7, 8-dihydroxyflavone Ameliorates Cholinergic Dysfunction, Inflammation, Oxidative Stress, and Apoptosis in a Rat Model of Vascular Dementia.

Vascular dementia (VD) is a degenerative cerebrovascular disorder associated with progressive cognitive decline. Previous reports have shown that 7,8-dihydroxyflavone (7,8-DHF), a well-known TrkB agonist, effectively ameliorates cognitive deficits in several disease models. Therefore, this study investigated the protective effects of 7,8-DHF against 2-VO-induced VD. VD was established in rats using the permanent bilateral carotid arteries occlusion (two-vessel occlusion, 2-VO) model. 7,8-DHF (5, 10, and 20 mg/kg) and Donepezil (10 mg/kg) were administered for 4 weeks. Memory function was assessed by the novel objective recognition task (NOR) and Morris water maze (MWM) tests. Inflammatory (TNF-α, IL-1ß, and NF-kß), oxidative stress, and apoptotic (BAX, BCL-2, caspase-3) markers, along with the activity of choline acetylcholinesterase (AChE) was assessed. p-AKT, p-CREB, BDNF, and neurotransmitter (NT) (GLU, GABA, and ACh) levels were also analyzed in the hippocampus of 2-VO rats. Our results show that 7,8-DHF effectively improved memory performance and cholinergic dysfunction in 2-VO model rats. Furthermore, 7,8-DHF treatment also increased p-AKT, p-CREB, and BDNF levels, suppressed oxidative, inflammatory, and apoptotic markers, and restored altered NT levels in the hippocampus. These findings imply that 7, 8-DHF may act via multiple mechanisms and as such serve as a promising neuroprotective agent in the context of VD.

Tetramethylpyrazine Attenuates Cognitive Impairment Via Suppressing Oxidative Stress, Neuroinflammation, and Apoptosis in Type 2 Diabetic Rats.

Cognitive dysfunction is an important complication observed in type 2 diabetes mellitus (T2DM) patients. Tetramethylpyrazine (TMP) is known to exhibit anti-diabetic and neuroprotective properties. Therefore, the present study aimed to investigate the possible therapeutic effects of TMP against type 2 diabetes-associated cognitive impairment in rats. High-fat diet (HFD) followed by a low dose of streptozotocin (35 mg/kg) was used to induce diabetes in Sprague-Dawley rats. TMP (20, 40, and 80 mg/kg) and Pioglitazone (10 mg/kg) were administered for 4 weeks. The Morris water maze (MWM) and novel objective recognition task (NOR) tests were used to assess memory function. Fasting blood glucose (FBG), lipid profile, HOMA-IR, glycosylated hemoglobin (HbA1c), and glucose tolerance were measured. Acetylcholinesterase (AChE) and choline acetytransferase (ChAT) activity, acetylcholine (ACh) levels, oxidative stress, apoptotic (Bcl-2, Bax, caspase-3), and inflammatory markers (TNF-α, IL-1ß, and NF-kß) were assessed. BDNF, p-AKT, and p-CREB levels were also measured. In the present work, we observed that treatment of diabetic rats with TMP alleviated learning and memory deficits, improved insulin sensitivity, and attenuated hyperglycemia and dyslipidemia. Furthermore, treatment with TMP increased BDNF, p-Akt, and p-CREB levels, normalized cholinergic dysfunction, and suppressed oxidative, inflammatory, and apoptotic markers in the hippocampus. Collectively, our results suggest that the TMP may be an effective neuroprotective agent in alleviating type 2 diabetes-associated cognitive deficits.

Antifungal prescription practices and consumption in a tertiary care hospital of a developing country.

