Anti-neoplastic pharmacophore benzophenone-1 coumarin (BP-1C) targets JAK2 to induce apoptosis in lung cancer.

Reigning of the abnormal gene activation associated with survival signalling in lung cancer leads to the anomalous growth and therapeutic failure. Targeting specific cell survival signalling like JAK2/STAT3 nexus has become a major focus of investigation to establish a target specific treatment. The 2-bromobenzoyl-4-methylphenoxy-acetyl hydra acetyl Coumarin (BP-1C), is new anti-neoplastic agent with apoptosis inducing capacity. The current study was aimed to develop antitumor phramacophore, BP-1C as JAK2 specific inhibitor against lung neoplastic progression. The study validates and identifies the molecular targets of BP-1C induced cell death. Cell based screening against multiple cancer cell lines identified, lung adenocarcinoma as its specific target through promotion of apoptosis. The BP-1C is able to induce, specific hall marks of apoptosis and there by conferring anti-neoplastic activity. Validation of its molecular mechanism, identified, BP-1C specifically targets JAK2Tyr1007/1008 phosphorylation, and inhibits its downstream STAT3Tyr705 signalling pathway to induce cell death. As a consequence, modulation in Akt/Src survival signal and altered expression of interwoven apoptotic genes were evident. The results were reproducible in an in-vivo LLC tumor model and in-ovo xenograft studies. The computational approaches viz, drug finger printing confers, BP-1C as novel class JAK2 inhibitor and molecular simulations studies assures its efficiency in binding with JAK2. Overall, BP-1C is a novel JAK2 inhibitor with experimental evidence and could be effectively developed into a promising drug for lung cancer treatment.

DNA Double-Strand Breaks as Pathogenic Lesions in Neurological Disorders.

The damage and repair of DNA is a continuous process required to maintain genomic integrity. DNA double-strand breaks (DSBs) are the most lethal type of DNA damage and require timely repair by dedicated machinery. DSB repair is uniquely important to nondividing, post-mitotic cells of the central nervous system (CNS). These long-lived cells must rely on the intact genome for a lifetime while maintaining high metabolic activity. When these mechanisms fail, the loss of certain neuronal populations upset delicate neural networks required for higher cognition and disrupt vital motor functions. Mammalian cells engage with several different strategies to recognize and repair chromosomal DSBs based on the cellular context and cell cycle phase, including homologous recombination (HR)/homology-directed repair (HDR), microhomology-mediated end-joining (MMEJ), and the classic non-homologous end-joining (NHEJ). In addition to these repair pathways, a growing body of evidence has emphasized the importance of DNA damage response (DDR) signaling, and the involvement of heterogeneous nuclear ribonucleoprotein (hnRNP) family proteins in the repair of neuronal DSBs, many of which are linked to age-associated neurological disorders. In this review, we describe contemporary research characterizing the mechanistic roles of these non-canonical proteins in neuronal DSB repair, as well as their contributions to the etiopathogenesis of selected common neurological diseases.

Seroprevalence of antibodies to SARS-CoV-2 in healthcare workers & implications of infection control practice in India.

Background & objectives: Healthcare workers (HCWs) are considered to be at a high risk of contracting COVID-19 infection. Besides, control of nosocomial infections transmitted from HCWs to the patients is also a cause of concern. This study was undertaken to investigate the seroprevalence of antibodies against the SARS-CoV-2 virus among the hospital staff of a tertiary care health facility in north India. Methods: The HCWs were tested for SARS-CoV-2 serology (IgG+IgM) using chemiluminescence immunoassay between June 22 and July 24, 2020. Venous blood (2 ml) was collected and tested for SARS-CoV-2 IgG and IgM antibodies. Results: Of the 3739 HCWs tested, 487 (13%) were positive for total SARS-CoV-2 antibodies. The highest seroprevalence was observed in administrative staff (19.6%) and least in physicians (5.4%). The staff who used public (20%) and hospital transportation (16.9%) showed higher seroprevalence compared to staff using personal transportation (12.4%). No difference was observed between HCWs posted in COVID versus non-COVID areas. All seropositive symptomatic HCWs in our study (53.6%) had mild symptoms, and the remaining 46.4 per cent were asymptomatic. The antibody positivity rate progressively increased from 7.0 per cent in the first week to 18.6 per cent in the fourth week during the study. Interpretation & conclusions: The presence of antibodies to SARS-CoV-2 in a significant number of asymptomatic HCWs, association with the use of public transport, relatively lower seroprevalence compared with the non-HCWs and rising trend during the period of the study highlight the need for serosurveillance, creating awareness for infection control practices including social distancing and study of infection dynamics in the community for effective control of an infectious pandemic.

