The DUSP domain of pseudophosphatase MK-STYX interacts with G3BP1 to decrease stress granules.

Mitogen activated protein kinase phosphoserine/threonine/tyrosine-binding protein (MK-STYX) is a dual specificity (DUSP) member of the protein tyrosine phosphatase family. It is a pseudophosphatase, which lacks the essential amino acids histidine and cysteine in the catalytic active signature motif (HCX5R). We previously reported that MK-STYX interacts with G3BP1 [Ras-GAP (GTPase-activating protein) SH3 (Src homology 3) domain-binding-1] and reduces stress granules, stalled mRNA. To determine how MK-STYX reduces stress granules, truncated domains, CH2 (cell division cycle 25 phosphatase homology 2) and DUSP, of MK-STYX were used. Wild-type MK-STYX and the DUSP domain significantly decreased stressed granules that were induced by sodium arsenite, in which G3BP1 (a stress granule nucleator) was used as the marker. In addition, HEK/293 and HeLa cells co-expressing G3BP1-GFP and mCherry-MK-STYX, mCherry-MK-STYX-CH2, mCherry-MK-STYX-DUSP or mCherry showed that stress granules were significantly decreased in the presence of wild-type MK-STYX and the DUSP domain of MK-STYX. Further characterization of these dynamics in HeLa cells showed that the CH2 domain increased the number of stress granules within a cell, relative to wild-type and DUSP domain of MK-STYX. To further analyze the interaction of G3BP1 and the domains of MK-STYX, coimmunoprecipitation experiments were performed. Cells co-expressing G3BP1-GFP and mCherry, mCherry-MK-STYX, mCherry-MK-STYX-CH2, or mCherry-MK-STYX-DUSP demonstrated that the DUSP domain of MK-STYX interacts with both G3BP1-GFP and endogenous G3BP1, whereas the CH2 domain of MK-STYX did not coimmunoprecipitate with G3BP1. In addition, G3BP1 tyrosine phosphorylation, which is required for stress granule formation, was decreased in the presence of wild-type MK-STYX or the DUSP domain but increased in the presence of CH2. These data highlight a model for how MK-STYX decreases G3BP1-induced stress granules. The DUSP domain of MK-STYX interacts with G3BP1 and negatively alters its tyrosine phosphorylation- decreasing stress granule formation.

Why Are Some Male Alcohol Misuse Disorder Patients High Utilisers of Emergency Health Services? An Asian Qualitative Study.

BACKGROUND: Certain alcohol misuse patients heavily utilise the Emergency Department (ED) and Emergency Medical Services (EMS) and may present with intoxication or long-term sequelae of alcohol misuse. Our study explored reasons for repeated ED/EMS utilisation and sought to understand perpetuating and protective factors for drinking. METHODS: Face-to-face semi-structured qualitative interviews were conducted. Participants were recruited from an ED in Singapore. Interviews were audio-recorded, transcribed verbatim and underwent manual thematic analysis. Emergent themes were independently reviewed for agreement. Data from medical records, interview transcripts, and field notes were triangulated for analysis. RESULTS: All participants were male (n = 20) with an average age of 55.6 years (SD = 8.86). Most were unemployed (75%), did not have tertiary education (75%), were divorced (55%), and had pre-existing psychiatric conditions (60%) and chronic cardiovascular conditions (75%). Reasons for utilisation included a perceived need due to symptoms, although sometimes it was bystanders who called the ambulance. ED/EMS was preferred due to the perceived higher quality and speed of care. Persistent drinking was attributed to social and environmental factors, and as a coping mechanism for stressors. Rehabilitation programs and meaningful activities reduced drinking tendencies. CONCLUSION: ED/EMS provide sought-after services for alcohol misuse patients, resulting in high utilisation. Social and medical intervention could improve drinking behaviours and decrease overall ED/EMS utilisation.

Photocatalytic hydrogen evolution over cyanine-sensitized Ag/TiO2.

