Association between baseline insulin resistance and hospital mortality in moderate-to-severe coronavirus disease 2019 patients without diabetes mellitus: An observational study.

Background: Insulin resistance is often implicated as a risk factor of cell-mediated immune dysfunction in sepsis patients and results in poor clinical outcome. However, it is unclear whether early insulin resistance is contributory to T-cell dysfunction and poor clinical outcome in coronavirus disease 2019 (COVID-19) patients. Methods: Adult patients with moderate-to-severe or critically ill COVID-19 infection were included in this study. Serum samples were collected at the time of diagnosis for fasting plasma glucose, serum insulin, serum cortisol, and serum glucagon measurements, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score was calculated. Results: One hundred and twenty-six subjects with a mean (standard deviation) age of 49.6 (16.3) years were recruited in this study, and 62.4% (78 of 125 patients) were male. HOMA-IR was a predictor of inhospital mortality with the area under the receiver operating characteristics curve (AUROC) (95% confidence interval [CI] of 0.61 [0.49-0.73]). With a cutoff value of 1.91, sensitivity was 75.5% and specificity was 45.2%. Higher serum insulin was associated with higher survival with AUROC (95% CI) of 0.65 (0.53-0.76), and the best cutoff was 7.15, with a sensitivity and specificity of 62.1% and 64.5%. Serum cortisol was also a predictor of inhospital mortality with an AUROC (95% CI) of 0.67 (0.56-0.77). Conclusion: An independent association between baseline serum cortisol and poor outcome in moderate-to-severe COVID-19 patients was observed. Hyperglycemia and HOMA-IR can also predict poor outcome in these patients with some accuracy.

Subphenotypes of SARS-CoV-2-Associated ARDS Overlap Each Other: A Retrospective Analysis.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-associated pneumonia and acute respiratory distress syndrome (ARDS) were often associated with hyperinflammation and elevation of several serum inflammatory markers but usually less than what is observed in non-coronavirus disease (COVID) ARDS. Elevated inflammatory markers such as C-reactive protein, interleukin (IL)-6, etc., are associated with severe infection. This study identified subphenotypes of COVID-19 ARDS patients by latent profile analysis in a cohort of Indian patients. Methods Data of n = 233 adult Indian patients with laboratory-confirmed SARS-CoV-2 infection admitted to a tertiary care teaching hospital were analyzed in this retrospective study. Only patients with acute respiratory failure (defined by partial pressure of oxygen/fraction of inspired oxygen ratio < 200 mm Hg) and chest X-ray showing bilateral infiltrates were included. Results The patients' mean (standard deviation) age was 53.3 (14.9) years, and 62% were male. A two subphenotypic model was formulated based on the lowest Bayesian information criterion. Neutrophil-to-lymphocyte ratio and serum IL-6 were latent variables in that model (entropy 0.91). The second phenotype (hyperinflammatory) had lower platelet count ( p = 0.02), higher serum creatinine ( p = 0.004), higher C-reactive protein ( p = 0.001), higher ferritin ( p < 0.001), and serum lactate dehydrogenase ( p = 0.009). Age-adjusted hospital mortality ( p = 0.007), duration of hospital stay ( p < 0.001), and duration of intensive care unit stay ( p < 0.001) were significantly higher in the second subphenotype. Conclusion Two distinct but overlapping subphenotypes were identified in SARS-CoV-2-associated respiratory failure. Hyperinflammatory subphenotype was associated with significantly poor short-term outcomes.

Ross procedure after prosthetic valve thrombosis in a patient with antiphospholipid syndrome and recurrent bleeding.

The Ross procedure allows replacement of a diseased aortic valve with pulmonary root autograft, possibly avoiding the highly thrombotic mechanical valves and immunologic deterioration of tissue valves in antiphospholipid syndrome (APS). Here, we present the use of the Ross procedure in a 42-year-old woman with mild intellectual disability, APS, and a complex anticoagulation history after she presented with thrombosis of her mechanical On-X aortic valve previously implanted for non-bacterial thrombotic endocarditis.

Effectiveness of Hoffman's Exercise in Postnatal Mothers With Grade 1 Inverted Nipples.

