Biolistics-mediated transformation of hornworts and its application to study pyrenoid protein localization.

Hornworts are a deeply diverged lineage of bryophytes that are sister to mosses and liverworts. Hornworts have an array of unique features that can be leveraged to illuminate not only the early evolution of land plants, but also alternative paths for nitrogen and carbon assimilation via cyanobacterial symbiosis and a pyrenoid-based CO2-concentrating mechanism (CCM), respectively. Despite this, hornworts are one of the few plant lineages with limited available genetic tools. Here we report an efficient biolistics method for generating transient-expression and stable transgenic lines in the model hornwort, Anthoceros agrestis. An average of 569 (± 268) cells showed transient expression per bombardment, with green fluorescent protein expression observed within 48-72 hours. A total of 81 stably transformed lines were recovered across three separate experiments, averaging six lines per bombardment. We followed the same method to transiently transform nine additional hornwort species, and obtained stable transformants from one. This method was further used to verify the localization of Rubisco and Rubisco activase in pyrenoids, which are central proteins for CCM function. Together, our biolistics approach offers key advantages over existing methods as it enables rapid transient expression and can be applied to widely diverse hornwort species.

Exploring Cytokine Networks in Resistant Hypertension.

BACKGROUND: Controlling high blood pressure (BP) continues to be a major concern because the associated complications can lead to an increased risk of heart, brain, and kidney disease. Those with hypertension, despite lifestyle and diet modifications and pharmacotherapy, defined as resistant hypertension, are at increased risk for further risk for morbidity and mortality. Understanding inflammation in this population may provide novel avenues for treatment. OBJECTIVES: This study aimed to examine a broad range of cytokines in adults with cardiovascular disease and identify specific cytokines associated with resistant hypertension. METHODS: A secondary data analysis was conducted. The parent study included 156 adults with a history of myocardial infarction within the past 3-7 years and with a multiplex plasma analysis yielding a cytokine panel. A network analysis with lasso penalization for sparsity was performed to explore associations between cytokines and BP. Associated network centrality measures by cytokine were produced, and a community graph was extracted. A sensitivity analysis BP was also performed. RESULTS: Cytokines with larger node strength measures were sTNFR2 and CX3. The graphical network highlighted six cytokines strongly associated with resistant hypertension. Cytokines IL-29 and CCL3 were found to be negatively associated with resistant hypertension, whereas CXCL12, MMP3, sCD163, and sIL6Rb were positively associated with resistant hypertension. DISCUSSION: Understanding the network of associations through exploring oxidative stress and vascular inflammation may provide insight into treatment approaches for resistant hypertension.

Factors Associated with Suicide Risk Behavior Outcomes Among Black High School Adolescents.

There is an urgent need for youth suicide research, particularly among Black adolescents, for whom there have been significant increases over time. This study examines associations between eight covariates and suicide ideation, planning, and attempts among a national sample of Black high school adolescents to inform prevention efforts. Utilizing the 2019 National Youth Risk Behavior Survey data, a sample of N = 6225 Black high school participants was analyzed. A weighted classification tree and network analysis were used to visualize data features, and weighted multinomial ordered logistic regression analyses with multiple imputation pooled using Rubin's rules were performed. Suicide ideation rates of 16% were found in the sample and a higher reported rate of suicide attempts (56%) for those who have reported both ideation and planning. Interpersonal and multilevel factors, including suffering from bullying/cyberbullying, carrying a weapon, or being a sexual minority, were significantly associated with all three suicide behaviors. Findings support an interrelated and multilevel nature of suicide risk factors. Prevention programs for Black adolescents should consider the intersectionality of identities and experiences.

Risk Adjustment of ICD-10-CM Coded Potential Inpatient Complications Using Administrative Data.

OBJECTIVE: To risk-adjust the Potential Inpatient Complication (PIC) measure set and propose a method to identify large deviations between observed and expected PIC counts. DATA SOURCES: Acute inpatient stays from the Premier Healthcare Database from January 1, 2019 to December 31, 2021. STUDY DESIGN: In 2014, the PIC list was developed to identify a broader set of potential complications that can occur as a result of care decisions. Risk adjustment for 111 PIC measures is performed across 3 age-based strata. Using patient-level risk factors and PIC occurrences, PIC-specific probabilities of occurrence are estimated through multivariate logistic regression models. Poisson Binomial cumulative mass function estimates identify deviations between observed and expected PIC counts across levels of patient-visit aggregation. Area under the curve (AUC) estimates are used to demonstrate PIC predictive performance in an 80:20 derivation-validation split framework. DATA COLLECTION/EXTRACTION METHODS: We used N=3,363,149 administrative hospitalizations between 2019 and 2021 from the Premier Healthcare Database. PRINCIPAL FINDINGS: PIC-specific model predictive performance was strong across PICs and age strata. Average area under the curve estimates across PICs were 0.95 (95% CI: 0.93-0.96), 0.91 (95% CI: 0.90-0.93), and 0.90 (95% CI: 0.89-0.91) for the neonate and infant, pediatric, and adult strata, respectively. CONCLUSIONS: The proposed method provides a consistent quality metric that adjusts for the population's case mix. Age-specific risk stratification further addresses currently ignored heterogeneity in PIC prevalence across age groups. Finally, the proposed aggregation method identifies large PIC-specific deviations between observed and expected counts, flagging areas with a potential need for quality improvements.

