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Abstract Microtubule-associated protein tau (MAPT/tau) accumulates in a family of neurodegenerative diseases, including Alzheimer’s disease (AD). In disease, tau is aberrantly modified by post-translational modifications (PTMs), including hyper-phosphorylation. However, it is often unclear which of these PTMs contribute to tau’s accumulation or what mechanisms might be involved. To explore these questions, we focus on a cleaved proteoform of tau (tauC3), which selectively accumulates in AD and was recently shown to be degraded by its direct binding to the E3 ubiquitin ligase, CHIP. Here, we find that phosphorylation of tauC3 at a single residue, pS416, is sufficient to weaken its interaction with CHIP. A co-crystal structure of CHIP bound to the C-terminus of tauC3 reveals the mechanism of this clash, allowing design of a mutation (CHIPD134A) that partially restores binding and turnover of pS416 tauC3. We confirm that, in our models, pS416 is produced by the known AD-associated kinase, MARK2/Par-1b, providing a potential link to disease. In further support of this idea, an antibody against pS416 co-localizes with tauC3 in degenerative neurons within the hippocampus of AD patients. Together, these studies suggest a molecular mechanism for how phosphorylation at a discrete site contributes to accumulation of a tau proteoform.

Background: Systemic juvenile idiopathic arthritis (sJIA) is marked with arthritis and several features of systemic inflammation, including fever, rashes, hepatosplenomegaly, lymphadenopathy, and serositis. Interleukin-1 receptor blockers have been used as one of the most effective biologics for the treatment of resistant types of disease. The main purpose of this study was to evaluate the safety and efficacy of PerkinRA in comparison with Kineret in patients with sJIA. Methods: This was a double-blind, randomized clinical trial conducted on 72 patients with sJIA. The patients were enrolled based on the 2018 International League of Associations for Rheumatology criteria and were treated at the outpatient clinic of Mofid Children’s Hospital, Pediatric Medical Center, and four other centers between February 2020 and March 2021. Patients were randomly assigned in a 1:1 ratio to one of two treatment groups: one group received PerkinRA (manufactured by Persis Gene, n = 36), while the other group received Kineret (manufactured by SOBI, n = 36). The primary outcome measure was the proportion of patients achieving an American College of Rheumatology (ACR) 30, ACR 50, and ACR 70 response. Secondary outcomes included changes in vital signs, incidence of adverse events, clinical laboratory assessments, and findings from physical examinations. These parameters were evaluated at 1, 2, 4, 8, 12, 16, 20, and 24 weeks after the first injection, and the two treatment groups were compared. Results: A total of 35 patients in the PerkinRA group and 32 patients in the Kineret group were included in the final analysis. The results showed no clinically significant differences between the two treatment groups. Patients in both the PerkinRA and Kineret groups achieved similar proportions of ACR 30, ACR 50, and ACR 70 responses over the 6-month evaluation period. Conclusion: Based on the findings of this study, the two investigational medications, PerkinRA and Kineret, demonstrated comparable efficacy in the treatment of sJIA. The two treatment groups showed no significant differences in the primary and secondary outcomes assessed. Therefore, it can be concluded that PerkinRA and Kineret are noninferior to each other for the management of sJIA.

BACKGROUND: Entrustable Professional Activities (EPA) and competencies represent components of a competency-based education framework. EPAs are assessed based on the level of supervision (LOS) necessary to perform the activity safely and effectively. The broad competencies, broken down into narrower subcompetencies, are assessed using milestones, observable behaviors of ones abilities along a developmental spectrum. Integration of the two methods, accomplished by mapping the most relevant subcompetencies to each EPA, may provide a cross check between the two forms of assessment and uncover those subcompetencies that have the greatest influence on the EPA assessment. OBJECTIVES: We hypothesized that 1) there would be a strong correlation between EPA LOS ratings with the milestone levels for the subcompetencies mapped to the EPA; 2) some subcompetencies would be more critical in determining entrustment decisions than others, and 3) the correlation would be weaker if the analysis included only milestones reported to the Accreditation Council for Graduate Medical Education (ACGME). METHODS: In fall 2014 and spring 2015, the Subspecialty Pediatrics Investigator Network asked Clinical Competency Committees to assign milestone levels to each trainee enrolled in a pediatric fellowship for all subcompetencies mapped to 6 Common Pediatric Subspecialty EPAs as well as provide a rating for each EPA based upon a 5-point LOS scale. RESULTS: One-thousand forty fellows were assessed in fall and 1048 in spring, representing about 27% of all fellows. For each EPA and in both periods, the average milestone level was highly correlated with LOS (rho range 0.59-0.74; p  0.05). CONCLUSIONS: We found a strong relationship between milestone level and EPA LOS rating but no difference if the subcompetencies were weighted, or if only milestones reported to the ACGME were used. Our results suggest that representative behaviors needed to effectively perform the EPA, such as key subcompetencies and milestones, allow for future language adaptations while still supporting the current model of assessment. In addition, these data provide additional validity evidence for using these complementary tools in building a program of assessment.