BACKGROUND: Breastfeeding provides perfect nutrition for infants. The inverted nipples in mothers make breastfeeding more challenging. Besides surgical approaches, non-pharmacological interventions are also gaining importance. RESEARCH AIM: To evaluate the effectiveness of Hoffman's exercise on breastfeeding among postnatal mothers with grade I inverted nipples. METHOD: A quantitative approach with a parallel arm randomized controlled trial was used in the study. Postnatal mothers were screened for inverted nipples using a pinch test. Participants with at least one inverted nipple (Grade 1) were randomly allocated into two groups: the experimental group (supported with Hoffman's exercise; n = 28, 50.9% ) and the control group (without Hoffman's exercise; n = 27, 49.1%). The pre-test data, including demographics, nipple length, and breastfeeding assessment, were collected. Breastfeeding assessment was evaluated using the Bristol Breastfeeding Assessment Tool (BBAT). On the 3rd day, the post-test data, including nipple length and Breastfeeding Assessment, were collected among the groups. RESULTS: The BBAT assessment was significantly higher in the post-test compared to that of the pre-test in the participants provided with Hoffman's exercise. The nipple length was found to be higher in participants provided with Hoffman's exercise. Furthermore, the variables-including age, gravida, nipple problems, and delivery type-were not found to have any significant effect with either pre-test or post-test levels of breastfeeding. CONCLUSIONS: Hoffman's exercise was found to be an effective method to improve breastfeeding in Grade 1 nipple-inverted among post-natal mothers. This nipple exercise is inexpensive, easy to follow, and results in the successful initiation of breastfeeding. CLINICAL TRIAL REGISTRY AND REGISTRATION NUMBER: CTRI/2019/05/019279, May 23, 2019 (retrospectively registered).

Colloidal Photonic Crystal-Enhanced Fluorescence of Gold Nanoclusters: A Highly Sensitive Solid-state Fluorescent Probe for Creatinine.

Gold nanoclusters (AuNCs) are an intensely pursued class of fluorophores with excellent biocompatibility, high water solubility, and ease of further conjugation. However, their low quantum yield limits their applications, such as ultra-sensitive chemical or molecular sensing. To address this problem, various strategies have been adopted for augmenting their fluorescence intensity. Herein, we report a facile and scalable approach for the fluorescence enhancement of bovine serum albumin (BSA) capped AuNCs (BSA-AuNCs) using periodic, close-packed polystyrene colloidal photonic crystals (CPCs). The slow photon effect at the bandgap edges is utilized for the increased light-matter interactions and thereby enhancing the fluorescence intensity of the BSA-AuNCs. Compared to the planar polystyrene control sample, the CPC film yielded a 14-fold enhancement in fluorescence intensity. Further, we demonstrated the as-prepared BSA-AuNCs-CPC as a solid-state platform for the highly sensitive and selective fluorescence turn-off detection of creatinine at nanomolar level.

Correction to "Direct Visualization of Crystalline Domains in Carboxylated Nanocellulose Fibers".

[This corrects the article DOI: 10.1021/acsomega.0c00410.].

Sulphur-doped graphene quantum dot based fluorescent turn-on aptasensor for selective and ultrasensitive detection of omethoate.

Development of selective, ultra-sensitive, rapid and facile methods for the detection of chemical residues of toxic pesticides and hazardous chemicals are quite important in food safety, environmental monitoring and safeguarding public health. Herein, we presented a fluorescent turn-on aptasensor based on sulphur-doped graphene quantum dot (S-GQD) utilizing specific recognition and binding property of aptamer for the ultra-sensitive and selective detection of omethoate (OM) which is a systemic organophosphorus pesticide. The detection method is based on tuning aggregation-disaggregation mechanism of S-GQD by way of conformational alteration of the recognition probe. Fluorescence 'turn-on' process includes aggregation-induced quenching of S-GQD with aptamer via S-GQD-aptamer complex formation and its subsequent fluorescence recovery with the addition of OM by structural switching of S-GQD-aptamer complex to aptamer-omethoate complex. The reported 'switch-on' aptasensor has exhibited a low limit of detection of 0.001 ppm with high selectivity for OM over other pesticides.

Evaluation of aryl hydrocarbon receptor expression in oral squamous cell carcinoma and normal oral mucosa using western blot.

