Valproic Acid-Induced Hyperammonemia with Encephalopathy (VIHE): A Case Report

Valproic acid (VPA) is a wide spectrum antiepileptic medication indicated for seizure prophylaxis across the spectrum of epilepsy. Since coming into clinical use, VPA has also been recommended for the management of a variety of other pathologies, including, most notably, mood stabilization in the manic patient. VPA’s common adverse effects include gastrointestinal, influenza-like symptoms, headache, and difficulties with sleep; nonetheless, in rare instances, VPA has been noted to cause the severe and potentially lethal condition of hyperammonemia with encephalopathy (VIHE). VIHE is the result of a dose-independent increase in ammonia levels. Often the patient is asymptomatic; if symptoms reach clinical threshold, lethargy is most common, though seizures, focal neurologic deficits and even coma are possible. VIHE can occur in patients despite normal hepatic function, normal loading doses, chronic stable doses and normal free serum drug levels. Once the diagnosis is confirmed, the first approach for symptomatic patients is to discontinue VPA, start alternative mood stabilizer as indicated, and supplement hyperammonemia treatment with lactulose, carnitine or carglumic acid. Below is a case report of VIHE that developed in an adolescent girl with a history of Bipolar I Disorder who was hospitalized in our facility for stabilization of mania.  As demonstrated below, early diagnosis of VIHE is pivotal in reducing morbidity and ultimately can be life-saving

Presentation with Personality changes and Tinnitus to a Vascular Intervention: Rare case of Carotid Body Paraganglioma

Background: Carotid body paragangliomas are rare neuroendocrine neoplasms of chromaffin negative glomus cells. This case report explains an atypical case with unusual presentation and treatment. Case Report: A healthy smoker technician by profession was brought to the emergency room (ER) with coprolalia. The general physical exam did not reveal any information. His history revealed unilateral tinnitus and odynophagia leading to a consultation by the neurologist with head imaging. Acoustic neuroma was ruled out and the caregiver was asked to elaborate the events mentioned in the history and a psychiatric examination was done. The personality changes were evaluated by the psychiatrist that showed overlapping of delirium and depression. The patient was further examined by a vascular surgeon. After careful revisiting of the history, examination and indication of tender mass in the neck by the patient's vascular surgeon, the diagnosis of carotid body paraganglioma was made which was followed by surgical resection for treatment. Conclusion: Carotid Body Paragangliomas are very vascular structures and their manipulation in a surgery setting requires expertise. This case presented with personality changes and tinnitus, a very less likely event to occur in a carotid body tumor. The present care report, thus adds on to the literature of carotid body tumors and its presenting symptoms

What is Emotional Pain? - A Review of Pathophysiology and Treatment Options

Pain is a dynamic process that involves multiple physiological systems for the perception and its outcomes. The basic pain process involves a complex neurological process. and biochemical changes. Emotional pain is an extended form of the already known pain where the stimuli are emotional of nature that involves abstract feelings, for example, losing a loved one. Like the pain, now there is a growing evidence that emotional pain also involves inflammatory process and the behavioral approach is directly linked with them. This association can help us modify the emotional pain by modulating the inflammatory processes that already known to us.   Other than therapeutic and known interventions, mindfulness, writing therapy, exposure based intervention and other actions can help us in just not treating the condition but can serve as exploration of other avenues of the pain physiology. Emotional Pain has always been the part of human history but one of the least discussed form of pain. Multiple neuropsychiatric studies can help further in evaluation of this process

A method for translational rat ex vivo lung perfusion experimentation

The application of ex vivo lung perfusion (EVLP) has significantly increased the successful clinical use of marginal donor lungs. While large animal EVLP models exist to test new strategies to improve organ repair, there is currently no rat EVLP model capable of maintaining long-term lung viability. Here, we describe a new rat EVLP model that addresses this need, while enabling the study of lung injury due to cold ischemic time (CIT). The technique involves perfusing and ventilating male Lewis rat donor lungs for 4 h before transplanting the left lung into a recipient rat and then evaluating lung function 2 h after reperfusion. To test injury within this model, lungs were divided into groups and exposed to different CITs (i.e., 20 min, 6 h, 12 h, 18 h and 24 h). Experiments involving the 24-h-CIT group were prematurely terminated due to the development of severe edema. For the other groups, no differences in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO₂/FIO₂) were observed during EVLP; however, lung compliance decreased over time in the 18-h group (P = 0.012) and the PaO₂/FIO₂ of the blood from the left pulmonary vein 2 h after transplantation was lower compared with 20-min-CIT group (P = 0.0062). This new model maintained stable lung function during 4-h EVLP and after transplantation when exposed to up to 12 h of CIT

