The omega-3 hydroxy fatty acid 7(S)-HDHA is a high-affinity PPARα ligand that regulates brain neuronal morphology.

The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) is emerging as an important target in the brain for the treatment or prevention of cognitive disorders. The identification of high-affinity ligands for brain PPARα may reveal the mechanisms underlying the synaptic effects of this receptor and facilitate drug development. Here, using an affinity purification-untargeted mass spectrometry (AP-UMS) approach, we identified an endogenous, selective PPARα ligand, 7(S)-hydroxy-docosahexaenoic acid [7(S)-HDHA]. Results from mass spectrometric detection of 7(S)-HDHA in mouse and rat brain tissues, time-resolved FRET analyses, and thermal shift assays collectively revealed that 7(S)-HDHA potently activated PPARα with an affinity greater than that of other ligands identified to date. We also found that 7(S)-HDHA activation of PPARα in cultured mouse cortical neurons stimulated neuronal growth and arborization, as well as the expression of genes associated with synaptic plasticity. The findings suggest that this DHA derivative supports and enhances neuronal synaptic capacity in the brain.

The effects of coronavirus disease 2019 (COVID-19) pandemic on people with epilepsy (PwE): an online survey-based study.

During the unprecedented COVID-19 pandemic in 2020, the whole world faced an unusual health emergency. Medical care of chronic neurological diseases, such as Epilepsy, is being neglected. In this survey, we aimed to evaluate the impact of the COVID-19 pandemic on the care of people with Epilepsy (PwE) and to identify their risk factors for seizure worsening to direct better future medical care. We administered a web-based survey (submitted on August 5, 2020). It included socio-demographic, Epilepsy-related, and psychometric data (The Depression, Anxiety, and Stress Scale-21 Items(DASS21) and The Pittsburgh Sleep Quality Index (PSQI). Regression analysis identified predictors of seizure worsening. We collected responses from an online survey of PwE during the pandemic. Out of 151 responders, 71 patients complained of issues related to Epilepsy management and all of whom reached the treating physician and solved their problems. Sleep quality was compromised in 84 patients (55.6%). Two-thirds of the patients in our cohort (66.2%) reported depression, 72.2% reported anxiety, and 75.5% reported stress. Eight patients (5.3%) got COVID-19 infection, and only one patient suffered from mild worsening of the seizure. The main concerns were shortage of medications for 46 (30.5%) patients, getting Coronavirus infection for 67 (44.4%) patients, and seizure worsening for 32 (21.3%) patients. Thirty-five patients (23.2%) reported seizure worsening, which was best explained by retirement or jobless state, having moderate or severe stress, poor sleep quality, vagus nerve stimulation (VNS), fear of getting COVID-19 infection, fear of worsening of seizures, or shortage of medication. During the current COVID-19 pandemic, a significant percentage of PwE experienced worsening of their seizures. This unusual, challenging experience clarifies the urgent need to establish telemedicine services and home-based management of Epilepsy, including ambulatory EEG, home video, and medication delivery to patients' homes to provide continuous medical care.

Safety and tolerability of the novel 2019 coronavirus disease (COVID-19) vaccines among people with epilepsy (PwE): A cross-sectional study.