Sensitization of TiO2 by dyes such as cyanine and their derivatives is used as a technique to improve potency for the production of hydrogen gas as an alternative green fuel. These dyes shift the spectrum of TiO2 from the UV region to the visible region, enabling it to harvest as much sunlight as possible. Herein, four different derivatives of cyanine (labelled C1, C2, C3, and C4) were prepared and doped in Ag/TiO2 via the impregnation method. The properties of the prepared photocatalysts were studied by XRD, SEM-EDS, FTIR, and UV-visible spectroscopy. The sensitized photocatalysts exhibited a similar morphology, nanoscale particle size, and good absorbance in the visible region. The rate constant for the photocatalytic activity of Ag/TiO2 showed a great enhancement for hydrogen evolution after sensitization from 0.088 to 0.33 µmol min-1. Doping of the C2 derivative in Ag/TiO2 promoted the photocatalytic and sonophotocatalytic rates of H2 production by 7.5 and 9 times, respectively. Also, the amount of photocatalyst had a significant effect on the photocatalytic activity of the sensitized Ag/TiO2, where 0.14 g was the optimum dose, giving the maximum yield at both the initial rate and 300 min. One of the important factors causing the efficiency to reach high levels is the inhibition of photogenerated electron/hole recombination. This was achieved by adding a small quantity of methanol, which increased the rate by 9 times. The stability of the prepared photocatalysts was tested, which gave good results even after their 5th use. All the results confirmed that the sensitization of metal oxides is a promising solution in industry to produce clean energy (H2) in high quantities over highly stable photocatalysts.

The quality of life among Sudanese patients with epilepsy, Khartoum, Sudan.

INTRODUCTION: This is the first study done in the National Center for Neurological Sciences, Khartoum State, to assess the quality of life among more than 100 Sudanese epileptic patients, in the period from September to December 2020. METHODOLOGY: This is a descriptive cross-sectional study; data were collected using an interview-based semi-structured structured questionnaire and this questionnaire was modified from the SF-36 model. RESULTS: Most of the patients were from urban areas and origin (60.2%), most of which were housewives; the majority of the patients were single and from low socioeconomic status, history of the disease was less than 3 years for most of the cases covered in this study, most of the cases were classified as generalized tonic clonic epilepsy, and normal EEG findings and normal MRI brain were found in 75.7% and 78.6%, respectively. Most patients mentioned that they experienced no attacks during the last month. Regarding mental health, 47.6% experienced symptoms of depression, and 75.7% had memory problems. In terms of physical health, 51.5% felt energetic all of the time, 9.7% experienced remarkable sleep disturbance, most of the patients are not driving nor have established hobbies during leisure time. 63.1% of the participants do not have health problems; 32% mentioned that they would feel stigmatized if an attack takes place in public. Commonest medication prescribed was carbamazepine, out of which 73.8% are fully compliant with their medication. 95.1% are not worried about long term use of medication. CONCLUSION: Lower levels of education and manual labor are associated with poor quality of life. Epilepsy has an adverse impact on social life. There is a global decrease in cognitive function, and most of the patients are not worried about the side effects and duration of the medication usage.

Immune Checkpoint Inhibitors in the Treatment of Cancer.

BACKGROUND: Immunotherapy drugs, known as immune checkpoint inhibitors (ICIs), work by blocking checkpoint proteins from binding with their partner proteins. The two main pathways that are specifically targeted in clinical practice are cytotoxic T-lymphocyte antigen-4 (CTLA- 4) and programmed cell death protein 1 (PD-1) that showed potent immune-modulatory effects through their function as negative regulators of T cell activation. METHODS: In view of the rapid and extensive development of this research field, we conducted a comprehensive review of the literature and updated on the use of CTLA-4, PD-1, and PD-L1 targeted therapy in the treatment of several types of cancer, including melanoma, non-small-cell lung carcinoma, breast cancer, hepatocellular carcinoma, Hodgkin lymphoma, cervical cancer, and head and neck squamous cell carcinoma. RESULTS: Based on the last updated list released on March 2019, seven ICIs are approved by the FDA, including ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, and cemiplimab. CONCLUSION: This review highlighted the most common adverse effects caused by ICIs which affect people in different ways.

Impact of pharmacist insulin injection re-education on glycemic control among type II diabetic patients in primary health clinics.

