Ashwagandha Diminishes Hippocampal Apoptosis Induced by Microwave Radiation by Acetylcholinesterase Dependent Neuro-Inflammatory Pathway in Male Coturnix coturnix Japonica.

Microwave radiation (MWR) has been linked to neurodegeneration by inducing oxidative stress in the hippocampus of brain responsible for learning and memory. Ashwagandha (ASW), a medicinal plant is known to prevent neurodegeneration and promote neuronal health. This study investigated the effects of MWR and ASW on oxidative stress and cholinergic imbalance in the hippocampus of adult male Japanese quail. One control group received no treatment, the second group quails were exposed to MWR at 2 h/day for 30 days, third was administered with ASW root extract orally 100 mg/day/kg body weight and the fourth was exposed to MWR and also treated with ASW. The results showed that MWR increased serum corticosterone levels, disrupted cholinergic balance and induced neuro-inflammation. This neuro-inflammation further led to oxidative stress, as evidenced by decreased activity of antioxidant enzymes SOD, CAT and GSH. MWR also caused a significant decline in the nissil substances in the hippocampus region of brain indicating neurodegeneration through oxidative stress mediated hippocampal apoptosis. ASW, on the other hand, was able to effectively enhance the cholinergic balance and subsequently lower inflammation in hippocampus neurons. This suggests that ASW can protect against the neurodegenerative effects of MWR. ASW also reduced excessive ROS production by increasing the activity of ROS-scavenging enzymes. Additionally, ASW prevented neurodegeneration through decreased expression of caspase-3 and caspase-7 in hippocampus, thus promoting neuronal health. In conclusion, this study showed that MWR induces apoptosis and oxidative stress in the brain, while ASW reduces excessive ROS production, prevents neurodegeneration and promotes neuronal health.

Bioimpedance: A Tool for Screening Oral Cancer - A Systematic Review.

Objective: The successful management of cancer depends on proper screening and treatment methods. Bioimpedance spectroscopy (BIS) is an established technique in detecting breast cancer, cervical cancer, and prostate cancer. This systematic review sought to investigate the current evidence regarding the clinical application of bioimpedance in the detection of oral squamous cell carcinoma and oral potentially malignant disorders. Study Design: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to perform this review. Electronic databases such as PubMed, MEDLINE, Embase, EBSCOhost, and Google Scholar were searched till March 2022. Articles published in the English medical literature on human participants report on the application of BIS in the screening of precancerous and cancerous lesions. The primary endpoint was defined as the ability to differentiate between normal and cancerous tissue. Results: A total of 6754 articles were identified; of which 481 were eligible for inclusion. Only five articles met the eligibility criteria and were included in the study. Qualitative analysis for each study was done to assess the data provided. All the studies demonstrated a significant divergence in BIS metrics between cancerous and normal tissue at 20 Hz and 50 KHz. Conclusion: Bioimpedance appears to be a promising novel tool for the detection of various malignancies which can be used in community screening due to its noninvasiveness and portability.

Focal Cortical Dysplasia with hippocampal sclerosis.

Focal Cortical Dysplasia (FCD) is a group of focal developmental malformations of the cerebral cortex cytoarchitecture. FCD usually manifests as medically intractable epilepsy, especially in young children. Live patients are diagnosed by radiological examination such as magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG PET), magnetoencephalography (MEG), diffusion-tensor imaging (DTI), and intracranial electroencephalogram (EEG). While some cases can be missed by radiological examination, they are usually diagnosed on the histopathological examination of the surgically removed specimens of medically intractable epilepsy patients. We report a case of a young girl with cerebral palsy, mental retardation, and seizure disorder who died in her sleep. The deceased was diagnosed with FCD type III with hippocampal sclerosis on histopathological examination at autopsy. H & E stain and NeuN immunohistochemistry neuronal cell marker were used to demonstrate the findings of FCD.

Symptom Assessment Following Surgery for Lung Cancer: A Canadian Population-based Retrospective Cohort Study.

