Recovery Following Peer and Text Messaging Support After Discharge From Acute Psychiatric Care in Edmonton, Alberta: Controlled Observational Study.

BACKGROUND: Peer support is an emotional, social, and practical help provided by nonprofessionals to assist others in sustaining health behaviors. Peer support is valued in recovery-oriented models of mental health and is becoming increasingly implemented at the organizational level. Text messaging is a relatively low-cost, high-impact, and easily scalable program that uses existing technology, is devoid of geographic barriers, and is easily accessible to end users. OBJECTIVE: This study aims to evaluate the effectiveness of an innovative peer support system plus a supportive text messaging program on the recovery of discharged patients from acute psychiatric care. METHODS: This prospective, rater blinded, controlled observational study included 181 patients who were discharged from acute psychiatric care. Patients were randomized to one of four conditions: treatment as usual (follow-up care), daily supportive text messages only, peer support only, or peer support plus daily supportive text messages. A standardized self-report measure of recovery (Recovery Assessment Scale [RAS]) was completed at baseline, 6 weeks, 3 months, and 6 months. Descriptive analysis, one-way analysis of variance, and repeated measures multivariate analysis of covariance were used to examine the changes in the RAS among the study groups and over the follow-up time points. RESULTS: A total of 65 patients completed the assessments at each time point. For the overall sample, higher scores were found for the peer support plus text message condition compared with the text message only and treatment as usual condition on several scales (ie, willingness to ask for help and personal confidence and hope) and total score on the RAS, after 6 months of intervention. CONCLUSIONS: Peer support plus supportive text messaging seems to result in improved recovery compared with other interventions. It may be advisable to incorporate the two interventions as part of routine practice for patients with psychiatric disorders upon hospital discharge.

Promising preventive and therapeutic effects of TaibUVID nutritional supplements for COVID-19 pandemic: towards better public prophylaxis and treatment (A retrospective study).

Adjuvant nutritional treatment is a commonly overlooked topic when treating lethal viral diseases as COVID-19 pandemic. We recently introduced TaibUVID nutritional supplements (nigella sativa, chamomile and natural honey) as adjuvants for COVID-19 contacts, patients and public prophylaxis. TaibUVID Forte adds costus, senna and fennel to TaibUVID. Meta-analyses and systematic reviews confirmed evidence-based therapeutic benefits of TaibUVID components in treating many human diseases e.g. diabetes mellitus and hypertension, common co-morbidities in COVID-19 patients. Double-blind clinical trials for treating COVID-19 patients with TaibUVID supplements were inapplicable. In this retrospective study in Egypt, COVID-19 patients and contacts knew TaibUVID via social media and voluntarily used them. 65% of COVID-19 patients (n = 13) received both pharmacological treatments and adjuvant TaibUVID nutritional supplements. 35% (n = 7) received TaibUVID only. Lymphopenia rapidly improved to lymphocytosis upon regular TaibUVID intake. TaibUVID nutritional supplements helped COVID-19 contacts' prophylaxis. 70% of COVID-19 contacts (n = 14) (on regular TaibUVID intake) did not get SARS-COV2 infection. 30% (n = 6) were not using TaibUVID regularly and got mild flu-like symptoms and upon using both TaibUVID and pharmacological treatments, all improved and got negative nasopharyngeal swabs PCR. COVID-19 contacts were mainly physicians (40%, n = 8) (dealing with COVID-19 patients daily) and members of physicians' families (45%). Main presentations reported by COVID-19 patients (n = 20) were cough (90%), fever (55%), anosmia (45%), taste loss (45%), sore throat (45%), respiratory difficulty (45%) and malaise (35%). TaibUVID inhalation therapy (nigella sativa/anthemis/costus solution nebulization) was used by 65% of COVID-19 patients (n = 13) and alleviated respiratory manifestations e.g. cough and respiratory difficulty and was life-saving in some cases. 70% of COVID-19 patients (n = 14) improved in 1-4 days, 25% (n = 5) improved in 5-10 days while 5% improved in more than 10 days. TaibUVID nutritional supplements were tolerable and significantly satisfactory (P<0.01). 81.25% of COVID-19 patients (n = 13) did not report side effects. 18.25% (n = 3) reported mild diarrhea, sweating and hyperglycemia (not confirmed to be due to TaibUVID supplements). 31.25% of patients (n = 5) were satisfied by 100% with TaibUVID nutritional supplements. 37.5% (n = 6) of patients were satisfied by 75%. In conclusion, TaibUVID nutritional supplements are recommended for public prophylaxis (to decrease emergence of new cases) and treatment in COVID-19 pandemic. Clinical trials and further investigations are recommended.

