Electroconvulsive therapy in single manic episodes: a case series

Objective: To evaluate the effectiveness of electroconvulsive therapy in the treatment of Bipolar I Disorder patients with a single manic episode. Method: In a retrospective study, we reviewed medical records of inpatients who had been admitted to treat a single manic episode of Bipolar I Disorder at Noor University Hospital, Isfahan, Iran between September 2004 and December 2008. Results: Out of a total of 275 single episode manic patients, 39 underwent ECT. Male/ female ratios were 19/20 (48.7% vs. 51.3%) for the ECT series and 137/99 (58% vs. 42%) for the exclusive pharmacological treatment series (p>0.05). Mean age of patients in the ECT series (23.64 ± 8.00) was significantly lower than the pharmacological treatment series (27.65± 11.30, p= 0.008). The mean length of stay (LOSs) for the ECT series (20.0± 7.90) was significantly higher than the other group (14.63± 9.84, p =0.001). The mean time to first administered ECT (tECT) was 4.35 ± 3.79. There was no significant difference between the mean LOSs of the pharmacologic treatment series and the mean “LOSs minus tECT“(LOS-tECT) variable (16.57±8.43) in the ECT series (p>0.05). The mean duration from the onset of the symptoms to time of admission was 19.22± 3.53 for the ECT series. Catatonia was the indication for application of ECT in one patient (2.6%), while 25 (64.10%) received ECT because of aggressive behavior. The proportion of patients administered chemical and physical restraints before ECT (77%) significantly dropped (7.7%) after ECT administration (

Supplementing glycine, serine, and threonine in low protein diets for meat type chickens

Reducing dietary protein has been of interest to the global poultry industry to improve bird health, welfare, and industry sustainability. Low protein (LP) diets are typically glycine (Gly) deficient and produce poor performance. Supplementing the diet with Gly or precursors of Gly can overcome this deficiency. A feeding experiment was conducted with 330 Ross 308 off-sex males across 5 treatments in a randomized design using 11 birds per pen replicated 6 times. Grower and finisher treatments were fed from day 7 to 21 and day 21 to 35, respectively. The objective was to test the efficacy of supplementation with Gly and Gly equivalents (Glyequiv), serine (Ser) and threonine (Thr), in plant-based LP diets on bird performance against a standard protein (SP) diet containing meat and bone meal. Glycine, Ser, or Thr were supplemented on Glyequiv basis to an approximately 3% lower CP diet to achieve the same digestible Gly and Ser level as the SP diet. Nitrogen efficiency, serum uric acid, blood plasma amino acids (AA) and AA digestibility were also investigated to monitor potential metabolic effects. Birds fed the LP diet were only 3.3% lower in final body weight than the SP treatment (2,556 vs. 2,641 g) while the supplementation of Gly or Ser had no effect. Supplementation of Thr reduced final body weight by 9.5% (P P P P equiv basis

Using crystalline amino acids to supplement broiler chicken requirements in reduced protein diets

Reducing dietary CP can reduce N pollution. Much research has been reported in corn-based diets; however, the amino acid (AA) profiles of wheat-based diets differ. Poor performance as a result of reduced protein (RP) has been overcome in corn-based diets with essential AA and glycine (Gly) supplementation. The current study examined RP levels and Gly in wheat-based diets. An industry standard protein (SP) diet plus 3 RP diets with and without Gly supplementation, to match the SP treatment at 0.713 and 0.648% digestible Gly for the grower and finisher periods respectively, were fed to male broilers from day 10 of age. Grower CP included 22.5, 20.6, 18.3, and 17.7% (days 10-21) and finisher CP included 19.7, 17.8, 16.2, and 15.5% (days 21-35). Performance, meat yield, N efficiency, water intake, and apparent ileal digestibility of N and AA were measured. No difference in body weight gain (BWG), feed intake, or feed conversion ratio (FCR) were observed at 20% CP compared to the SP treatment. However, further reducing protein reduced BWG (P P P P P P 2 = 0.69) and finisher (R2 = 0.80) treatments. Water intake decreased (R2 = 0.83) with decreasing CP intake. Apparent ileal digestibility of AA and N were higher in RP diets (

Structure-guided microbial targeting of antistaphylococcal prodrugs

Carboxy ester prodrugs are widely employed to increase oral absorption and potency of phosphonate antibiotics. Prodrugging can mask problematic chemical features that prevent cellular uptake and may enable tissue-specific compound delivery. However, many carboxy ester promoieties are rapidly hydrolyzed by serum esterases, limiting their therapeutic potential. While carboxy ester-based prodrug targeting is feasible, it has seen limited use in microbes as microbial esterase-specific promoieties have not been described. Here we identify the bacterial esterases, GloB and FrmB, that activate carboxy ester prodrugs i

Effects of delayed feeding, sodium butyrate and glutamine on intestinal permeability in newly-hatched broiler chickens

The aim of the current study was to investigate the effects of delayed feeding, and supplementation with sodium butyrate or glutamine in drinking water, on intestinal permeability (IP) in young broiler chickens. Newly-hatched male chickens (Ross 308) were allocated to four groups comprising Control, 24 h delayed fed (DF), DF supplemented with sodium butyrate (0.1%) in the drinking water and DF supplemented with glutamine (1%) in the drinking water. On days 2, 4 and 7, twelve birds per group were randomly selected, weighed and orally gavaged with fluorescein isothiocyanate dextran (FITC-d) at 2.2 mg / ml / chicken. Serum FITC-d concentration was analysed by spectrophotometry while serum diamine oxidase and D-lactic acid concentrations were analysed by microplate reader. FITC-d concentrations in the Control and DF groups were not statistically different on any day, suggesting that delayed feeding did not affect IP. Additionally, sodium butyrate increased IP compared to DF and Control on day 2 only (p

