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Salmonella enterica and Escherichia coli use the inner membrane transporter DctA to import the pyrimidine biosynthetic pathway intermediate orotate from the environment. To study the regulation of dctA expression, we used an S. enterica serovar Typhimurium pyrimidine auxotroph to select a mutant that could grow in an otherwise nonpermissive culture medium containing glucose and a low concentration of orotate. Whole genome sequencing revealed a point mutation upstream of dctA in the putative cyclic AMP receptor protein (CRP) binding site. The C→T transition converted the least favourable base to the most favourable base for CRP–DNA affinity. A dctA::lux transcriptional fusion confirmed that the mutant dctA promoter gained responsiveness to CRP even in the presence of glucose. Moreover, dctA expression was higher in the mutant than the wild type in the presence of alternative carbon sources that activate CRP.

Limited reports exist regarding adeno-associated virus (AAV) biodistribution in swine. This study assessed biodistribution following antegrade intracoronary and intravenous delivery of two self-complementary serotype 9 AAV (AAV9sc) biologics designed to target signaling in the cardiomyocyte considered important for the development of heart failure. Under the control of a cardiomyocyte-specific promoter, AAV9sc.shmAKAP and AAV9sc.RBD express a small hairpin RNA for the perinuclear scaffold protein muscle A-kinase anchoring protein β (mAKAPβ) and an anchoring disruptor peptide for p90 ribosomal S6 kinase type 3 (RSK3), respectively. Quantitative PCR was used to assess viral genome (vg) delivery and transcript expression in Ossabaw and Yorkshire swine tissues. Myocardial viral delivery was 2–5 × 105 vg/µg genomic DNA (gDNA) for both infusion techniques at a dose ∼1013 vg/kg body wt, demonstrating delivery of ∼1–3 viral particles per cardiac diploid genome. Myocardial RNA levels for each expressed transgene were generally proportional to dose and genomic delivery, and comparable with levels for moderately expressed endogenous genes. Despite significant AAV9sc delivery to other tissues, including the liver, neither biologic induced toxic effects as assessed using functional, structural, and circulating cardiac and systemic markers. These results indicate successful targeted delivery of cardiomyocyte-selective viral vectors in swine without negative side effects, an important step in establishing efficacy in a preclinical experimental setting.

Background We aimed to study organizational aspects, case mix, and practices in Indian intensive care units (ICUs) from 2018 to 2019, following the Indian Intensive Care Case Mix and Practice Patterns Study (INDICAPS) of 2010–2011. Methods An observational, 4-day point prevalence study was performed between 2018 and 2019. ICU, patient characteristics, and interventions were recorded for 24 hours, and ICU outcomes till 30 days after the study day. Adherence to selected compliance measures was determined. Data were analyzed for 4,669 adult patients from 132 ICUs. Results On the study day, mean age, acute physiology and chronic health evaluation (APACHE II), and sequential organ failure assessment (SOFA) scores were 56.9 ± 17.41 years, 16.7 ± 9.8, and 4.4 ± 3.6, respectively. Moreover, 24% and 22.2% of patients received mechanical ventilation (MV) and vasopressors or inotropes (VIs), respectively. On the study days, 1,195 patients (25.6%) were infected and 1,368 patients (29.3%) had sepsis during their ICU stay. ICU mortality was 1,092 out of 4,669 (23.4%), including 737 deaths and 355 terminal discharges (TDs) from ICU. Compliance for process measures related to MV ranged between 62.7 and 85.3%, 11.2 and 47.4% for monitoring delirium, sedation, and analgesia, and 7.7 and 25.3% for inappropriate transfusion of blood products. Only 34.8% of ICUs routinely used capnography. Large hospitals with ≥500 beds, closed ICUs, the APACHE II and SOFA scores, medical admissions, the presence of cancer or cirrhosis of the liver, the presence of infection on the study day, and the need for MV or VIs were independent predictors of mortality. Conclusions Hospital size and closed ICUs are independently associated with worse outcomes. The proportion of TDs remains high. There is a scope for improvements in processes of care. Registered at clinicaltrials.gov (NCT03631927). How to cite this article Divatia JV, Mehta Y, Govil D, Zirpe K, Amin PR, Ramakrishnan N, et al. Intensive Care in India in 2018–2019: The Second Indian Intensive Care Case Mix and Practice Patterns Study. Indian J Crit Care Med 2021;25(10):1093–1107.

