Comparative study on Antibacterial efficacy of a series of chromone sulfonamide derivatives against drug-resistant and MDR-isolates.

Sulfonamide derivatives have numerous pharmaceutical applications having antiviral, antibacterial, antifungal, antimalarial, anticancer, and antidepressant activities. The structural flexibility of sulfonamide derivatives makes them an excellent candidate for the development of new multi-target agents, although long-time exposure to sulfonamide drugs results in many toxic impacts on human health. However, sulfonamides may be functionalized for developing less toxic and more competent drugs. In this work, sulfonamides including Sulfapyridine (a), Sulfathiazole (b), Sulfamethoxazole (c), and Sulfamerazine (d) are used to synthesize Schiff bases of 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbalde-hyde (1a-1d). The synthesized compounds were spectroscopically characterized and tested against hospital isolates of three Gram-positive (Methicillin-resistant Staphylococcus aureus PH217, Ampicillin-resistant Coagulase-negative Staphylococcus aureus, multidrug-resistant (MDR) Enterococcus faecalis PH007R) and two Gram-negative bacteria (multidrug-resistant Escherichia coli, and Salmonella enterica serovar Typhi), compared to the quality control strains from ATCC (S. aureus 29213, E. faecalis 25922, E. coli 29212) and MTCC (S. Typhi 734). Two of the four Schiff bases 1a and 1b are found to be more active than their counterpart 1c and 1d; while 1a have showed significant activity by inhibiting MRSA PH217 and MDR isolates of E. coli at the minimum inhibitory concentration (MIC) of 150 µg/mL and 128 µg/mL with MBC of 1024 µg/mL, respectively. On the other hand, the MIC of 1b was 150 µg/mL against both S. aureus ATCC 29213 and Salmonella Typhi MTCC 734, compared to the control antibiotics Ampicillin and Gentamycin. Scanning electron microscopy demonstrated the altered surface structure of bacterial cells as a possible mechanism of action, supported by the in-silico molecular docking analysis.

Unveiling Therapeutic Targets for Esophageal Cancer: A Comprehensive Review.

Esophageal cancer is a highly aggressive and deadly disease, ranking as the sixth leading cause of cancer-related deaths worldwide. Despite advances in treatment, the prognosis remains poor. A multidisciplinary approach is crucial for achieving complete remission, with treatment options varying based on disease stage. Surgical intervention and endoscopic treatment are used for localized cancer, while systemic treatments like chemoradiotherapy and targeted drug therapy play a crucial role. Molecular markers such as HER2 and EGFR can be targeted with drugs like trastuzumab and cetuximab, and immunotherapy drugs like pembrolizumab and nivolumab show promise by targeting immune checkpoint proteins. Epigenetic modifications offer new avenues for targeted therapy. Treatment selection depends on factors like stage, tumor location, and patient health, with post-operative and rehabilitation care being essential. Early diagnosis, appropriate treatment, and supportive care are key to improving outcomes. Continued research is needed to develop effective targeted drugs with minimal side effects. This review serves as a valuable resource for clinicians and researchers dedicated to enhancing esophageal cancer treatment outcomes.

ADAR-mediated regulation of PQM-1 expression in neurons impacts gene expression throughout C. elegans and regulates survival from hypoxia.

The ability to alter gene expression programs in response to changes in environmental conditions is central to the ability of an organism to thrive. For most organisms, the nervous system serves as the master regulator in communicating information about the animal's surroundings to other tissues. The information relay centers on signaling pathways that cue transcription factors in a given cell type to execute a specific gene expression program, but also provide a means to signal between tissues. The transcription factor PQM-1 is an important mediator of the insulin signaling pathway contributing to longevity and the stress response as well as impacting survival from hypoxia. Herein, we reveal a novel mechanism for regulating PQM-1 expression specifically in neural cells of larval animals. Our studies reveal that the RNA-binding protein (RBP), ADR-1, binds to pqm-1 mRNA in neural cells. This binding is regulated by the presence of a second RBP, ADR-2, which when absent leads to reduced expression of both pqm-1 and downstream PQM-1 activated genes. Interestingly, we find that neural pqm-1 expression is sufficient to impact gene expression throughout the animal and affect survival from hypoxia, phenotypes that we also observe in adr mutant animals. Together, these studies reveal an important posttranscriptional gene regulatory mechanism in Caenorhabditis elegans that allows the nervous system to sense and respond to environmental conditions to promote organismal survival from hypoxia.

