Sex-specific effects of sucrose withdrawal on anxiety-like behavior and neuroimmune response.

Sugar bingeing induces maladaptive neuroadaptations to decrease dietary control and promote withdrawal symptoms. This study investigated sex differences in sucrose bingeing, sucrose withdrawal-induced negative mood effects and underlying neuroimmune response in the prefrontal cortex (PFC) and nucleus accumbens (NAc) of C57BL/6J male and female mice. Two-bottle sucrose choice paradigm was used to develop sucrose dependence in mice. Female mice consumed more sucrose than male mice when given free access to water and 10% sucrose for four weeks. A significant increase in the mRNA expression of neuroinflammatory markers (Il1ß, Tnfα) was found in the PFC of males exposed to sucrose withdrawal. Sucrose bingeing and subsequent sucrose withdrawal showed elevated protein levels of pro-inflammatory cytokines/chemokines/growth factors in the PFC (IL-1ß, IL-6, TNFα, IFN-γ, IL-10, CCL5, VEGF) and NAc (IL-1ß, IL-6, IL-10, VEGF) of male mice as compared to their water controls. These effects were concurrent with reduced mRNA expression of neuronal activation marker (cFos) in the PFC of sucrose withdrawal males. One week of sucrose withdrawal after prolonged sucrose consumption showed anxiety-like behavior in male mice, not in females. In conclusion, this study demonstrates that repeated access to sucrose induces anxiety-like behavior when the sugar is no longer available in the diet and these effects are male-specific. Elevated neuroinflammation in reward neurocircuitry may underlie these sex-specific effects.

Investigation of The Effect of Metal-based Medicine Arsenicum album on Humoral Immune Response in SRBC-immunized Mice.

BACKGROUND: In complementary and alternative medicinal systems, the Arsenicum album in ultra-high dilution was used in various therapeutic conditions, considering its effects on the body's immune system, including the COVID-19 pandemic. However, scientific evidence regarding its immunomodulatory effects is insufficient. OBJECTIVE: The current study aimed to investigate the immunomodulatory effects of Arsenicum album in an experimental mouse model. MATERIALS AND METHODS: Immunomodulatory activity of potentized dilutions of Arsenicum album i.e., 6C, 30C, 200C in BALB/c mice was evaluated by humoral antibody titer and delayed- type hypersensitivity assays wherein a fixed concentration (0.5 ml of 1× 109 cells/ml) of freshly prepared sheep RBC was administered as a foreign antigen to generate primary and secondary antibodies. RESULTS: Arsenicum album showed significant immunomodulatory activity by increasing primary antibody titer evaluated on day 21 of the treatment in all the dilutions as compared to SRBC and vehicle control group in humoral immune response assay without showing any effect on delayed-type hypersensitivity. CONCLUSION: The results of this preliminary study indicate that oral administration of Arsenicum album has the potential to augment primary humoral response at all dilutions. Hence, the possibility of using the Arsenicum album could be explored to treat immunological conditions, infections, etc., as an alternative therapy alongwith modern medicines.

Nrf2 Signaling Pathway: a Potential Therapeutic Target in Combating Oxidative Stress and Neurotoxicity in Chemotherapy-Induced Cognitive Impairment.

Chemotherapy-induced cognitive impairment (CICI) is one of the major adverse effects of antineoplastic drugs, which decrease the quality of life in cancer survivors. Extensive experimental and clinical research suggests that chemotherapeutic drugs generate an enormous amount of reactive oxygen species (ROS), contributing to oxidative stress, neuroinflammation, blood-brain barrier (BBB) disruption, and neuronal death, eventually leading to CICI. Despite the progress in exploring different pathological mechanisms of CICI, effective treatment to prevent CICI progression has not been developed yet. Nrf2 is the principal transcription factor that regulates cellular redox balance and inflammation-related gene expression. Emerging evidence suggests that upregulation of Nrf2 and its target genes could suppress oxidative stress, and neuroinflammation, restore BBB integrity, and increase neurogenesis. This review discusses the role of Nrf2 in CICI, how it responds to oxidative stress, inflammation, neurotoxicity, and potential Nrf2 activators that could be used to enhance Nrf2 activation in CICI.