OBJECTIVE: To conduct a population-level analysis of temporal trends and risk factors for high symptom burden in patients receiving surgery for non-small cell lung cancer (NSCLC). BACKGROUND: A population-level overview of symptoms after curative intent surgery is necessary to inform decision making and supportive care for patients with lung cancer. METHODS: Retrospective cohort study of patients receiving surgery for stages I to III NSCLC between January 2007 and September 2018. Prospectively collection Edmonton Symptom Assessment System (ESAS) scores, linked to provincial administrative data, were used to describe the prevalence, trajectory, and predictors of moderate-to-severe symptoms in the year following surgery. RESULTS: A total of 5350 patients, with 28,490 unique ESAS assessments, were included in the analysis. Moderate-to-severe tiredness (68%), poor wellbeing (63%), and shortness of breath (60%) were the most common symptoms reported. The rise and fall in the proportion of patients experiencing moderate-to-severe symptoms after surgery coincided with the median time to first (58 days, interquartile range: 47-72) and last cycle of chemotherapy (140 days, interquartile range: 118-168), respectively. There was eventual stabilization, albeit above the preoperative baseline, within 6 to 7 months after surgery. Female sex (relative risk [RR] 1.09- 1.26), lower income (RR 1.08-1.23), stage III disease (RR 1.15-1.43), adjuvant therapy (RR 1.09-1.42), chemotherapy within 2 weeks of an ESAS assessment (RR 1.14-1.73), and pneumonectomy (RR 1.05-1.15) were associated with moderate-to-severe symptoms following surgery. CONCLUSIONS: Knowledge of population-level prevalence, trajectory, and predictors of moderate-to-severe symptoms after surgery for NSCLC can be used to facilitate shared decision making and improve symptom management throughout the course of illness.

Long-term Functional Outcomes Among Older Adults Undergoing Video-assisted Versus Open Surgery for Lung Cancer: A Population-based Cohort Study.

OBJECTIVE: To examine the long-term healthcare dependency outcomes of older adults undergoing VATS compared to open lung cancer resection. SUMMARY OF BACKGROUND DATA: Although the benefits of VATS for lung cancer resection have been reported, there is a knowledge gap related to long-term functional outcomes central to decision-making for older adults. METHODS: We conducted a population-based retrospective comparative cohort study of patients ≥70 years old undergoing lung cancer resection between 2010 and 2017 using linked administrative health databases. VATS was compared to open surgery for lung cancer resection. Outcomes were receipt of homecare and high time-at-home, defined as <14 institution-days within 1 year, in 5 years after surgery. We used time-to-event analyses. Homecare was analyzed as recurrent dichotomous outcome with Andersen-Gill multivariable models, and high time-at-home with Cox multivariable models. RESULTS: Of 4974 patients, 2951 had VATS (59.3%). In the first three months postoperatively, homecare use ranged from 17.5% to 34.4% for VATS and 23.0% to 36.6% for open surgery. VATS was independently associated with lower need for postoperative homecare over 5 years (hazard ratio 0.82, 95% confidence interval 0.74-0.92). 1- and 5-year probability of high "time-at-home" were superior for VATS (74.4% vs 66.7% and 55.6% vs 45.4%, p < 0.001). VATS was independently associated with higher probability of high "time-at-home" (hazard ratio 0.81, 95% confidence interval 0.74-0.89) compared to open surgery. CONCLUSIONS: Compared to open surgery, VATS was associated with lower homecare needs and higher probability of high "time-at-home," indicating reduced long-term functional dependence. Those important patient-centered endpoints reflect the overall long-term treatment burden on mortality and morbidity that can inform surgical decision-making.

Focal Cortical Dysplasia with hippocampal sclerosis

ABSTRACT Focal Cortical Dysplasia (FCD) is a group of focal developmental malformations of the cerebral cortex cytoarchitecture. FCD usually manifests as medically intractable epilepsy, especially in young children. Live patients are diagnosed by radiological examination such as magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG PET), magnetoencephalography (MEG), diffusion-tensor imaging (DTI), and intracranial electroencephalogram (EEG). While some cases can be missed by radiological examination, they are usually diagnosed on the histopathological examination of the surgically removed specimens of medically intractable epilepsy patients. We report a case of a young girl with cerebral palsy, mental retardation, and seizure disorder who died in her sleep. The deceased was diagnosed with FCD type III with hippocampal sclerosis on histopathological examination at autopsy. H & E stain and NeuN immunohistochemistry neuronal cell marker were used to demonstrate the findings of FCD.

2.45 GHz microwave radiation induced oxidative stress: Role of inflammatory cytokines in regulating male fertility through estrogen receptor alpha in Gallus gallus domesticus.

Due to the growing number of gadgets emitting electromagnetic radiation (EMR), particularly microwave (MW) radiation, in our daily lives, it is believed that EMR have both long-term and short-term biological impacts that are quite concerning for avian as well as human health. Due to the negative impact of MW emitting equipment on the biological system this study looks into the mechanistic approach by which low-level of 2.45 GHz MW radiation causes an oxidative stress and inflammatory response in the testes micro-environment which further gets regulated by estrogen receptor alpha (ERα) expression in immature Gallus gallus domesticus leading to male infertility. Two weeks old immature male chickens were exposed to non-thermal low-level 2.45-GHz MW radiation for 2 h/day for 30 days (power density = 0.1264 mw/cm2 and SAR = 0.9978 W/kg). In the exposed group, morphometric examination of the testes revealed decreased testicular weight, volume and gonado-somatic index. Further, histological staining demonstrated a substantial reduction in the diameter of seminiferous tubules in the exposed group as compared to the control. The degree of oxidative stress was also determined showing an increase in oxidative stress parameters after exposure. The radiation exposed testes showed a significant increase in IL-1ß immunoreactivity and decline in IL-10 immunoreactivity, indicating a sense of MW radiation-induced oxidative stress-regulated inflammatory response. A substantial reduction in ERα expression was also observed in exposed testes by Western blotting. Our investigations conclude that testes being vulnerable to free radical damage become an easy target organ for MW exposure induced oxidative and inflammatory stress. Therefore it becomes evident that it may cause male infertility in chicks via downregulation of ER-α in testis.

Expression of aldehyde dehydrogenase 1A1 in oral squamous cell carcinoma and its correlation with clinicopathological parameters.

Background: Aldehyde dehydrogenase 1A1 (ALDH1A1) is a key aldehyde dehydrogenase (ALDH) isozyme, related to the cancer stem cells which are responsible for initiating tumor growth, progression, and recurrence. High expression of ALDH1A1 has been reported in several tumor types in humans and its expression is associated with poor prognosis. The aim of this study was to assess the expression of the ALDH1A1 in oral squamous cell carcinoma (SCC) and its correlation with various clinicopathological parameters. Materials and Methods: ALDH1A1 expression was analyzed by using immunohistochemistry on paraffin blocks of 112 cases of primary oral SCC and their corresponding 68 lymph nodes with metastatic deposits. ALDH1A1 expression was also correlated with various clinicopathological parameters. Statistical analysis was done with statistical analysis software, the Statistical Package for the Social Sciences version 21.0. Results: High ALDH1A1 expression was observed in 31.2% of cases of primary oral SCC as compared to 73.5% in lymph node metastasis. A statistically significant difference (P = 0.04) was observed in high TNM stages (68.6%) of the tumor as compared to low TNM stages (31.4%). However, histopathological grades of tumor showed nonsignificant correlation with ALDH1A1 expression (P = 0.093). 40.2% of patients were expired at the end of the study, and the rate of mortality was significantly higher (P = 0.01) in patients with high ALDH1A1 expression as compared to low expression (60.0% vs. 31.2%). Conclusion: High ALDH1A1 expression was associated with higher TNM tumor stage and high nodal stage. It was also associated with high mortality rate which validates it as a marker of invasiveness and poor prognosis in oral SCC.

Osteoclastic variant of anaplastic thyroid carcinoma: An insight into a rarest of rare entity.