Somatic symptoms in schizophrenia: Association with socio-demographic and clinical characteristics, disability and quality of life.

Background and Aims: There is lack of research on somatic symptoms in schizophrenia. We aimed at finding prevalence and types of somatic symptoms in patients with schizophrenia and assessed their association with socio-demographic and clinical characteristics. Methods: We assessed somatic symptoms using Patient Health Questionnaire-15 (PHQ-15) in 93 patients with schizophrenia diagnosed on ICD10-DCR. Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms, WHO Disability Assessment Schedule 2.0, WHO Quality of Life (BREF) Hindi version and Liverpool University Neuroleptic Side-Effect Rating Scale were used to assess psychopathology, disability, quality of life and side effects. Results: Significant somatic symptoms (n ≥5 on PHQ-15) were present in 62 (67.7%) patients with schizophrenia. Forty three (69.4%) had mild (n = 5-9 on PHQ-15), 17 (27.4%) had moderate (n = 10-14 on PHQ-15), and only 2 (3.2%) had severe (n = ≥15 on PHQ -15) somatic symptoms. Mean somatic symptoms score on PHQ-15 was 7.28 (± 3.83); 96.8% reported feeling tired, 76.3% had constipation or diarrhoea, 67.7% trouble in sleeping, 61.3% nausea or indigestion, 52.7% back pain and 51.6% headache. Patients with somatic symptoms were older in age, had longer duration of illness and treatment, and had more negative symptoms. They had higher disability and poor quality of life especially in physical domain. Conclusion: Somatic symptoms are common in patients with schizophrenia and are associated with chronicity, refractoriness and negative symptoms, significant disability and poor quality of life. Thus during routine clinical practice, somatic symptoms should be assessed and managed in these patients.

Anti-HSV nucleoside and non-nucleoside analogues: spectroscopic characterisation of naphthyl and coumarinyl amides and their mode and mechanism of antiviral action.

Nucleoside analogues acyclovir, valaciclovir, and famciclovir are the preferred drugs against human Herpes Simplex Viruses (HSVs). However, the viruses rapidly develop resistance against these analogues which demand safer, more efficient, and nontoxic antiviral agents. We have synthesized two non-nucleoside amide analogues, 2-Oxo-2H-chromene-3-carboxylic acid [2-(pyridin-2-yl methoxy)-phenyl]-amide (HL1) and 2-hydroxy-1-naphthaldehyde-(4-pyridine carboxylic) hydrazone (HL2). The compounds were characterized by different physiochemical methods including elementary analysis, FT-IR, Mass spectra, 1H-NMR; and evaluated for their antiviral efficacy against HSV-1F by Plaque reduction assay. The 50% cytotoxicity (CC50), determined by MTT test, revealed that HL1 (270.4 µg/ml) and HL2 (362.6 µg/ml) are safer, while their antiviral activity (EC50) against HSV-1F was 37.20 µg/ml and 63.4 µg/ml against HL1 and HL2 respectively, compared to the standard antiviral drug Acyclovir (CC50 128.8 ± 3.4; EC50 2.8 ± 0.1). The Selectivity Index (SI) of these two compounds are also promising (4.3 for HL1 and 9.7 for HL2), compared to Acyclovir (49.3). Further study showed that these amide derivatives block the early stage of the HSV-1F life cycle. Additionally, both these amides make the virus inactive, and reduce the number of plaques, when infected Vero cells were exposed to HL1 and HL2 for a short period of time. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03658-0.

ADARs employ a neural-specific mechanism to regulate PQM-1 expression and survival from hypoxia.