BACKGROUND: Antifungal stewardship is a less explored component of antimicrobial stewardship programmes, especially in developing countries. OBJECTIVE: We aimed to determine antifungal prescription practices in a tertiary centre of a developing country to identify the challenges for antifungal stewardship programmes. METHODS: Four single-day point prevalent surveys were performed in inpatient units and data were collected from medical records. Antifungal use was recorded in terms of consumption, therapeutic strategies and appropriateness. RESULTS: We found a 2.42%-point prevalence of antifungal prescriptions. Antifungal use was higher in children than adults (4.1% vs. 2.03%), medical than surgical units (3.7% vs. 1.24%) and ICUs than general wards (5.8% vs. 1.9%). The highest antifungal use was observed in the haematology-oncology units (29.3%) followed by emergency (16.2%) and gastroenterology units (11.6%). Among 215 prescriptions, amphotericin B was the most commonly prescribed (50.2%) followed by fluconazole (31.6%). The targeted antifungal therapy was practised more commonly (31.5%) than empiric (29.1%), pre-emptive (22.6%) and prophylactic (16.8%) therapy. Amphotericin B was commonly used for pre-emptive (p = .001) and targeted (p = .049) therapy, while fluconazole (p = .001) and voriconazole (p = .011) for prophylaxis. The prescriptions were inappropriate in 25.1% due to the wrong choice of antifungal (44.4%), indication (27.7%) and dosage (24%). The overall mean antifungal consumption was 2.71 DDD/1000 PD and 8.96 DOT/1000 PD. CONCLUSIONS: We report here the low prevalence of antifungal use at a tertiary care centre in a developing country. Though training for antifungal use would be important for antifungal stewardship, the challenge would remain with the affordability of antifungals.

A multicentre point prevalence survey (PPS) of antimicrobial use amongst admitted patients in tertiary care centres in India.

OBJECTIVES: Data from point prevalence surveys (PPSs) in India are scarce. Conducting PPSs is especially challenging in the absence of electronic medical records, a lack of dedicated resources and a high patient load in resource-poor settings. This multicentre survey was conducted to provide background data for planning and strengthening antimicrobial stewardship programmes across the country. METHODS: This inpatient PPS was conducted over 2 weeks in May 2019 simultaneously across five study centres in India. Data about patient characteristics, indications for antimicrobials use and details of each antimicrobial prescribed including supportive investigation reports were collected in predesigned forms. RESULTS: A total of 3473 admitted patients in wards and ICUs were covered across five study centres. Of these, 1747 (50.3%) patients were on antimicrobials, with 46.9% patients being on two or more antimicrobials. Out of the total antimicrobials prescribed, 40.2% of the antimicrobials were prescribed for community-acquired infection requiring hospitalization followed by surgical prophylaxis (32.6%). Third-generation cephalosporins and drugs from the 'Watch' category were prescribed most commonly. Only 22.8% of the antimicrobials were based on microbiology reports. CONCLUSIONS: The survey demonstrated a high use of antimicrobials in admitted patients with a considerable proportion of drugs from the 'Watch' category. The targets for interventions that emerged from the survey were: improving surgical prophylaxis, decreasing double anaerobic cover, initiating culture of sending cultures and de-escalation with targeted therapy.

Dimethyl fumarate attenuates 2-VO-induced vascular dementia via activating the Nrf2 signaling pathway in rats.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) induced oxidative stress and inflammation is known to be implicated in the pathogenesis of vascular dementia. The nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a potential therapeutic target for neuroprotection. In the present study, we investigated the beneficial effects of dimethyl fumarate (DMF), an Nrf2 activator in an experimental model of vascular dementia. METHODS: Permanent occlusion of the bilateral common carotid arteries (2-VO) was performed to induce CCH in adult male Sprague-Dawley rats. DMF (15, 30, and 60 mg/kg) was administered for 4 weeks. Cognitive performance was assessed using the Morris water maze (MWM) and novel object (NOR) tests. After behavior tests, various oxidative and inflammatory markers were assessed in the hippocampus. RESULTS: The obtained results indicate that treatment with DMF significantly improved 2 VO-induced cognitive deficits. DMF decreased MDA (p < 0.001), protein carbonyl (PCO) contents (p < 0.001), and acetylcholinesterase (p < 0.01) activities, and inhibited inflammatory markers (TNF-α, IL-1ß, NF-κß, and COX-2) levels. Furthermore, our results showed that DMF augmented GSH (p < 0.001) levels and SOD (p < 0.05), CAT, and GSH-Px (p < 0.001) activities in the hippocampus. Nrf2 (p < 0.05) and its downstream targets HO-1 levels (p < 0.01) and NQO1 (p < 0.05) levels were also up-regulated after DMF treatment. CONCLUSION: Taken together, the results demonstrate that DMF could serve as a promising neuroprotective agent for treating vascular dementia.