BP-1T, an antiangiogenic benzophenone-thiazole pharmacophore, counteracts HIF-1 signalling through p53/MDM2-mediated HIF-1α proteasomal degradation.

Hypoxia is a feature of all solid tumours, contributing to tumour progression. Activation of HIF-1α plays a critical role in promoting tumour angiogenesis and metastasis. Since its expression is positively correlated with poor prognosis for cancer patients, HIF-1α is one of the most convincing anticancer targets. BP-1T is a novel antiproliferative agent with promising antiangiogenic effects. In the present study, the molecular mechanism underlying cytotoxic/antiangiogenic effects of BP-1T on tumour/non-tumour angiogenesis was evaluated. Evidences show that BP-1T exhibits potent cytotoxicity with prolonged activity and effectively regressed neovessel formation both in reliable non-tumour and tumour angiogenic models. The expression of CoCl2-induced HIF-1α was inhibited by BP-1T in various p53 (WT)-expressing cancer cells, including A549, MCF-7 and DLA, but not in mutant p53-expressing SCC-9 cells. Mechanistically, BP-1T mediates the HIF-1α proteasomal degradation by activating p53/MDM2 pathway and thereby downregulated HIF-1α-dependent angiogenic genes such as VEGF-A, Flt-1, MMP-2 and MMP-9 under hypoxic condition of in vitro and in vivo solid tumour, eventually leading to abolition of migration and invasion. Based on these observations, we conclude that BP-1T acts on HIF-1α degradation through p53/MDM2 proteasome pathway.

Scutellarein antagonizes the tumorigenesis by modulating cytokine VEGF mediated neoangiogenesis and DFF-40 actuated nucleosomal degradation.

Neoplastic cells often reside in distinctive tumor hypoxia armed with a series of adaptive responses including oxidative stress, defective apoptotic machinery and neoangiogenesis, through that further confer cell survival improvement. Plants still acts as reservoir of natural chemicals to provide newer active pharmacophores. Scutellarein is flavones which has wide range of pharmacophoral effects. In our current research, scutellarein employed for targeting oxidative stress mediated tumor angiogenesis and apoptotic nuclear fragmentation. Experimental results revealed that scutellarein has antiproliferative index against multiple cancer cell lines and diminished the oxidative stress and tumor development of murine ascitic lymphoma & inflammatory hepatocellular carcinoma. Eventual consequences lead to reduced neovessel formation by abrogating angiogeneic factors cytokine-VEGF-A, Flt-1, HIF-1α, MMP-2 and MMP-9 and reversing of evading apoptosis by activating caspase-3 activated DNA fragmentation factor (DFF-40) mediated nucleosomal degradation. In summary, our experimental evidences suggest that scutellarein has strong potentiality to attenuate the tumor development by modulating sprouting neovasculature and DFF-40 mediated apoptosis.

FUS unveiled in mitochondrial DNA repair and targeted ligase-1 expression rescues repair-defects in FUS-linked motor neuron disease.