BackgroundCholera outbreaks are surging worldwide. Growing research supports case-area targeted interventions (CATIs), whereby teams provide a package of interventions to case and neighboring households, as an effective strategy in cholera outbreak control, particularly in humanitarian settings. While research exists on individual CATI interventions, research gaps exist on outcomes of integrated interventions during CATI responses.Methodology/principal findingsWe conducted a prospective observational cohort study on CATIs during the 2021 cholera outbreak in Northeast Nigeria. During CATI response in Borno, Adamawa, and Yobe, research enumerators accompanied CATI teams to households and observed interventions (including provision of soap, Aquatabs, educational materials, and jerrycans; latrine and bedding disinfection; and hygiene promotion) and collected data on demographics, existing household water, sanitation, and hygiene, and household water free chlorine residual (FCR). Enumerators returned to households 10-14 days later to conduct follow-up surveys. We tested differences in reported delivery and receipt of interventions, and household drinking water FCR concentrations before and after CATIs. We also analyzed the associated relationship between CATI and environmental factors and odds of FCR Conclusions/significanceThese findings suggest that CATIs improved household drinking water FCR, a key protective measure against cholera, in Northeast Nigeria. Our research highlights factors associated with FCR concentrations

Pneumonia is the leading cause of death in children globally. In low- and middle-income countries (LMICs) pneumonia diagnosis relies on accurate assessment of respiratory rate, which can be unreliable when completed by nurses with less-advanced training. To inform more accurate measurements, we investigate the repeatability of the RRate app used by nurses in Ugandan district hospitals. This secondary analysis included 3,679 children aged 0-5 years. The dataset had two sequential measurements of respiratory rate collected by 14 nurses using the RRate app. We measured agreement between respiratory rate observations while indicating observations' clustering around WHO fast-breathing thresholds. WHO thresholds are 60 breaths per minute (bpm) for under two months (Age-1), 50 bpm for two to 12 months (Age-2), and 40 bpm for 12.1 to 60 months (Age-3). We assessed the repeatability of the paired measurements per user through the Intraclass Correlation Coefficient (ICC) and calculated an overall ICC value. The respiratory rate measurement took less than 15 seconds for 7,277 (98.9%) of the measurements. Despite respiratory rates clustering around WHO thresholds, breathing classification based on the thresholds (Fast vs normal) was altered between sequential measurements in only 12.6% of children. The mean (SD) respiratory rate by age group was 60 (13.1) bpm for Age-1, 49 (11.9) bpm for Age-2, and 38 (10.1) for Age-3, and the bias (Limits of Agreements) were 0.3 (-10.8-11.3) bpm, 0.4 (-8.5-9.3) bpm, and 0.1 (-6.8, 7.0) bpm for Age-1, Age-2, and Age-3 respectively. The repeatability of the paired respiratory rate measurements was high, with an ICC ≥ 90% for 12 of 14 users and an overall ICC value (95% CI) of 0.95 (0.94-0.95). The RRate measurements were efficient and repeatable. The simplicity, repeatability, and efficiency support its usage in LMICs healthcare facilities, and endorses a more widespread clinical adoption.