The ability to alter gene expression programs in response to changes in environmental conditions is central to the ability of an organism to thrive. For most organisms, the nervous system serves as the master regulator in communicating information about the animal's surroundings to other tissues. The information relay centers on signaling pathways that cue transcription factors in a given cell type to execute a specific gene expression program, but also provide a means to signal between tissues. The transcription factor PQM-1 is an important mediator of the insulin signaling pathway contributing to longevity and the stress response as well as impacting survival from hypoxia. Herein, we reveal a novel mechanism for regulating PQM-1 expression specifically in neural cells of larval animals. Our studies reveal that the RNA binding protein, ADR-1, binds to pqm-1 mRNA in neural cells. This binding is regulated by the presence of a second RNA binding protein, ADR-2, which when absent leads to reduced expression of both pqm-1 and downstream PQM-1 activated genes. Interestingly, we find that neural pqm-1 expression is sufficient to impact gene expression throughout the animal and affect survival from hypoxia; phenotypes that we also observe in adr mutant animals. Together, these studies reveal an important post-transcriptional gene regulatory mechanism that allows the nervous system to sense and respond to environmental conditions to promote organismal survival from hypoxia.

Internalized stigma related to COVID-19 and its psychosocial and mental health correlates: a multicentric health facility based observational study from Nepal.

Introduction: The COVID-19 pandemic has led to physical and psychological complications and social consequences in the form of illness-related stigma. This study aimed (1) to assess the sociodemographic and clinical variable, as well as COVID-19 related knowledge and perception of persons admitted for COVID-19/Suspected COVID-19 in Nepal, (2) to determine their levels of COVID-19- related internalized stigma, depression, and anxiety symptoms, and (3) to evaluate the correlates of COVID-19- related internalized stigma. Materials and methods: It was a cross-sectional exploratory study with a convenience sample of 395 participants (306 confirmed cases, 89 suspected cases) conducted between July-October 2020 in four health facilities in Madhesh and Lumbini provinces of Nepal. We used a semi-structured questionnaire to assess sociodemographic details, clinical information, COVID-19-related knowledge, perception, COVID-19-related internalized stigma, and the Hamilton Anxiety Depression Scale (HADS) in Nepali language. Descriptive statistics, correlation analyses, and linear regression analyses were performed. The level of statistical significance was considered at p < 0.05. Results: Around 23.3% of the patients had anxiety symptoms, 32.9% had depressive symptoms, and 20.3% had high COVID-19-related internalized stigma (mean ISMI score: 2.51-4.00). Linear regression analyses showed a significant positive association of COVID-19-related internalized stigma total score, with the following eight factors, i.e., no income in the past one month (p = 0.013), below average socioeconomic status (p = 0.004), anxiety symptoms (p = <0.001), depressive symptoms (p = <0.001), recent testing positive for COVID-19 (p = <0.001), involuntary admission (p = <0.001), prior experience of being in isolation and quarantine (p = 0.045), and those who blame others for COVID-19 (p = 0.025). Conclusion: COVID-19 survivors and suspects are vulnerable to symptoms of depression, anxiety, and COVID-19-related internalized stigma. For the first time from Nepal, our data suggests that COVID-19-related internalized stigma is associated with anxiety and depression symptoms, perceived below-average socioeconomic status, involuntary admission, prior experience of being in isolation and quarantine, recent COVID-19 positive report, self-blame, below-average socioeconomic status and no income in the past one month. Mitigating and preventing internalized stigma associated with a public health crisis such as COVID-19 is imperative by diagnosing and treating such mental health issues early and designing interventions and policies especially targeting vulnerable populations focusing on their economic background and socio-cultural beliefs.

Meditation-induced psychosis: a narrative review and individual patient data analysis.