To create a model of the anatomic distribution, recurrence, and growth patterns of recurrent respiratory papillomatosis (RRP).Prospective, multi-institutional cohort study.Adult patients with a diagnosis of RRP evaluated between August 1, 2018 and February 1, 2021 at six participating centers were invited to enroll. At each office or operating room encounter, laryngologists recorded the location and size of RRP lesions using a 22-region schematic. A generalized linear mixed effects model was used to compare region variations in lesion prevalence and recurrence.The cohort comprised 121 patients: 74% were male, 81% had been diagnosed with adult-onset RRP, and a plurality (34%) had undergone 0 to 3 RRP interventions prior to enrollment. Across the study period, the odds of a lesion occurring in the glottis was significantly higher (odds ratio [OR]: 26.51; 95% confidence interval [CI]: 11.76-59.75, P .001) compared with all other areas of the larynx and trachea. Within the true vocal folds, the membranous vocal folds had significantly higher odds (OR: 6.16; 95% CI: 2.66-14.30, P .001) of lesion occurrence compared to the cartilaginous vocal folds. Despite these strong trends in lesion distribution, there were no differences in the odds of lesion recurrence, growth, or in the time to recurrence, between anatomic subsites.RRP lesions are most likely to occur in the glottis, particularly the membranous vocal folds, compared with other regions of the larynx or trachea. However, all lesions demonstrate similar behavior with respect to recurrence, growth, and time to recurrence regardless of anatomic location.3 Laryngoscope, 132:2403-2411, 2022.

Data envelopment analysis (DEA) is a widely used mathematical programming approach for assessing the efficiency of decision-making units (DMUs) in various sectors. Inverse DEA is a post-DEA sensitivity analysis approach developed initially for solving resource allocation. The main objective of inverse DEA is to determine the optimal quantity of inputs and/or outputs for each DMU under input and/or output perturbation (s), which would allow them to reach a given efficiency target. Since the early 2000s, inverse DEA has been extended theoretically and applied successfully in different areas including banking, energy, education, sustainability and supply chain management. In recent years, research has demonstrated the potential of inverse DEA for solving novel inverse problems, such as estimating merger gains, minimizing production pollution, optimizing business partnerships and more. This paper provides a comprehensive survey of the latest theoretical and practical advancements in inverse DEA while also highlighting potential areas for future research and development in this field. One such area is exploring the use of heuristic algorithms and optimization techniques in conjunction with inverse DEA models to address issues of infeasibility and nonlinearity. Moreover, applying inverse DEA to new sectors such as healthcare, agriculture and environmental and climate change issues holds great promise for future research. Overall, this paper sets the stage for further advancements in this promising approach.

Carbohydrate esters are significant in medicinal chemistry because of their efficacy for the synthesis of biologically active drugs. In the present study, methyl β-D-galactopyranoside (MGP) was treated with various acyl halides to produce 6-O-acyl MGP esters by direct acylation method with an excellent yield. To obtain newer products for antimicrobial assessment studies, the 6-O-MGP esters were further modified into 2,3,4-tri-O-acyl MGP esters containing a wide variety of functionalities in a single molecular framework. The chemical structures of the newly synthesized compounds were elucidated by analyzing their physicochemical, elemental, and spectroscopic data. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) revealed that these MGP estes have promising antifungal functionality compared to their antibacterial activities. The antimicrobial tests demonstrated that the compounds 3 and 10 were the most potent against Bacillus subtilis and Escherichia coli strains, with the minimum inhibitory concentration (MIC) values ranging from 0.352 ± 0.02 to 0.703 ± 0.01 mg/ml and minimum bactericidal concentration (MBC) values ranging from 0.704 ± 0.02 to 1.408 ± 0.04 mg/ml. Density functional theory (DFT) at the B3LYP/3-21G level of theory was employed to enumerate, frontier orbital energy, enthalpy, free energy, electronic energy, MEP, dipole moment which evaluated the effect of certain groups (aliphatic and aromatic) on drug properties. They discovered that all esters were more thermodynamically stable than the parent molecule. Molecular docking is performed using AutoDock Vina to determine the binding affinities and interactions between the MGP esters and the SARS-CoV-2 main protease. The modified esters strongly interact with the prime Cys145, His41, MET165, GLY143, THR26, and ASN142 residues. The MGP esters’ shape and ability to form multiple electrostatic and hydrogen bonds with the active site match other minor-groove binders’ binding modes. The molecular dynamics simulation validates the molecular docking results. The pharmacokinetic characterization of the optimized inhibitor demonstrates that these MGP esters appear to be safer inhibitors and a combination of in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction and drug-likeness had promising results due to their improved kinetic properties. Structure activity relationships (SAR) study including in vitro and silico results revealed that the acyl chain, palmitoyl (C16) and 4-chlorobenzoyl (4.ClC6H4CO-) in combination with sugar were found the most potential activates against human and fungal pathogens. After all, our comprehensive computational and statistical analysis shows that these selected MGP esters can be used as potential inhibitors against the SARS-CoV-2. Supplementary Information The online version contains supplementary material available at 10.1007/s10719-021-10039-3.