This study establishes the physiological role of Fused in Sarcoma (FUS) in mitochondrial DNA (mtDNA) repair and highlights its implications to the pathogenesis of FUS-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with and recruits mtDNA Ligase IIIα (mtLig3) to DNA damage sites within mitochondria, a relationship essential for maintaining mtDNA repair and integrity in healthy cells. Using ALS patient-derived FUS mutant cell lines, a transgenic mouse model, and human autopsy samples, we discovered that compromised FUS functionality hinders mtLig3's repair role, resulting in increased mtDNA damage and mutations. These alterations cause various manifestations of mitochondrial dysfunction, particularly under stress conditions relevant to disease pathology. Importantly, rectifying FUS mutations in patient-derived induced pluripotent cells (iPSCs) preserves mtDNA integrity. Similarly, targeted introduction of human DNA Ligase 1 restores repair mechanisms and mitochondrial activity in FUS mutant cells, suggesting a potential therapeutic approach. Our findings unveil FUS's critical role in mitochondrial health and mtDNA repair, offering valuable insights into the mechanisms underlying mitochondrial dysfunction in FUS-associated motor neuron disease.

RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability.

TDP43 is an RNA/DNA binding protein increasingly recognized for its role in neurodegenerative conditions including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to the formation of detrimental cytosolic aggregates and a reduction in nuclear functionality within neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expressions. Here, we show that TDP43 depletion or overexpression directly affects the expression of key MMR genes. Alterations include MLH1, MSH2, MSH3, MSH6, and PMS2 levels across various primary cell lines, independent of their proliferative status. Our results specifically establish that TDP43 selectively influences the expression of MLH1 and MSH6 by influencing their alternative transcript splicing patterns and stability. We furthermore find aberrant MMR gene expression is linked to TDP43 proteinopathy in two distinct ALS mouse models and post-mortem brain and spinal cord tissues of ALS patients. Notably, MMR depletion resulted in the partial rescue of TDP43 proteinopathy-induced DNA damage and signaling. Moreover, bioinformatics analysis of the TCGA cancer database reveals significant associations between TDP43 expression, MMR gene expression, and mutational burden across multiple cancers. Collectively, our findings implicate TDP43 as a critical regulator of the MMR pathway and unveil its broad impact on the etiology of both neurodegenerative and neoplastic pathologies.

Delayed elevation in carbamazepine concentrations after overdose: a retrospective poison center study.

An initial carbamazepine concentration may initially be supratherapeutic, therapeutic, or even subtherapeutic only to persist to rise over time. The aim of this study was to report the frequency of toxic carbamazepine concentrations continuing to rise and to estimate how often an initially therapeutic or subtherapeutic concentration misrepresents the potential toxicity of an acute carbamazepine overdose. An 8-year retrospective search of all carbamazepine exposures reported to the Illinois Poison Center (January 1, 2001 through December 31, 2008) was reviewed. Inclusion criteria were acute poisonings with a documented carbamazepine concentration of >12 µg/mL at any time. Those with initial concentrations of >12 µg/mL that subsequently increased over time were recorded. Additionally, those cases that initially had therapeutic (4-12 µg/mL) or subtherapeutic (<4 µg/mL) concentration were identified. Descriptive statistics were used to analyze the data. A total of 1424 cases were reported. Of the 523 patients with documented concentrations of >12 µg/mL, 93 patients (17.8%) had initial carbamazepine concentrations >12 µg/mL and continued to rise. Sixteen patients (3.5%) had initial carbamazepine concentrations that were therapeutic (4-12 µg/mL) and 7 patients (1.3%) had initial carbamazepine concentrations <4 µg/mL before rising >12 µg/mL. Certain patients had progressive decreases in level of consciousness corresponding to increasing carbamazepine concentrations. Additionally, several patients with initial levels of therapeutic or subtherapeutic concentration later became comatose and required ventilator management. Initial serum carbamazepine concentrations can be misleading. Serial measurements documenting a declining carbamazepine concentration or prolonged observation are recommended when managing these overdoses.

Mathematical model and solution for fingering phenomenon in double phase flow through homogeneous porous media.

The present paper analytically discusses the phenomenon of fingering in double phase flow through homogenous porous media by using variational iteration method. Fingering phenomenon is a physical phenomenon which occurs when a fluid contained in a porous medium is displaced by another of lesser viscosity which frequently occurred in problems of petroleum technology. In the current investigation a mathematical model is presented for the fingering phenomenon under certain simplified assumptions. An approximate analytical solution of the governing nonlinear partial differential equation is obtained using variational iteration method with the use of Mathematica software.