BACKGROUND: People with epilepsy (PwE) were concerned about the safety of the novel 2019 Coronavirus Disease (COVID-19) vaccines. OBJECTIVE: This study aimed to assess the side effects experienced by PwE following vaccination with COVID-19 vaccines and to identify the causes of vaccine hesitation. METHODS: We administered a questionnaire to PwE, who visited the epilepsy clinic at Ibn Sina Hospital in Kuwait during the first two working weeks of April 2021. It included socio-demographic, epilepsy status, and vaccination data. In addition, we asked those who were not vaccinated yet about the reasons and their plan. RESULTS: A total of 111 PwE were surveyed, with 82 being vaccinated and 29 being unvaccinated. Out of the 82 vaccinated, 66 (80.5%) reported at least one side effect. Patients who received the Pfizer BioNTech mRNA vaccine (BNT162b2) (first, second dosage); and the Oxford-AstraZenecaa chimpanzee adenovirus-vectored vaccine (ChAdOx1nCoV-19) (first dose) had the following reactions: Pain at the injection site (40%, 67.6%), 43.8%, fatigue (47%, 32.4%), 46.9%, Headache (33.3%, 35.3%), 34.4% and Myalgia (40%, 35%), 50% respectively. Local site effects, including pain (67.6% vs. 40%, p = < 0.001) and redness (26.5% vs 6.7%, p = 0.019), were more statistically significantly after the second dose of BNT162b2 vaccine compared to the first dose of the same vaccine. While there was no significant difference in systemic side effects frequencies between the two doses of the BNT162b2 vaccine. The systemic side effects were more statistically significantly after the first dose of ChAdOx1nCoV-19 compared to the first dose of the BNT162b2 vaccine and those included fever (56.3% vs 13.3%, p = < 0.001), chills (37.5% vs 6.7%, p = < 0.001), myalgia (50% vs 40%, p = < 0.001) and arthralgia (25% vs 6.7%, p = 0.021). The local site reactions were not significantly different between the first doses of both vaccines. Among the subgroup who had vaccine-related side effects, 66.7% were females, 90.9% were 55 or younger, 63.6% were on polytherapy, 74% had side effects for one day or less, and 95% were symptoms free by the end of the first-week post-vaccination. Symptoms were mild in 68% of the patients and moderate in 29.3%. Most patients (93.9%) did not report seizure worsening after vaccination. The relative risk of seizure worsening after the first and second doses of BNT162b2 and the first dose of ChAdOx1nCoV-19 vaccines was 1.027 (95% CI 0.891-1.183), 1.019 (95% CI 0.928-1.119), and 1.026 (95% CI 0.929-1.134) respectively. After the first dose of BNT162b2, one patient reported the development of status epilepticus. Among the non-vaccinated group, 34.9% were still indecisive, while 37.9% rejected the vaccination. Fear of adverse effects (42.9%) and fear of epilepsy worsening (23.8%) were the main reasons for vaccine hesitation. CONCLUSIONS: This study shows that the two vaccines under consideration (BNT162b2 and ChAdOx1nCoV-19) have a good safety profile and a low risk of epilepsy worsening among a cohort of PwE in Kuwait.

Impact of domestic violence against pregnant women in Minia governorate, Egypt: a cross sectional study.

BACKGROUND: Domestic violence is a common problem that is related to many serious short-term and long-term health hazards around the world. METHODS: During obtaining the medical history from the participants, the questions used to assess the abuse were derived from the widely used Abuse Assessment Screen (AAS). Potential risk factors including a variety of socio-demographic and reproductive health-relation indicators were assessed. The influence of violence on the pregnancy outcome was determined by the continuous follow-up till giving birth. RESULTS: 513 pregnant women were included. The prevalence of violence among them was 50.8%. The prevalence of physical, sexual, verbal, and emotional abuse was 30.2, 20, 41.7, and 45.4% respectively. Exposure to violence during pregnancy had significant effects on the women and their pregnancy outcome in the form of development of vaginal infection (P-value =0.036), vaginal bleeding (P-value = 0.008), preterm labour (P-value = 0.003), premature rupture of membrane (P-value = 0.001). CONCLUSION: Violence against pregnant women in Minia Governorate, Egypt is common especially emotional violence and it has many adverse effects on the women and their pregnancy outcome. One of the most important risk factors is the fear of the husband which makes violence a continuous vicious circle.

The Effects of Non-Nutritive Artificial Sweeteners, Aspartame and Sucralose, on the Gut Microbiome in Healthy Adults: Secondary Outcomes of a Randomized Double-Blinded Crossover Clinical Trial.