Devastating impacts of COVID-19: An experience of abandoned child at a tertiary care hospital.

There were many challenges faced by both health-care workers and the common population during the COVID-19 pandemic. One such case was witnessed where a migrant worker abandoned his child in a tertiary care hospital, while he was undergoing treatment for acute liver disease and was reported COVID-19 positive. The child was treated for COVID-19 in the dedicated isolation facility of the hospital as per the guidelines. Later, when the child was declared COVID-19 negative and was ready to discharge, treating doctors found it difficult to hand over the child. The timely intervention and extraordinary efforts by the department of hospital administration and child welfare committee reunited the child with his family.

Hand hygiene compliance of respiratory physiotherapists: An analysis of trends over eight years including the COVID-19 pandemic period.

BACKGROUND: Respiratory physiotherapists (RPs) are an integral part of healthcare workers delivering care to intubated patients. Our study aimed to evaluate the effect of awareness campaigns on hand hygiene (HH) compliance among RPs. METHOD: An observational single-center study was conducted between 2015 and 2022 in different ICU types in both adult and paediatric settings. The hand hygiene compliance rates were monitored prospectively and the quality improvement interventions included various hand hygiene campaigns and awareness sessions with RPs. Compliance was calculated as a percentage of events over total opportunities observed. RESULTS: There was a significant increase in compliance rates for all five moments of HH (p-value: <0.05). Overall, mean compliance rate in ICUs was significantly higher than wards for Moment 1 (p-value: 0.0045), Moment 4 (p-value: 0.0372) and Moment 5 (p-value: 0.0036) by 24.2%, 22.7% and 21.5% respectively. Also, paediatric ICUs had higher HH compliance than adult ICUs for Moment 1 (87.5% vs 61.1%; p-value: 0.0459) and Moment 4 (93.7% vs 79.3%; p-value: 0.0255). A significant increase in HH compliance was observed in post-COVID-19 period compared to pre-COVID-19 period with respect to Moment 1, 2 and 5. CONCLUSION: This study adds to the almost non-existent literature on this important category of healthcare workers working in respiratory ICUs. Our results project an increase compliance after the HH awareness programmes over the years among RP which is critical to prevent spread infection by multidrug resistant organisms among the hospitals.

Perception and Attitude of Health Care Personnel Regarding Integration of Nursing Education and Nursing Services for Patient Care at a Tertiary Care Center of Northern India.

This study aims to assess the perception and attitude of health care personnel regarding integration of nursing education and nursing services. Using purposive and stratified random sampling technique, 92 medical faculty, 32 nursing faculty and 346 nursing officers were enrolled. A three-point Likert scale consisting of 15 items and six open ended questions was used to collect the data. Overall, the concept of integration of nursing education and nursing services at their institute was welcomed by 74.4% of health care personnel. Medical faculty (47.8%), nursing faculty (37.5%) and nursing officers (57.5%) scored the concept of integration as very good.

Management of Nursing Resource during the Covid 19 Pandemic: Lessons on the Ground.

During the covid 19 pandemic, management of nursing resource which forms the crux of patient care emerged as one of the major challenges amongst many. The strategies for staff mobilization, redeployment and recruitment, along with laying down standard operating procedures evolved as the pandemic progressed. The safety of the staff has to be a major focus area. Guidelines for covid duty exemption, orientation and training of staff must be drafted, reviewed and revised as required. Issues related to accommodation, psychosocial support and wellbeing have to be addressed. It is very important to adapt to the ever changing needs for nursing resource and be vigilant for emerging issues for an effective response to the pandemic.