BACKGROUND: Insulin injection technique re-education and diabetes knowledge empowerment has led to improved glycemic control. OBJECTIVES: To evaluate the impact of pharmacist's monthly re-education on insulin injection technique (IT), lipohypertrophy, patients' perception on insulin therapy and its effect on glycaemic control. METHODS: This randomized controlled, multi-centered study was conducted among type 2 diabetics from 15 government health clinics. 160 diabetics with baseline HbA1C ≥ 8% and unsatisfactory IT technique were randomized into control or intervention group. Control group received standard pharmacist counselling during initiation and at 4th month. Intervention group received monthly counselling and IT re-education for 4 months. Assessment of diabetes, IT knowledge, adherence and perception towards diabetes were conducted using validated study tools Insulin Treatment Appraisal Scale (ITAS) and Medication Compliance Questionnaire (MCQ)). RESULTS: 139 patients completed the study; control group (69), intervention group (70). In control group, all outcomes shown improvement except for patient's perception. Mean HbA1C decreased 0.79% ± 0.24 (p = 0.001). In intervention group, all outcomes improved significantly. HbA1c reduces significantly by 1.19% ± 0.10 (p < 0.001). Monthly re-education improved patient's perception towards insulin therapy (ITAS score reduced 1.44 ± 2.36; p = 0.021). Between groups, interventional arm shown significantly better improvement in all outcomes. Improvement was shown in IT technique (+2.02 score; p < 0.001), medication adherence (+1.48 score; p < 0.001) and ITAS (-1.99 score; p = 0.037). Mean HbA1C reduced an additional of 0.63% (p = 0.008) compared to control arm. CONCLUSION: Re-education is more effective in increasing adherence, reducing lipohypertrophy, improving injection technique and patient's perception on insulin therapy, thereby providing better glycaemic control.

Growth assessment and risk factors of malnutrition in children with cystic fibrosis.

OBJECTIVES: To evaluate the nutritional status, to screen for the presence of malnutrition, and to study the possible risk factors associated with malnutrition in patients with cystic fibrosis (CF). METHODS: A retrospective cross-sectional review of medical records of all diagnosed CF patients in the Pediatric Department, Salmaniya Medical Complex, Manama, Kingdom of Bahrain, between January 1984 and May 2015 was conducted. Demographic and anthropometric data were collected from records of last visit to CF clinic. Nutritional status and risk factors of malnutrition were assessed. RESULTS: All records of 109 CF patients were reviewed. Forty-seven pediatric patients were included in the study. All included patients were on pancreatic enzyme replacement and 42 (89%) received high-calorie supplementation. Growth failure was noted in 34 (72%) patients, 19 (56%) were wasted and stunted, 8 (23.5%) were wasted only, and 7 (20.5%) were stunted. Low birth weight (p=0.032), and the presence of gastroesophageal reflux disease (GERD) (p=0.039) were the significant risk factors for malnutrition. CONCLUSIONS: Most CF patients in Bahrain (72%) are malnourished. Low birth weight and the presence of GERD are risk factors.

Toll-like receptor 4 blocker as potential therapy for acetaminophen-induced organ failure in mice.

Acetaminophen (APAP, 4-hydroxyacetanilide) is the most common cause of acute liver failure in the United States. In addition to exhibiting hepatotoxicity, APAP exerts a nephrotoxic effect may be independent of the induced liver damage. Toll-like receptors (TLRs) have been suggested as a potential class of novel therapeutic targets. The aim of the present study was to investigate the potential of the TLR-4 blocker TAK-242 in the prevention of APAP-induced hepato-renal failure. Four groups of C57BL mice were studied: Vehicle-treated/control (VEH), APAP-treated (APAP), N-acetyl cysteine (NAC)-pretreated plus APAP (APAP + NAC) and TAK-242-pretreated plus APAP (APAP + TAK) groups. Mice were clinically assessed then perfused 4 h later. Liver and kidney tissues were collected and examined histologically using basic hematoxylin and eosin staining to detect signs of necrosis and inflammation. Plasma samples were collected to measure the levels of alanine transaminase, aspartate transaminase and serum creatinine. In addition, liver and kidney tissues were assayed to determine the levels of reduced glutathione. The results of the present study indicate the potential role of TLR-4 in APAP-induced organ toxicity. In the APAP + TAK and APAP + NAC groups, histopathological examination indicated that pretreatment with TAK-242 or NAC afforded protection against APAP-induced injury. However, this protective effect was more clinically evident in the APAP + TAK group compared with the APAP + NAC group. The various biochemical parameters (serum enzymes and reduced glutathione) revealed no significant protection in either of the pretreated groups. Therefore, the present study indicated that the TLR-4 blocker had protective effects against acute APAP toxicity in liver and kidney tissues. These effects were identified clinically, histologically and biochemically. Furthermore, the TLR-4 blocker TAK-242 exhibited antioxidant properties in addition to anti-inflammatory effects.