The experiences of mothers of children and young people with intellectual disabilities during the first COVID-19 lockdown period.

BACKGROUND: Recent COVID-19 lockdown restrictions resulted in reduced access to educational, professional and social support systems for children with intellectual disabilities and their carers. AIM: The aim of this study was to gain insight into the ways mothers of children with intellectual disabilities coped during the first 2020 lockdown period. METHODS: Eight mothers of children with intellectual disabilities were interviewed. The recordings of these interviews were subjected to a thematic analysis. RESULTS: Three main themes were identified: carrying the burden; a time of stress; and embracing change and looking to the future. CONCLUSIONS: All mothers experienced increased burden and stress. However, some also described some positive impact of lockdown conditions on them as well as on their child's well-being and behaviour. These findings are discussed in the light of the (Journal of Applied Research in Intellectual Disabilities, 33, 2020, 1523) survey results on parental coping and suggestions for future service provision during pandemic conditions are proposed.

Candidate driver genes involved in genome maintenance and DNA repair in Sézary syndrome.

Sézary syndrome (SS) is a leukemic variant of cutaneous T-cell lymphoma (CTCL) and represents an ideal model for study of T-cell transformation. We describe whole-exome and single-nucleotide polymorphism array-based copy number analyses of CD4(+) tumor cells from untreated patients at diagnosis and targeted resequencing of 101 SS cases. A total of 824 somatic nonsynonymous gene variants were identified including indels, stop-gain/loss, splice variants, and recurrent gene variants indicative of considerable molecular heterogeneity. Driver genes identified using MutSigCV include POT1, which has not been previously reported in CTCL; and TP53 and DNMT3A, which were also identified consistent with previous reports. Mutations in PLCG1 were detected in 11% of tumors including novel variants not previously described in SS. This study is also the first to show BRCA2 defects in a significant proportion (14%) of SS tumors. Aberrations in PRKCQ were found to occur in 20% of tumors highlighting selection for activation of T-cell receptor/NF-κB signaling. A complex but consistent pattern of copy number variants (CNVs) was detected and many CNVs involved genes identified as putative drivers. Frequent defects involving the POT1 and ATM genes responsible for telomere maintenance were detected and may contribute to genomic instability in SS. Genomic aberrations identified were enriched for genes implicated in cell survival and fate, specifically PDGFR, ERK, JAK STAT, MAPK, and TCR/NF-κB signaling; epigenetic regulation (DNMT3A, ASLX3, TET1-3); and homologous recombination (RAD51C, BRCA2, POLD1). This study now provides the basis for a detailed functional analysis of malignant transformation of mature T cells and improved patient stratification and treatment.

AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking.

Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis.

Effect of secondary metabolite of Actinidia deliciosa on the biofilm and extra-cellular matrix components of Acinetobacter baumannii.

Acinetobacter baumannii, opportunistic nosocomial pathogen, increases gradually in the clinical setup. The high level of resistance mechanisms acquired by these bacteria makes their eradication difficult and biofilm formation is one of them. Biofilm comprises of closely packed bacterial population crowded together by extra-cellular matrix (ECM). ECM contains bacterial secreted polymers such as exopolysaccharides (EPS), proteins and extracellular-DNA (e-DNA) and rarely amyloidogenic proteins. Biofilm offers protection of underlying bacterial population against chemotherapeutic agents and host immune system. Therefore, present efforts are focused to find a novel therapeutic that targets biofilm-associated infections. Plants are used as a natural therapeutic for numerous ailments. In order to find an alternative of the available antibacterial drugs, we have focused on the natural herbal active compounds. In this study, we have extracted active compounds from various medicinal plants and screened its anti-biofilm activity against carbapenem resistant strain of A. baumannii. Results showed that polar extract of kiwi (Actinidia deliciosa) and clove (Syzygium aromaticum) exhibit effective anti-biofilm activity. These two plants were also used for their phytochemical screening and TLC profiling to find out the constituting secondary metabolites. Actinidia deliciosa extract contains an alkaloid (sanquinarine) as well as a flavonoid (hydroxyflavone). Anti-biofilm effect of this extract on the ECM of A. baumannii showed that it reduces EPS, protein and eDNA contents in the ECM. Proteins of ECM have also shown to form amyloid like structure, which was evident from its interaction with the Congo Red. CFU counting after Actinidia deliciosa extract treatment also supported the results. Therefore, it can be concluded that polar extract of A. deliciosa can be used to find suitable alternative therapeutic to control biofilm formation by carbapenem resistant strain of Acinetobacter baumannii.