BACKGROUND: Meditation is associated with health benefits; however, there are reports that it may trigger or exacerbate psychotic states. In this review, we aim to collate case reports of psychotic disorders occurring in association with meditative practice and to discuss the relationship between psychosis and meditation. METHODOLOGY: We performed case-based analysis of all the existing studies published in English language using PubMed, PsycINFO, Cochrane, Scopus, EMBASE, CINAHL and Google Scholar with the search terms; 'Psychosis' OR 'Psychotic Symptoms' OR 'Schizophrenia' AND 'Meditation.' RESULTS: A total of 19 studies and 28 cases were included in the review. The patients described had an age range of 18-57 years; there was equal distribution of males and females. The diagnoses included acute psychosis in 14 cases, schizophrenia in 7 cases, mania with psychotic symptoms in 3 cases, and schizoaffective disorder in 1 case. The types of meditation described were Transcendent, Mindfulness, Buddhist Meditation like Qigong, Zen, and Theraveda, and others like Bikram yoga, Pranic Healing, and Hindustan Type meditation. Of the 28 cases reported, 14 patients had certain precipitating factors like insomnia, lack of food intake, history of mental illness, stress, and psychoactive substance use. CONCLUSION: There are case reports of psychotic disorder arising in association with meditative practice; however, it is difficult to attribute a causal relationship between the two. At the same time, there is a body of research describing the beneficial effect of meditative practice in clinical settings for patients with psychotic disorders. Appropriately designed studies are needed to further investigate the relationship between meditative practice and psychosis.

A bio-compatible pyridine-pyrazole hydrazide based compartmental receptor for Al3+ sensing and its application in cell imaging.

For practical applications, the development of bio-compatible organic molecules as p-block ion chemosensors is critical. Herein, we report the single crystal (SC) of new pyridine-pyrazole derived Al3+ sensor H2PPC [(Z)-N'-(2,3-dihydroxybenzylidene)-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazide] as well as its Cu-complex SC. The probe exhibits an "off-on" fluorescence response towards Al3+ ions, and this has been modulated with different solvents. For selective detection of Al3+ ions, a special coordination pocket in the structural backbone is advantageous. The chemosensor exhibits a submicromolar detection level (LOD = 4.78 µM) for Al3+. The density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations of H2PPC and [Al(HPP)2]+ (1) reveal that a change of the structural conformation of probe H2PPC upon complexation causes the pyrazole and pyridine units to create a specific cavity to tether Al3+, and consequently H2PPC proves to be a promising molecule for Al3+ detection. Furthermore, the probe has been successfully used to evaluate Al3+ as a low-cost kit using filter paper strips, and the in situ Al3+ ion imaging in Vero cells as well as A549 cell lines shows the sensor's nuclear envelope penetrability, indicating that it has great potential for biological and environmental applications.

Case series associated with COVID-19 pandemic in causing psychiatric morbidity.

The COVID-19 has emerged as a public health emergency across the globe. Countries all over the world have been forced to enforce nationwide lockdowns to curb the transmission of this illness, affecting millions of people. The disorder and the lockdowns enforced have resulted in a complex set of psychosocial stressors in the lives of people, affecting their resilience and causing psychological stress and mental health issues. In this case series, we aim to highlight the role of such psychosocial stressors in causing mental health problems, especially in a vulnerable individual. The first case reports the onset of first-episode mania in a healthy individual with a family history of mental illness, after the sudden demise of the patient's mother due to COVID-19. The second case highlights the onset of psychosis in an adolescent girl following academic stress due to the inability to carry on her education through online classes. The third case demonstrates the exacerbation of dissociative episodes in a child following the financial crisis in the family during the lockdown period. In low-income to middle-income countries such as India, there is a complex interplay of the psychosocial stressors due to the COVID-19 pandemic with pre-existing issues such as poverty, socioeconomic disparity and inequity of resources leading to a 'double hit' for people from disadvantaged sections of the society and individuals with pre-existing mental illness or vulnerability for mental illness.

An extract of Stephania hernandifolia, an ethnomedicinal plant, inhibits herpes simplex virus 1 entry.

