Temporal trends in associations between severe mental illness and risk of cardiovascular disease: A systematic review and meta-analysis.

BACKGROUND: Severe mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and CVD-related mortality. To date, no systematic review has investigated changes in population level CVD-related mortality over calendar time. It is unclear if this relationship has changed over time in higher-income countries with changing treatments. METHODS AND FINDINGS: To address this gap, a systematic review was conducted, to assess the association between SMI and CVD including temporal change. Seven databases were searched (last: November 30, 2021) for cohort or case-control studies lasting ≥1 year, comparing frequency of CVD mortality or incidence in high-income countries between people with versus without SMI. No language restrictions were applied. Random effects meta-analyses were conducted to compute pooled hazard ratios (HRs) and rate ratios, pooled standardised mortality ratios (SMRs), pooled odds ratios (ORs), and pooled risk ratios (RRs) of CVD in those with versus without SMI. Temporal trends were explored by decade. Subgroup analyses by age, sex, setting, world region, and study quality (Newcastle-Ottawa scale (NOS) score) were conducted. The narrative synthesis included 108 studies, and the quantitative synthesis 59 mortality studies (with (≥1,841,356 cases and 29,321,409 controls) and 28 incidence studies (≥401,909 cases and 14,372,146 controls). The risk of CVD-related mortality for people with SMI was higher than controls across most comparisons, except for total CVD-related mortality for BD and cerebrovascular accident (CVA) for mixed SMI. Estimated risks were larger for schizophrenia than BD. Pooled results ranged from SMR = 1.55 (95% confidence interval (CI): 1.33 to 1.81, p < 0.001), for CVA in people with BD to HR/rate ratio = 2.40 (95% CI: 2.25 to 2.55, p < 0.001) for CVA in schizophrenia. For schizophrenia and BD, SMRs and pooled HRs/rate ratios for CHD and CVD mortality were larger in studies with outcomes occurring during the 1990s and 2000s than earlier decades (1980s: SMR = 1.14, 95% CI: 0.57 to 2.30, p = 0.71; 2000s: SMR = 2.59, 95% CI: 1.93 to 3.47, p < 0.001 for schizophrenia and CHD) and in studies including people with younger age. The incidence of CVA, CVD events, and heart failure in SMI was higher than controls. Estimated risks for schizophrenia ranged from HR/rate ratio 1.25 (95% CI: 1.04 to 1.51, p = 0.016) for total CVD events to rate ratio 3.82 (95% CI: 3.1 to 4.71, p < 0.001) for heart failure. Incidence of CHD was higher in BD versus controls. However, for schizophrenia, CHD was elevated in higher-quality studies only. The HR/rate ratios for CVA and CHD were larger in studies with outcomes occurring after the 1990s. Study limitations include the high risk of bias of some studies as they drew a comparison cohort from general population rates and the fact that it was difficult to exclude studies that had overlapping populations, although attempts were made to minimise this. CONCLUSIONS: In this study, we found that SMI was associated with an approximate doubling in the rate ratio of CVD-related mortality, particularly since the 1990s, and in younger groups. SMI was also associated with increased incidence of CVA and CHD relative to control participants since the 1990s. More research is needed to clarify the association between SMI and CHD and ways to mitigate this risk.

Exercise for premenstrual syndrome: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Exercise is recommended as a treatment for premenstrual syndrome (PMS) in clinical guidelines, but this is currently based on poor-quality trial evidence. AIM: To systematically review the evidence for the effectiveness of exercise as a treatment for PMS. DESIGN & SETTING: This systematic review searched eight major databases, including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), and two trial registries from inception until April 2019. METHOD: Randomised controlled trials (RCTs) comparing exercise interventions of a minimum of 8-weeks duration with non-exercise comparator groups in women with PMS were included. Mean change scores for any continuous PMS outcome measure were extracted from eligible trials and standardised mean differences (SMDs) were calculated where possible. Random-effects meta-analysis of the effect of exercise on global PMS symptoms was the primary outcome. Secondary analyses examined the effects of exercise on predetermined clusters of psychological, physical, and behavioural symptoms. RESULTS: A total of 436 non-duplicate returns were screened, with 15 RCTs eligible for inclusion (n = 717). Seven trials contributed data to the primary outcome meta-analysis (n = 265); participants randomised to an exercise intervention reported reduced global PMS symptom scores (SMD = -1.08; 95% confidence interval [CI] = -1.88 to -0.29) versus comparator, but with substantial heterogeneity (I 2 = 87%). Secondary results for psychological (SMD = -1.67; 95% CI = -2.38 to -0.96), physical (SMD = -1.62; 95% CI = -2.41 to -0.83) and behavioural (SMD = -1.94; 95% CI = -2.45 to -1.44) symptom groupings displayed similar findings. Most trials (87%) were considered at high risk of bias. CONCLUSION: Based on current evidence, exercise may be an effective treatment for PMS, but some uncertainty remains.

