Interactions of Surfactants with the Bacterial Cell Wall and Inner Membrane: Revealing the Link between Aggregation and Antimicrobial Activity.

Surfactants with their intrinsic ability to solubilize lipid membranes are widely used as antibacterial agents, and their interactions with the bacterial cell envelope are complicated by their differential aggregation tendencies. We present a combined experimental and molecular dynamics investigation to unravel the molecular basis for the superior antimicrobial activity and faster kill kinetics of shorter-chain fatty acid surfactant, laurate, when compared with the longer-chain surfactants studied in contact time assays with live Escherichia coli (E. coli). From all-atom molecular dynamics simulations, translocation events across peptidoglycan were the highest for laurate followed by sodium dodecyl sulfate, myristate, palmitate, oleate, and stearate. The translocation kinetics were positively correlated with the critical micellar concentration, which determined the free monomer surfactant concentration available for translocation across peptidoglycan. Interestingly, aggregates showed a lower propensity to translocate across the peptidoglycan layer and longer translocation times were observed for oleate, thereby revealing an intrinsic sieving property of the bacterial cell wall. Molecular dynamics simulations with surfactant-incorporated bacterial inner membranes revealed the greatest hydrophobic mismatch and membrane thinning in the presence of laurate when compared with the other surfactants. The enhanced antimicrobial efficacy of laurate over oleate was further verified by experiments with giant unilamellar vesicles, and electroporation molecular dynamics simulations revealed greater inner membrane poration tendency in the presence of laurate when compared with the longer-chain surfactants. Our study provides molecular insights into surfactant translocation across peptidoglycan and chain length-induced structural disruption of the inner membrane, which correlate with contact time kill efficacies observed as a function of chain length with E. coli. The insights gained from our study uncover unexplored barrier properties of the bacterial cell envelope to rationalize the development of antimicrobial formulations and therapeutics.

An Evaluation of the Changing Trends in Substance Use Behavior Among Patients in the Tertiary Care Setting After the Implementation of Liquor Prohibition in Bihar, India: A Cross-Sectional Study.

Background and objective Substance use disorders pose significant global public health challenges, with India being no exception. Bihar, one of India's most populous states, implemented alcohol prohibition in April 2016 to address the adverse effects of alcohol abuse. However, the impact of this policy on overall substance use behavior among patients in healthcare settings remains to be explored. This cross-sectional study aimed to evaluate the changing trends in substance use behavior among patients in the tertiary care setting following the prohibition of alcohol use in Bihar. Methods A total of 372 patients diagnosed with substance use disorders were recruited from tertiary care facilities in Bihar. Data on demographic characteristics, types of substances used, frequency and quantity of use, reasons for use, and awareness of prohibition laws were collected through structured interviews and reviews of medical records. Descriptive and inferential statistics were used for data analysis. Results The majority of the participants were male (n = 346, 93.01%), with a mean age of 38.5 years. While tobacco use remains stable, there are significant increases in opioid and cannabis consumption post-prohibition, highlighting unintended consequences (p-values - opioids: 0.008, cannabis: 0.021). Additionally, heightened daily and weekly substance use after prohibition is evident (p-values: daily: 0.008, weekly: 0.021), emphasizing the necessity for nuanced policy considerations. Reasons for substance use, including coping with stress and peer pressure, showed significant differences before and after the prohibition (p<0.05). Moreover, awareness of alcohol prohibition laws increased significantly after the implementation of the prohibition (p = 0.003). Conclusions Our findings suggest that while alcohol prohibition in Bihar did not significantly lead to any changes in terms of the types of substances used among patients in tertiary care settings, it did influence the frequency and quantity of tobacco and cannabis consumption. Increased awareness of prohibition laws underscores the importance of policy enforcement and public education initiatives in addressing substance use behavior.

Effect of locosamide as an add-on therapy in the management of dissociative disorders.

The role of lacosamide (LCM) as add on treatment modality in dissociative disorders (DD) is of interest. It was a randomized control trial in which 300 patients diagnosed with dissociative disorders having treatment for the dissociative disorders were included. They were divided into two groups. Group one consisted of intervention group in which LCM was also administered along with conventional psychiatric medication for different dissociative disorders. Group two consisted of control group where the patients of dissociative disorders were found to have conventional medication. There was analysis of improvements in recovery of symptoms and quality of life. There was statistically significant increase in excellent, very good, good and fair quality of life and decrease in poor and satisfactory quality of life in intervention group after drug intervention. It was observed that symptoms of the patients improved in 50.67% cases in intervention group and 10.67% cases in control group. There was greater improvement in recovery of symptoms and quality of life in patients of DD in which LCM was administered as add on medication.