PURPOSE: The current study addressed work-related stress and burnout experienced by health care workers (HCWs) in Cairo University isolation hospital and its impact on the cognitive domain of their executive functioning. METHODS: Arabic validated questionnaires of Beverly Potter for sources of work-related burnout and Maslach Burnout Inventory Human Services Survey for evaluation of burnout degree of 81 HCWs were used. Wisconsin Card Sorting Test was used to examine the HCWs cognitive executive functioning during hospital work and 2 weeks after home isolation. RESULTS: A high degree of work-related stress was evident by a high score on Beverly questionnaire with a mean ± SD of (132.08 ± 12.573). A high degree of burnout was marked with a mean ± SD of (28.48 ± 6.622) for Emotional Exhaustion module, (31.85 ± 5.439) Personal Achievement, and (17.52 ± 6.707) Depersonalization. Health care workers experienced impairment of executive functioning in the form of increased total errors of Wisconsin Card Sorting Test during hospital shifts compared to 2 weeks after. There is a positive significant correlation between work-related stress level and Maslach Burnout Inventory and the total errors of Wisconsin Card Sorting Test results during the hospital stay (p = < 0.001), as well as 2 weeks after (p = < 0.001).This cognitive decline manifested in increased errors during HCWs' clinical work. CONCLUSIONS: Health care workers on the front line experienced a high degree of work-related stress in addition to burnout in the form of Emotional Exhaustion, Depersonalization, and reduced Personal Achievement. They also suffered from impaired cognitive executive functioning due to such stressful exposure.

As of August 15, 2020, Bangladesh lost 3591 lives since the first Coronavirus disease 2019 (COVID-19) case announced on March 8. The objective of the study was to report the clinical manifestation of both symptomatic and asymptomatic COVID-19-positive patients. An online-based cross-sectional survey was conducted for initial recruitment of participants with subsequent telephone interview by the three trained physicians in 237 adults with confirmed COVID-19 infection in Bangladesh. The study period was 27 April to 26th May 2020. Consent was ensured before commencing the interview. Collected data were entered in a pre-designed case record form and subsequently analyzed by SPSS 20.0. The mean±SD age at presentation was 41.59±13.73 years and most of the cases were male (73.0%). A total of 90.29% of patients reside in urban areas. Among the positive cases, 13.1% (n=31) were asymptomatic. Asymptomatic cases were significantly more common in households with 2 to 4 members (p=0.008). Both symptomatic and asymptomatic patients shared similar ages of presentation (p=0.23), gender differences (p=0.30) and co-morbidities (p=0.11). Only 5.3% of patients received ICU care during their treatment. The most frequent presentation was fever (88.3%), followed by cough (69.9%), chest pain (34.5%), body ache (31.1%), and sore throat (30.1%). Thirty-nine percent (n=92) of the patients had co-morbidities, with diabetes and hypertension being the most frequently observed. There has been an upsurge in COVID-19 cases in Bangladesh. Patients were mostly middle-aged and male. Typical presentations were fever and cough. Maintenance of social distancing and increased testing are required to meet the current public health challenge.

Chitosan is a biodegradable natural compound that has a great potentiality in agriculture for controlling plant diseases. An attempt was made to control Fusarium wilt caused by Fusarium oxysporum f. sp. melongenae under inoculated field condition and increase the growth and yield of brinjal by chitosan. Before setting the experiments in the field, preliminary laboratory experiments were carried out to select virulent isolate and effective dose of chitosan against the mycelial growth of the selected pathogen. F. oxysporum f. sp. melongenae isolate F-1 was found to be the most virulent on brinjal in pathogenicity test. Chitosan @ 1.0% concentration was appeared to be the highest inhibitory to the test pathogen at in vitro condition. Additionally, seed treatment with 1.0% chitosan for 12 hrs resulted in the highest increased in germination and seedling growth of brinjal. The field experiment was conducted following Randomized Complete Block Design (RCBD) with four treatments. No treatment was given in T1, the pathogen was inoculated in T2 and seed treatment and soil amendment with 1.0% chitosan was done in T3 and T4, respectively, in test pathogen inoculated condition. Application of 1.0% chitosan as a seed treatment (T3) or soil amendment (T4) significantly reduced pre- and post-emergence seedling mortality, incidence and severity of Fusarium wilt as well as enhanced germination percentage, plant growth and yield of brinjal. On the contrary, pre-emergence and post-emergence seedling mortality, disease incidence and severity of Fusarium wilt were highest in treatment T2 where the soil was inoculated with pathogen without chitosan. Therefore, chitosan could be used against this vascular disease as an alternative to inorganic fungicides and augment yield.