Family Members' Perspectives on Family and Social Support Available to Suicidal Patients, and Health Systems' Interactions and Responses to Suicide Cases in Alberta: Protocol for a Quantitative Research Study.

BACKGROUND: Suicide is a major cause of preventable death globally and a leading cause of death by injury in Canada. To support people who experience suicidal thoughts and behaviors and to ultimately prevent people from dying by suicide, it is important to understand individual and familial experiences with the health care system. OBJECTIVE: We present the protocol for a study, the objective of which is to explore how people who died by suicide, and their family members, interacted with the health care system. METHODS: This is a quantitative research study. Data will be collected through a self-administered paper-based or online survey of the family member of patients who died by suicide. The sample size was calculated to be 385 (margin of error ±3%). RESULTS: Data collection will start in October 2020 and results will be available by March 2021. We expect the results to shed light on the experiences of individuals who died by suicide and their family members with the health care system. The study has received ethical clearance from the Health Ethics Research Board of the University of Alberta (Pro00096342). CONCLUSIONS: Our study may inform practice, policy, and future research. The findings may shape how members of the health care system respond to people who are at risk of suicide and their families. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/19112.

Repetitive Transcranial Magnetic Stimulation With and Without Internet-Delivered Cognitive-Behavioral Therapy for the Treatment of Resistant Depression: Protocol for Patient-Centered Randomized Controlled Pilot Trial.

BACKGROUND: Major depression is a severe, disabling, and potentially lethal clinical disorder. Only about half of patients respond to an initial course of antidepressant pharmacotherapy. At least 15% of all patients with major depressive disorder (MDD) remain refractory to any treatment intervention. By the time that a patient has experienced 3 definitive treatment failures, the likelihood of achieving remission with the fourth treatment option offered is below 10%. Repetitive transcranial magnetic stimulation (rTMS) is considered a treatment option for patients with MDD who are refractory to antidepressant treatment. It is not currently known if the addition of internet-delivered cognitive-behavioral therapy (iCBT) enhances patients' responses to rTMS treatments. OBJECTIVE: This study will evaluate the initial comparative clinical effectiveness of rTMS with and without iCBT as an innovative patient-centered intervention for the treatment of participants diagnosed with treatment-resistant depression (TRD). METHODS: This study is a prospective, two-arm randomized controlled trial. In total, 100 participants diagnosed with resistant depression at a psychiatric care clinic in Edmonton, Alberta, Canada, will be randomized to one of two conditions: (1) enrolment in rTMS sessions alone and (2) enrolment in the rTMS sessions plus iCBT. Participants in each group will complete evaluation measures (eg, recovery, general symptomatology, and functional outcomes) at baseline, 1 month, 3 months, and 6 months. The primary outcome measure will be the mean change to scores on the Hamilton Depression Rating Scale. Patient service utilization data and clinician-rated measures will also be used to gauge patient progress. Patient data will be analyzed with descriptive statistics, repeated measures, and correlational analyses. RESULTS: We expect the results of the study to be available in 24 months. We hypothesize that participants enrolled in the study who receive rTMS plus iCBT will achieve superior outcomes in comparison to participants who receive rTMS alone. CONCLUSIONS: The concomitant application of psychotherapy with rTMS has not been investigated previously. We hope that this project will provide us with a concrete base of data to evaluate the practical application and efficacy of using a novel combination of these two treatment modalities (rTMS plus iCBT). TRIAL REGISTRATION: ClinicalTrials.gov NCT0423965; https://clinicaltrials.gov/ct2/show/NCT04239651. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/18843.

P219L substitution in human D-amino acid oxidase impacts the ligand binding and catalytic efficiency.

Human D-amino acid oxidase (DAO) is a flavoenzyme that is implicated in neurodegenerative diseases. We investigated the impact of replacement of proline with leucine at Position 219 (P219L) in the active site lid of human DAO on the structural and enzymatic properties, because porcine DAO contains leucine at the corresponding position. The turnover numbers (kcat) of P219L were unchanged, but its Km values decreased compared with wild-type, leading to an increase in the catalytic efficiency (kcat/Km). Moreover, benzoate inhibits P219L with lower Ki value (0.7-0.9 µM) compared with wild-type (1.2-2.0 µM). Crystal structure of P219L in complex with flavin adenine dinucleotide (FAD) and benzoate at 2.25 Å resolution displayed conformational changes of the active site and lid. The distances between the H-bond-forming atoms of arginine 283 and benzoate and the relative position between the aromatic rings of tyrosine 224 and benzoate were changed in the P219L complex. Taken together, the P219L substitution leads to an increase in the catalytic efficiency and binding affinity for substrates/inhibitors due to these structural changes. Furthermore, an acetic acid was located near the adenine ring of FAD in the P219L complex. This study provides new insights into the structure-function relationship of human DAO.