Stephania hernandifolia (Nimukho), an ethnomedicinal herb from rural Bengal, has been used traditionally for the management of nerve, skin, urinary, and digestive ailments. Here, we attempted to confirm the antiviral potential of aqueous, methanol, and chloroform extracts of S. hernandifolia against herpes simplex virus type 1 (HSV-1), the causative agent of orolabial herpes in humans, and decipher its underlying mechanism of action. The bioactive extract was standardized and characterized by gas chromatography-mass spectroscopy, while cytotoxicity and antiviral activity were evaluated by MTT and plaque reduction assay, respectively. Two HSV strains, HSV-1F and the clinical isolate VU-09, were inhibited by the chloroform extract (CE) with a median effective concentration (EC50) of 4.32 and 4.50 µg/ml respectively, with a selectivity index (SI) of 11. Time-of-addition assays showed that pre-treatment of virus-infected cells with the CE and its removal before infection reduced the number of plaques without lasting toxicity to the cell, indicating that the CE affected the early stage in the viral life cycle. The number of plaques was also reduced by direct inactivation of virions and by the addition of CE for a short time following attachment of virions. These results together suggest that modification of either the virion surface or the cell surface by the CE inhibits virus entry into the host cell.

Phenomenological analysis of maladaptive daydreaming associated with internet gaming addiction: a case report.

Maladaptive daydreaming (MD) is an immersive fantasy activity that leads to distress and socio-occupational dysfunction. MD has many features suggestive of behavioural addiction, but research exploring the phenomenology of this clinical construct is limited. MD has also been purported to be a maladaptive strategy to cope with distress, but often leads to uncontrollable absorption in fantasy world, social withdrawal and neglected aspects of everyday life. In this paper, we report the case of a 16-year-old boy who developed internet gaming disorder and MD after experiencing cyberbullying from his peers. The patient engaged in vivid, fanciful imagery that lasted for hours, leading to social dysfunction and academic deterioration. Baseline assessment revealed a Maladaptive Daydreaming Scale-16 score of 65 (cut-off 50) and an Internet Gaming Test-20 score of 86 (cut-off 71). The patient was managed primarily with psychological intervention. The therapy focused on behaviour modification and cognitive restructuring. Patients in clinical setting should be questioned about MD when presenting with excessive use of technology or other forms of behavioural addictions. Further studies are necessary to determine the biopsychosocial factors of MD and its correlates. There is also a need to study treatment and management approaches for treating MD.

To protect and modify double-stranded RNA - the critical roles of ADARs in development, immunity and oncogenesis.

Adenosine deaminases that act on RNA (ADARs) are present in all animals and function to both bind double-stranded RNA (dsRNA) and catalyze the deamination of adenosine (A) to inosine (I). As inosine is a biological mimic of guanosine, deamination by ADARs changes the genetic information in the RNA sequence and is commonly referred to as RNA editing. Millions of A-to-I editing events have been reported for metazoan transcriptomes, indicating that RNA editing is a widespread mechanism used to generate molecular and phenotypic diversity. Loss of ADARs results in lethality in mice and behavioral phenotypes in worm and fly model systems. Furthermore, alterations in RNA editing occur in over 35 human pathologies, including several neurological disorders, metabolic diseases, and cancers. In this review, a basic introduction to ADAR structure and target recognition will be provided before summarizing how ADARs affect the fate of cellular RNAs and how researchers are using this knowledge to engineer ADARs for personalized medicine. In addition, we will highlight the important roles of ADARs and RNA editing in innate immunity and cancer biology.

Prevalence and predictors of family accommodation in obsessive-compulsive disorder in an Indian setting.

BACKGROUND: Family accommodation (FA) is a phenomenon whereby caregivers assist/facilitate rituals or behaviors related to obsessive-compulsive disorder (OCD). FA, however, has been explored primarily in the Western population, and it is unclear to what extent it might be present in diverse cultural settings. At present, little is known about the extent and predictors of FA among caregivers of adult OCD patients in India. AIMS: The study aims to assess the extent, clinical correlates, and predictors of FA in the caregivers of adults with OCD. SETTINGS AND DESIGN: Cross-sectional study conducted in an outpatient setting in a tertiary-care hospital. MATERIALS AND METHODS: Hundred and one adult patients of either gender with Diagnostic and Statistical Manual of Mental Disorders-5 diagnosis of OCD and 101 caregivers were included. The patients were assessed using Yale-Brown Obsessive Compulsive Scale (YBOCS), Hamilton Rating Scale for Depression (HAM-D), World Health Organization Disability Assessment Schedule Version 2.0 12-item version (WHO-DAS 2.0.12), Clinical Global Impressions Scale for Severity (CGI-S), and Clinical Global Impressions Scale for Improvement. The FA Scale-Self Rated Version (FAS-SR) was applied on caregivers after Hindi translation. STATISTICAL ANALYSIS: Descriptive statistics, group comparisons, and Pearson's product moment correlations were carried out. Multiple linear regression modeling was performed with the total FAS-SR score as the dependent variable. RESULTS: About 92% of caregivers displayed at least some form of FA. Higher scores on HAM-D, YBOCS, WHODAS, and CGI-S were associated with higher scores on FAS-SR scale, which reached statistical significance (P < 0.01). CONCLUSIONS: FA in OCD appears to be a frequent phenomenon. Higher FA is associated with higher symptom severity and disability, emphasizing its clinical and research relevance for future studies.