Physical activity for primary dysmenorrhea: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Primary dysmenorrhea is cramping abdominal pain associated with menses. It is prevalent, affects quality of life, and can cause absenteeism. Although evidence-based medical treatment options exist, women may not tolerate these or may prefer to use nonmedical treatments. Physical activity has been recommended by clinicians for primary dysmenorrhea since the 1930s, but there is still no high-quality evidence on which to recommend its use. OBJECTIVE: We sought to determine the effectiveness of physical activity for the treatment of primary dysmenorrhea. STUDY DESIGN: Systematic literature searches of MEDLINE, Embase, Cochrane, Web of Science, CINAHL, PsycINFO, SPORTDiscus, PEDro, Allied and Complimentary Medicine Database, World Health Organization International Clinical Trials Registry Platform, Clinicaltrials.gov, and OpenGrey were performed, from database inception to May 24, 2017. Google searches and citation searching of previous reviews were also conducted. Studies were selected using the following PICOS criteria: participants were nonathlete females experiencing primary dysmenorrhea; intervention was physical activity delivered for at least 2 menstrual cycles; comparator was any comparator; outcomes were pain intensity or pain duration; and study type was randomized controlled trials. Study quality was assessed using the Cochrane risk of bias tool. Random effects meta-analyses for pain intensity and pain duration were conducted, with prespecified subgroup analysis by type of physical activity intervention. Strength of the evidence was assessed using GRADE. RESULTS: Searches identified 15 eligible randomized controlled trials totaling 1681 participants. Data from 11 studies were included in the meta-analyses. Pooled results demonstrated effect estimates for physical activity vs comparators for pain intensity (-1.89 cm on visual analog scale; 95% CI, -2.96 to -1.09) and pain duration (-3.92 hours; 95% CI, -4.86 to -2.97). Heterogeneity for both of these results was high and only partly mitigated by subgroup analysis. Primary studies were of low or moderate methodological quality but results for pain intensity remained stable during sensitivity analysis by study quality. GRADE assessment found moderate-quality evidence for pain intensity and low-quality evidence for pain duration. CONCLUSION: Clinicians can inform women that physical activity may be an effective treatment for primary dysmenorrhea but there is a need for high-quality trials before this can be confirmed.

Direct imaging of the structure, relaxation, and sterically constrained motion of encapsulated tungsten polyoxometalate lindqvist ions within carbon nanotubes.

The imaging properties and observation of the sterically regulated translational motion of discrete tungsten polyoxometalate Linqvist ions (i.e., [W(6)O(19)](2-)) within carbon nanotubes of specific internal diameter are reported. The translational motion of the nonspheroidal anion within the nanotube capillary is found to be impeded by its near-perfect accommodation to the internal van der Waals surface of the nanotube wall. Rotational motion of the anion about one remaining degree of freedom permits translational motion of the anion along the nanotube followed by locking in at sterically favorable positions in a mechanism similar to a molecular ratchet. This steric locking permits the successful direct imaging of the constituent octahedral cation template of individual [W(6)O(19)](2-) anions by high resolution transmission electron microscopy thereby permitting meterological measurements to be performed directly on the anion. Direct imaging of pairs of equatorial W(2) atoms within the anion reveal steric relaxation of the anion contained within the nanotube capillary relative to the bulk anion structure.

Repair of tandem base lesions in DNA by human cell extracts generates persisting single-strand breaks.

Clustered DNA damage, where two or more lesions are located proximal to each other on the same or opposite DNA strands, is frequently produced as a result of exposure to ionising radiation. It has been suggested that such complex damaged sites pose problems for repair pathways. In this study, we addressed the question of how two 8-oxoguanine lesions, located two nucleotides apart on the same DNA strand, are repaired. We find that in human cell extracts repair of either of the 8-oxoguanine lesions within a tandem damaged site is initiated randomly and that the majority of the initiated repair proceeds to completion. However, a fraction of the initiated repair is delayed at the stage of an incised AP site and the rate of further processing of this incised AP site is dependent on the position of the remaining 8-oxoguanine. If the remaining 8-oxoguanine residue is located near the 5' terminus of the incised abasic site, repair continues as efficiently as repair of a single 8-oxoguanine residue. However, repair is delayed after the incision step when the remaining 8-oxoguanine residue is located near the 3' terminus. Although the presence of the 8-oxoguanine residue near the 3' terminus did not affect either DNA polymerase beta activity or poly(ADP)ribose polymerase-1 affinity and turnover on an incised AP site, we find that 8-oxoguanine-DNA glycosylase has reduced ability to remove an 8-oxoguanine residue located near the 3' terminus of the incised AP site. We find that binding of the 8-oxoguanine-DNA glycosylase to this 8-oxoguanine residue inhibits DNA repair synthesis by DNA polymerase beta, thus delaying repair. We propose that interference between a DNA glycosylase and DNA polymerase during the repair of tandem lesions may lead to accumulation of the intermediate products that contain persisting DNA strand breaks.

Orchestration of base excision repair by controlling the rates of enzymatic activities.

Base excision repair (BER) is one of the major pathways for repair of simple DNA base lesions and is carried out through a series of coordinated reactions relying on several different enzymatic activities and accessory proteins. Imbalance of BER activities has been reported to be linked to genetic instability and cancer. To experimentally address the mechanisms orchestrating BER, we monitored both the overall rate and the rate-limiting steps in the repair in cell-free extracts of five different endogenously occurring DNA lesions (abasic site, uracil, 8-oxoguanine, hypoxanthine and 5,6-dihydrouracil) and the effect of addition of rate-limiting BER components on the rate and co-ordination of BER reactions. We find that several mechanisms including regulation of DNA glycosylase turnover and involvement of poly(ADP-ribose) polymerase participate in synchronization of the repair events. We also find that repair of different DNA lesions involves different mechanisms for optimizing repair rates without accumulation of intermediates. Repair of some lesions such as 8-oxoguanine is regulated by glycosylase turnover and progress without substantial accumulation of repair intermediates. However, during repair of the apurinic/apyrimidinic (AP) sites or 5,6-dihydrouracil, poly(ADP-ribose) polymerase plays an important role in the coordination of the rates of repair reactions.