BACKGROUND: Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that acts as a binding site for toxic chemicals, particularly the dioxin group of chemicals. Elevated levels of AHR have been observed in various human cancers, including lung carcinomas, hepatic carcinomas and in mammary tumors. However, the expression of AHR in oral squamous cell carcinoma (OSCC) patients who are tobacco users are less explored. AIMS AND OBJECTIVES: The aim of the present study is to evaluate and compare AHR levels in OSSC patients and in normals using Western blot technique in an attempt to explore the possible role of AHR in oral carcinogenesis. MATERIALS AND METHODS: The study sample consisted of ten oral squamous cell carcinoma cases which were diagnosed clinically and confirmed histopathologically as OSCC and four samples of the normal oral mucosa. AHR protein expression was evaluated using Western blot technique and chemiluminescence detection kit. The densitometry was performed on a Microtek scan maker MSP flatbed scanner and quantified using Image J software. Mean AHR protein levels were calculated and compared between OSCC and normal oral mucosa using Student's t-test. RESULTS: The mean AHR protein level in OSCC samples (n = 10) was 2878.90 ± 1231.27 and 975.75 ± 227.27 in the normal oral mucosa (n = 4). The OSCC samples showed significantly higher levels of AHR protein compared to the normal oral mucosa (P = 0.008). CONCLUSION: The study showed a significantly higher expression of AHR in oral squamous cell carcinoma samples when compared to the normal oral mucosa, suggesting a possible role of AHR in the initiation, promotion and progression of oral squamous cell carcinoma.

Vanadium pentoxide nanoparticle mediated perturbations in cellular redox balance and the paradigm of autophagy to apoptosis.

The redox-active transition metals such as copper, iron, chromium, vanadium, and silica are known for its ROS generation via mechanisms such as Haber-Weiss and Fenton-type reactions. Nanoparticles of these metals induce oxidative stress due to acellular factors owing to their small size and more reactive surface area, leading to various cellular responses. The intrinsic enzyme-like activity of nano vanadium has fascinated the scientific community. However, information concerning their cellular uptake and time-dependent induced effects on their cellular organelles and biological activity is lacking. This comprehensive study focuses on understanding the precise molecular interactions of vanadium pentoxide nanoparticles (VnNp) and evaluate their specific "nano" induced effects on MDA-MB-231 cancer cells. Understanding the mechanism behind NP-induced ROS generation could help design a model for selective NP induced toxicity, useful for cancer management. The study demonstrated the intracellular persistence of VnNp and insights into its molecular interactions with various organelles and its overall effects at the cellular level. Where triple-negative breast cancer MDA-MB-231 cells resulted in 59.6% cell death towards 48 h of treatment and the normal fibroblast cells showed only 15.4% cell death, indicating an inherent anticancer property of VnNp. It acts as an initial reactive oxygen species quencher, by serving itself as an antioxidant, while; it was also found to alter the cellular antioxidant system with prolonged incubation. The VnNp accumulated explicitly in the lysosomes and mitochondria and modulated various cellular processes including impaired lysosomal function, mitochondrial damage, and autophagy. At more extended time points, VnNp influenced cell cycle arrest, inhibited cell migration, and potentiated the onset of apoptosis. Results are indicative of the fact that VnNp selectively induced breast cancer cell death and hence could be developed as a future drug molecule for breast cancer management. This could override the most crucial challenge of chemo-resistance that still remain as the main hurdle to cancer therapy.

Computerized Cognitive Rehabilitation Training for Ugandan Seniors Living with HIV: A Validation Study.

The feasibility, acceptability and preliminary efficacy of computerized cognitive rehabilitation therapy (CCRT) for mitigating neurocognitive decline was evaluated in African adults ≥50 years old. Eighty-one Ugandans with (n = 40) and without (n = 41) chronic human immunodeficiency viruses (HIV) were allocated CCRT-i.e., 20-45-min cognitive training sessions with culturally adapted video games delivered via Captain's Log Software, or standard of care (SOC). Pre and post (i.e., 8-weeks later) intervention performance based neurocognitive tests, quality of life (QOL) and frailty related phenotype (FRP) were determined in all respondents. Multivariable linear regression estimated CCRT- vs. SOC-related differences (ß) in neurocognitive batteries, QOL and FRP. Effect sizes (ES) for estimated ß were calculated. CCRT protocol was completed by 92.8% of persons allocated to it. Regardless of HIV status, CCRT was associated with higher performance in learning tests than SOC-interference list (ß = 1.00, 95%CI: (0.02, 1.98); ES = 0.43) and delayed recall (ß = 1.04, 95%CI: (0.06, 2.02); ES = 0.47). CCRT effect on verbal fluency was clinically important (ES = 0.38), but statistical significance was not reached (ß = 1.25, 95%CI: (-0.09, 2.58)). Among HIV-positive adults, clinically important post-CCRT improvements were noted for immediate recall (ES = 0.69), working memory (ES = 0.51), verbal fluency (ES = 0.51), and timed gait (ES = -0.44) tasks. Among HIV-negative adults, CCRT resulted in moderate post-intervention improvement in learning tests (ES = 0.45) and large decline in FRP (ES = -0.71), without a positive effect on simple attention and visuomotor coordination tasks. CCRT intervention is feasible among older Ugandan adults with potential benefit for learning and verbal fluency tests regardless of HIV status and lowering FRP in HIV-negative older adults.