Resilience related to novel coronavirus among doctors and undergraduate medical students-A study from India.

BACKGROUND: There are no studies pertaining to resilience related to novel coronavirus focusing primarily on doctors and undergraduate medical students in India. The objectives of this survey were to assess the resilience and its various domains that are needed for dealing with novel coronavirus among doctors, interns, and undergraduate students and to see its correlation with various sociodemographic factors. MATERIALS AND METHOD: An online cross-sectional survey was done among doctors and undergraduate medical students during the first COVID-19 wave from May 19, 2020 to June 8, 2020. A total of 434 responses were recorded during the study period. All the recorded full responses were considered for data analysis. Snowball sampling was used for this study. Resilience was assessed using three items, which were taken from the Brief Resilience Scale (BRS). RESULT: Out of 434 responses, 51.7% (224/433) of the respondents were non-resilient. The presence of the elderly at home was significantly associated with poor resilience (P = 0.02). Resilience was not significantly associated with other socio-demographic factors. Younger respondents (P = 0.019) and females (P =0.0004) were of the opinion that they recovered late from stressful events. Elderly respondents (P = 0.003) and those with chronic illness (P = 0.008) reported that it is hard for them to snap back if something bad happens (P = 0.003). CONCLUSIONS: More than half of the doctors and undergraduate medical students were found to be non-resilient, underscoring the urgent need to take steps to improve the resilience of this group of frontline workers.

Psychiatric morbidity in patients with psoriasis.

Psoriasis is a common skin disorder that is associated with impairments in quality of life (QOL) and psychological distress. In this study, we investigated the prevalence and determinants of psychiatric morbidity (ie, psychiatric disorders) in 104 patients with chronic plaque psoriasis who presented to the Departments of Dermatology, Venereology, and Leprology at a tertiary-level teaching hospital in North India. A 2-stage, cross-sectional study using standardized self-assessment questionnaires assessing psoriasis severity and QOL were administered followed by an evaluation conducted by a psychiatrist. Our findings suggest a need for effective screening for psychiatric disorders in psoriasis patients, greater sensitivity among dermatologists to the association of impairments in QOL and psychiatric morbidity with this condition, and collaboration with mental health professionals to ensure better treatment outcomes in psoriasis patients.

Screening for depressive disorders in outpatients with mild to moderate psoriasis: a study from North India.

BACKGROUND: Psoriasis and depressive disorders commonly occur together. Depressive disorders have an impact on the quality of life and the outcome of psoriasis. AIMS: The aim of this study was to test the feasibility of using a modification of the Hindi translation of the Patient Health Questionnaire-9 (PHQ-9) as a verbal, clinician administered, short screening questionnaire for detecting depressive disorders. MATERIALS AND METHODS: One hundred and four out-patients with psoriasis were recruited in the study. In the first stage of the study, socio-demographic data, Psoriasis Area Severity Index (PASI) score, and Dermatological Quality of Life (DLQI) score were recorded. The modified questionnaire was administered by the dermatologist. In the second stage, psychiatric diagnoses were confirmed using the Mini International Neuropsychiatric Interview. RESULTS: The prevalence of depressive disorders was 39.4%. Receiver operating curve (ROC) analysis showed that the questionnaire had a good discriminant ability in detecting depressive disorders (area under curve: 0.81, SE = 0.04, 95% confidence interval = 0.72-0.89). LIMITATIONS: The sample size is small and more studies are needed with the screening questions in different languages to validate the findings of the study. CONCLUSION: The questionnaire can be a useful screening instrument for detecting depressive disorders in patients with psoriasis.

Clozapine-induced stuttering: a case report and analysis of similar case reports in the literature.

There is limited literature reporting clozapine-associated stuttering. In this case report, we present a case of a young male who developed stuttering with clozapine, which improved with dose reduction. Computer-assisted searches on clozapine-induced stuttering yielded 16 cases, and analysis of these case reports suggests that stuttering may be linked to seizures or movement disorders, but other putative mechanisms may be at work, which need further research.

Refractory delirium tremens: a case report and brief review.

Delirium tremens is a common presentation in tertiary care hospitals. Severe and/or refractory delirium tremens is not as common, is potentially lethal, and requires intensive management. Usually delirium tremens responds to management with standard doses of benzodiazepines. Limited literature is available, however, for the management of refractory delirium tremens. We describe a case of refractory delirium tremens in which the patient was successfully managed with a combination of high doses of lorazapam, midazolam, and phenytoin.