Background The cause of acute paediatric hepatitis of unknown aetiology (2022) has not been established despite extensive investigation.Objective To summarise the evidence for and against a causal role for human adenovirus (HAdv), adeno-associated virus 2 (AAV-2) and SARS-CoV-2 in outbreaks of paediatric hepatitis in 2022.Methods We appraised and summarised relevant evidence for each of the Bradford Hill criteria for causality using quantitative (statistical modelling) and qualitative (narrative coherence) approaches. Each team member scored the evidence base for each criterion separately for HAdv, AAV-2 and SARS-CoV-2; differences were resolved by discussion. We additionally examined criteria of strength and temporality by examining the lagged association between SARS-CoV-2 positivity, respiratory HAdv positivity, positive faecal HAdv specimens and excess A&E attendances in 1–4 years for liver conditions in England.Results Assessing criteria using the published literature and our modelling: for HAdv three Bradford Hill criteria (strength, consistency and temporality) were partially met; and five criteria (consistency, coherence, experimental manipulation, analogy and temporality) were minimally met. For AAV-2, the strength of association criterion was fully met, five criteria (consistency, temporality, specificity, biological gradient and plausibility) were partially met and three (coherence, analogy and experimental manipulation) were minimally met. For SARS-CoV-2, five criteria (strength of association, plausibility, temporality, coherence and analogy) were fully met; one (consistency) was partially met and three (specificity, biological gradient and experimental manipulation) were minimally met.Conclusion Based on the Bradford Hill criteria and modelling, HAdv alone is unlikely to be the cause of the recent increase in hepatitis in children. The causal link between SARS-CoV-2, and to a lesser degree AAV-2, appears substantially stronger but remains unproven. Hepatitis is a known complication of multisystem inflammatory syndrome in children following COVID-19, and SARS-CoV-2 has been linked to increased susceptibility to infection post-COVID-19, which may suggest complex causal pathways including a possible interaction with AAV-2 infection/reactivation in hosts that are genetically susceptible or sensitised to infection.

Introduction Vietnam has achieved significant reductions in its malaria caseload over the past decades and is progressing towards malaria elimination. To achieve malaria elimination, the Vietnam Ministry of Health issued Guidelines for Malaria Surveillance and Prevention, a surveillance guide that describes malaria reactive surveillance and response (RASR) strategies—its implementation—is yet to be evaluated. Here, the facilitators, barriers and acceptability of the implementation of RASR strategies in Vietnam are explored and discussed thoroughly to provide recommendations for improvement of RASR strategies.Methods A mixed-methods study was conducted in Binh Thuan and Phu Yen Provinces in Vietnam from November 2021 to April 2022 including quantitative surveys with health stakeholders and staff (n=36) and frontline health service providers (n=38), qualitative focus group discussions with frontline health service providers and mobile migrant populations (n=70) and semistructured in-depth interview with health stakeholders and staff (n=28). Quantitative and qualitative data were analysed descriptively and thematically.Results Vietnam’s health system supports RASR strategies, and the RASR implementation data are well captured in the electronic communicable disease surveillance system of the Ministry of Health. Overall, RASR strategies are acceptable to both stakeholders and community members. However, successful implementation of RASR strategies is hindered by declining community interest in malaria elimination programme and limitations of infrastructure, budget, human resources, and terrain difficulties.Conclusions Overall health system support and policy commitment are key to successful implementation of RASR strategies and therefore for achieving malaria elimination. Despite high-performance and well-accepted RASR strategies, more financial and human resource investments are warranted to investigate and respond to all malaria foci in time. Village health workers could be used effectively to engage community members and mobile migrant populations in RASR activities.

Statement of the problem: Previous longitudinal studies have found that patients with shortened dental arches (SDA) have a higher risk of long-term tooth loss than complete dental arch (CDA). However, the difference between SDA and CDA concerning oral function has yet to be demonstrated. Purpose: We aimed to clarify the influence of molar occlusal support on oral function in SDA and CDA participants cross-sectionally and longitudinally. Materials and methods: We enrolled independent older adults (≥65 years) living in rural areas of Japan. Of these, 257 had CDA, and 21 had SDA without removable prostheses. We assessed the oral function (number of functional teeth, masticatory performance using gummy jelly, occlusal force, oral cleanliness, oral dryness, and maximum tongue pressure) during baseline and two years after baseline (follow-up). Comparison of oral function between SDA and CDA and changes over time were examined using repeated measures analysis of variance and post-hoc test. Results: Cross-sectional analysis showed that both masticatory performance and occlusal force were significantly lower in SDA than in CDA. The functional teeth tended to decrease over time more in SDA than in CDA (p