Alpha-Lipoic Acid Ameliorates Doxorubicin-Induced Cognitive Impairments by Modulating Neuroinflammation and Oxidative Stress via NRF-2/HO-1 Signaling Pathway in the Rat Hippocampus.

Chemotherapy-induced cognitive impairment (CICI) is a common complication associated with the use of chemotherapeutics. Doxorubicin (DOX) is a reactive oxygen species (ROS) producing anticancer agent capable of causing potential neurotoxic effects via cytokine-induced oxidative and nitrosative damage to brain tissues. On the other hand, alpha-lipoic acid (ALA), a nutritional supplement, is reputable for its excellent antioxidant, anti-inflammatory, and anti-apoptotic activities. Consequently, the objective of the current investigation was to examine any potential neuroprotective and memory-improving benefits of ALA against DOX-induced behavioral and neurological anomalies. DOX (2 mg/kg/week, i.p.) was administrated for 4 weeks to Sprague-Dawley rats. ALA (50, 100, and 200 mg/kg) was administered for 4 weeks. The Morris water maze (MWM) and novel objective recognition task (NORT) tests were used to assess memory function. Biochemical assays with UV-visible spectrophotometry were used to analyze oxidative stress markers [malondialdehyde (MDA), protein carbonylation (PCO)], endogenous antioxidants [reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)] and acetylcholinesterase (AChE) activity in hippocampal tissue. Inflammatory markers [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor kappa B (NF-κB)], nuclear factor erythroid 2-related factor-2 (NRF-2) and hemeoxygenase-1 (HO-1) levels were estimated using enzyme-linked immunosorbent assay (ELISA). In addition, reactive oxygen species (ROS) levels were measured in hippocampus tissue using 2-7-dichlorofluorescein-diacetate (DCFH-DA) assay with fluorimetry. ALA treatment significantly protected against DOX-induced memory impairment. Furthermore, ALA restored hippocampal antioxidants, halted DOX-induced oxidative and inflammatory insults via upregulation of NRF-2/HO-1 levels, and alleviated the increase in NF-κB expression. These results indicate that ALA offers neuroprotection against DOX-induced cognitive impairment, which could be attributed to its antioxidant potential via the NRF-2/HO-1 signaling pathway.

Clinical features, management, and mortality because of COVID-19 in an intensive care unit in Surguja, a tribal district in Central India: A single-centre descriptive study.

Background: The clinical features and management of severe coronavirus disease 2019 (COVID-19) have been well documented in urban India. However, little data exist on the management and outcomes of severe COVID-19 in rural and tribal areas. Methods: This was a retrospective chart review of the patients admitted in a 20-bedded COVID-19 intensive care unit (ICU) set up at the Government District Hospital, Ambikapur, Chhattisgarh, between 17 May and 17 July 2021 during the second wave of COVID-19 in India. The ICU was managed by a team of primary care providers, family physicians, and nurses under the supervision of three specialists. Data related to socio-demographic, clinical, laboratory, and treatment profiles were extracted using a data extraction tool and analysed. Results: A total of 55 of the 63 (87.3%) patients admitted in the ICU during the study period were eligible for the study. The mean age of the patients was 50.95 [standard deviation (SD) 15.76] years; 66% were < 60 years of age, and 63.6% were men. The mean duration of symptoms before ICU admission was 7.52 (SD 4.16) days. Breathlessness (63.6%), fever (58.2%), cough (52.7%), and altered sensorium (38.2%) were the most common presenting symptoms. 67% of the patients had any co-morbidity, and 43% had two or more co-morbidities. 32.7% patients needed non-invasive (14 out of 55) or invasive ventilation (4 out of 55). 12.7% of the patients (7 out of 55) needed dialysis. The intra-ICU mortality was 47%. Patients who died had higher prevalence of heart disease, hypoxia, and altered sensorium. Conclusion: Our study highlights the need for critical care services in Government District Hospitals in India and the feasibility of providing such care by primary care providers through specialist mentoring.

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.

The Impact of a Laparoscopic Surgery Training Course in a Developing Country.

INTRODUCTION: Surgeons training junior colleagues to perform laparoscopic surgery find the 'apprenticeship' model of surgical training inadequate. Therefore, the use of training courses involving simulation have become an important way to teach laparoscopic surgery. An annual laparoscopic surgery course began in Nepal in 2013. It is difficult to assess the impact of the course on trainees and demonstrate a subsequent improvement in patient outcomes, but one way is to ask delegates for reflections on their experience of the course and their perception of how it has impacted patients. METHODS: The course involved simulation and patient-based training. A questionnaire to collect quantitative data and qualitative comments was sent to all 80 previous delegates (at least 9 months after the course) in September 2018. RESULTS: Twenty-eight delegates responded. The majority demonstrated career progression since completing the course (independent practitioners increased from 7 to 50%) and progression in their practice (18% had performed >20 laparoscopic procedures at the time of the course, vs 70% at the time of the questionnaire). All delegates felt that laparoscopic training is useful in the Nepalese context. Delegates felt the course was useful in developing skills, and improving confidence and safety. Suggestions for improvement included lengthening the course and increasing the amount of practical exposure. CONCLUSION: There was a positive outcome of the course to Kirkpatrick level 2. There is a need to expand the course's scope to an advanced level, increase its length and start courses in other centres, to ensure the most possible benefit to patients.

Aviation-based teamwork skills work for surgeons: time for an 'aviation bundle'?

BACKGROUND: Aviation systems were developed to improve safety and have achieved remarkable results. Medicine has looked to replicate these systems; however, the gap in outcomes between the two industries remains vast. Bridging this chasm requires an in-depth analysis of the applicability of the aviation safety model in surgery. This study uses qualitative methods to explore how aviation-based practices may be adapted and applied more effectively in theatre. METHODS: Data were collected using multiprofessional focus groups in a single centre. The focus groups involved discussion around teamwork and aviation-based non-technical skills. With consent, audio recordings were anonymized and transcribed. Qualitative (thematic) analysis was used to identify themes. RESULTS: Five focus groups were conducted. Eight themes emerged, with a total of 18 sub-themes. Themes were: current practice, customization, applicability, team performance, human factors, analogy, incidents and integration of skills. Extent and limitations of the aviation surgery analogy also emerged. CONCLUSIONS: The new insights gained through this qualitative analysis highlight the need to tailor aviation-based practices to the operating theatre. To achieve this, we propose the 'aviation bundle' of non-technical skills. This blueprint aims to promote a culture of safety and efficiency in surgical practice and could be developed into a training programme for theatre staff.

Effect of Social Deprivation on the Stage and Mode of Presentation of Colorectal Cancer.

PURPOSE: Based in a hospital serving one of the most deprived areas in the United Kingdom (UK), we aimed to investigate, using the Indices of Deprivation 2010, the hypothesis that deprivation affects the stage and mode of presentation of colorectal cancer. METHODS: All newly diagnosed patients with colorectal cancer presenting to a District General Hospital in the UK between January 2010 and December 2014 were included. Data were collected from the Somerset National Cancer Database. The effect of social deprivation, measured using the Index of Multiple Deprivation Score, on the stage and mode of presentation was evaluated utilizing Microsoft Excel and IBM SPSS ver. 22.0. RESULTS: A total of 701 patients (54.5% male; mean age, 76 years) were included; 534 (76.2%) underwent a surgical procedure, and 497 (70.9%) underwent a colorectal resection. Of the patients undergoing a colorectal resection, 86 (17.3%) had an emergency surgical resection. Social deprivation was associated with Duke staging (P = 0.09). The 90-day mortality in patients undergoing emergency surgery was 12.8% compared to 6.8% in patients undergoing elective surgery (P = 0.06). No association was found between deprivation and emergency presentation (P = 0.97). A logistic regression analysis showed no increase in the probability of metastasis amongst deprived patients. CONCLUSION: This study suggests an association between deprivation and the stage of presentation of colorectal cancer. Patients undergoing emergency surgery tend to have a higher 90-day mortality rate, although this was not related to deprivation. This study highlights the need to develop an individual measure to assess social deprivation.