Direct Visualization of Crystalline Domains in Carboxylated Nanocellulose Fibers.

Direct visualization of soft organic molecules like cellulose is extremely challenging under a high-energy electron beam. Herein, we adopt two ionization damage extenuation strategies to visualize the lattice arrangements of the ß-(1→4)-d-glucan chains in carboxylated nanocellulose fibers (C-NCFs) having cellulose II crystalline phase using high-resolution transmission electron microscopy. Direct imaging of individual nanocellulose fibrils with high-resolution and least damage under high-energy electron beam is achieved by employing reduced graphene oxide, a conducting material with high electron transmittance and Ag+ ions, with high electron density, eliminating the use of sample-specific, toxic staining agents, or other advanced add-on techniques. Furthermore, the imaging of cellulose lattices in a C-NCF/TiO2 nanohybrid system is accomplished in the presence of Ag+ ions in a medium revealing the mode of association of C-NCFs in the system, which validates the feasibility of the presented strategy. The methods adopted here can provide further understanding of the fine structures of carboxylated nanocellulose fibrils for studying their structure-property relationship for various applications.

Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio as Predictors of the Early Requirement of Mechanical Ventilation in COVID-19 Patients.

How to cite this article: Nair PR, Maitra S, Ray BR, Anand RK, Baidya DK, Subramaniam R. Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio as Predictors of the Early Requirement of Mechanical Ventilation in COVID-19 Patients. Indian J Crit Care Med 2020;24(11):1143-1144.

Identification of second arginine-glycine-aspartic acid motif of ovine vitronectin as the complement C9 binding site and its implication in bacterial infection.

Vitronectin (Vn), a multifunctional protein of blood and extracellular matrix, interacts with complement C9. This interaction may modulate innate immunity. Details of Vn-C9 interactions are limited. Vn-C9 interactions were assessed by employing a goat homologous system and observing Vn binding to C9 in three different assays. Using recombinant fragments, C9 binding was mapped to the N-terminus of Vn. Site directed mutagenesis was performed to alter the second arginine glycine aspartic acid (RGD) sequence (RGD-2) of Vn. Changing R to G or D to A in RGD-2 caused significant decrease in Vn binding to C9 whereas changing of R to G in the first RGD motif (RGD-1) had no effect on Vn binding to C9. These results imply that the RGD-2 of goat Vn is involved in C9 binding. In a competitive binding assay, the presence of soluble RGD peptide inhibited Vn binding to C9 whereas heparin had no effect. Vn binding to C9 was also evaluated in terms of bacterial pathogenesis. Serum dependent inhibition of Escherichia coli growth was significantly reverted when Vn or its N-fragment were included in the assay. The C-fragment, which did not support C9 binding, also partly nullified serum-dependent inhibition of bacterial growth, probably through other serum component(s).

Hoxb13, a potential prognostic biomarker for prostate cancer.

HOXB13, a member of the homeobox proteins family, is a key regulator of the epithelial differentiation in the prostate gland. HOXB13 is overexpressed during malignant progression of the prostatic tissue and suspected to contribute in the pathogenesis of the prostate gland. In androgen deprived conditions, HOXB13 is thought to act through inhibition of the tumour suppressor protein p21. Since HOXB13 has a multifaceted role in ventral prostate development, its critical partners in the cascade need to be elucidated for a further understanding of its role in prostate malignancy. In this report, we review the functions attributed to HOXB13, by highlighting the most recent findings supporting the hypothesis that HOXB13 might serve as a novel biomarker for the prognosis of prostate cancer.

Machine learning methods for the classification of gliomas: Initial results using features extracted from MR spectroscopy.