Non-nutritive artificial sweeteners (NNSs) may have the ability to change the gut microbiota, which could potentially alter glucose metabolism. This study aimed to determine the effect of sucralose and aspartame consumption on gut microbiota composition using realistic doses of NNSs. Seventeen healthy participants between the ages of 18 and 45 years who had a body mass index (BMI) of 20-25 were selected. They undertook two 14-day treatment periods separated by a four-week washout period. The sweeteners consumed by each participant consisted of a standardized dose of 14% (0.425 g) of the acceptable daily intake (ADI) for aspartame and 20% (0.136 g) of the ADI for sucralose. Faecal samples collected before and after treatments were analysed for microbiome and short-chain fatty acids (SCFAs). There were no differences in the median relative proportions of the most abundant bacterial taxa (family and genus) before and after treatments with both NNSs. The microbiota community structure also did not show any obvious differences. There were no differences in faecal SCFAs following the consumption of the NNSs. These findings suggest that daily repeated consumption of pure aspartame or sucralose in doses reflective of typical high consumption have minimal effect on gut microbiota composition or SCFA production.

Effect of sucralose and aspartame on glucose metabolism and gut hormones.

Non-nutritive sweeteners are thought to be useful replacements for caloric sweeteners in sweet food and beverages, since the reduction in energy and carbohydrate intake may lead to health benefits stemming from weight management and glycemic control. However, the potential effects of non-nutritive sweeteners on glucose metabolism and gut hormones have not been determined definitively. Here, the available evidence of the effects of aspartame and sucralose consumption on glucose metabolism and gut hormones is reviewed. A majority of studies have found that consumption of aspartame or sucralose has no effect on concentrations of blood glucose, insulin, or gut hormones; however, 2 trials have shown that aspartame consumption affects glucose, insulin, and glucagon-like peptide 1 concentrations, while only a few trials have shown that sucralose consumption affects glucose, insulin, and glucagon-like peptide 1 concentrations. One study found higher glucose concentrations after sucralose consumption, while 3 studies found lower concentrations and 33 studies found no change in glucose concentrations. Moreover, only 4 studies reported increased concentrations of glucagon-like peptide 1. Three studies reported decreased insulin sensitivity following sucralose consumption, while 1 trial reported an increase in insulin sensitivity. In summary, the evidence from the clinical trials conducted to date is contradictory because of the different protocols used.

The effect of the artificial sweeteners on glucose metabolism in healthy adults: a randomized, double-blinded, crossover clinical trial.

This study aimed to determine the effect of pure forms of sucralose and aspartame, in doses reflective of common consumption, on glucose metabolism. Healthy participants consumed pure forms of a non-nutritive sweetener (NNS) that were mixed with water and standardized to doses of 14% (0.425 g) of the acceptable daily intake (ADI) for aspartame and 20% (0.136 g) of the ADI for sucralose every day for 2 weeks. Blood samples were collected and analyzed for glucose, insulin, active glucagon-like peptide-1 (GLP-1), and leptin. Seventeen participants (10 females and 7 males; age, 24 ± 6.8 years; body mass index, 22.9 ± 2.5 kg/m2) participated in the study. The total area under the curve values of glucose, insulin, active GLP-1 and leptin were similar for the aspartame and sucralose treatment groups compared with the baseline values in healthy participants. There was no change in insulin sensitivity after NNS treatment compared with the baseline values. These findings suggest that daily repeated consumption of pure sucralose or aspartame for 2 weeks had no effect on glucose metabolism among normoglycaemic adults. However, these results need to be tested in studies with longer durations. Novelty Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on glucose metabolism. Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on insulin sensitivity among healthy adults.

Recent evidence for the effects of nonnutritive sweeteners on glycaemic control.