Steroidal alkaloid solanidine impedes hypoxia-driven ATM phosphorylation to switch on anti-angiogenesis in lung adenocarcinoma.

PURPOSE: The declined oxygen tension in the cancer cell leads to the hypoxic adaptive response and favors establishment of tumor micro environment [TEM]. The complex TME consists of interwoven hypoxic HIF-1α and DNA damage repair ATM signaling. The ATM/HIF-1α phosphorylation switch on angiogenesis and abort apoptosis. Targeting this signaling nexus would be a novel therapeutic strategy for the treatment of cancer. BACKGROUND: Steroidal alkaloid solanidine is known for varied pharmacological role but with less molecular evidences. Our earlier findings on solanidine proven its anti-neoplastic activity by inducing apoptosis in lung cancer. In continued research, efforts have been made to establish the underlying molecular signaling in induction of DNA damage in prevailing hypoxic TME. METHODS: The solanidine induced DNA damage was assessed trough alkali COMET assay; signaling nexus and gene expression profile analysis through IB, qRT-PCR, Gelatin Zymography, IHC, IF and ELISA. Pathophysiological modulations assessed through tube formation, migration, invasion assays. Anti-angiogenic studies through CAM, rat aorta, matrigel assays and corneal neovascularization assay. Anti-tumor activity through in-vivo DLA ascites tumor model and LLC model. RESULTS: The results postulates, inhibition of hypoxia driven DDR proteins pATMser1981/pHIF-1αser696 by solanidine induces anti-angiogenesis. Systematic study of both non-tumorigenic and tumorigenic models in-vitro as well as in-vivo experimental system revealed the angio-regression mediated anticancer effect in lung cancer. These effects are due to the impeded expression of angiogenic mediators such as VEGF, MMP2&9 and inflammatory cytokines IL6 and TNFα to induce pathophysiological changes CONCLUSION: The study establishes new role of solanidine by targeting ATM/HIF-1α signaling to induce anti-angiogenesis for the first time. The study highlights the potentiality of plant based phytomedicine solanidine which can targets the multiple hallmarks of cancer by targeting interwoven signaling crosstalk. Such an approach through solanidine necessary to counteract heterogeneous complexity of cancer which could be nearly translated into drug.

FUS Unveiled in Mitochondrial DNA Repair and Targeted Ligase-1 Expression Rescues Repair-Defects in FUS-Linked Neurodegeneration.

This study establishes the physiological role of Fused in Sarcoma (FUS) in mitochondrial DNA (mtDNA) repair and highlights its implications to the pathogenesis of FUS-associated neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with and recruits mtDNA Ligase IIIα (mtLig3) to DNA damage sites within mitochondria, a relationship essential for maintaining mtDNA repair and integrity in healthy cells. Using ALS patient-derived FUS mutant cell lines, a transgenic mouse model, and human autopsy samples, we discovered that compromised FUS functionality hinders mtLig3's repair role, resulting in increased mtDNA damage and mutations. These alterations cause various manifestations of mitochondrial dysfunction, particularly under stress conditions relevant to disease pathology. Importantly, rectifying FUS mutations in patient-derived induced pluripotent cells (iPSCs) preserves mtDNA integrity. Similarly, targeted introduction of human DNA Ligase 1 restores repair mechanisms and mitochondrial activity in FUS mutant cells, suggesting a potential therapeutic approach. Our findings unveil FUS's critical role in mitochondrial health and mtDNA repair, offering valuable insights into the mechanisms underlying mitochondrial dysfunction in FUS-associated neurodegeneration.

Human papillomavirus-driven repression of NRF2 signalling confers chemo-radio sensitivity and predicts prognosis in head and neck squamous cell carcinoma.

