Actigraphic sleep monitoring in patients with post-traumatic stress disorder (PTSD): A meta-analysis.

OBJECTIVE: Sleep disruption is a common complaint among patients with post-traumatic stress disorder (PTSD). Modern technology of activity monitoring (actigraphy) enables extended, objective, unobtrusive recording and measuring of daytime and nighttime activity. We conducted a meta-analysis to investigate the actigraphic sleep patterns in PTSD compared with healthy controls. METHODS: We searched through seven electronic databases from inception to July 2022. Only case-control studies comparing rest-activity variables measured by actigraphy devices between clinically diagnosed PTSD patients and healthy individuals were included. RESULTS: We identified 12 eligible studies comparing 323 PTSD patients and 416 healthy controls. Using a random-effects model, we showed that PTSD patients have significantly lower sleep efficiency (SMD: -0.26, 95 % CI = -0.51 to -0.004, p < .05, I2 = 29.31 %), more fragmented sleep (SMD: 0.52, 95 % CI = 0.17 to 0.87, p < .01, I2 = 0 %), and longer time in bed (SMD: 0.41, 95 % CI = 0.07 to 0.74, p < .05, I2 = 0 %) compared to healthy controls. LIMITATIONS: This study included a limited number of studies. Publication bias was not examined on all variables, which could lead to an overestimation of effect size. Four studies involved veterans, which likely differ from civilians regarding traumatic exposure. CONCLUSION: This meta-analytic review highlighted a pattern of sleep disturbances in PTSD patients compared with non-PTSD individuals. High-quality, large-scale studies are necessary to draw a definitive conclusion regarding the distinctive sleep profile in PTSD. Future research can pay attention to sleep-specific mechanisms underlying PTSD and explore the momentary interactions between sleep-wake variables.

The major trimeric antenna complexes serve as a site for qH-energy dissipation in plants.

Plants and algae are faced with a conundrum: harvesting sufficient light to drive their metabolic needs while dissipating light in excess to prevent photodamage, a process known as nonphotochemical quenching. A slowly relaxing form of energy dissipation, termed qH, is critical for plants' survival under abiotic stress; however, qH location in the photosynthetic membrane is unresolved. Here, we tested whether we could isolate subcomplexes from plants in which qH was induced that would remain in an energy-dissipative state. Interestingly, we found that chlorophyll (Chl) fluorescence lifetimes were decreased by qH in isolated major trimeric antenna complexes, indicating that they serve as a site for qH-energy dissipation and providing a natively quenched complex with physiological relevance to natural conditions. Next, we monitored the changes in thylakoid pigment, protein, and lipid contents of antenna with active or inactive qH but did not detect any evident differences. Finally, we investigated whether specific subunits of the major antenna complexes were required for qH but found that qH was insensitive to trimer composition. Because we previously observed that qH can occur in the absence of specific xanthophylls, and no evident changes in pigments, proteins, or lipids were detected, we tentatively propose that the energy-dissipative state reported here may stem from Chl-Chl excitonic interaction.

Intramuscular midazolam, olanzapine, or haloperidol for the management of acute agitation: A multi-centre, double-blind, randomised clinical trial.

BACKGROUND: The safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated. METHODS: A pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18-75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam (n = 56), olanzapine (n = 54), or haloperidol (n = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118). FINDINGS: Of 206 patients randomised, 167 (mean age, 42 years; 98 [58·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8·5 (IQR 8·0), 11·5 (IQR 30·0), and 23·0 (IQR 21·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine (p = 0·03) and haloperidol (p = 0·002). Adverse event rates were similar across the three arms. Dystonia (n = 1) and cardiac arrest (n = 1) were reported in the haloperidol group. INTERPRETATION: Midazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects. FUNDING: Research Grants Council, Hong Kong.

Antipsychotics and Risk of Neuroleptic Malignant Syndrome: A Population-Based Cohort and Case-Crossover Study.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare and acute adverse drug reaction associated with antipsychotic therapy. However, few data on the risk and epidemiology of NMS are available. OBJECTIVES: The aim of this study was to ascertain the incidence risk and all-cause mortality of NMS associated with antipsychotic use, and to assess the association of recent antipsychotic exposure and NMS. METHODS: We did a population-based study using data from the Hong Kong Hospital Authority's Clinical Data Analysis and Reporting System database. Cases had a first diagnosis of NMS between 1 January 2004 and 30 November 2017. A case-crossover analysis was used to compare antipsychotic exposure 30 days before the diagnosis of NMS (index date) and a reference period 91-120 days before the index date. To adjust for potential time trends in antipsychotic exposure, we sampled from cases to match current cases and future cases, and further adjusted for select medications and acute medical conditions. RESULTS: 297,647 patients were prescribed antipsychotics, and the incidence risk of NMS was 0.11%. Of the 336 cases included in the case-crossover analysis, 20 (6%) died within 30 days after the index date; only one case had NMS recorded as the primary cause of death. When compared with the reference period, cases were more frequently prescribed multiple antipsychotics (15.8% vs 26.8%; standardized mean difference [SMD] 0.27) and short-acting injectable antipsychotics (3.6% vs 13.7%; SMD 0.37) during the 30 days prior to the diagnosis of NMS. Odds ratios for antipsychotic exposure in the case-crossover, case-crossover adjusted for time trend, and case-crossover adjusted for time trend and potential confounders analysis were 8.00 (95% confidence interval 3.42-18.69), 5.88 (2.46-14.04), and 4.77 (1.95-11.66). CONCLUSIONS: Our results suggest that recent use of antipsychotics is associated with NMS. Although a case-only design inherently controls for confounding by time-invariant factors, residual confounding by acute medical conditions with similar presentations to NMS cannot be fully excluded.