Health related quality of life in hypertensive patients in a tertiary care teaching hospital.

BACKGROUND: Quality of life (QOL) evaluation has emerged as an important outcome measure for chronic diseases like hypertension. AIMS: To determine QOL in patients suffering from hypertension using MINICHAL and WHOQOL-BREF tools. METHODS AND MATERIAL: The study was carried out for eight weeks in medicine outpatient department of a tertiary care hospital. All patients diagnosed with essential hypertension and on drug therapy for at least one month were included. Their socio-demographic and clinical data were noted. Patients were interviewed for QOL using two questionnaires - WHOQOL-BREF and MINICHAL scale. RESULTS: Total 269 patients had mean age and duration of hypertension 58.25 ± 10.35 and 7.65 ± 8.00 years respectively. Age, duration of illness, number of symptoms, systolic blood pressure and number of drugs prescribed showed statistically significant (P < 0.05) negative correlation with WHOQOL-BREF score while number of symptoms, systolic blood pressure and duration of illness showed statistically significant positive correlation with MINICHAL scale (P < 0.05). MINICHAL scale and WHOQOL-BREF were significantly correlated with each other (P < 0.01). Women had significantly poorer QOL compared to men. CONCLUSIONS: Age, female gender, duration, number of symptoms, systolic blood pressure and number of medications may be important predictors of QOL in hypertensive patients.

Evaluation of rationality in prescribing, adherence to treatment guidelines, and direct cost of treatment in intensive cardiac care unit: A prospective observational study.

BACKGROUND: Cardiovascular diseases (CVDs) remain the most common cause of sudden death. Hence, appropriate drug therapy in intensive cardiac care unit (ICCU) is crucial in managing cardiovascular emergencies and to decrease morbidity and mortality. OBJECTIVE: To evaluate prescribing pattern of drugs and direct cost of therapy in patients admitted in ICCU. MATERIALS AND METHODS: Patients admitted in ICCU of a tertiary care teaching hospital were enrolled. Demographic data, clinical history, and complete drug therapy received during their stay in ICCU were noted. Data were analyzed for drug utilization pattern and direct cost of treatment calculated using patient's hospital and pharmacy bills. Rationality of therapy was evaluated based on American College of Cardiology/American Heart Association (ACC/AHA) guidelines. RESULT: Data of 170 patients were collected over 2 months. Mean age of patients was 54.67 ± 13.42 years. Male to female ratio was 2.33:1. Most common comorbid condition was hypertension 76 (44.7%). Most common diagnosis was acute coronary syndrome (ACS) 49.4%. Mean stay in ICCU was 4.42 ± 1.9 days. Mean number of drugs prescribed per patient was 11.43 ± 2.85. Antiplatelet drugs were the most frequently prescribed drug group (86.5%). Mean cost of pharmacotherapy per patient was '2701.24 ± 3111.94. Mean direct cost of treatment per patient was '10564.74 ± 14968.70. Parenteral drugs constituted 42% of total drugs and 90% of total cost of pharmacotherapy. Cost of pharmacotherapy was positively correlated with number of drugs (P = 0.000) and duration of stay (P = 0.027). CONCLUSION: Antiplatelet drugs were the most frequently prescribed drug group. Mean number of drugs per encounter were high, which contributed to the higher cost of pharmacotherapy. ACC/AHA guidelines were followed in majority of the cases.

New acute onset of ocular myasthenia gravis after COVID-19 vaccine: A case report.

Reports have shown the association of coronavirus disease 2019 (COVID-19) with several neuromuscular disorders. Myasthenia gravis (MG) is an autoimmune disease in which antibodies bind to acetyl choline receptors in the postsynaptic membrane at the neuromuscular junction. The characteristic clinical feature of the disease is weakness of the ocular muscle, bulbar muscle, and extremity muscles; when the weakness is limited to the ocular muscle only, the condition is known as ocular myasthenia gravis. Diagnosis is usually confirmed by the acetylcholine receptor antibodies. Symptoms of MG may be aggravated by various types of infections and medications. Here, we are presenting a rare case of a new and acute onset of ocular MG presented after administration of Covishield vaccine.

Iron Status in Sickle Cell Anemia: Deficiency or Overload?

Background Sickle cell anemia (SCA) is a hereditary disease with defective hemoglobin (Hb) synthesis causing severe hemolytic anemia, pain crisis, and target organ damage. In SCA, several factors independently or in combination lead to derangement in iron stores. Some centers incorrectly prescribe iron therapy on the presumption that SCA would be associated with iron deficiency, but it is not always the case. This study attempts to evaluate the iron status in SCA patients and records the target organ damage present. Methodology A single-center cross-sectional study of 180 patients with sickle cell disease was carried out at a tertiary-care center in Western India. Patients >12 years of age were included in the study after confirming SCA using high-performance liquid chromatography (HPLC). The iron status of each patient was identified and patients were labeled as iron sufficient based on the following values: Hb (8.1-12 gm%), serum iron (S. iron) level (50-150 µg/dl), serum ferritin (S. ferritin) (50-200 ng/ml), and total iron binding capacity (TIBC) (251-450 µg/dl). The iron status of patients with different target organ damage was also analyzed. Results Demographic data revealed that 21-30 years was the most common age group affected by SCA along with a male preponderance. The most common presenting complaint was joint pain (68.9%), the most common sign was pallor (64.4%), most patients had a history of pain crisis (95.6%), and half of the patients had organomegaly (51.1%). Most of the patients had no complications, however, for those who did, hepatopathy (28.9%) was the most common. Conclusion While the majority of patients were iron sufficient, a considerable number had either iron deficiency or iron overload states, which emphasizes the necessity of investigating the iron status before deciding the course of treatment in SCA patients. Although the majority were unaffected, screening for end-organ damage should be carried out in all SCA patients.

Transepidermal elimination of suture material in lip biopsy specimen.

Transepidermal elimination (TE) is a well-known phenomenon by which dermal materials are expelled through an active epithelial-dermal connective tissue interaction. It has been associated with many cutaneous disorders and described as a regular or sporadic occurrence in a variety of dermatologic conditions. TE as a means of expulsion by skin, either externally introduced or endogenously generated foreign material, is well recognized but rarely appreciated phenomenon. Hence, here we are presenting a case of TE of suture material from the labial surface of the lower lip in a patient who was previously operated for mucocele a year back and reported with the impression of the recurrent lesion.

Tics of Trauma: Unique Case of Trauma-Associated Psychogenic Tics in an Adolescent Patient.

Tic disorders are a common psychiatric diagnosis in adolescents. While often a primary disorder, there have been few reports of trauma-associated secondary psychogenic tics. In this case, we detail a 16-year-old girl with a history of trauma who initially presented with depression and trauma-related anxiety. During the course of treatment, she also developed verbal and motor tic-like symptoms that worsened with stress and court proceedings. We classify these new symptoms as psychogenic tics secondary to the trauma associated with sexual abuse. We explore the implication of psychiatric comorbidities, socio-legal stressors, and medication changes in the patient's new-onset motor and vocal tics. This case points toward a need for consideration of this unique psychiatric manifestation of trauma-associated tics in adolescents with a history of sexual abuse and with otherwise normal neurological and physical examinations.

Patients With Advanced Cancer Requiring Intensive Care: Reasons for ICU Admission, Mortality Outcomes, and the Role of Palliative Care.