PURPOSE: To investigate the role of NRF2 signalling in conferring superior prognosis in patients with HPV positive (HPV+ve) head & neck squamous cell carcinomas (HNSCC) compared to HPV negative (HPV-ve) HNSCC and develop molecular markers for selection of HPV+ve HNSCC patients for treatment de-escalation trials. METHODS: NRF2 activity (NRF2, KEAP1, and NRF2-transcriptional targets), p16, and p53 levels between HPV+ve HNSCC and HPV-ve HNSCC in prospective and retrospective tumor samples as well as from TCGA database were compared. Cancer cells were transfected with HPV-E6/E7 plasmid to elucidate if HPV infection represses NRF2 activity and sensitizes to chemo-radiotherapy. RESULTS: Prospective analysis revealed a marked reduction in expression of NRF2, and its downstream genes in HPV+ve tumors compared to HPV-ve tumors. A retrospective analysis by IHC revealed significantly lower NQO1 in p16high tumors compared to p16low tumors and the NQO1 expression correlated negatively with p16 and positively with p53. Analysis of the TCGA database confirmed low constitutive NRF2 activity in HPV+ve HNSCC compared to HPV-ve HNSCC and revealed that HPV+ve HNSCC patients with 'low NQO1' expression showed better overall survival compared to HPV+ve HNSCC patients with 'high NQO1' expression. Ectopic expression of HPV-E6/E7 plasmid in various cancer cells repressed constitutive NRF2 activity, reduced total GSH, increased ROS levels, and sensitized the cancer cells to cisplatin and ionizing radiation. CONCLUSION: Low constitutive NRF2 activity contributes to better prognosis of HPV+ve HNSCC patients. Co-expression of p16high, NQO1low, and p53low could serve as a predictive biomarker for the selection of HPV + ve HNSCC patients for de-escalation trials.

Development of Moringa oleifera as functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems.

Pharmacological activation of nuclear factor erythroid 2 related factor 2 (NRF2) provides protection against several environmental diseases by inhibiting oxidative and inflammatory injury. Besides high in protein and minerals, Moringa oleifera leaves contain several bioactive compounds, predominantly isothiocyanate moringin and polyphenols, which are potent inducers of NRF2. Hence, M. oleifera leaves represent a valuable food source that could be developed as a functional food for targeting NRF2 signaling. In the current study, we have developed a palatable M. oleifera leaf preparation (henceforth referred as ME-D) that showed reproducibly a high potential to activate NRF2. Treatment of BEAS-2B cells with ME-D significantly increased NRF2-regulated antioxidant genes (NQO1, HMOX1) and total GSH levels. In the presence of brusatol (a NRF2 inhibitor), ME-D-induced increase in NQO1 expression was significantly diminished. Pre-treatment of cells with ME-D mitigated reactive oxygen species, lipid peroxidation and cytotoxicity induced by pro-oxidants. Furthermore, ME-D pre-treatment markedly inhibited nitric oxide production, secretory IL-6 and TNF-α levels, and transcriptional expression of Nos2, Il-6, and Tnf-α in macrophages exposed to lipopolysaccharide. Biochemical profiling by LC-HRMS revealed glucomoringin, moringin, and several polyphenols in ME-D. Oral administration of ME-D significantly increased NRF2-regulated antioxidant genes in the small intestine, liver, and lungs. Lastly, prophylactic administration of ME-D significantly mitigated lung inflammation in mice exposed to particulate matter for 3-days or 3-months. In conclusion, we have developed a pharmacologically active standardized palatable preparation of M. oleifera leaves as a functional food to activate NRF2 signaling, which can be consumed as a beverage (hot soup) or freeze-dried powder for reducing the risk from environmental respiratory disease.

"Constrained Medical Oxygen Supply Chain in India During COVID-19: Red-tapism, the Elephant in the Room?"