Neuregulin and ErbB expression is regulated by development and sensory experience in mouse visual cortex.

Neuregulins (NRGs) are protein ligands that impact neural development and circuit function. NRGs signal through the ErbB receptor tyrosine kinase family. NRG1/ErbB4 signaling in parvalbumin-expressing (PV) inhibitory interneurons is critical for visual cortical plasticity. There are multiple types of NRGs and ErbBs that can potentially contribute to visual cortical plasticity at different developmental stages. Thus, it is important to understand the normal developmental expression profiles of NRGs and ErbBs in specific neuron types in the visual cortex, and to study whether and how their expression changes in PV inhibitory neurons and excitatory neurons track with sensory perturbation. Cell type-specific translating ribosome affinity purification and qPCR was used to compare mRNA expression of nrg1,2,3,4 and erbB1,2,3,4 in PV and excitatory neurons in mouse visual cortex. We show that the expression of nrg1 and nrg3 decreases in PV neurons at the critical period peak, postnatal day 28 (P28) after monocular deprivation and dark rearing, and in the adult cortex (at P104) after 2-week long dark exposure. In contrast, nrg1 expression by excitatory neurons is unchanged at P28 and P104 following sensory deprivation, whereas nrg3 expression by excitatory neurons shows changes depending on the age and the mode of sensory deprivation. ErbB4 expression in PV neurons remains consistently high and does not appear to change in response to sensory deprivation. These data provide new important details of cell type-specific NRG/ErbB expression in the visual cortex and support that NRG1/ErbB4 signaling is implicated in both critical period and adult visual cortical plasticity.

Assessment of caregiver needs in parents of children suffering from neurodevelopmental disorders in an Indian population.

Parents of children with neurodevelopmental disorders have significant unmet needs in various domains, particularly in a Low-Middle Income Country setting such as India. This study assessed parental needs using a Hindi version of the Caregiver Needs Scale (CNS) and found that 65.7% of the respondents expressed a definite need for help in all the items of the scale. The total score on CNS showed a significant negative correlation with the age of the child. Age of parent showed a significant negative correlation with scores for community and support needs.

Family caregivers' needs of young patients with first episode psychosis: A qualitative study.

BACKGROUND: The caregivers of patients with first episode psychosis (FEP) experience significant distress. It is important to understand their needs to plan adequate interventions for them. AIM: The aim of this study was to explore the needs of caregivers of young patients with FEP in India, using a qualitative approach. METHODS: The study was conducted in two phases. In phase I, a script for conducting focus group discussions (FGDs) with caregivers was developed, based on literature search and expert opinion generated from FGD with mental health professionals. In phase II, five FGDs were conducted with 30 caregivers of young patients with FEP having minimal of 6 participants in each FGD. Data was analyzed using principles of grounded theory. RESULTS: Seven broad themes and subthemes of the needs of caregivers emerged from the FGDs. The final themes, which highlighted the needs of caregivers of young patients with FEP, were (in order of ranking) as follows: information regarding treatment, information regarding illness, services provided by the government, optimum quality of care from treatment facility, management of psychosocial issues related to patient's illness, availability and accessibility of treatment, and identification and recognition of mental health and physical problems in family members. CONCLUSION: Qualitative method was useful to identify the needs of the caregivers of young patients with FEP in multiple domains.