Medical advancements in oncology and critical care during the past 2 decades have led to more patients with cancer being admitted to intensive care units. This article discusses the most common reasons for intensive care unit admission and factors associated with mortality among patients with cancer. It also reviews the multiple benefits of palliative care services in caring for critically ill patients with cancer and opportunities for critical care nurses working with these patients.

Importance and correlation of sudden onset, presence and recovery of olfactory and gustatory dysfunctions in COVID-19 patients: A cross-sectional study.

BACKGROUND: Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), may be associated with acute onset of smell and taste dysfunction along with other common presenting symptoms such as cough, fever and myalgia. Our study aims to analyze the presence of olfactory and gustatory dysfunctions Olfactory and gustatory dysfunctions (OGDs) in patients with COVID-19 and to assess their onset and recovery. MATERIALS AND METHODS: The cross-sectional study was conducted in March 2021 retrospectively at Care Multispecialty Hospital, Vadodara. A total 301 patients were admitted, among those 280 qualify according to inclusion criteria and 3 patients denied to participate in the study. All patients presenting with laboratory-confirmed real-time reverse transcriptase polymerase chain reaction test for SARS-CoV-2 were included in the study. All 277 patients were undergone a diagnostic questionnaire through telephonic conversation which include patient main symptoms and self-assessment of loss of smell and taste and their onset and recovery. RESULTS: Two hundred and seventy-seven patients were included in this study. One hundred and fifty-three patients (55%) reported olfactory and gustatory disorders. Loss of taste and smell were more frequently reported in female patients (72.8%) than male patients (48%). Onset of these symptoms concomitant with other typical symptoms of COVID-19 is in 58.2% of cases. Recovery of symptoms in most patients was in 5-10 days and faster in younger patients. CONCLUSION: Olfactory and gustatory disorders (OGDs) related to COVID-19 are frequently reported and more common in female patients. Rapid recovery was observed in most cases. Altogether OGDs can possibly act pivot screening or diagnostic tool for COVID-19 pandemic.

The Experiences of Carers of Adults With Intellectual Disabilities During the First COVID-19 Lockdown Period.

Background: The recent COVID-19 pandemic led to widespread international restrictions, severely impacting on health and social care services. For many individuals with an intellectual disability (ID) this meant reduced access to services and support for them and their carers. Aim: The aim of this study was to gain insight into the ways parents of adults with ID coped during the first 2020 lockdown period. Methods: Eight parents of adults with ID were interviewed. The recordings of these interviews were subjected to a thematic analysis. Results: Four main themes were identified: powerless and unappreciated; coping under lockdown; support; and the impact of lockdown on well-being. Conclusions: The parents of adults with ID who made up our sample reported that they received little support from services and experienced a sense of powerlessness. Nevertheless, they were open to accepting support from family and friends and showed remarkable resilience. These findings are discussed in the light of the Willner et al. (2020) survey results on parental mental health and coping, and suggestions for future service provision during pandemic conditions are proposed.

Frequent and Persistent PLCG1 Mutations in Sézary Cells Directly Enhance PLCγ1 Activity and Stimulate NFκB, AP-1, and NFAT Signaling.

Phospholipase C Gamma 1 (PLCG1) is frequently mutated in primary cutaneous T-cell lymphoma (CTCL). This study functionally interrogated nine PLCG1 mutations (p.R48W, p.S312L, p.D342N, p.S345F, p.S520F, p.R1158H, p.E1163K, p.D1165H, and the in-frame indel p.VYEEDM1161V) identified in Sézary Syndrome, the leukemic variant of CTCL. The mutations were demonstrated in diagnostic samples and persisted in multiple tumor compartments over time, except in patients who achieved a complete clinical remission. In basal conditions, the majority of the mutations confer PLCγ1 gain-of-function activity through increased inositol phosphate production and the downstream activation of NFκB, AP-1, and NFAT transcriptional activity. Phosphorylation of the p.Y783 residue is essential for the proximal activity of wild-type PLCγ1, but we provide evidence that activating mutations do not require p.Y783 phosphorylation to stimulate downstream NFκB, NFAT, and AP-1 transcriptional activity. Finally, the gain-of-function effects associated with the p.VYEEDM1161V indel suggest that the C2 domain may have a role in regulating PLCγ1 activity. These data provide compelling evidence to support the development of therapeutic strategies targeting mutant PLCγ1.