TaibUVID nutritional supplements help rapid cure of COVID-19 infection and rapid reversion to negative nasopharyngeal swab PCR: for better public prophylaxis and treatment of COVID-19 pandemic.

Public prophylaxis to decrease the emergence of new daily COVID-19 cases is vital. Adjuvant TaibUVID nutritional supplements are promising home-made or hospital-made supplements suggested for rapidly preventing and treating COVID-19 pandemic. We report here a 44 years old male physician who caught COVID-19 infection at hospital in Egypt with confirmed positive nasopharyngeal swab PCR. Ethical committee approval and informed patient's consent were gained before performing this study. Chest X-ray revealed increased bronchovascular markings. Close follow-up was done with no treatment given and he was sent for home isolation. Few days later, he developed progressive non-productive cough and a sense of difficult breathing with no associated fever or chest pain. An antitussive drug was given to him. The patient read about TaibUVID supplements from social media and started to feel improvement after TaibUVID inhalation therapy (using the heated solution of nigella sativa and chamomile five times a day). He also received a home-made TaibUVID nutritional supplement (nigella sativa, chamomile and natural honey) five times daily for four consecutive days. The next day, he was quite better with mild symptoms. Two days later, nasopharyngeal swab PCR was negative while other patients still had positive nasopharyngeal swabs. As few attacks of mild cough and breathing difficulty existed, he was admitted to hospital. A nasopharyngeal swab PCR was done for him again and the result was negative also. Blood gases were normal. He had lymphocytosis (possibly due to TaibUVID effects) that counteract lymphopenia seen in COVID-19 patients. Biochemical and hematological evaluation were quite normal apart from increased serum chloride and lactate dehydrogenase. There was a mild decrease in serum CO2 and alkaline phosphatase. Chest CT report revealed symmetrically inflated both lungs with non-specific focal nodular infiltrates (scattered in basal and medial lung segments) in left lower lobes with faint ground glass opacities. He was discharged home. Few days later, he was quite improved with no symptoms and returned to his work comfortably. In conclusion, TaibUVID nutritional supplements may be effective in rapidly changing the nasopharyngeal swab PCR from positive to negative. TaibUVID nutritional supplements are advisable as a natural, safe and effective prophylaxis to stop COVID-19 infectiousness, transmission and emergence of new cases. Clinical studies to investigate TaibUVID nutritional benefits are strongly recommended. TaibUVID may be promising and recommended for public prophylaxis to decrease emergence of new COVID-19 cases.

A new antiproliferative noscapine analogue: chemical synthesis and biological evaluation.

Noscapine, a naturally occurring opium alkaloid, is a widely used antitussive medication. Noscapine has low toxicity and recently it was also found to possess cytotoxic activity which led to the development of many noscapine analogues. In this paper we report on the synthesis and testing of a novel noscapine analogue. Cytotoxicity was assessed by MTT colorimetric assay using SKBR-3 and paclitaxel-resistant SKBR-3 breast cancer cell lines using different concentrations for both noscapine and the novel compound. Microtubule polymerization assay was used to determine the effect of the new compound on microtubules. To compare the binding affinity of noscapine and the novel compound to tubulin, we have done a fluorescence quenching assay. Finally, in silico methods using docking calculations were used to illustrate the binding mode of the new compound to α,ß-tubulin. Our cytotoxicity results show that the new compound is more cytotoxic than noscapine on both SKBR-3 cell lines. This was confirmed by the stronger binding affinity of the new compound, compared to noscapine, to tubulin. Surprisingly, our new compound was found to have strong microtubule-destabilizing properties, while noscapine is shown to slightly stabilize microtubules. Our calculation indicated that the new compound has more binding affinity to the colchicine-binding site than to the noscapine site. This novel compound has a more potent cytotoxic effect on cancer cell lines than its parent, noscapine, and hence should be of interest as a potential anti-cancer drug.

Antitumor Activity of Lankacidin Group Antibiotics Is Due to Microtubule Stabilization via a Paclitaxel-like Mechanism.

Lankacidin group antibiotics show strong antimicrobial activity against various Gram-positive bacteria. In addition, they were shown to have considerable antitumor activity against certain cell line models. For decades, the antitumor activity of lankacidin was associated with the mechanism of its antimicrobial action, which is interference with peptide bond formation during protein synthesis. This, however, was never confirmed experimentally. Due to significant similarity to paclitaxel-like hits in a previous computational virtual screening study, we suggested that the cytotoxic effect of lankacidin is due to a paclitaxel-like action. In this study, we tested this hypothesis computationally and experimentally and confirmed that lankacidin is a microtubule stabilizer that enhances tubulin assembly and displaces taxoids from their binding site. This study serves as a starting point for optimization of lankacidin derivatives for better antitumor activities. It also highlights the power of computational predictions and their aid in guiding experiments and formulating rigorous hypotheses.