KRASG12D Inhibition Reprograms the Microenvironment of Early and Advanced Pancreatic Cancer to Promote Fas-Mediated Killing by CD8+ T Cells

The KRASG12D mutation is present in nearly half of pancreatic adenocarcinomas (PDAC). We investigated the effects of inhibiting the KRASG12D mutant protein with MRTX1133, a non-covalent small molecule inhibitor of KRASG12D, on early and advanced PDAC and its influence on the tumor microenvironment. Employing 16 different models of KRASG12D-driven PDAC, we demonstrate that MRTX1133 reverses early PDAC growth, increases intratumoral CD8+ effector T cells, decreases myeloid infiltration, and reprograms cancer-associated fibroblasts. MRTX1133 leads to regression of both established PanINs and advanced PDAC. Regression of advanced PDAC requires CD8+ T cells and immune checkpoint blockade (ICB) synergizes with MRTX1133 to eradicate PDAC and prolong overall survival. Mechanistically, inhibition of KRASG12D in advanced PDAC and human patient derived organoids induces FAS expression in cancer cells and facilitates CD8+ T cell-mediated death. Collectively, this study provides a rationale for a synergistic combination of MRTX1133 with ICB in clinical trials

Cognitive reactivity: cultural adaptation and psychometric testing of the Persian version of the Leiden Index of Depression Sensitivity Revised (LEIDS-R) in an Iranian sample

Cognitive reactivity (CR) to the experimental induction of sad mood has been found to predict relapse in recovered depressed patients. The Leiden Index of Depression Sensitivity Revised (LEIDS-R) is a self-report measure of CR. The aim of the present study was to establish the validity and reliability of the Persian version of the LEIDS-R. The participants were recovered depressed and non-depressed Iranian individuals (n = 833). The analyses included content validation, factor analysis, construct validity, and reliability testing. Preliminary construct validation analysis confirmed that factor analysis was appropriate for the Persian version of the LEIDS-R. Factor analysis displayed similar factor loadings to the original English version. The total internal consistency of the translated version, which was assessed using Cronbach’s alpha coefficient, was equal to 0.90. The test-retest reliability of the total score was equal to that of the test-retest conducted after a two-week interval at 0.94. Content validity, face validity, and construct validity, as well as reliability analysis were all found to be satisfactory for the Persian version of the LEIDS-R. The Persian version of the LEIDS-R appears to be valid and reliable for use in future studies, and has properties comparable to the original version and to that obtained in previous studies

Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine.

Homozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. Homozygous MTAP-deleted cell lines in culture show elevation of MTAP\u27s substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protein arginine methyltransferase 5 (PRMT5), which sensitizes MTAP-deleted cells to PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibition. While this concept has been extensively corroborated in vitro, the clinical relevance relies on exhibiting significant MTA accumulation in human glioblastoma. In this work, using comprehensive metabolomic profiling, we show that MTA secreted by MTAP-deleted cells in vitro results in high levels of extracellular MTA. We further demonstrate that homozygous MTAP-deleted primary glioblastoma tumors do not significantly accumulate MTA in vivo due to metabolism of MTA by MTAP-expressing stroma. These findings highlight metabolic discrepancies between in vitro models and primary human tumors that must be considered when developing strategies for precision therapies targeting glioblastoma with homozygous MTAP deletion

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from −90% to +30%, were reported in many countries following early COVID-19 pandemic response measures (‘lockdowns’). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95–0.98, P value <0.0001), second (0.96, 0.92–0.99, 0.03) and third (0.97, 0.94–1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96–1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88–1.14, 0.98), third (0.99, 0.88–1.12, 0.89) and fourth (1.01, 0.87–1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02–1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03–1.15, 0.002), third (1.10, 1.03–1.17, 0.003) and fourth (1.12, 1.05–1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways

National guidelines for cognitive assessment and rehabilitation of Iranian traumatic brain injury patients

Background: Individuals with moderate to severe traumatic brain injury (TBI) often have prolonged cognitive impairments, resulting in long-term problems with their real-life activities. Given the urgent need for evidence-based recommendations for neuropsychological management of Iranian TBI patients, the current work aimed to adapt eligible international guidelines for cognitive assessment and rehabilitation of the TBI patients in Iran. Methods: The project was led by an executive committee, under the supervision of the Iranian Ministry of Health and Medical Education (MOHME). Following a systematic literature search and selection process, four guidelines were included for adaptation. Clinical recommendations of the source guidelines were tabulated as possible clinical scenarios for 90 PICO clinical questions covering all relevant phases of care. After summing up the scenarios, our initial list of recommendations was drafted according to the Iranian patients� conditions. The final decision-making, with the contribution of a national interdisciplinary panel of 37 experts from across the country, was conducted in two rounds using online and offline survey forms (Round 1), and face-to-face and telephone meetings (Round 2). Results: A total of 63 recommendations in six sections were included in the final list of recommendations, among which 24 were considered as key recommendations. In addition, some of the recommendations were identified as fundamental, meaning that proper implementation of the other recommendations is largely dependent on their implementation. Conclusion: Iranian health policy makers and rehabilitation program managers are recommended to address some fundamental issues to provide the necessary infrastructure to set up an efficient cognitive rehabilitation service system. © 2020 Academy of Medical Sciences of I.R. Iran. All rights reserved