Anaplastic thyroid carcinoma is a rare and a very aggressive thyroid malignancy with a dismal prognosis. It has a short history and presents with a rapidly increasing neck mass associated with compressive symptoms like pain, hoarseness of voice, dysphagia and shortness of breath. Osteoclastic variant is an extremely rare variant, which is, characterize by presence of a large number of multinucleated giant cells, which resemble osteoclasts. Here we report two cases of this unusual variant in a 68 years old and 49 years old male with a short history of thyroid swelling.

Textbook Outcome and Survival in Patients With Gastric Cancer: An Analysis of the Population Registry of Esophageal and Stomach Tumours in Ontario (PRESTO).

OBJECTIVE: To examine the association between Textbook Outcome (TO)-a new composite quality measurement-and long-term survival in gastric cancer surgery. BACKGROUND: Single-quality indicators do not sufficiently reflect the complex and multifaceted nature of perioperative care in patients with gastric adenocarcinoma. METHODS: All patients undergoing gastrectomy for nonmetastatic gastric adenocarcinoma registered in the Population Registry of Esophageal and Stomach Tumours of Ontario (PRESTO) between 2004 and 2015 were included. TO was defined according to negative margins; >15 lymph nodes sampled; no severe complications; no re-interventions; no unplanned ICU admission; length of stay ≤21 days; no 30-day readmission; and no 30-day mortality. Three-year survival was estimated using the Kaplan-Meier method. A marginal multivariable Cox proportional-hazards model was used to estimate the association between achieving TO metrics and long-term survival. E-value methodology was used to assess for risk of residual confounding. RESULTS: Of the 1836 patients included in this study, 402 (22%) achieved all TO metrics. TO patients had a higher 3-year survival rate compared to non-TO patients (75% vs 55%, log-rank P < 0.001). After adjustments for covariates and clustering within hospitals, TO was associated with a 41% reduction in mortality (adjusted hazards ratio 0.59, 95% confidence interval 0.48, 0.72, P < 0.001). These results were robust to potential residual confounding. CONCLUSIONS: Achieving TO is strongly associated with improved long-term survival in gastric cancer patients and merits further focus in surgical quality improvement efforts.

Upfront Small Bowel Resection for Small Bowel Neuroendocrine Tumors With Synchronous Metastases: A Propensity-score Matched Comparative Population-based Analysis.

OBJECTIVE: We examined the impact of upfront small bowel resection (USBR) for metastatic small bowel neuroendocrine (SB-NET) compared to nonoperative management (NOM) on long-term healthcare utilization and survival outcomes. SUMMARY OF BACKGROUND DATA: The role of early resection of the primary tumor in metastatic SB-NET remains controversial. Conflicting data exist regarding its clinical and survival benefits. METHODS: This is a population-based retrospective matched comparative cohort study of adults diagnosed with synchronous metastatic SB-NET between 2001 and 2017 in Ontario. USBR was defined as resection within 6 months of diagnosis. Primary outcomes were subsequent unplanned acute care admissions and small bowel-related surgery. Secondary outcome was overall survival. USBR and NOM patients were matched 2:1 using a propensity-score. We used time-to-event analyses with cumulative incidencefunctions and univariate Andersen-Gill regression for primary outcomes. E value methods assessed the potential for residual confounding. RESULTS: Of 1000 patients identified, 785 had USBR. The matched cohort included 348 patients with USBR and 174 with NOM. Patients with USBR had lower 3-year risk of subsequent admissions (72.6% vs 86.4%, P < 0.001) than those with NOM, with hazard ratio 0.72 (95% confidence interval 0.570.91). USBR was associated with lower risk of subsequent small bowel-related surgery (15.4% vs 40.3%, P < 0.001), with hazard ratio 0.44 (95% confidence interval 0.29-0.67). E -values indicated it was unlikely that the observed risk estimates could be explained by an unmeasured confounder. Sensitivity analysis excluding emergent resections to define USBR did not alter the results. CONCLUSIONS: USBR for SB-NETs in the presence of metastatic disease was associated with better patient-oriented outcomes of decreased subsequent admissions and interventions, compared to NOM. USBR should be considered for metastatic SB-NETs.

Unusual cutaneous presentation in a corrosive acid ingestion.

Corrosive digestive tract injuries are considered to be a source of morbidity and mortality worldwide. The cases of acid ingestion in Forensic Medicine practice are not infrequent. Corrosive ingestion usually presents with injuries over the face, oropharynx, esophagus, and gastrointestinal tract. We report a case of a 65-year-old woman who was brought to the emergency department with a history of ingestion of toilet cleaner at her home. Following this, she developed blackish-brown discoloration over the abdomen. The patient survived for less than one day. An autopsy confirmed the perforation of the stomach and small intestine. 500 ml of blackish fluid was present in the peritoneal cavity which resulted in corrosive peritonitis. The chemical examiner's report showed corrosive mixtures comprising sulfate, nitrate, and chloride ions in the peritoneal contents. This case report highlights atypical cutaneous presentation over the abdomen following corrosive acid ingestion, which has not been reported previously. The possible explanation for this cutaneous manifestation was corrosive effects of the underlying viscera due to its close proximation to the abdominal wall and presence of minimal intra-abdominal fat. A direct physical connection between perforation and cutaneous findings was not identified. The case emphasizes the need for a comprehensive approach in managing such cases, analyzing ingested material, and following standard autopsy protocols in case of death.

Geographic impact on access to care and survival for non-curative esophagogastric cancer: a population-based study.

BACKGROUND: Among patients not undergoing curative-intent therapy for esophagogastric cancer, access to care may vary. We examined the geographic distribution of care delivery and survival and their relationship with distance to cancer centres for non-curative esophagogastric cancer, hypothesising that patients living further from cancer centres have worse outcomes. METHODS: We conducted a population-based analysis of adults with non-curative esophagogastric cancer from 2005 to 2017 using linked administrative healthcare datasets in Ontario, Canada. Outcomes were medical oncology consultation, receipt of chemotherapy, and overall survival. Using geographic information system analysis, we mapped locations of cancer centres and outcomes across census divisions. Bivariate choropleth maps identified regional outcome discordances. Multivariable regression models assessed the relationship between distance from patient residence to the nearest cancer centre and outcomes, adjusting for demographic, clinical, and socioeconomic factors. RESULTS: Of 10,228 patients surviving a median 5.1 months (IQR: 2.0-12.0), 68.5% had medical oncology consultation and 32.2% received chemotherapy. Certain distances (reference ≤ 10 km) were associated with lower consultation [relative risk 0.79 (95% CI 0.63-0.97) for ≥ 101 km], chemotherapy receipt [relative risk 0.67 (95% CI 0.53-0.85) for ≥ 101 km], and overall survival [hazard ratio 1.07 (95% CI 1.02-1.13) for 11-50 km, hazard ratio 1.13 (95% CI 1.04-1.23) for 51-100 km]. CONCLUSION: A third of patients did not see medical oncology and most did not receive chemotherapy. Outcomes exhibited high geographic variability. Location of residence influenced outcomes, with inferior outcomes at certain distances > 10 km from cancer centres. These findings are important for designing interventions to reduce access disparities for non-curative esophagogastric cancer care.

Association Between Preoperative Patient-Reported Symptoms and Postoperative Outcomes in Rectal Cancer Patients: A Retrospective Cohort Study.

BACKGROUND: Rectal cancer patients undergoing preoperative radiotherapy experience a significant symptom burden. However, it is unknown whether symptoms during radiotherapy may portend adverse postoperative outcomes and healthcare utilization. METHODS: A retrospective cohort study was performed of rectal cancer patients undergoing neoadjuvant radiotherapy and proctectomy in Ontario from 2007 to 2014. The primary outcome was a complicated postoperative course-a dichotomous variable created as a composite of postoperative mortality, major morbidity, or hospital readmission. Patient-reported Edmonton Symptom Assessment System (ESAS) scores, collected routinely at outpatient provincial cancer center visits, were linked to administrative healthcare databases. The receiver-operating characteristic analysis was used to compare ESAS scoring approaches and to stratify patients into low versus high symptom score groups. Multivariable regression models were constructed to evaluate associations between preoperative symptom scores and postoperative outcomes. RESULTS: 1455 rectal cancer patients underwent sequential radiotherapy and proctectomy during the study period and recorded symptom assessments. Patients with high preoperative symptom scores were significantly more likely to experience a complicated postoperative course (OR 1.55, 95% CI 1.23-1.95). High preoperative ESAS scores were also associated with the secondary outcomes of emergency department visits (OR 1.34, 95% CI 1.08-1.66) and longer length of stay (IRR 1.23, 95% CI 1.04-1.45). CONCLUSIONS: Rectal cancer patients reporting elevated symptom scores during neoadjuvant radiotherapy have increased odds of experiencing a complicated postoperative course. Preoperative patient-reported outcome screening may be a useful tool to identify at-risk patients and to efficiently direct perioperative supportive care.