COVID-19 management: Opportunity to reassess protocols?

The COVID 19 pandemic ravaged the globe with a remarkable ferocity and has not entirely abated till now with cases flaring up at various places at different times. The expected course is for it to become endemic with recurring exacerbations. Over the past two years, we have become wiser to its pathology, diagnosis, and treatment. However, it is imperative for us to regularly and consistently reassess our protocols to assimilate the current and ever-growing knowledge in this direction. Doing so will help us to use our resources judiciously, improve patient care, and enhance the overall benefit to stakeholders. In this article, we aim draw the researchers' attention to few issues which may not be at the forefront at this point in time but important nevertheless. These include the use of personal protective equipment (PPE), universal gloving, isolation criteria, and handling of dead bodies, among others. We hope that a reassessment of the challenges involved in the said procedures will help us to be better prepared to face and tackle potential future waves and the multiple challenges that would potentially ensue post-spikes in infection incidences.

Nursing personnel management during COVID-19 pandemic: An exemption trend in view of health reasons.

Background: In the COVID-19 pandemic, the healthcare system faced unprecedented challenges with increased number of patients and limited resources. Managing nursing resource was a major challenge for hospital administration. They had to be on the frontline, but their safety was of paramount importance. Aim: This study aims to analyze the measures taken for the management and effective engagement of nursing personnel for deployment in the COVID area of the hospital and the exemption trend based on their health status. Methodology: A retrospective cross-sectional descriptive study was carried out to analyze the requests of nursing staff received for exemption of duty in COVID patient care areas. These requests were categorized and examined by the medical board constituted for this purpose. Microsoft Excel was used to interpret the results. Results: The study evaluated the health reasons of nursing officers on the basis of which exemption was given for deployment of nursing officers in COVID areas. They were mostly medical reasons (91.1%) and few personal reasons (8.77%). The majority suffered from diseases affecting two or more than two specialties. Out of 376 applications, 223 were exempted, 81 were not exempted, 13 were given short-term exemption, and 26 were shifted to administrative assignments. Thirty-three staff members were referred to an appropriate forum.

A Simple Infection Prevention 'Bundle' Including Preoperative Bath With Hair-Wash to Reduce Surgical Site Infection (SSI) Following Elective Caesarean and Gynaecological Surgery in India.

Background: Surgical site infections (SSIs) may be reduced by following SSI prevention measures. We assessed the SSI rate following caesarean section (CS) and gynaecologic surgery after implementing a simple SSI prevention bundle including preoperative bath and hair wash. Methods: The study was carried out in two hospitals in North India (Post Graduate Institute of Medical Education and Research [PGIMER] and Civil Hospital CH) from August 2018 to July 2019. The SSI rate during intervention period (9 months) was compared with baseline rate (3 months). Womens' knowledge about SSI was assessed preoperatively and after counselling, postoperatively. Results: The baseline SSI rate after CS (n = 165) was 11.1% at PGIMER and 8.5% at CH. After gynae surgery (n = 172), it was 13% at PGIMER and 11.5% at CH. During intervention, (CS = 585, gynae surgery = 503), SSI rate was reduced significantly at PGIMER (CS: 11.1% to 3.7%, P = 0.048; gynae surgery: 13% to 7.1%, P = 0.027), but not at CH (CS: 8.5% to 8.2%, P = 0.903; gynae surgery: 11.5% to 11.4%, P = 0.984). Three measures were followed more often at PGIMER than at CH: before CS, bath with hair-wash: 99.3% vs 78.5%, P = 0.00, hair-clipper vs razor: 100% vs 5.1%, P = 0.00 and antibiotic prophylaxis ≤120 min: 100% vs 92.4%, P = 0.00; and before gynae surgery, bath with hair-wash: 93.2% vs 71%, P = 0.00, hair-clipper vs razor: 93.6% vs 1.9%, P = 0.00 and antibiotic prophylaxis ≤120 min: 100% vs 80.8%, P = 0.00. Postoperatively, womens' knowledge about SSI prevention improved significantly at the two sites. Conclusion: The reduction in SSI at PGIMER was attributed to better compliance to SSI prevention measures listed above. Counselling women about simple SSI prevention method like preoperative bath with scalp hair wash increased their knowledge about these significantly.