Isolation of soluble scFv antibody fragments specific for small biomarker molecule, L-Carnitine, using phage display.

Isolation of single chain antibody fragment (scFv) clones from naïve Tomlinson I+J phage display libraries that specifically bind a small biomarker molecule, L-Carnitine, was performed using iterative affinity selection procedures. L-Carnitine has been described as a conditionally essential nutrient for humans. Abnormally high concentrations of L-Carnitine in urine are related to many health disorders including diabetes mellitus type 2 and lung cancer. ELISA-based affinity characterization results indicate that selectants preferentially bind to L-Carnitine in the presence of key bioselecting component materials and closely related L-Carnitine derivatives. In addition, the affinity results were confirmed using biophysical fluorescence quenching for tyrosine residues in the V segment. Small-scale production of the soluble fragment yielded 1.3mg/L using immunopure-immobilized protein A affinity column. Circular Dichroism data revealed that the antibody fragment (Ab) represents a folded protein that mainly consists of ß-sheets. These novel antibody fragments may find utility as molecular affinity interface receptors in various electrochemical biosensor platforms to provide specific L-Carnitine binding capability with potential applications in metabolomic devices for companion diagnostics and personalized medicine applications. It may also be used in any other biomedical application where detection of the L-Carnitine level is important.

Potential cytotoxic effect of hydroxypyruvate produced from D-serine by astroglial D-amino acid oxidase.

D-amino acid oxidase (DAO) is a flavoenzyme that exists in the kidney, liver and brain of mammals. This enzyme catalyzes the oxidation of D-amino acids to the corresponding α-keto acid, hydrogen peroxide and ammonia. Recently D-serine, one of the substrates of DAO, has been found in the mammalian brain, and shown to be a co-agonist of the N-methyl-D-aspartate (NMDA) receptor in glutamate neurotransmission. In this study, we investigated the metabolism of extracellular D-serine and the effects of D-serine metabolites to study the pathophysiological role of DAO. Treatment with a high dose of D-serine induced the cell death in dose-dependent manner in DAO-expressing cells. Moreover, overexpression of DAO in astroglial cells induced the enhanced cytotoxicity. The treatment with 1 mM beta-hydroxypyruvate (HPA), uniquely produced from the D-serine metabolism by DAO activity, also induced cell death, comprising apoptosis, in the astroglial cell, but not in the other cells derived from liver and kidney. Taken together, we consider that high dose of extracellular D-serine induced cell death by the production of not only hydrogen peroxide but also HPA as a result of DAO catalytic activity in astroglial cell. Furthermore, this cytotoxicity of HPA is observed uniquely in astroglial cells expressing DAO.

Potential pathophysiological role of D-amino acid oxidase in schizophrenia: immunohistochemical and in situ hybridization study of the expression in human and rat brain.

D-Amino acid oxidase (DAO) is a peroxisomal flavoenzyme that catalyzes oxidative deamination of a wide range of D-amino acids. Among the possible substrates of DAO in vivo, D-serine is proposed to be a neuromodulator of the N-methyl-D-aspartate (NMDA) type glutamate receptor. The gene for DAO was reported to be associated with schizophrenia. Since DAO is expected to be one of the key enzymes in the regulation of NMDA neurotransmission, the modulation of the enzyme activity is expected to be therapeutical for neuronal disorders. In search of the pathophysiological role of DAO, we analyzed the distribution of DAO mRNA and protein in the rat and human brain. In rat, the distribution of DAO mRNA was newly detected in choroid plexus (CP) epithelial cells in addition to glial cells of pons, medulla oblongata, and especially Bergmann glia of cerebellum. Moreover, to investigate how DAO expression level is altered in schizophrenia, we performed immunohistochemistry in the human brain. In agreement with the results in the rat brain, the immunoreactivity for DAO was detected in glial cells of rhombencephalon and in CP. Furthermore, higher level of DAO expression was observed in schizophrenic CP epithelial cells than that in non-schizophrenic cases. These results suggest that an increase in DAO expression in parts of the brain is involved in aberrant D-amino acid metabolism. In particular, gene expression of DAO in CP suggests that DAO may regulate D-amino acid concentration by modulating the cerebrospinal fluid and may be regarded as a potential therapeutic target for schizophrenia.