Background: The combined sensory index (CSI) test is more precise in diagnosing carpal tunnel syndrome (CTS) early cases. Another useful tool for early detection of CTS is the diagnostic ultrasonography. Objective: The present study was conducted to compare between the CSI test and its sensitivity with diagnostic ultrasonography IOR (inlet outlet ratio) in suspected or early cases of carpal tunnel syndrome (CTS). Patients and methods: The presentcase-control study involved 20 subjects with signs and symptoms suggestive of early cases of CTS with duration less than 6 months, in addition to 20 apparently healthy subjects who were clinically examined and underwent EDX and US evaluation. We excluded patients with severe CTS, proximal cervical lesion, or other neurological diseases. Results: By comparison, CSI shows a higher sensitivity than IOR. Combining both tests induced elevated substantial differences between patients as well as controls (P

Nausea is a common disease symptom, yet there is no consensus regarding its physiological markers. In contrast, the process of vomiting is well documented as sequential muscular contractions of the diaphragm and abdominal muscles and esophageal shortening. Nausea, like other self-reported perceptions, is difficult to distinguish in preclinical models, but based on human experience emesis is usually preceded by nausea. Here we focused on measuring gastrointestinal and cardiorespiratory changes prior to emesis to provide additional insights into markers for nausea. Felines were instrumented to chronically record heart rate, respiration, and electromyographic (EMG) activity from the stomach and duodenum before and after intragastric delivery of saline or copper sulfate (CuSO4, from 83 to 322 mg). CuSO4is a prototypical emetic test agent that triggers vomiting primarily by action on GI vagal afferent fibers when administered intragastrically. CuSO4infusion elicited a significant increase in heart rate, decrease in respiratory rate, and a disruption of gastric and intestinal EMG activity several minutes prior to emesis. The change in EMG activity was most consistent in the duodenum. Administration of saline did not induce these effects. Increasing the dose of CuSO4did not alter the physiologic changes induced by the treatment. It is postulated that the intestinal EMG activity was related to a retrograde movement of chyme from the intestine to the stomach. These findings suggest that monitoring of intestinal EMG activity, perhaps in combination with heart rate, may provide the best indicator of the onset of nausea following treatments and in disease conditions, including GI disease, associated with emesis.

Background There is a knowledge gap regarding the risk for labour market marginalisation among younger cohorts of refugees and non-refugee immigrants. We investigated if the risk of long-term unemployment (LTU) and disability pension (DP) differs between young refugees and non-refuge immigrants compared to the Swedish-born. The role of age at arrival, duration of residency and morbidity in this association was also investigated. Methods All 19- to 25-year-olds residing in Sweden on 31 December 2004 (1691 refugees who were unaccompanied by a parent at arrival, 24,697 accompanied refugees, 18,762 non-refugee immigrants and 621,455 Swedish-born individuals) were followed from 2005 to 2016 regarding LTU (>180 days annually) and DP using nationwide register data. Cox regression models were used to estimate crude and multivariate-adjusted (adjusted for several socio-demographic, labour market and health-related covariates) hazard ratios (aHRs) with 95% confidence intervals. Results Compared to the Swedish-born, all migrant groups had around a 1.8-fold higher risk of LTU (range aHR=1.71-1.83) and around a 30% lower risk of DP (range aHR=0.66-0.76). Older age at arrival was associated with a higher risk of LTU only for non-refugee immigrants. Both older age at arrival and a shorter duration of residency were associated with a lower risk of DP for all migrant groups. Psychiatric morbidity had the strongest effect on subsequent DP, with no significant differences between migrant groups and the Swedish-born (range aHR=5.1-6.1). Conclusions Young immigrants had a higher risk of LTU and a lower risk of DP than their Swedish-born peers. No differences between the different immigrant groups were found. Age at arrival, psychiatric morbidity and duration of residency are strong determinants of being granted DP. Key messages

Inverse data envelopment analysis (DEA) determines the optimal level of inputs and/or outputs of decision-making units (DMUs) to reach efficiency targets. This paper presents a new inverse DEA model for determining minimum inputs for working capital management. The proposed model is employed in the Indian textile industry to calculate working capital efficiency. Given the working capital efficiency, the decision maker’s preferences will be estimating the change in inputs when outputs increase. Furthermore, unlike the standard inverse DEA model, this article discusses the inverse DEA model when negative ratio data exist. The DEA model requires additional attention when ratio data are present; therefore, a novel inverse DEA ratio model is proposed. The input targets obtained from the proposed model are less than the standard inverse DEA model. Also, the proposed model is a closer estimate of the production probability set for ratio data.