CONTEXT: With the advent of new imaging modalities, radiologists are faced with handling increasing volumes of data for diagnosis and treatment planning. The use of automated and intelligent systems is becoming essential in such a scenario. Machine learning, a branch of artificial intelligence, is increasingly being used in medical image analysis applications such as image segmentation, registration and computer-aided diagnosis and detection. Histopathological analysis is currently the gold standard for classification of brain tumors. The use of machine learning algorithms along with extraction of relevant features from magnetic resonance imaging (MRI) holds promise of replacing conventional invasive methods of tumor classification. AIMS: The aim of the study is to classify gliomas into benign and malignant types using MRI data. SETTINGS AND DESIGN: Retrospective data from 28 patients who were diagnosed with glioma were used for the analysis. WHO Grade II (low-grade astrocytoma) was classified as benign while Grade III (anaplastic astrocytoma) and Grade IV (glioblastoma multiforme) were classified as malignant. METHODS AND MATERIALS: Features were extracted from MR spectroscopy. The classification was done using four machine learning algorithms: multilayer perceptrons, support vector machine, random forest and locally weighted learning. RESULTS: Three of the four machine learning algorithms gave an area under ROC curve in excess of 0.80. Random forest gave the best performance in terms of AUC (0.911) while sensitivity was best for locally weighted learning (86.1%). CONCLUSIONS: The performance of different machine learning algorithms in the classification of gliomas is promising. An even better performance may be expected by integrating features extracted from other MR sequences.

Omega-3 Fatty acids could alleviate the risks of traumatic brain injury - a mini review.

Traumatic brain injury (TBI) is an acquired brain trauma that occurs when any sudden trauma/injury causes damage to the brain. TBI is characterized by tissue damage and imbalance in the cerebral blood flow and metabolism. It has been established through laboratory experiments that the dietary supplementation of omega-3 fatty acids (FAs) could reduce the oxidative stress developed in brain due to TBI. The inclusion of omega-3 FA in diet could normalize the levels of brain-derived neurotrophic factor (BDNF), and thus, it could restore the survival of neuronal cells. BDNF improves the synaptic transmission by regulating synapsin 1 and cyclic adenosine monophosphate (cAMP) response element binding protein. The brain tissue analysis of TBI models supplemented with omega-3 polyunsaturated fatty acids (PUFAs) showed significantly reduced lipid peroxidation, nucleic acid and protein oxidation, thereby promoting neuronal and glial cell survival. Thus, omega-3 FA intake could be considered as a therapeutic option to reduce the secondary neuronal damages initiated by TBI.

Nutritional status, assessment, requirements and adequacy of traumatic brain injury patients.

Traumatic Brain Injury (TBI) has been considered as a serious public health problem. Each year, traumatic brain injuries are contributing to a substantial number of cases of permanent disability and deaths and it can be classified according to the severity into penetrating and closed head injury. Symptoms, beside to be unconscious can be defined as vomiting, nausea, headache, dizziness, lack of motor coordination, difficulty in balancing, blurred vision and lightheadedness, bad taste in the mouth, ringing in the ears, fatigue and lethargy as well as changes in sleep patterns. The brain is known to be the functional regulator for all the metabolic activities inside the body and TBI patients mostly have a complex metabolic alterations including aberrant cellular metabolism, abnormal metabolic processes, changes in hormones functions and inflammatory cascade. The TBI patient's status needed to be assessed medically and nutritionally since the medical status of the patients can affect the nutrition part. Data from the four assessment tools are needed to be correctly used and interpreted in order to make a proper nutritional diagnosis, clinical assessment, biochemistry as well as anthropometric measurements. Regardless the methods used for assessing TBI patients, having adequate intake and medical care can lead to a reduction in hospital costs, numbers of day hospitalized, numbers of hours of mechanical ventilation and in the overall infection rates.

Size controlled synthesis of biocompatible gold nanoparticles and their activity in the oxidation of NADH.

Size and shape controlled synthesis remains a major bottleneck in the research on nanoparticles even after the development of different methods for their preparation. By tuning the size and shape of a nanoparticle, the intrinsic properties of the nanoparticle can be controlled leading tremendous potential applications in different fields of science and technology. We describe a facile route for the one pot synthesis of gold nanoparticles in water using monosodium glutamate as the reducing and stabilizing agent in the absence of seed particles. The particle diameter can be easily controlled by varying the pH of the reaction medium. Nanoparticles were characterized using scanning electron microscopy, UV-vis absorption spectroscopy, cyclic voltammetry, and dynamic light scattering. Zeta potential measurements were made to compare the stability of the different nanoparticles. The results suggest that lower pH favours a nucleation rate giving rise to smaller particles and higher pH favours a growth rate leading to the formation of larger particles. The synthesized nanoparticles are found to be stable and biocompatible. The nanoparticles synthesized at high pH exhibited a good electrocatalytic activity towards oxidation of nicotinamide adenine dinucleotide (NADH).