BACKGROUND: Recent disruption of medical oxygen during the second wave of coronavirus disease 2019 (COVID-19) has caused nationwide panic. This study attempts to objectively analyze the medical oxygen supply chain in India along the principles of value stream mapping (VSM), identify bottlenecks, and recommend systemic improvements. METHODS: Process mapping of the medical oxygen supply chain in India was done. Different licenses and approvals, their conditions, compliances, renewals, among others were factored in. All relevant circulars (Government Notices), official orders, amendments, and gazette notifications pertaining to medical oxygen from April 2020 to April 2021 were studied and corroborated with information from Petroleum and Explosives Safety Organization (PESO) official website. RESULTS: Steps of medical oxygen supply chain right from oxygen manufacture to filling, storage, and transport up to the end users; have regulatory bottlenecks. Consequently, flow of materials is sluggish and very poor information flow has aggravated the inherent inefficiencies of the system. Government of India has been loosening regulatory norms at every stage to alleviate the crisis. CONCLUSIONS: Regulatory bottlenecks have indirectly fueled the informal sector over the years, which is not under Government's control with difficulty in controlling black-marketing and hoarding. Technology enabled, data-driven regulatory processes with minimum discretionary human interface can make the system more resilient.

It's the data, stupid: Inflection point for Artificial Intelligence in Indian healthcare.

Indian healthcare is fast growing and with significant chunk of it being in small, fragmented, informal sector; Artificial Intelligence (AI) is pegged as a magical tool for a better healthcare system. There is an inclination to merely mimic the US approach in the on-going policy making and legislative exercises, which can have serious fallouts for Indian healthcare. India needs a different approach to suite her unique requirements. In this regard, each of the five stages in AI development lifecycle has been analyzed in the light of current on-ground realities. These boil down to three fold challenges of how to increase adoption of digital health, prevent data silos and create maximum value from data. Availability of quality data for value addition without barriers and restrictions is the common denominator for leveraging the full potential of AI. This requires liberal policies enabling secondary use of data in developing countries with rapidly growing healthcare sector akin to India. This has to be carefully balanced with data privacy and security. Restrictive healthcare data policies and laws can slow down adoption of digitization, perpetuate status-quo, be biased towards the incumbent players, cause Industry stagnation and thus will do more harm than good. It is therefore the data policies that will make or break AI in Indian healthcare.

Antiproliferative pharmacophore azo-hydrazone analogue BT-1F exerts death signalling pathway targeting STAT3 in solid tumour.

BACKGROUND: Anomalous activation of intra-cellular signalling cascades confers neoplastic properties on malignant cells. The JAK2/STAT3 proteins play a pivotal role in the pathogenesis of most of the solid malignancies. The over expression of STAT3 in these tumours results in an evasion of apoptosis and thereby pathogenesis. Hence, strategy to target STAT3 to regress tumour development is an emerging new concept. As an approach, anti-neoplastic drug, Azo-hydrozone analogue, BT-1F with potential anti-proliferative effect was evaluated to demonstrate its capacity to counteract STAT3 signal with mechanistic approach. METHODS: Cell based screening for cytotoxicity was performed through MTT, LDH and Trypan blue. The BT-1F induced anti-clonogenic property by clonogenic assay. The apoptotic capacity was examined by crystal violet staining, flow cytometry, Annexin-FITC, DAPI and TUNEL assay. The altered signalling events were studied using immunoblot. The drug-induced anti-tumour effect was evaluated in an in-vivo solid tumour model and molecular interaction was further validated by in-silico studies. RESULTS: The BT-1F exerts chemo-sensitivity specifically against EAC and A549 cells without altering its normal counterpart. The anti-proliferative/anti-clonogenic effect was due to the induction of apoptosis through inhibition of STAT3Tyr705 signal. Eventually downstream signalling proteins p53, Bax, Bad and Bcl-xL were significantly altered. Further in-vivo experimental results validated  in-vitro findings. The computational approaches assures the BT-1F efficiency in binding with STAT3. CONCLUSION: Systemic validation of STAT3 target drug, BT-1F in in-vitro, in-silico and in-vivo models has promising strategy for solid cancer treatment.

How informed is the informed consent?