PURPOSE OF REVIEW: By replacing sugar, nonnutritive sweeteners (NNSs) are thought to aid in weight management and decrease insulin resistance. We reviewed the latest randomized clinical trials (RCTs) investigating the effects NNSs on glycaemic control. RECENT FINDINGS: Six RCTs addressed this topic between 2017 and 2018; the majority tested artificial NNS (sucralose or aspartame), with only one testing natural NNS (stevia and monk fruit extract). Most found no effect of NNS on blood glucose, insulin, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) levels; however, two trials showed an effect of sucralose on the acute insulin response. SUMMARY: We are still incapable of reaching a definite judgement on which types of NNS, if any, impact glycaemic control. There is a need for more research to overcome the limitations of recent RCTs, related to sample size, intervention duration, dose, form of NNSs used, and inclusion of males or female participants only. Future studies should also compare different NNS types with each other, and include the increasingly popular 'natural' NNS.

Contributions of the Lectin and Polypeptide Binding Sites of Calreticulin to Its Chaperone Functions in Vitro and in Cells.

Calreticulin is a lectin chaperone of the endoplasmic reticulum that interacts with newly synthesized glycoproteins by binding to Glc1Man9GlcNAc2 oligosaccharides as well as to the polypeptide chain. In vitro, the latter interaction potently suppresses the aggregation of various non-glycosylated proteins. Although the lectin-oligosaccharide association is well understood, the polypeptide-based interaction is more controversial because the binding site on calreticulin has not been identified, and its significance in the biogenesis of glycoproteins in cells remains unknown. In this study, we identified the polypeptide binding site responsible for the in vitro aggregation suppression function by mutating four candidate hydrophobic surface patches. Mutations in only one patch, P19K/I21E and Y22K/F84E, impaired the ability of calreticulin to suppress the thermally induced aggregation of non-glycosylated firefly luciferase. These mutants also failed to bind several hydrophobic peptides that act as substrate mimetics and compete in the luciferase aggregation suppression assay. To assess the relative contributions of the glycan-dependent and -independent interactions in living cells, we expressed lectin-deficient, polypeptide binding-deficient, and doubly deficient calreticulin constructs in calreticulin-negative cells and monitored the effects on the biogenesis of MHC class I molecules, the solubility of mutant forms of α1-antitrypsin, and interactions with newly synthesized glycoproteins. In all cases, we observed a profound impairment in calreticulin function when its lectin site was inactivated. Remarkably, inactivation of the polypeptide binding site had little impact. These findings indicate that the lectin-based mode of client interaction is the predominant contributor to the chaperone functions of calreticulin within the endoplasmic reticulum.

Factors Associated with Readmission After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis.

PURPOSE: Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal carcinomatosis is a morbid endeavor. Despite improvement in perioperative management of these patients, there are subsets of patients requiring hospital readmission after discharge. We sought to identify variables associated with readmission rates for CRS/HIPEC. METHODS: We conducted a retrospective review of CRS/HIPEC cases at the University of Cincinnati between 1999 and 2014. Patient-, tumor-, and treatment-specific characteristics were evaluated. The association between patient- and outcome-specific variables for 30- and 90-day readmission were evaluated. RESULTS: Of 215 CRS/HIPEC patients, the 7-, 30-, and 90-day readmission rates were 9.8 % (n = 21), 14.9 % (n = 32), and 21.4 % (n = 46), respectively. The most common reasons for readmission within 90 days included abdominal pain (n = 14), intra-abdominal abscess (n = 9), malnutrition/failure to thrive (n = 8), and bowel obstruction (n = 7). The primary factor associated with readmission at all time points (7, 30, and 90 days) was the presence of an enterocutaneous fistula (p < 0.01). Six patients (2.8 %) had multiple readmissions; 3 of these had ECF. Factors not associated with higher admission rates included sex, age, race, operative blood loss, pancreatectomy or liver resection at the index operation, and postoperative complications of wound infection, line infection, and thromboembolic events. CONCLUSIONS: In patients undergoing CRS/HIPEC, readmission was primarily associated with poor pain control, malnutrition, and infectious complications. Patients with enterocutaneous fistula were also disproportionately readmitted multiple times. These data should inform clinicians about patients at high risk for readmission after CRS/HIPEC and encourage more comprehensive coordination of postdischarge planning and care for specific patient populations.