Activation of the Nrf2/HO-1 signaling pathway by dimethyl fumarate ameliorates complete Freund's adjuvant-induced arthritis in rats.

The nuclear factor erythroid 2-related factor (Nrf2) signaling pathway has recently emerged as a novel therapeutic target in treating various diseases. Therefore, the present study aimed to assess the protective role of the Nrf2 activator, dimethyl fumarate (DMF) in the complete Freund's adjuvant (CFA)- induced arthritis model. DMF (25, 50, and 100 mg/kg) and dexamethasone (2 mg/kg) were orally administered for 14 days. Pain-related tests, paw volume, and arthritic scores were measured weekly. Serum TNF-α, IL-1ß, cyclic citrullinated peptide (CCP), C-reactive protein (CRP), and rheumatoid factor (RF) levels were estimated. Nitrite, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), catalase (CAT), and myeloperoxidase (MPO) levels were also evaluated. NF-κB, Nrf2, HO-1, and COX-2 levels were estimated in the joint tissue. DMF treatment exerted anti-arthritic activity by enhancing the nociceptive threshold, improving arthritis scores, and reducing paw edema. Also, DMF suppressed changes in oxidative stress markers and inflammatory mediators and enhanced Nrf2 and HO-1 levels in CFA-injected rats. These findings indicate that the anti-arthritic activity of DMF may be mediated by the activation of the Nrf2/HO-1 pathway, which reduced oxidative damage and inflammation.

Beneficial effects of ferulic acid alone and in combination with insulin in streptozotocin induced diabetic neuropathy in Sprague Dawley rats.

BACKGROUND: Ferulic acid (FA) is a phenolic phytochemical known to protect against various diabetic complications. However, its role in diabetic neuropathy is still unclear. The present study investigated the potential protective effects of FA alone and its combination with insulin against streptozotocin (STZ)-induced diabetic neuropathy in rats. METHODS: STZ (55 mg/kg) was injected in adult Sprague-Dawley rats to induce diabetes. Diabetic rats were treated with FA (25, 50, and 100 mg/kg, p.o), insulin (10 IU/kg, s.c.) and the combination of FA (100 mg/kg, p.o.) with insulin (10 IU/kg, s.c.) for four weeks. Body weight, blood glucose, insulin, glycosylated hemoglobin, nerve conduction velocity and pain parameters were measured. Moreover, oxidative stress, inflammatory (TNF-α, IL-1ß, COX-2) and apoptotic markers (Bcl-2, Bax, caspase 3) were assessed in the sciatic nerve tissue. Na+-K+-ATPase activity and nerve growth factor (NGF) levels were also determined. RESULTS: FA attenuated STZ induced alteration in metabolic parameters, nociceptive threshold, motor nerve conduction velocity, NGF levels and Na+-K+-ATPase activity. In addition, FA boosted anti-oxidant defenses and suppressed oxidative stress, pro-inflammatory mediators and apoptotic markers. Furthermore, diabetic rats treated with insulin-FA (100 mg/kg) combination demonstrated more pronounced beneficial effects as compared to either agent alone. CONCLUSIONS: Collectively, our results suggest that FA either alone or in combination with insulin therapy could serve as an efficacious agent for treating diabetic neuropathy.

Astaxanthin attenuates oxidative stress and inflammatory responses in complete Freund-adjuvant-induced arthritis in rats.