Health-related Quality of Life of Patients with Type 2 Diabetes Mellitus at A Tertiary Care Hospital in India Using EQ 5D 5L.

OBJECTIVE: To assess the health-related quality of life of Type 2 Diabetes mellitus patients attending outpatient departments of a tertiary hospital using EQ-5D-5L. METHODS: The study was conducted at a tertiary care hospital in India. The quality of life of patients with type 2 Diabetes mellitus, age 18 years and older, attending outpatient departments of Medicine and Endocrinology was assessed with the help of EQ-5D-5L, a measure of self-reported health related quality of life. Data was analyzed to obtain EQ-5D-5L scores for the five dimensions and EQ VAS score. Correlation of EQ VAS score with different variables was analyzed. RESULTS: Out of total 358 participants, 208 had comorbidities, hypertension being the most common. Mean age was 60.71 ± 11.41 years and 216 (58.9%) were female participants. Out of five dimensions, Mobility, Self-care, Usual activities, and Pain/discomfort were most affected in age group 71 years and above while anxiety/depression affected age group 18-30 years the most. Mean EQ VAS score was 78.83 ± 15.02. Female participants had significantly higher EQ VAS score (P = 0.00) than male participants. EQ VAS score showed significant negative correlation with uncontrolled state of diabetes (P = 0.000). There was significant difference in EQ VAS score between patients with and without comorbidities. (P =0.004) Cronbach alpha for EQ-5D-5L was 0.76. CONCLUSION: The results suggest that EQ-5D-5L is a reliable measure for assessing health related quality of life of patients with Type 2 Diabetes mellitus. Type 2 Diabetes adversely affects the quality of life of patients. Uncontrolled disease and comorbidities can further compromise the quality of life.

In-silico screening and experimental validation reveal L-Adrenaline as anti-biofilm molecule against biofilm-associated protein (Bap) producing Acinetobacter baumannii.

Acinetobacter baumannii, an ESKAPE pathogen, causes various nosocomial infections and has capacity to produce biofilm. Biofilm produced by this bacterium is highly tolerant to environmental factors and different antibiotics. Biofilm-associated protein (Bap) plays a significant role in the biofilm formation by A. baumannii and found in the extra cellular matrix of the biofilm. Therefore, it becomes essential to find a potential drug against Bap that has capacity to inhibit biofilm formation by A. baumannii. In-silico screening, molecular mechanics and molecular dynamics studies identified ZINC00039089 (L-Adrenaline) as an inhibitor for Bap of A. baumannii. Recently, it is reported that Bap can form amyloid like structure; hence we have created dimer of Bap protein. This inhibitor can bind to dimeric Bap with good affinity. It confirms that ZINC00039089 (L-Adrenaline) can bind with Bap monomer as well as oligomeric Bap, responsible for amyloid formation and biofilm formation. Hence, we have tested Adrenaline as an anti-biofilm molecule and determined its IC50 value against biofilm. The result showed Adrenaline has anti-biofilm activity with IC50 value of 75µg/ml. Therefore; our finding suggests that L-Adrenaline can be developed to inhibit biofilm formation by carbapenem resistant strain of Acinetobacter baumannii.

Students' perceptions on feedback module in pharmacology.