Impact of Geography on Care Delivery and Survival for Noncurable Pancreatic Adenocarcinoma: A Population-Based Analysis.

BACKGROUND: Little is known about how the geographic distribution of cancer services may influence disparities in outcomes for noncurable pancreatic adenocarcinoma. We therefore examined the geographic distribution of outcomes for this disease in relation to distance to cancer centers. METHODS: We conducted a retrospective population-based analysis of adults in Ontario, Canada, diagnosed with noncurable pancreatic adenocarcinoma from 2004 through 2017 using linked administrative healthcare datasets. The exposure was distance from place of residence to the nearest cancer center providing medical oncology assessment and systemic therapy. Outcomes were medical oncology consultation, receipt of cancer-directed therapy, and overall survival. We examined the relationship between distance and outcomes using adjusted multivariable regression models. RESULTS: Of 15,970 patients surviving a median of 3.3 months, 65.6% consulted medical oncology and 38.5% received systemic therapy. Regions with comparable outcomes were clustered throughout Ontario. Mapping revealed regional discordances between outcomes. Increasing distance (reference, ≤10 km) was independently associated with lower likelihood of medical oncology consultation (relative risks [95% CI] for 11-50, 51-100, and ≥101 km were 0.90 [0.83-0.98], 0.78 [0.62-0.99], and 0.77 [0.55-1.08], respectively) and worse survival (hazard ratios [95% CI] for 11-50, 51-100, and ≥101 km were 1.08 [1.04-1.12], 1.17 [1.10-1.25], and 1.10 [1.02-1.18], respectively), but not with likelihood of receiving therapy. Receipt of therapy seems less sensitive to distance, suggesting that distance limits entry into the cancer care system via oncology consultation. Regional outcome discordances suggest inefficiencies within and protective factors outside of the cancer care system. CONCLUSIONS: These findings provide a basis for clinicians to optimize their practices for patients with noncurable pancreatic adenocarcinoma, for future studies investigating geographic barriers to care, and for regional interventions to improve access.

Prevalence, patterns and sociocultural factors associated with use of tobacco-based dentifrices (Gul) in India.

BACKGROUND: India poses a novel tobacco problem with majority of the tobacco users consuming smokeless form of tobacco (21.4%). Gul is one such Smokeless Tobacco (ST) product that is manufactured commercially as a dentifrice to be applied to the teeth and then to gums many times during the day, making it a cheap and easy tobacco source. Hence, the aim of the present study was to estimate the usage of Gul and its social determinants among adults in the capital city of India, Delhi. METHODS: The cross-sectional study was conducted among 1300 adults across 27 Delhi government dispensaries across 3 districts of Delhi through multistage stratified random sampling. A structured, close-ended, validated questionnaire inquiring about the tobacco practices was used for all the participants and a specially constructed, structured, close-ended, validated proforma was used for Gul users to assess practice and pattern of use. RESULTS: The overall prevalence of Gul users was found to be 4.9% with a mean usage duration of 6.28 ± 6.75 years. The usage was found to be more among males (67.7%) and unskilled workers (45.2%). 74.9% started using Gul to treat dental pain with 93.47% of them reporting pain relief. CONCLUSION: Gul usage is an emerging menace in Delhi. Awareness programs and initiatives are the need of the hour to bring this tobacco product under the tobacco control policy radar and at the same time educate people about the actual contents and ill effects of Gul usage.