AbstractThis paper examines how the gender of CEOs affect product and process innovations at the firm level, focusing on how SEZ features affect the gender-innovations nexus. The study employs data containing 328 firms from 2018 to 2021 and panel logit and treatment estimation models. The results show that female CEOs are more likely to lead registered SEZ firms and engage more in product and process innovations. Moreover, while female CEOs contribute positively to product and process innovations, female CEOs in registered SEZ firms and SEZ enclaves tend to have a higher and profound contribution to product and process innovations than their counterparts. These results suggest that national and corporate policymakers should develop and implement corporate and national level policies that (i) limits the glass ceiling barriers in order to propel the contribution of females to innovations and (ii) lower the bureaucratic and complex administrative procedures for operationalizing SEZ firms in order to harness the innovational-enhancing effects of gender inclusiveness.

AbstractDespite evidence that improving financial sector transparency (FST) can help tame clientele (households, businesses and corporate) debts, the empirical literature fails to explore how improving FST can lower/tame the unsustainable soaring government or (regulator) debts, particularly in Africa where alternative government debt management is inevitable. Hence, this study examines the complementarity and nonlinear threshold effects of private and public sector-led financial transparencies on government debts in Africa for the first time. Using a dynamic GMM panel data strategy covering periods between 2004 and 2020, the results show that the joint term of public and private sector-led financial sector transparency has complementary-synergetic effects on long-term debts and interest on debts while having substitutive effects on gross and short-term government debts, implying that private and public sector-led financial transparencies are substitutes to each other or can be used to complement gross and short-term government debts but complementary on long-term debt and interest on debts. Similarly, it is reported that there is a nonlinear inverted U-shaped threshold effect of financial sector transparencies on government debts, implying that financial sector transparencies must reach a minimum threshold/level to induce the desirable reducing effect of financial sector transparencies on government debts in Africa. These results create awareness of how financial regulators can employ FST as a debt-reducing tool and require policymakers to expand and deepen FST information to hasten it and reinforce the reducing effect of financial sector transparencies on government debts.

Objectives: A quarter of West Africa's population are adolescents 10–19 years. Their mental, sexual, and reproductive health is inter-related. We therefore aimed to examine published evidence on effectiveness of interventions for adolescent mental, sexual and reproductive health in the Economic Community of West African States (ECOWAS) to inform development, implementation and de-implementation of policies and programs. Study design: The study design was a scoping review. Methods: We considered all qualitative and quantitative research designs that included adolescents 10–19 years in any type of intervention evaluation that included adolescent mental, sexual and reproductive health. Outcomes were as defined by the researchers. PubMed/Medline, APA PsycINFO, CAIRN, and Google Scholar databases were searched for papers published between January 2000 and November 9, 2023.1526 English and French language papers were identified. After eliminating duplicates, screening abstracts and then full texts, 27 papers from studies in ECOWAS were included. Results: Interventions represented three categories: service access, quality, and utilization; knowledge and information access and intersectionality and social determinants of adolescent health. Most studies were small-scale intervention research projects and interventions focused on sexual and reproductive or mental health individually rather than synergistically. The most common evaluation designs were quasi-experimental (13/27) followed by observational studies (8/27); randomized, and cluster randomized controlled trials (5/27), and one realist evaluation. The studies that evaluated policies and programs being implemented at scale used observational designs. Conclusion: Research with robust evaluation designs on synergistic approaches to adolescent mental, sexual and reproductive health policies, interventions, implementation and de-implementation is urgently needed to inform adolescent health policies and programs.

This study examines the co-movement and time-varying integration between equity, exchange rate, and international market volatility indices across different time–frequency domains using - bi-partial wavelet, - supplemented by dynamic conditional correlation-generalised autoregressive conditional heteroskedasticity (DCC-GARCH), - and BEKK GARCH model for selected African countries. First, the findings indicate that the co-movement between equity and exchange rates during the pandemic was exacerbated by global COVID-19 media coverage. The findings indicate that there has been a substantial risk transfer between exchange rates and stock returns during the COVID-19 pandemic, resulting in a decline in domestic stock returns and subsequent capital outflows, which in turn increased the exchange rate. Given the growing difficulties in diversification, specific information on the volatility of financial market connectedness is required to plan hedging strategies. To explore the influence of global market volatility on Africa’s equity and currency markets, it is crucial to analyse the relationship between regional and global market fluctuations, especially given the negative impact of the COVID-19 pandemic. Our empirical research demonstrates that the VIX and OVXCL indices play a significant role in transmitting spillovers to currency and equity markets in Africa. This suggests that the sentiment indicators provided by the VIX and OVXCL can be useful in predicting the behaviour of Africa’s currency and equity markets.

Over the past decade, there has been a rapid development in the use of magnetic three dimensional (3D) based cell culture systems. Concerning the skeletal muscle, 3D culture systems can provide biological insights for translational clinical research in the fields of muscle physiology and metabolism. These systems can enhance the cell culture environment by improving spatially-oriented cellular assemblies and morphological features closely mimicking the in vivo tissues/organs, since they promote strong interactions between cells and the extracellular matrix (ECM). However, the time-consuming and complex nature of 3D traditional culture techniques pose a challenge to the widespread adoption of 3D systems. Herein, a bench protocol is presented for creating an innovative, promptly assembled and user-friendly culture platform for the magnetic 3D bioprinting of skeletal muscle spheroids. Our protocol findings revealed consistent morphological outcomes and the functional development of skeletal muscle tissue, as evidenced by the expression of muscle-specific contractile proteins and myotubes and the responsiveness to stimulation with cholinergic neurotransmitters. This proof-of-concept protocol confirmed the future potential for further validation and application of spheroid-based assays in human skeletal muscle research.

Intrinsic optical signal imaging (IOSI) is a staple technique in modern neuroscience. Pioneered >30 years ago, IOSI allows macroscopic mapping of neuronal activity throughout the cortex. The technique has been used to study sensory processing and experience-dependent plasticity, and is often used as an adjunctive procedure to localize cortical areas for subsequent targeting by other imaging or physiology techniques. Despite the ubiquity of IOSI in neuroscience, there are few commercially available turn-key IOSI systems. As a result, investigators have typically resorted to building their own imaging systems. Over the years, simplified systems built either as dedicated rigs or incorporated into existing microscope platforms have been developed. Here we present a straightforward set of adaptations that can be applied to any standard upright microscope, using readily available, inexpensive, commercial parts for illumination, optics, and signal detection, that enables high-sensitivity IOSI. Using these adaptations, we are able to readily map sensory-evoked signals across the somatosensory and visual cortex, including single-whisker barrel cortical activity maps in mice. We show that these IOSI maps are highly reproducible across animals and can be used to study plasticity mechanisms in the somatosensory cortex. We also provide open-source applications to control illumination and analyze raw data to generate activity maps. We anticipate that these resources will be useful for neuroscience investigators looking to add IOSI capabilities to an existing microscope in the laboratory on a budget.

Hyper-phosphorylated tau accumulates as insoluble fibrils in Alzheimers disease (AD) and related dementias. The strong correlation between phosphorylated tau and disease has led to an interest in understanding how cellular factors discriminate it from normal tau. Here, we screen a panel of chaperones containing tetratricopeptide repeat (TPR) domains to identify those that might selectively interact with phosphorylated tau. We find that the E3 ubiquitin ligase, CHIP/STUB1, binds 10-fold more strongly to phosphorylated tau than unmodified tau. The presence of even sub-stoichiometric concentrations of CHIP strongly suppresses aggregation and seeding of phosphorylated tau. We also find that CHIP promotes rapid ubiquitination of phosphorylated tau, but not unmodified tau, in vitro. Binding to phosphorylated tau requires CHIPs TPR domain, but the binding mode is partially distinct from the canonical one. In cells, CHIP restricts seeding by phosphorylated tau, suggesting that it could be an important barrier in cell-to-cell spreading. Together, these findings show that CHIP recognizes a phosphorylation-dependent degron on tau, establishing a pathway for regulating the solubility and turnover of this pathological proteoform.