CONTEXT: Feedback is an integral part of formative assessment though underutilized in medical education. The objective of this study was to review our feedback module through students' perceptions. METHODOLOGY: We have developed a feedback module which is practiced by us for last 10 years for term ending examination that gives collective feedback to the whole class, followed by individual student-teacher interactions. Students were also exposed to 6-7 multiple choice questions (MCQs) based assessment during the course of pharmacology. Immediately after each MCQ test the answer keys is displayed along with an explanation. Two classes of students were requested to give their perceptions about the feedback by responding on Likert scale for the statements in the questionnaire. All the 206 students who volunteered for the study were enrolled in the study. Mann-Whitney test was used to calculate the difference in perceptions. RESULTS: Of 278 students of two classes, 206 responded (74%). Students' agreement varied from 93% to 98% for 5 items in the questionnaire for the feedback after term ending examinations. Perception of students attending one or more than one feedback session did not differ significantly. For MCQs, tests agreement was 91% to 98% for the 4 items. There was no significant difference between two classes in their perceptions regarding feedback practices (P < 0.05). CONCLUSION: Students gave a favorable opinion for our feedback module. In the medical colleges with a large number of students, this module is feasible for feedback in formative assessment in the form of written tests.

Off-label drug use in Psychiatry Outpatient Department: A prospective study at a Tertiary Care Teaching Hospital.

INTRODUCTION: Off-label drug prescribing is very common in Psychiatry. US-Food and Drug Administration has defined off-label drug as "use of drugs for the indication, dosage form, regimen, patient or other use constraint not mentioned in the approved labeling." OBJECTIVE: The objective was to evaluate off-label drug use in patients attending Outpatient Department of Psychiatry. MATERIALS AND METHODS: One year prospective, cross sectional study was conducted on patients attending Psychiatry Outpatient Department. Demographic data, clinical history, and complete prescription were noted in the predesigned proforma and prescriptions were analyzed for off-label drug use as per British National Formulary-2011. RESULT: A total of 250 patients were enrolled with mean age 40.36 ± 12.3 years. Most common diagnosis was major depressive disorder 101 (40.4%). A total of 980 drugs (mean 3.68 ± 1.42) were prescribed out of which 387 (39.5%) were off-label. Of 250 patients, 198 (79.2%) received at least one off-label drug. Psychopharmacological agents most frequently used in off-label manner were clonazepam 31 (12.4%), lorazepam 30 (12%), and trihexyphenidyl HCl 25 (10%). Prevalence of off-label use of these three drugs was significantly higher than other off-label drugs (P < 0.0001, P < 0.0001 and P < 0.0001 respectively). Inappropriate indication was the most common category of off-label use. There was positive and significant correlation between off-label prescribing and number of drugs (r = 0.722, P ≤ 0.000). Off-label prescribing was statistically significantly higher in 21-40 year age group, but no difference was seen in any co-morbid condition or in between any psychiatric disorder. CONCLUSION: Off-label drugs use is common in psychiatric OPD in our setup. Clonazepam, lorazepam, and trihexyphenidyl HCl were the most frequently used drugs in off-label manner.

Mild serotonin syndrome: A report of 12 cases.

Serotonin syndrome (SS) is an under diagnosed and under reported condition. Mild SS is easily overlooked by physicians. Every patient with mild SS is a potential candidate for developing life-threatening severe SS because of inadvertent overdose or the addition of the second serotonergic drug. Herein, we describe 12 patients with mild SS observed over 12 months in neurology outpatient clinic. It is a retrospective chart review of 12 consecutive patients who had hyperreflexia with tremor (defined as mild SS Hunter's criteria) and had received serotonergic agents in the past 5 weeks. Only four patients (33%) reported tremor as a presenting or main feature. The presenting features in another eight patients were: Dizziness, generalized body pain, headache, and seizure. Five patients responded to the removal of the offending agents and got a complete response in 2-7 days. There were no or minimal responses in another seven patients to the removal of the serotonergic drugs. Cyproheptadine was started in these patients, at the dose of 8 mg three times daily. Response started within 1-3 days of initiation of the drug and the complete responses were noted in 5-14 days. There were no side effects from cyproheptadine in any patient. We suggest that any patient on serotonergic drug developing new symptoms should be examined for the presence of tremor, hypertonia, hyperreflexia, and clonus to look for mild SS. In addition, every patient on any serotonergic drug should be examined for the presence of mild SS before escalating the dose or before adding a new one.