Red Rubiscos and opportunities for engineering green plants.

Nature's vital, but notoriously inefficient, CO2-fixing enzyme Rubisco often limits the growth of photosynthetic organisms including crop species. Form I Rubiscos comprise eight catalytic large subunits and eight auxiliary small subunits and can be classified into two distinct lineages-'red' and 'green'. While red-type Rubiscos (Form IC and ID) are found in rhodophytes, their secondary symbionts, and certain proteobacteria, green-type Rubiscos (Form IA and IB) exist in terrestrial plants, chlorophytes, cyanobacteria, and other proteobacteria. Eukaryotic red-type Rubiscos exhibit desirable kinetic properties, namely high specificity and high catalytic efficiency, with certain isoforms outperforming green-type Rubiscos. However, it is not yet possible to functionally express a high-performing red-type Rubisco in chloroplasts to boost photosynthetic carbon assimilation in green plants. Understanding the molecular and evolutionary basis for divergence between red- and green-type Rubiscos could help us to harness the superior CO2-fixing power of red-type Rubiscos. Here we review our current understanding about red-type Rubisco distribution, biogenesis, and sequence-structure, and present opportunities and challenges for utilizing red-type Rubisco kinetics towards crop improvements.

Group brief cognitive behavioral therapy for suicide prevention compared to dialectal behavior therapy skills group for military service members: a study protocol of a randomized controlled trial.

BACKGROUND: Suicide is a pressing matter for the military. Not only does it pose a health risk, but suicide also compromises operational readiness. Despite provision of suicide prevention clinical best practices, the Department of Defense suffers several challenges (e.g., clinician shortages) limiting the agency's ability to effectively respond to service member suicide. Implementation of evidence-based suicide-specific group therapy is a possible solution to service member well-being needs and system challenges. Service members can also gain coping skills useful beyond managing suicidal thoughts and behaviors. METHODS: This 2-arm non-inferiority randomized controlled trial compares a group therapy format of Brief Cognitive Behavioral Therapy (i.e., G-BCBT) with Dialectical Behavior Therapy (DBT) Skills Group. Both therapies are delivered in-person at a United States Naval Medical Center. Participants (N = 136) are active-duty service members with recent suicidal thoughts or suicidal behavior. Evaluation features electronically delivered questionnaires at baseline, after each treatment session, and at 3- and 6-month follow-up. DISCUSSION: The primary outcome concerns G-BCBT impacts on suicidal ideation. Secondary outcomes of interest are suicide attempt, psychological distress (e.g., symptoms of depression, anxiety), and self-regulatory skills (e.g., emotion regulation). We also examine self-regulatory skills as treatment moderators. Clinical trial strengths and limitations are reviewed. TRIAL REGISTRATION: This study was registered at Clinicaltrials.gov (protocol NCT05401838).

Physical and mental health of informal caregivers before and during the COVID-19 pandemic in the United States.

BACKGROUND: Informal caregiving, a common form of social support, can be a chronic stressor with health consequences for caregivers. It is unclear how varying restrictions during the COVID-19 pandemic affected caregivers' physical and mental health. This study explores pre-post March 2020 differences in reported days of poor physical and mental health among informal caregivers. METHODS: Data from the 2019/2020 Behavioral Risk Factor Surveillance System survey were used to match, via propensity scores, informal caregivers who provided care during COVID-19 restrictions to those who provided care before the pandemic. Negative binomial weighted regression models estimated incidence rate ratios (IRRs) and differences by demographics of reporting days of poor physical and mental health. A sensitivity analysis including multiple imputation was also performed. RESULTS: The sample included 9,240 informal caregivers, of whom 861 provided care during the COVID-19 pandemic. The incidence rate for days of poor physical health was 26% lower (p = 0.001) for those who provided care during the COVID-19 pandemic, though the incidence rates for days of poor mental health were not statistically different between groups. Informal caregivers with low educational attainment experienced significantly higher IRRs for days of poor physical and mental health. Younger informal caregivers had a significantly lower IRR for days of poor physical health, but higher IRR for days of poor mental health. CONCLUSIONS: This study contends that the physical and mental health burden associated with informal caregiving in a period of great uncertainty may be heightened among certain populations. Policymakers should consider expanding access to resources through institutional mechanisms for informal caregivers, who may be likely to incur a higher physical and mental health burden during public health emergencies, especially those identified as higher risk.

The dependency of red Rubisco on its cognate activase for enhancing plant photosynthesis and growth.

Plant photosynthesis and growth are often limited by the activity of the CO2-fixing enzyme Rubisco. The broad kinetic diversity of Rubisco in nature is accompanied by differences in the composition and compatibility of the ancillary proteins needed for its folding, assembly, and metabolic regulation. Variations in the protein folding needs of catalytically efficient red algae Rubisco prevent their production in plants. Here, we show this impediment does not extend to Rubisco from Rhodobacter sphaeroides (RsRubisco)-a red-type Rubisco able to assemble in plant chloroplasts. In transplastomic tobRsLS lines expressing a codon optimized Rs-rbcLS operon, the messenger RNA (mRNA) abundance was ∼25% of rbcL transcript and RsRubisco ∼40% the Rubisco content in WT tobacco. To mitigate the low activation status of RsRubisco in tobRsLS (∼23% sites active under ambient CO2), the metabolic repair protein RsRca (Rs-activase) was introduced via nuclear transformation. RsRca production in the tobRsLS::X progeny matched endogenous tobacco Rca levels (∼1 µmol protomer·m2) and enhanced RsRubisco activation to 75% under elevated CO2 (1%, vol/vol) growth. Accordingly, the rate of photosynthesis and growth in the tobRsLS::X lines were improved >twofold relative to tobRsLS. Other tobacco lines producing RsRubisco containing alternate diatom and red algae S-subunits were nonviable as CO2-fixation rates (kcatc) were reduced >95% and CO2/O2 specificity impaired 30-50%. We show differences in hybrid and WT RsRubisco biogenesis in tobacco correlated with assembly in Escherichia coli advocating use of this bacterium to preevaluate the kinetic and chloroplast compatibility of engineered RsRubisco, an isoform amenable to directed evolution.

Estimation of recurrent atherosclerotic cardiovascular event risk in patients with established cardiovascular disease: the updated SMART2 algorithm.

AIMS: The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations. METHODS AND RESULTS: Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2-12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] in BACS/BAMI to 0.772 (95% CI 0.659-0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options. CONCLUSION: The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk.

County-Level Sociodemographic Factors Associated with COVID-19 Incidence and Mortality in North and South Carolina.

BACKGROUND There is limited research regarding associations between county-level factors and COVID-19 incidence and mortality. While the Carolinas are geographically connected, they are not homogeneous, with statewide political and intra-state socioeconomic differences leading to heterogeneous spread between and within states.METHODS Infection and mortality data from Johns Hopkins University during the 7 months since the first reported case in the Carolinas was combined with county-level socioeconomic/demographic factors. Time series imputations were performed whenever county-level reported infections were implausible. Multivariate Poisson regression models were fitted to extract incidence (infection and mortality) rate ratios by county-level factor. State-level differences in filtered trends were also calculated. Geospatial maps and Kaplan-Meier curves were constructed stratifying by median county-level factor. Differences between North and South Carolina were identified.RESULTS Incidence and mortality rates were lower in North Carolina than South Carolina. Statistically significant higher incidence and mortality rates were associated with counties in both states with higher proportions of Black/African American populations and those without health insurance aged < 65 years. Counties with larger populations aged ≥ 75 years were associated with increased mortality (but decreased incidence) rates.LIMITATIONS COVID-19 data contained multiple inconsistencies, so imputation was needed, and covariate-based data was not synchronous and potentially insufficient in granularity given the epidemiology of the disease. County-level analyses imply within-county homogeneity, an assumption increasingly breached by larger counties.CONCLUSION While statewide interventions were initially implemented, inter-county racial/ethnic and socioeconomic variability points to the need for more heterogeneous interventions, including policies, as populations within particular counties may be at higher risk.

Associations between attainment of incentivised primary care indicators and incident diabetic retinopathy in England: a population-based historical cohort study.

BACKGROUND: The associations between England's incentivised primary care-based diabetes prevention activities and hard clinical endpoints remain unclear. We aimed to examine the associations between attainment of primary care indicators and incident diabetic retinopathy (DR) among people with type 2 diabetes. METHODS: A historical cohort (n = 60,094) of people aged ≥ 18 years with type 2 diabetes and no DR at baseline was obtained from the UK Clinical Practice Research Datalink (CPRD). Exposures included attainment of the Quality and Outcomes Framework (QOF) HbA1c (≤ 7.5% or 59 mmol/mol), blood pressure (≤ 140/80 mmHg), and cholesterol (≤ 5 mmol/L) indicators, and number of National Diabetes Audit (NDA) care processes completed (categorised as 0-3, 4-6, or 7-9), in 2010-2011. Outcomes were time to development of DR and sight-threatening diabetic retinopathy (STDR). Nearest neighbour propensity score matching was undertaken and Cox proportional hazards models then fitted using the matched samples. Concordance statistics were calculated for each model. RESULTS: 8263 DR and 832 STDR diagnoses were observed over mean follow-up periods of 3.5 (SD 2.1) and 3.8 (SD 2.0) years, respectively. HbA1c and blood pressure (BP) indicator attainment were associated with lower rates of DR (adjusted hazard ratios (aHRs) 0.94 (95% CI 0.89-0.99) and 0.87 (0.83-0.92), respectively), whereas cholesterol indicator attainment was not (aHR 1.03 (0.97-1.10)). All QOF indicators were associated with lower rates of STDR (aHRs 0.74 (0.62-0.87) for HbA1c, 0.78 (0.67-0.91) for BP, and 0.82 (0.67-0.99) for cholesterol). Completion of 7-9 vs. 0-3 NDA processes was associated with fewer STDR diagnoses (aHR 0.72 (0.55-0.94)). CONCLUSIONS: Attainment of key primary care indicators is associated with lower incidence of DR and STDR among patients with type 2 diabetes in England.

Associations between attainment of incentivized primary care indicators and incident sight-threatening diabetic retinopathy in England: A population-based historical cohort study.

AIM: To examine the impact of attainment of primary care diabetes clinical indicators on progression to sight-threatening diabetic retinopathy (STDR) among those with mild non-proliferative diabetic retinopathy (NPDR). MATERIALS AND METHODS: An historical cohort study of 18,978 adults (43.63% female) diagnosed with type 2 diabetes before 1 April 2010 and mild NPDR before 1 April 2011 was conducted. The data were obtained from the UK Clinical Practice Research Datalink during 2010-2017, provided by 330 primary care practices in England. Exposures included attainment of the Quality and Outcomes Framework HbA1c (≤59 mmol/mol [≤7.5%]), blood pressure (≤140/80 mmHg) and cholesterol (≤5 mmol/L) indicators in the financial year 2010-2011, as well as the number of National Diabetes Audit processes completed in 2010-2011. The outcome was time to incident STDR. Nearest neighbour propensity score matching was undertaken, and univariable and multivariable Cox proportional hazards models were then fitted using the matched samples. Concordance statistics were calculated for each model. RESULTS: A total of 1037 (5.5%) STDR diagnoses were observed over a mean follow-up of 3.6 (SD 2.0) years. HbA1c, blood pressure and cholesterol indicator attainment were associated with lower rates of STDR (adjusted hazard ratios [95% CI] 0.64 [0.55-0.74; p < .001], 0.83 [0.72-0.94; p = .005] and 0.80 [0.66-0.96; p = .015], respectively). CONCLUSIONS: Our findings provide support for meeting appropriate indicators for the management of type 2 diabetes in primary care to bring a range of benefits, including improved health outcomes-such as a reduction in the risk of STDR-for people with type 2 diabetes.

The impact of the Luton social prescribing programme on mental well-being: a quantitative before-and-after study.

BACKGROUND: Social prescribing programmes expand the range of options available to primary care health professionals to address patients' psychosocial needs, impacting on their health and well-being. The objective of this study was to assess the change in the mental well-being of service users after participation in the Luton social prescribing programme. METHODS: Skew-normal (SN) regression was applied to analyse the change in mental well-being post-intervention (N = 63). The short Warwick-Edinburgh mental well-being scale was used as the outcome measure. RESULTS: The SN regression found a statistically significant change (P < 0.0001) in the average difference score between baseline and post-intervention measures. However, the observed change does not appear to be of clinical relevance. No significant associations in mental well-being scores by gender, age or working status were found. CONCLUSION: Findings of this study indicate that social prescribing may have the potential to improve the mental well-being of service users. The study findings contribute to the sparse evidence base on social prescribing outcomes by socio-demographic characteristics of participants and highlight the importance of considering subgroup analysis in future research.

Testing a multicomponent lifestyle intervention for combatting childhood obesity.

BACKGROUND: Childhood obesity is a major global health concern. Weight-management camps involving delivery of a program of physical activity, health education, and healthy eating are an effective treatment, although post-intervention weight-management is less well understood. Our objective was to assess the effectiveness of a weight-management camp followed by a community intervention in supporting weight-management for overweight children and children with obesity. METHODS: Participants were overweight Qatari schoolchildren or schoolchildren with obesity, ages 8-14 years, (n = 300) recruited over a three-year period across 14 randomly selected schools in the Doha area. They attended a two-week weight management camp, then a 10-week program of weekly lifestyle education and physical activity sessions, which also included behavior change techniques. The programme was cognitive behavioural therapy (CBT)-focused with a strong element of behavioural economics blended in. RESULTS: Participants saw a significant BMI SDS reduction as a result of the entire intervention (camp + education and activity sessions) both at the individual (p < 0.0001) and cluster/school (p = 0.0002) levels, and weight loss occurred during each intervention stage separately for the camp (p < 0.0001 for both the individual and cluster/school levels) and the lifestyle education and activity phase (p < 0.0001 and p = 0.0220 at the individual and cluster/school levels, respectively). CONCLUSIONS: Weekly lifestyle education and activity sessions which include behavior change techniques may be useful in promoting continued weight management in the period following intensive, immersive childhood obesity interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02972164 , November 23, 2016.

A unique structural domain in Methanococcoides burtonii ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) acts as a small subunit mimic.

The catalytic inefficiencies of the CO2-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) often limit plant productivity. Strategies to engineer more efficient plant Rubiscos have been hampered by evolutionary constraints, prompting interest in Rubisco isoforms from non-photosynthetic organisms. The methanogenic archaeon Methanococcoides burtonii contains a Rubisco isoform that functions to scavenge the ribulose-1,5-bisphosphate (RuBP) by-product of purine/pyrimidine metabolism. The crystal structure of M. burtonii Rubisco (MbR) presented here at 2.6 Å resolution is composed of catalytic large subunits (LSu) assembled into pentamers of dimers, (L2)5, and differs from Rubiscos from higher plants where LSus are glued together by small subunits (SSu) into hexadecameric L8S8 enzymes. MbR contains a unique 29-amino acid insertion near the C terminus, which folds as a separate domain in the structure. This domain, which is visualized for the first time in this study, is located in a similar position to SSus in L8S8 enzymes between LSus of adjacent L2 dimers, where negatively charged residues coordinate around a Mg2+ ion in a fashion that suggests this domain may be important for the assembly process. The Rubisco assembly domain is thus an inbuilt SSu mimic that concentrates L2 dimers. MbR assembly is ligand-stimulated, and we show that only 6-carbon molecules with a particular stereochemistry at the C3 carbon can induce oligomerization. Based on MbR structure, subunit arrangement, sequence, phylogenetic distribution, and function, MbR and a subset of Rubiscos from the Methanosarcinales order are proposed to belong to a new Rubisco subgroup, named form IIIB.

Light therapies for acne.

BACKGROUND: Acne vulgaris is a very common skin problem that presents with blackheads, whiteheads, and inflamed spots. It frequently results in physical scarring and may cause psychological distress. The use of oral and topical treatments can be limited in some people due to ineffectiveness, inconvenience, poor tolerability or side-effects. Some studies have suggested promising results for light therapies. OBJECTIVES: To explore the effects of light treatment of different wavelengths for acne. SEARCH METHODS: We searched the following databases up to September 2015: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We searched ISI Web of Science and Dissertation Abstracts International (from inception). We also searched five trials registers, and grey literature sources. We checked the reference lists of studies and reviews and consulted study authors and other experts in the field to identify further references to relevant randomised controlled trials (RCTs). We updated these searches in July 2016 but these results have not yet been incorporated into the review. SELECTION CRITERIA: We included RCTs of light for treatment of acne vulgaris, regardless of language or publication status. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 71 studies, randomising a total of 4211 participants.Most studies were small (median 31 participants) and included participants with mild to moderate acne of both sexes and with a mean age of 20 to 30 years. Light interventions differed greatly in wavelength, dose, active substances used in photodynamic therapy (PDT), and comparator interventions (most commonly no treatment, placebo, another light intervention, or various topical treatments). Numbers of light sessions varied from one to 112 (most commonly two to four). Frequency of application varied from twice daily to once monthly.Selection and performance bias were unclear in the majority of studies. Detection bias was unclear for participant-assessed outcomes and low for investigator-assessed outcomes in the majority of studies. Attrition and reporting bias were low in over half of the studies and unclear or high in the rest. Two thirds of studies were industry-sponsored; study authors either reported conflict of interest, or such information was not declared, so we judged the risk of bias as unclear.Comparisons of most interventions for our first primary outcome 'Participant's global assessment of improvement' were not possible due to the variation in the interventions and the way the studies' outcomes were measured. We did not combine the effect estimates but rated the quality of the evidence as very low for the comparison of light therapies, including PDT to placebo, no treatment, topical treatment or other comparators for this outcome. One study which included 266 participants with moderate to severe acne showed little or no difference in effectiveness for this outcome between 20% aminolevulinic acid (ALA)-PDT (activated by blue light) versus vehicle plus blue light (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.72 to 1.04, low-quality evidence). A study (n = 180) of a comparison of ALA-PDT (activated by red light) concentrations showed 20% ALA was no more effective than 15% (RR 1.05, 95% CI 0.96 to 1.15) but better than 10% ALA (RR 1.22, 95% CI 1.05 to 1.42) and 5% ALA (RR 1.47, 95% CI 1.19 to 1.81). The number needed to treat for an additional beneficial outcome (NNTB) was 6 (95% CI 3 to 19) and 4 (95% CI 2 to 6) for the comparison of 20% ALA with 10% and 5% ALA, respectively.For our second primary outcome 'Investigator-assessed changes in lesion counts', we combined three RCTs, with 360 participants with moderate to severe acne and found methyl aminolevulinate (MAL) PDT (activated by red light) was no different to placebo cream plus red light with regard to change in inflamed lesions (ILs) (mean difference (MD) -2.85, 95% CI -7.51 to 1.81), percentage change in ILs (MD -10.09, 95% CI -20.25 to 0.06), change in non-inflamed lesions (NILs) (MD -2.01, 95% CI -7.07 to 3.05), or in percentage change in NILs (MD -8.09, 95% CI -21.51 to 5.32). We assessed the evidence as moderate quality for these outcomes meaning that there is little or no clinical difference between these two interventions for lesion counts.Studies comparing the effects of other interventions were inconsistent or had small samples and high risk of bias. We performed only narrative synthesis for the results of the remaining trials, due to great variation in many aspects of the studies, poor reporting, and failure to obtain necessary data. Several studies compared yellow light to placebo or no treatment, infrared light to no treatment, gold microparticle suspension to vehicle, and clindamycin/benzoyl peroxide combined with pulsed dye laser to clindamycin/benzoyl peroxide alone. There were also several other studies comparing MAL-PDT to light-only treatment, to adapalene and in combination with long-pulsed dye laser to long-pulsed dye laser alone. None of these showed any clinically significant effects.Our third primary outcome was 'Investigator-assessed severe adverse effects'. Most studies reported adverse effects, but not adequately with scarring reported as absent, and blistering reported only in studies on intense pulsed light, infrared light and photodynamic therapies. We rated the quality of the evidence as very low, meaning we were uncertain of the adverse effects of the light therapies.Although our primary endpoint was long-term outcomes, less than half of the studies performed assessments later than eight weeks after final treatment. Only a few studies assessed outcomes at more than three months after final treatment, and longer-term assessments are mostly not covered in this review. AUTHORS' CONCLUSIONS: High-quality evidence on the use of light therapies for people with acne is lacking. There is low certainty of the usefulness of MAL-PDT (red light) or ALA-PDT (blue light) as standard therapies for people with moderate to severe acne.Carefully planned studies, using standardised outcome measures, comparing the effectiveness of common acne treatments with light therapies would be welcomed, together with adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.

Automated telephone communication systems for preventive healthcare and management of long-term conditions.

BACKGROUND: Automated telephone communication systems (ATCS) can deliver voice messages and collect health-related information from patients using either their telephone's touch-tone keypad or voice recognition software. ATCS can supplement or replace telephone contact between health professionals and patients. There are four different types of ATCS: unidirectional (one-way, non-interactive voice communication), interactive voice response (IVR) systems, ATCS with additional functions such as access to an expert to request advice (ATCS Plus) and multimodal ATCS, where the calls are delivered as part of a multicomponent intervention. OBJECTIVES: To assess the effects of ATCS for preventing disease and managing long-term conditions on behavioural change, clinical, process, cognitive, patient-centred and adverse outcomes. SEARCH METHODS: We searched 10 electronic databases (the Cochrane Central Register of Controlled Trials; MEDLINE; Embase; PsycINFO; CINAHL; Global Health; WHOLIS; LILACS; Web of Science; and ASSIA); three grey literature sources (Dissertation Abstracts, Index to Theses, Australasian Digital Theses); and two trial registries (www.controlled-trials.com; www.clinicaltrials.gov) for papers published between 1980 and June 2015. SELECTION CRITERIA: Randomised, cluster- and quasi-randomised trials, interrupted time series and controlled before-and-after studies comparing ATCS interventions, with any control or another ATCS type were eligible for inclusion. Studies in all settings, for all consumers/carers, in any preventive healthcare or long term condition management role were eligible. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods to select and extract data and to appraise eligible studies. MAIN RESULTS: We included 132 trials (N = 4,669,689). Studies spanned across several clinical areas, assessing many comparisons based on evaluation of different ATCS types and variable comparison groups. Forty-one studies evaluated ATCS for delivering preventive healthcare, 84 for managing long-term conditions, and seven studies for appointment reminders. We downgraded our certainty in the evidence primarily because of the risk of bias for many outcomes. We judged the risk of bias arising from allocation processes to be low for just over half the studies and unclear for the remainder. We considered most studies to be at unclear risk of performance or detection bias due to blinding, while only 16% of studies were at low risk. We generally judged the risk of bias due to missing data and selective outcome reporting to be unclear.For preventive healthcare, ATCS (ATCS Plus, IVR, unidirectional) probably increase immunisation uptake in children (risk ratio (RR) 1.25, 95% confidence interval (CI) 1.18 to 1.32; 5 studies, N = 10,454; moderate certainty) and to a lesser extent in adolescents (RR 1.06, 95% CI 1.02 to 1.11; 2 studies, N = 5725; moderate certainty). The effects of ATCS in adults are unclear (RR 2.18, 95% CI 0.53 to 9.02; 2 studies, N = 1743; very low certainty).For screening, multimodal ATCS increase uptake of screening for breast cancer (RR 2.17, 95% CI 1.55 to 3.04; 2 studies, N = 462; high certainty) and colorectal cancer (CRC) (RR 2.19, 95% CI 1.88 to 2.55; 3 studies, N = 1013; high certainty) versus usual care. It may also increase osteoporosis screening. ATCS Plus interventions probably slightly increase cervical cancer screening (moderate certainty), but effects on osteoporosis screening are uncertain. IVR systems probably increase CRC screening at 6 months (RR 1.36, 95% CI 1.25 to 1.48; 2 studies, N = 16,915; moderate certainty) but not at 9 to 12 months, with probably little or no effect of IVR (RR 1.05, 95% CI 0.99, 1.11; 2 studies, 2599 participants; moderate certainty) or unidirectional ATCS on breast cancer screening.Appointment reminders delivered through IVR or unidirectional ATCS may improve attendance rates compared with no calls (low certainty). For long-term management, medication or laboratory test adherence provided the most general evidence across conditions (25 studies, data not combined). Multimodal ATCS versus usual care showed conflicting effects (positive and uncertain) on medication adherence. ATCS Plus probably slightly (versus control; moderate certainty) or probably (versus usual care; moderate certainty) improves medication adherence but may have little effect on adherence to tests (versus control). IVR probably slightly improves medication adherence versus control (moderate certainty). Compared with usual care, IVR probably improves test adherence and slightly increases medication adherence up to six months but has little or no effect at longer time points (moderate certainty). Unidirectional ATCS, compared with control, may have little effect or slightly improve medication adherence (low certainty). The evidence suggested little or no consistent effect of any ATCS type on clinical outcomes (blood pressure control, blood lipids, asthma control, therapeutic coverage) related to adherence, but only a small number of studies contributed clinical outcome data.The above results focus on areas with the most general findings across conditions. In condition-specific areas, the effects of ATCS varied, including by the type of ATCS intervention in use.Multimodal ATCS probably decrease both cancer pain and chronic pain as well as depression (moderate certainty), but other ATCS types were less effective. Depending on the type of intervention, ATCS may have small effects on outcomes for physical activity, weight management, alcohol consumption, and diabetes mellitus. ATCS have little or no effect on outcomes related to heart failure, hypertension, mental health or smoking cessation, and there is insufficient evidence to determine their effects for preventing alcohol/substance misuse or managing illicit drug addiction, asthma, chronic obstructive pulmonary disease, HIV/AIDS, hypercholesterolaemia, obstructive sleep apnoea, spinal cord dysfunction or psychological stress in carers.Only four trials (3%) reported adverse events, and it was unclear whether these were related to the interventions. AUTHORS' CONCLUSIONS: ATCS interventions can change patients' health behaviours, improve clinical outcomes and increase healthcare uptake with positive effects in several important areas including immunisation, screening, appointment attendance, and adherence to medications or tests. The decision to integrate ATCS interventions in routine healthcare delivery should reflect variations in the certainty of the evidence available and the size of effects across different conditions, together with the varied nature of ATCS interventions assessed. Future research should investigate both the content of ATCS interventions and the mode of delivery; users' experiences, particularly with regard to acceptability; and clarify which ATCS types are most effective and cost-effective.

Transtheoretical model stages of change for dietary and physical exercise modification in weight loss management for overweight and obese adults.

BACKGROUND: Obesity is a global public health threat. The transtheoretical stages of change (TTM SOC) model has long been considered a useful interventional approach in lifestyle modification programmes, but its effectiveness in producing sustainable weight loss in overweight and obese individuals has been found to vary considerably.  OBJECTIVES: To assess the effectiveness of dietary intervention or physical activity interventions, or both, and other interventions based on the transtheoretical model (TTM) stages of change (SOC) to produce sustainable (one year and longer) weight loss in overweight and obese adults. SEARCH METHODS: Studies were obtained from searches of multiple electronic bibliographic databases. We searched The Cochrane Library, MEDLINE, EMBASE and PsycINFO. The date of the last search, for all databases, was 17 December 2013. SELECTION CRITERIA: Trials were included if they fulfilled the criteria of randomised controlled clinical trials (RCTs) using the TTM SOC as a model, that is a theoretical framework or guideline in designing lifestyle modification strategies, mainly dietary and physical activity interventions, versus a comparison intervention of usual care; one of the outcome measures of the study was weight loss, measured as change in weight or body mass index (BMI); participants were overweight or obese adults only; and the intervention was delivered by healthcare professionals or trained lay people at the hospital and community level, including at home. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data, assessed studies for risk of bias and evaluated overall study quality according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). We resolved disagreements by discussion or consultation with a third party. A narrative, descriptive analysis was conducted for the systematic review. MAIN RESULTS: A total of three studies met the inclusion criteria, allocating 2971 participants to the intervention and control groups. The total number of participants randomised to the intervention groups was 1467, whilst 1504 were randomised to the control groups. The length of intervention was 9, 12 and 24 months in the different trials. The use of TTM SOC in combination with diet or physical activity, or both, and other interventions in the included studies produced inconclusive evidence that TTM SOC interventions led to sustained weight loss (the mean difference between intervention and control groups varied from 2.1 kg to 0.2 kg at 24 months; 2971 participants; 3 trials; low quality evidence). Following application of TTM SOC there were improvements in physical activity and dietary habits, such as increased exercise duration and frequency, reduced dietary fat intake and increased fruit and vegetable consumption (very low quality evidence). Weight gain was reported as an adverse event in one of the included trials. None of the trials reported health-related quality of life, morbidity, or economic costs as outcomes. The small number of studies and their variable methodological quality limit the applicability of the findings to clinical practice. The main limitations include inadequate reporting of outcomes and the methods for allocation, randomisation and blinding; extensive use of self-reported measures to estimate the effects of interventions on a number of outcomes, including weight loss, dietary consumption and physical activity levels; and insufficient assessment of sustainability due to lack of post-intervention assessments. AUTHORS' CONCLUSIONS: The evidence to support the use of TTM SOC in weight loss interventions is limited by risk of bias and imprecision, not allowing firm conclusions to be drawn. When combined with diet or physical activity, or both, and other interventions we found very low quality evidence that it might lead to better dietary and physical activity habits. This systematic review highlights the need for well-designed RCTs that apply the principles of the TTM SOC appropriately to produce conclusive evidence about the effect of TTM SOC lifestyle interventions on weight loss and other health outcomes.

Factors Associated With Suicide Risk Behavior Outcomes Among Black Middle School Adolescents.

OBJECTIVE: Early adolescent self-identifying Black youth present with high rates of suicidality. This study assesses associations among 7 explanatory variables (sex, weapon carrying, weight perceptions, grades, grade level, bullying at school, and cyberbullying) and suicide ideation, planning, and attempts, and identifies associations with suicidality as a composite measure among a sample of Black middle school adolescents (BMSA) in the United States. METHOD: Data were extracted from the 2019 Middle School Youth Risk Behavior Survey. Descriptive statistics were calculated, and associations between suicide ideation, planning, and attempts were explored. A network graphical representation of polychoric and tetrachoric correlations across suicidality outcomes and explanatory variables was performed. A multivariable, multinomial logistic regression model estimated associations among explanatory variables and suicide ideation (with and without planning) and planning (with and without ideation). Both suicide attempt and a composite suicidality metric were explored using independent logistic models with multiple imputation. RESULTS: The sample included 7,643 self-identifying BMSA. Our findings indicate that approximately 28% reported suicidality. Prevalence rates were found of about 1 in 4 BMSA for suicidal ideation, 1 in 6 for suicidal planning, and 1 in 10 for attempting suicide. Female BMSA, victims of cyberbullying, and BMSA carrying a weapon experienced significantly higher odds of all suicidality outcome measures. CONCLUSION: Practical implications for identifying and screening suicidality among BMSA to guide suicide prevention efforts are necessary. Findings validate the need for informed cultural approaches to suicide screening and prevention efforts to reduce suicide risk outcomes, especially when identifiable environmental factors are strongly associated with those outcomes. DIVERSITY AND INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list.

Difference in the physical and mental health of informal caregivers pre- and post-COVID-19 National Emergency Declaration in the United States.

Background: The burden of informal caregiving represents a chronic stressor for the informal caregivers (ICs). The study investigates differences in the physical and mental health of ICs and that of non-informal caregivers before and during COVID-19. Methods: We used data from the 2019/2020 Behavioral Risk Factor Surveillance System (BRFSS) to investigate differences in the rates of days of poor physical and mental health among ICs compared to non-informal caregivers before and after the COVID-19 National Emergency Declaration (NED). A propensity score model simulated a pseudo experimental design, comparing ICs ("treated") with non-informal caregivers ("control"). A difference-in-difference regression model estimated the incidence rate ratios for days of poor physical and mental health as a function of IC status and time of care provision. Results: A total of 44,583 respondents were identified with valid responses on informal caregiving status and key sociodemographic characteristics. Of those, 6.24% (n = 3073) were ICs, matched against 15,365 non-informal caregivers. In the matched sample (n = 18,848), the incidence rate for days of poor physical health among ICs was 17% (p = 0.003) higher compared to non-informal caregivers. The incidence rate for days of poor physical health was 23% (p < 0.001) lower in the post-NED compared to the pre-NED periods. The incidence rate for days of poor mental health was 44% (p < 0.001) higher among ICs compared to non-informal caregivers and 22% higher among respondents who took the survey post-NED compared to those who answered during the pre-NED period. No statistically significant differences were found between the two groups in their incidence rates for days of poor physical and mental health from the pre-to the post-NED period. Conclusion: These findings suggest a need to balance between the benefits conferred by public health restrictions versus the mental health burden that may result among certain groups, including ICs, who experience higher negative mental health outcomes.