Heterocyclic Aromatic Amines in Meat: Formation, Isolation, Risk Assessment, and Inhibitory Effect of Plant Extracts

: Heterocyclic aromatic amines (HAAs) are potent carcinogenic compounds induced by the Maillard reaction in well-done cooked meats. Free amino acids, protein, creatinine, reducing sugars and nucleosides are major precursors involved in the production of polar and non-polar HAAs. The variety and yield of HAAs are linked with various factors such as meat type, heating time and temperature, cooking method and equipment, fresh meat storage time, raw material and additives, precursor's presence, water activity, and pH level. For the isolation and identification of HAAs, advanced chromatography and spectroscopy techniques have been employed. These potent mutagens are the etiology of several types of human cancers at the ng/g level and are 100- to 2000-fold stronger than that of aflatoxins and benzopyrene, respectively. This review summarizes previous studies on the formation and types of potent mutagenic and/or carcinogenic HAAs in cooked meats. Furthermore, occurrence, risk assessment, and factors affecting HAA formation are discussed in detail. Additionally, sample extraction procedure and quantification techniques to determine these compounds are analyzed and described. Finally, an overview is presented on the promising strategy to mitigate the risk of HAAs by natural compounds and the effect of plant extracts containing antioxidants to reduce or inhibit the formation of these carcinogenic substances in cooked meats

Acceptance of COVID-19 vaccine in Pakistan: A nationwide cross-sectional study

Introduction: The coronavirus disease 2019 (COVID-19) vaccine is available across various countries worldwide, with public-private partnerships ensuring all individuals are vaccinated through a phased approach. Irrespective of the geographical spread, several myths pertaining to the COVID-19 vaccine have stemmed, ultimately limiting the national administration of vaccines and rollouts. This study assessed the acceptance of the COVID-19 vaccine among the general public in Pakistan.Methods: A pre-validated questionnaire was administered from January 2021 to February 2021 to assess the public attitude and acceptance of the COVID-19 vaccine. Logistic regression analyses were run to identify factors associated with the acceptance among the population.Results: A total of 936 responses were elicited, where 15% perceived their risk of being infected at 20-30% with an overall 70% agreeing to be vaccinated if recommended. Multivariate analysis identified higher acceptance in the male gender, healthcare workers, and students. Of all, 66% respondents chose healthcare workers and public officials, whereas 15.6% chose scientific literature, and 12.9% chose social media as the most reliable source of COVID-19 information.Conclusion: Given the relatively greater trust in healthcare providers for information regarding COVID-19, healthcare workers ought to be on the frontline for vaccine campaigns and public outreach efforts, with governmental efforts in addition to the promotion of scientific materials for population-level understanding

Crocin: Functional characteristics, extraction, food applications and efficacy against brain related disorders

Crocin is a bioactive compound that naturally occurs in some medicinal plants, especially saffron and gardenia fruit. Different conventional and novel methods are used for its extraction. Due to some control conditions, recent methods such as ultrasonic extraction, supercritical fluid extraction, enzyme-associated extraction, microwave extraction, and pulsed electric field extraction are widely used because these methods give more yield and efficiency. Crocin is incorporated into different food products to make functional foods. However, it can also aid in the stability of food products. Due to its ability to protect against brain diseases, the demand for crocin has been rising in the pharmaceutical industry. It also contain antioxidant, anti-inflammatory, anticancer and antidepressant qualities. This review aims to describe crocin and its role in developing functional food, extraction, and bioavailability in various brain-related diseases. The results of the literature strongly support the importance of crocin against various diseases and its use in making different functional foods

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials