pressure (MAP) was significantly higher in survivors (70.14±19.54 vs. 48.53±26.86). The mean qSOFA significantly predicted mortality (1.81 vs. 2.63; P<0.0001). The mean lactate on days one, three and seven in survivors were 2.27±0.91, 1.72±0.77 and 1.14±0.48, respectively, while it was 4.32±2.35, 3.57±2.28 and 2.13±1.22, respectively, in the non-survivor group (P<0.001). The new score LqSOFA2 also significantly predicted mortality between non survivors and survivors (3.52±0.71 vs. 2.37±0.91). There was a significant correlation of qSOFA with SOFA and APACHE II on day one. Lactate levels and SOFA correlated on all three days. Interpretation & conclusions: qSOFA, a novel score and lactate can independently predict mortality in patients with sepsis. They correlate with APACHE II and SOFA but fail to equilibrate with either. The combination score LqSOFA2 showed marginal (statistically insignificant) increase in predictive accuracy and specificity when compared to lactate or qSOFA alone. Early diagnosis by LqSOFA2 makes it a good standalone bedside prognostic marker.

Pre-clinical and cellular toxicity evaluation of 7-methylxanthine: an investigational drug for the treatment of myopia.

The present study entails the toxicity evaluation of 7-methyl xanthine (7-MX), first of its kind molecule found effective in phase II clinical trials for the treatment of myopia, in comparison to other clinically used xanthines i.e., caffeine and theobromine. For acute toxicity evaluation, 7-MX was administered orally in two rodent species (rat and mice) at the doses of 300 mg/kg and 2000 mg/kg and for repeated dose 28-d oral toxicity, at 250, 500, and 1000 mg/kg in rats. Further, cellular toxicity was evaluated in normal breast epithelial (fR2), rat brain C6 glioma (C6 glioma) and human colorectal (Caco-2) cell lines. Also, the cell uptake assay to determine the intestinal permeability of drug was performed in Caco-2 cells. In acute toxicity, 7-MX treatment showed no mortality and toxicity, whereas 66.6% (mice) and 33.3% (rat) mortality was observed in both caffeine and theobromine treatment groups. In repeated dose 28-d oral toxicity, 7-MX treatment was found to have no-observed-adverse-effect level up to the dose of 1000 mg/kg in the present study conducted as per OECD guidelines 407. Also, very high IC50 value of 305.5 and 721 µg/mL was observed for 7-MX in fR2 and C6 glioma cells, respectively. In Caco-2 cells, linear bioavailability and high % cell viability was observed. Thus, 7-MX may be classified as Globally Harmonized System (GHS) category 5 drug with LD50 >2000-5000 mg/kg. Also, the repeated dose 28-d oral toxicity study demonstrated 7-MX to be nontoxic in nature, with cell line toxicity results further endorsing its nontoxic nature.

A hidden Markov model for analyzing eye-tracking of moving objects : Case study in a sustained attention paradigm.

Eye-tracking provides an opportunity to generate and analyze high-density data relevant to understanding cognition. However, while events in the real world are often dynamic, eye-tracking paradigms are typically limited to assessing gaze toward static objects. In this study, we propose a generative framework, based on a hidden Markov model (HMM), for using eye-tracking data to analyze behavior in the context of multiple moving objects of interest. We apply this framework to analyze data from a recent visual object tracking task paradigm, TrackIt, for studying selective sustained attention in children. Within this paradigm, we present two validation experiments to show that the HMM provides a viable approach to studying eye-tracking data with moving stimuli, and to illustrate the benefits of the HMM approach over some more naive possible approaches. The first experiment utilizes a novel 'supervised' variant of TrackIt, while the second compares directly with judgments made by human coders using data from the original TrackIt task. Our results suggest that the HMM-based method provides a robust analysis of eye-tracking data with moving stimuli, both for adults and for children as young as 3.5-6 years old.

Adrenomedullin and Its Possible Role in Improved Survival in Female Patients with Sepsis: A Study in the South East Asian Region.

AIMS AND OBJECTIVES: Serum adrenomedullin (ADM) as a prognostic biomarker to study the gender-related differences in mortality pattern and its correlation with the sequential organ failure assessment (SOFA) and acute physiologic assessment and chronic health evaluation II (APACHE II) scores in patients of sepsis. MEASUREMENTS AND MAIN RESULTS: Eighty patients of sepsis of which 36 were males and 44 were females, were taken in the study as per sepsis III guidelines. They were followed up for a period of 28 days. Serum ADM was measured on day 1 and day 5. The endpoint was mortality or survival at day 28 after admission. The death rate among males was higher, with 23 of the total 36 (63.89%) patients having died when compared with females in which 25 patients out of 44 (56.82%) had died. The observed mortality rates correlated well with average APACHE II scores. The average APACHE II score was slightly higher in males (29 ± 8.97) when compared with females (27.02 ± 8.69). Similarly, day 1 SOFA and mean SOFA values were higher in males (10.22 ± 5.36) and (10.73 ± 6.01) when compared with females (8.27 ± 4.79) and (8.89 ± 5.6), respectively. Males despite having higher mortality rates, higher APACHE II, SOFA, and mean SOFA values were still having less mean levels of serum ADM (454.40 ± 81.13 pg/mL) when compared with females (479.62 ± 126.97 pg/mL). CONCLUSION: Adrenomedullin is a protective neurohormone with antibacterial and anti-inflammatory properties. It is elevated in all patients with sepsis but the rise is more so in the female when compared with males. Higher ADM levels in females may suggest the protective effect of ADM as a part of the general protective neurohormonal stress response, which may explain the low death rate in females in sepsis. HOW TO CITE THIS ARTICLE: Daga MK, Kumar L, Mawari G, Kumar N, Singh S, Mishra TK. Adrenomedullin and Its Possible Role in Improved Survival in Female Patients with Sepsis: A Study in the South East Asian Region. Indian J Crit Care Med 2020;24(12):1180-1184.

Soft tissue reactions following cochlear implantation.

INTRODUCTION: Cochlear implantation is a boon to children with hearing loss. Rarely, it can be associated with complications. Soft tissue reaction can be a particularly distressing complication. MATERIALS AND METHODS: The study was conducted on all patients presenting with soft tissue reaction post-cochlear implant in a tertiary care referral institute from March 2011 to June 2018. We graded the severity of soft tissue reaction as per the severity and then managed these patients accordingly. RESULTS: Thirty-five patients were included in this study. Grade 1 had 12 patients, grade 2 had 9, grade 3 had 4 and grade 4 had 9 patients. Grade 1, 2 and 3 reactions were managed conservatively, while grade 4 required surgery. The incidence of explantations increased with the grade severity. CONCLUSION: Soft tissue reaction post-cochlear implant is a rare, but distressing complication. Grading and analyzing them can help us manage them in a better way.