Base of tongue (BOT) dysfunction is common following oropharyngeal concurrent chemoradiation therapy (CCRT). We present a clinically relevant animal model quantifying the effects of CCRT on tongue strength and elasticity over time.Fifty-three male and 53 female Sprague-Dawley rats were randomized to control or experimental groups. Experimental animals received cisplatin, 5-fluorouracil, and 5 fractions of 7 Gy directed to the BOT. Controls received no intervention. At 2 weeks, 5 months, or 10 months after CCRT, animals underwent non-survival surgery to measure twitch and tetanic tongue strength, which were analyzed using multivariate linear mixed effects models. Tongue displacement, a surrogate for tongue elasticity, was also determined via stress-strain testing and analyzed via a multivariate linear mixed effects model.Reporting the combined results of both sexes, the estimated experimental group mean peak twitch forces became more divergent over time compared to controls, being 8.3% lower than controls at 2 weeks post-CCRT, 15.7% lower at 5 months, and 31.6% lower at 10 months. Estimated experimental group mean peak tetanic forces followed a similar course and were 2.9% lower than controls at 2 weeks post CCRT, 20.7% lower at 5 months, and 27.0% lower at 10 months. Stress-strain testing did not find CCRT to have a significant effect on tongue displacement across experimental timepoints.This study demonstrates an increasing difference in tongue strength over time between controls and animals exposed to CCRT. Tongue elasticity was not significantly affected by CCRT, suggesting that changes in strength may not be caused by fibrosis.NA Laryngoscope, 2022.

Several carbohydrate-based drugs are currently being used to treat a number of diseases in humans worldwide. Thus, our research group has focused on the synthesis of new methyl alpha-D-mannopyranoside (MDM) derivatives and their antimicrobial evaluation through computational studies. A series of MDM derivatives (2-6) were synthesized through facile regioselective acylation, using the direct method affording 6-O-(3-chlorobenzoyl) derivatives. This isolated 6-O-derivative was further transformed to 2,3,4-tri-O-acyl derivatives, bearing a wide variety of functionalities in a single molecular framework. The structures of the newly designed molecules were elucidated with the aid of IR, H-1 NMR, mass spectroscopy, and elemental analysis. The prediction of the activity spectra for the compounds (PASS) and their in vitro antimicrobial evaluation were performed, demonstrating them to be potential antimicrobial agents. The antimicrobial tests demonstrated that the compounds 3 and 5 were the most potent with the minimum inhibitory concentration (MIC) values, ranging from 0.312 +/- 0.01 to 1.25 +/- 0.03 mg/mL, and minimum bactericidal concentration (MBC) values, ranging from 0.625 +/- 0.02 to 2.50 +/- 0.05 mg/mL. A quantum chemical study was performed to calculate the thermodynamic, molecular orbital and electrostatic potential properties of the designed compounds. Molecular docking simulation was carried out against SARS-CoV-2 M-pro protein 7BQY and 6Y84 to investigate their binding energy and binding tactics with the viral protein, and better binding affinity than that of the parent drug was observed. Also, pharmacokinetic prediction revealed an improved drug-likeness profile for all MDM derivatives.

Digital filter bank of DWT (discrete wavelet transform) provides the approximate and detail components of a signal, whereas the perfection of the filter bank depends on recovery of the signal. In this paper, we convert an image into a one dimensional signal vector then the perfection of the filter bank is observed on recovery of signal vector hence the image. Here orthogonal FIR (finite impulse response), FIR under window method, IIR (infinite impulse response) Butterworth, Chebyshev type-I, type-II and synchrosqueezed transform are compared in context of image recovery under statistical parameters: mean error, variance of error, difference of skewness and kurtosis, cross-correlation coefficient, PSNR (peak signal to noise ratio) and histogram. The orthogonal FIR combination gives the best results and synchrosqueezed transform is the worst case for reconstruction of image.

Mergers and acquisitions are mainly due to financial and technological innovations but could also be due to changes in the structure of the economy, which alters the optimal production functions of banks. Banks that seek to be operationally efficient would focus more on expanding their asset size, in the face of bad loans, leading to the acquisition of less efficient banks. This paper develops two‐stage inverse data envelopment analysis (DEA) models for estimating potential gains from bank mergers for the top US commercial banks. The results show additional intermediate and final outputs at different predefined target levels of technical efficiencies.