BACKGROUND: Astaxanthin (ATX), a natural xanthophyll carotenoid, has shown to exert significant protective effects against various diseases via its antioxidant and anti-inflammatory properties. However, its potential role in arthritis is still not reported. Therefore, the aim of the present study was to investigate the potential anti-arthritic properties of ATX against complete Freund's adjuvant (CFA)-induced arthritis rats. METHODS: Adjuvant arthritis was induced by single intraplantar injection of complete Freund's adjuvant (CFA) in the left hind paw of adult female Wistar rats. ATX (25, 50 and 100 mg/kg) and indomethacin (5 mg/kg) were given orally from days 14 to 28. The anti-arthritic activity was evaluated through various nociceptive behavioral tests (mechanical allodynia, mechanical hyperalgesia, cold allodynia, and thermal hyperalgesia), paw edema assessment, and arthritis scores. Serum tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and cyclic citrullinated peptide (CCP) antibody levels were assessed. Moreover, malondialdehyde (MDA), nitrite, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels were also evaluated. RESULTS: Oral administration of ATX (50 and 100 mg/kg) exhibited significant anti-arthritic activity via enhancing the nociceptive threshold, reducing paw edema and improving arthritis scores. Moreover, ATX treatment also markedly suppressed inflammatory and oxidative mediators in adjuvant-administered rats. CONCLUSIONS: Our findings suggest that ATX possesses potential anti-arthritic activity, which could be attributed to its anti-inflammatory and antioxidant properties.

The Probiotic Mixture VSL#3 Reverses Olanzapine-Induced Metabolic Dysfunction in Mice.

Atypical antipsychotic drugs (AAPDs) such as olanzapine (OLZ) are associated with serious metabolic adverse effects such as weight gain, visceral fat accretion, glucose intolerance, and lipid abnormalities. Compelling evidence suggests that the gut microbiota is known to regulate metabolic homeostasis and therefore microbiota-modulating strategies such as probiotics may serve as an excellent approach for treating metabolic adverse effects associated with atypical antipsychotic drugs (AAPDs). The therapeutic potential of VSL#3 (20 × 109 CFU/day), in reversing olanzapine-induced metabolic dysfunction, was assessed. VSL#3 administration led to attenuation of OLZ-induced body weight gain, uterine fat deposition, impaired glucose tolerance, and insulin resistance. Moreover olanzapine treatment also decreased inflammatory markers, abolished oxidative stress in the vWAT, and prevented shifts in gut microbiota abundance levels. These results indicate that VSL#3 via its ability to manipulate the gut microbiome confers beneficial metabolic effects and may, therefore, represent a novel therapeutic approach for reversing antipsychotic-induced metabolic dysfunction.

Increase in hospital purchase of hand hygiene products: The importance of focusing on the right product.

Alcohol-based handrub (AHR) consumption is positively correlated with increases in hand hygiene (HH) compliance. In our 2,000-bed hospital in India, multiple awareness drives have been conducted to promote HH. This study aimed to determine the quantitative effect of these campaigns on use of HH products (soap and AHR) in the hospital. Over the last 6 years, bar soap consumption has increased by 389.15%, whereas that of AHR increased by 146.7%. We also evaluated microbial contamination of 99 bar soap and 60 liquid soap samples in our hospital for a year. Of the samples, 61 (61.6%) of the bar soaps and 2 (3.3%) of the liquid soaps were found to be contaminated with various organisms (P < .0002). To conclude, the focus should be to increase the right kind of HH product so that hospitals in developing countries procure liquid soaps instead of bar soaps for handwashing purposes.

Evaluation of the short-term and long-term effect of a short series of hand hygiene campaigns on improving adherence in a tertiary care hospital in India.

Hand hygiene compliance at our institution was monitored by direct observation before and after a series of 2 hand hygiene awareness campaigns across an18-month time period to analyze the effect of these campaigns. A total of 5,059 opportunities for hand hygiene were observed. Compliance increased from 28.1% (95% confidence interval [CI], 18.7%-43.2%) to 42.5% (95% CI, 30.7%-54.8%) after the 2 campaigns (P < .0001) but dropped to 36.4% (95% CI, 30.5%-44.5%) after 2 years (P < .001). Three of the 8 intensive care units that showed a significant increase after the campaigns did not maintain the increased compliance at 2 years' follow-up. We conclude that educational programs should be repeatedly conducted to maintain high adherence to hand hygiene standards in health care settings.