BACKGROUND: Informed consent is a cornerstone of the ethics of modern medical care. In an ideal world, informed consent is a process of education - a conversation between a surgeon and a patient or family that allows the patient or family to make the best possible decision regarding care. OBJECTIVE: The study was conducted with objectives of assessing information given to the patient before taking consent for surgery and determining the compliance to various contents of the consent forms. MATERIAL AND METHODS: This was a prospective study over a period of 12 weeks in wards of various surgical departments of a 1000+ bedded tertiary care hospital. Patient interviews were conducted to assess their level of information and the consent forms were reviewed to assess the compliance. OBSERVATIONS: The overall level of information r4egarding various aspects among the participants was 75.14%. The level of information varied statistically with age, literacy level, annual income and the type of surgery. All the patients (100%) stated that they were informed about the current clinical condition/ problem, while only 34% were informed about risk and 26% about the alternative options. All the forms (100%) had a statement regarding the explanation of procedure to the patient/ guardian and none of the forms (0%) contained names of all practitioners performing the procedure. CONCLUSION: There is need to create awareness among doctors and also to educate patients regarding the importance of informed consent.

More from less: Study on increasing throughput of COVID-19 screening and testing facility at an apex tertiary care hospital in New Delhi using discrete-event simulation software.

BACKGROUND: One of the challenges has been coping with an increasing need for COVID-19 testing. A COVID-19 screening and testing facility was created. There was a need for increasing throughput of the facility within the existing space and limited resources. Discrete event simulation was used to address this challenge. METHODOLOGY: A cross-sectional interventional study was done from September 2020 to October 2020. Detailed process mapping with all micro-processes was done. Patient arrival patterns and time taken at each step were measured by two independent observers at random intervals over two weeks. The existing system was simulated and a bottleneck was identified. Two possible alternatives to the problem were simulated and evaluated. RESULTS: Scenario 1 showed a maximum throughput of 316. The average milestone times of all the processes after the step of "Preparation of sampling kits" jumped 62%; from 82 to 133 min. Staff state times also showed that staff at this step was stretched and medical lab technicians were underutilized. Scenario 2 simulated the alternative with lesser time spent on sampling kit preparation with a 22.4% increase in throughput, but could have led to impaired quality check. Scenario 3 simulated with increased manpower at the stage of bottleneck with 26.5% increase in throughput and was implemented on-ground. CONCLUSION: Discrete event simulation helped to identify the bottleneck, simulate possible alternative solutions without disturbing the ongoing work, and finally choose the most suitable intervention to increase throughput, without the need for additional space allocation. It therefore helped to optimally utilize resources and get "more from less."

Impact of COVID-19 on the patients' income and work in Delhi, India.

BACKGROUND: Currently, there is no data on the impact of COVID-19 on patients' income and work in India. METHODS: We conducted a cross-sectional study at a tertiary hospital in New Delhi. We included all the patients who were ≥18 years of age and consecutively diagnosed with COVID-19 between the 1st of May 2020 to 31st July 2020. Patients were interviewed by a physician using a semi-structure questionnaire. Data were collected on socio-economic status, occupation, income loss, leaves taken, decrease in work efficiency (self-perceived) and about-facing any stigma/discrimination at the workplace. RESULTS: Out of 245 patients, 190 patients were employed. A total of 126 patients (66.3%) self-reported their work was affected due to COVID-19 disease. A total of 30.5% of patients (n = 58/190) reported deduction in their salary. The median amount of salary loss was INR 10,000 (IQR 9000-25000). Decrease in income and work efficiency (self-perceived) was found to be 37.3% (n = 71) and 12.1% (n = 23), respectively. A total of 47 patients (37.3%) took personal leaves (median number - 17 days (IQR 14-25), and discrimination/stigma related to the COVID-19 at the workplace was faced by 22.6% of patients. CONCLUSION: Income and work of a substantial number of patients was affected due to COVID-19, as there was a decrease in income and work efficiency. Patients also had to take personal leaves and face stigma in the workplace. This will inform the policymakers to formulate strategies to mitigate the impact of COVID-19.