Background: Enterovirus D68 (EV-D68) is an important reemerging pathogen that causes severe acute respiratory infection and acute flaccid paralysis, mainly in children. Since 2014, EV-D68 outbreaks have been reported in the United States, Europe, and east Asia; however, no outbreaks have been reported in southeast Asian countries, including Myanmar, during the previous 10 years. Methods: EV-D68 was detected in nasopharyngeal swabs from children with acute lower respiratory infections in Myanmar. The samples were previously collected from children aged 1 month to 12 years who had been admitted to the Yankin Children Hospital in Yangon, Myanmar, between May 2017 and January 2019. EV-D68 was detected with a newly developed EV-D68–specific real-time PCR assay. The clade was identified by using a phylogenetic tree created with the Bayesian Markov chain Monte Carlo method. Results: During the study period, nasopharyngeal samples were collected from 570 patients. EV-D68 was detected in 42 samples (7.4 %)—11 samples from 2017 to 31 samples from 2018. The phylogenetic tree revealed that all strains belonged to clade B3, which has been the dominant clade worldwide since 2014. We estimate that ancestors of currently circulating genotypes emerged during the period 1980–2004. Conclusions: To our knowledge, this is the first report of EV-D68 detection in children with acute lower respiratory infections in Yangon, Myanmar, in 2017–2018. Detection and detailed virologic analyses of EV-D68 in southeast Asia is an important aspect of worldwide surveillance and will likely be useful in better understanding the worldwide epidemiologic profile of EV-D68 infection.

Pre-harvest sprouting (PHS) poses a significant global challenge to cereal production, impacting both yield and quality. In this study, we employed genome-wide association studies (GWAS) on diverse rice accessions to identify novel PHS-associated haplotypes. An assessment of 127 cultivated accessions for panicle germination (PHS) and detached grain germination (germination rate of detached grains at the 14th day (D14)) revealed considerable phenotypic variation among rice ecotypes. GWAS analysis identified 91 significant signals at –log10(P-value)>5, including 15 SNPs for PHS and 76 SNPs for D14. A subsequent linkage disequilibrium (LD) block-based GWAS analysis detected 227 significant SNPs for both traits, consisting of 18 nonsynonymous substitutions located on the coding regions of nine genes. Further haplotype analysis identified 32 haplotypes, with 10 specific to cultivated accessions, 19 specific to the wild type, and three shared between them. A phenotypic assessment of major haplotypes revealed significant differences between resistant (Hap1 and Hap2) and susceptible haplotypes (Hap5, Hap27, and Hap28), distinguished by a G/A SNP within a novel gene, Os04g0545200. The identified haplotypes offer promising prospects for haplotype-based breeding aimed at enhancing PHS resistance in rice.

Abstract An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.5% (6/11) CyCMV/Flu-vaccinated MCM survived. Survival correlates with the magnitude of lung-resident influenza-specific CD4 + T cells prior to challenge. These data demonstrate that CD4 + T cells targeting conserved internal influenza proteins can protect against highly pathogenic heterologous influenza challenge and support further exploration of effector memory T cell-based vaccines for universal influenza vaccine development.

Background: Orlistat, a weight loss medication, is often less effective due to poor adherence to the dietary and exercise recommendations. However, its effectiveness is often compromised by poor adherence to recommended lifestyle changes and side effects like steatorrhea. Combining orlistat with resveratrol may enhance weight loss and offer additional metabolic benefits. Objective: This study evaluated the real-world efficacy and safety of orlistat combined with resveratrol versus orlistat alone in overweight or obese individuals in Myanmar. Method: Obese adults (BMI ≥ 25 kg/m2) were randomized into two groups for a 12-week study. The Orlistat (O) group received orlistat 120 mg three times daily, while the Orlistat & Resveratrol (O-R) group took orlistat 120 mg plus resveratrol 100 mg thrice daily. Primary outcome measured was weight change; secondary outcomes included Total Cholesterol, LDL-cholesterol, Blood pressure, HbA1c, alanine transaminase (ALT), controlled attenuation parameter (CAP), Liver stiffness, and Total Body Fat. Adverse events were also recorded. Result: The O-R group lost more weight (−3.31 kg, 95 % CI: 2.36–5.04, p