Efficacy and safety of naltrexone for amfetamine and methamfetamine use disorder: a systematic review of randomized controlled trials.

INTRODUCTION: Amfetamine and methamfetamine abuse remains a prevalent health problem, increasing the burden on healthcare. Naltrexone, a µ-opioid receptor antagonist, has been suggested as a promising treatment for amfetamine and methamfetamine use disorder. OBJECTIVE: To review the current evidence for the efficacy and safety of naltrexone as a pharmacological treatment for amfetamine and methamfetamine use disorder. The primary outcome was defined as abstinence or reduction of use. Secondary outcomes were, attenuated "positive" subjective effects (e.g., "feel good," "craving," etc.) of amfetamine or methamfetamine after naltrexone treatment, adverse events and physiological changes (e.g., blood pressure, heart rate). METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A systematic literature search was conducted on 2 April 2017, and updated on 31 March 2018. Records were retrieved from databases including PubMed, EMBASE Classic plus EMBASE 1980 via Ovid, and the databases were searched using keywords and/or headings: (naltrexone AND amfetamine AND dependence) OR (naltrexone AND amfetamine AND craving) OR (vivitrol AND amfetamine) OR (revia AND amfetamine) OR (naltrexone AND amfetamine) OR (naltrexone AND methamfetamine dependence) OR (naltrexone AND methamfetamine AND craving) OR (vivitrol AND methamfetamine) OR (revia AND methamfetamine) OR (naltrexone AND ice) OR (naltrexone AND crystal meth) OR (naltrexone AND methamfetamine). Studies investigating the effects of naltrexone on amfetamine or methamfetamine use were eligible for inclusion. All studies were rated as low risk of bias using the Cochrane tool for risk of bias. RESULTS: Among 591 identified studies, there were four randomized controlled trials. Two studies investigated the effects of naltrexone on amfetamine use disorder and two on methamfetamine use. Compared to placebo, the abstinence rate was increased significantly (p < 0.05) by naltrexone in one of two amfetamine studies, whereas there was no statistical difference in the only study reporting methamfetamine use. In one out of two amfetamine studies, naltrexone significantly attenuated either craving levels or subjective effects (e.g., "want more," "like effect") relative to placebo (p < 0.05). Additionally, only in one of two methamfetamine studies did naltrexone produce a significant reduction (p < 0.05) in craving levels or attenuated subjective effects. Both amfetamine and methamfetamine studies showed good tolerability of naltrexone, with few adverse events seen. CONCLUSIONS: There is presently insufficient evidence to support the use of naltrexone in amfetamine and metamfetamine use disorders. There is a compelling need for high-quality studies to further evaluate the potential use of naltrexone.

Tian Xian Liquid (TXL) induces apoptosis in HT-29 colon cancer cell in vitro and inhibits tumor growth in vivo.

BACKGROUND: Tian Xian Liquid (TXL) is a Chinese medicine decoction and has been used as an anticancer dietary supplement. The present study aims to investigate the effects of TXL on the apoptosis of HT-29 cells and tumor growth in vivo. METHOD: HT-29 colon cancer cells were treated with gradient dilution of TXL. The mitochondrial membrane potential was measured by JC-1 assay. The release of cytochrome c from mitochondrial and apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3, 9 were examined by Western blot analysis. HT-29 cells were implanted in nude mice to examine the effects of TXL on tumor growth. RESULT: TXL inhibited HT-29 xenografted model and showed a strong and dose-dependent inhibitory effect on the proliferation of HT-29 cells. Mitochondrial membrane potential was reduced by TXL at the concentration of 0.5% above. For Western blot analysis, an increase in Bax expression and a decrease in Bcl-2 expression were observed in TXL-treated cells. TXL treatment increased the protein level of cleaved casepase-3 and caspase-9, and the release of cytochrome c in cytoplasm was up-regulated as well. CONCLUSION: TXL significantly inhibits cell proliferation in the HT-29 cells and HT-29 xenografted model via the mitochondrial cell death pathway.

NMR structure of a type IVb pilin from Salmonella typhi and its assembly into pilus.

The structure of the N-terminal-truncated Type IVb structural pilin (t-PilS) from Salmonella typhi was determined by NMR. Although topologically similar to the recently determined x-ray structure of pilin from Vibrio cholerae toxin-coregulated pilus, the only Type IVb pilin with known structure, t-PilS contains many distinct structural features. The protein contains an extra pair of beta-strands in the N-terminal alphabeta loop that align with the major beta-strands to form a continuous 7-stranded antiparallel beta-sheet. The C-terminal disulfide-bonded region of t-PilS is only half the length of that of toxin-coregulated pilus pilin. A model of S. typhi pilus has been proposed and mutagenesis studies suggested that residues on both the alphabeta loop and the C-terminal disulfide-bonded region of PilS might be involved in binding specificity of the pilus. This model structure reveals an exposed surface between adjacent subunits of PilS that could be a potential binding site for the cystic fibrosis transmembrane conductance regulator.