The impact of anorexia nervosa and BMI polygenic risk on childhood growth: A 20-year longitudinal population-based study.

Growth deviating from the norm during childhood has been associated with anorexia nervosa (AN) and obesity later in life. In this study, we examined whether polygenic scores (PGSs) for AN and BMI are associated with growth trajectories spanning the first two decades of life. AN PGSs and BMI PGSs were calculated for participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 8,654). Using generalized (mixed) linear models, we associated PGSs with trajectories of weight, height, body mass index (BMI), fat mass index (FMI), lean mass index (LMI), and bone mineral density (BMD). Female participants with AN PGSs one standard deviation (SD) higher had, on average, 0.004% slower growth in BMI between the ages 6.5 and 24 years and a 0.4% slower gain in BMD between the ages 10 and 24 years. Higher BMI PGSs were associated with faster growth for BMI, FMI, LMI, BMD, and weight trajectories in both sexes throughout childhood. Female participants with both a high AN PGS and a low BMI PGS showed slower growth compared to those with both a low AN PGS and a low BMI PGS. We conclude that AN PGSs and BMI PGSs have detectable sex-specific effects on growth trajectories. Female participants with a high AN PGS and low BMI PGS likely constitute a high-risk group for AN, as their growth was slower compared to their peers with high PGSs on both traits. Further research is needed to better understand how the AN PGS and the BMI PGS co-influence growth during childhood and whether a high BMI PGS can mitigate the effects of a high AN PGS.

Translation and evaluation of psychometric properties of the Amharic pediatric quality of life inventory 4.0 generic core scale for children with cancer.

BACKGROUND: Childhood cancer negatively impacts a child's physical, mental, and behavioural health and significantly affects their health-related quality of life. The Pediatric Quality of Life Inventory 4.0 Generic Core Scale (PedsQL™ 4.0 GCS) is one of the most commonly used measures of the quality of life in children. However, the Amharic version of PedsQL™ 4.0 GCS has not been validated in a paediatric oncology population. This study aimed to translate and evaluate the psychometric properties of the Amharic PedsQL™ 4.0 GCS (PedsQL™ 4.0 GCS (A)) for Ethiopian children with cancer. METHODS: A descriptive cross-sectional study was conducted among children aged 8-18 years with any type of cancer across the cancer trajectory. Cronbach's alpha and intraclass correlation coefficient were computed to determine the internal consistency and test-retest reliability of the scale. The convergent validity was established by examining the correlation of the PedsQL™ 4.0 GCS (A) with the Amharic version of the Revised Child Anxiety and Depression Scale (RCADS-25(A)). Factorial validity was evaluated by conducting a confirmatory factor analysis. RESULTS: The study included 142 participants with childhood cancer. PedsQL™ 4.0 GCS (A) had good validity and reliability. It demonstrated high internal consistency with a Cronbach's alpha of 0.96 for the scale and 0.82-0.95 for the subscales. The intraclass correlation coefficient for the scale was 0.9 and that for the subscales was 0.76-0.90. The PedsQL™ 4.0 GCS (A) was highly correlated with RCADS-25 (A) (r = - 0.97, p < 0.001), supporting its convergent validity. The four-factor structure of the model fitted the data satisfactorily (χ2/df = 1.28; CFI = 0.97; TLI = 0.97; RMSEA = 0.05; SRMR = 0.05), supporting the factorial validity of the PedsQL™ 4.0 GCS (A). CONCLUSION: The PedsQL™ 4.0 GCS (A) demonstrates desirable psychometric properties for assessing quality of life among Ethiopian children with cancer. The scale can be used in clinical settings for assessing and evaluating quality of life in children with cancer. The use of parent-report versions and studies in those with different health conditions and healthy populations are necessary to further establish the psychometric properties of the PedsQL™ 4.0 GCS (A).

Polygenic and environmental determinants of tics in the Avon Longitudinal Study of Parents and Children.

Tourette syndrome (TS) is caused by multiple genetic and environmental factors. Yet, little is known about the interplay of these factors in the occurrence of tics. We investigated whether polygenic risk score (PRS) of TS and pregnancy-related factors together enhance the explained variance of tic occurrence in the Avon Longitudinal Study of Parents and Children (Ncases  = 612; Ncontrols  = 4,201; 50% male; mean age 13.8 years). We included a cumulative adverse pregnancy risk score, maternal anxiety and depression, and maternal smoking and alcohol use during pregnancy. We investigated possible joint effects of genetic and pregnancy-related risk factors using a multivariable approach, and explored mediation effects between the pregnancy-related risk factors in explaining tic presence. The PRS and the cumulative adverse pregnancy risk score, maternal anxiety, or maternal depression explained significantly more variance of tic presence compared to models including only the PRS. Furthermore, we found that the cumulative adverse pregnancy risk score mediated the association between several pregnancy-related factors (maternal anxiety, depression, and smoking) and tics. The combination of a PRS and pregnancy-related risk factors explained more variance of tics in a general population cohort compared to studying these factors in isolation.

Parental feeding and childhood genetic risk for obesity: exploring hypothetical interventions with causal inference methods.

BACKGROUND: Parental-feeding behaviors are common intervention targets for childhood obesity, but often only deliver small changes. Childhood BMI is partly driven by genetic effects, and the extent to which parental-feeding interventions can mediate child genetic liability is not known. Here we aim to examine how potential interventions on parental-feeding behaviors can mitigate some of the association between child genetic liability and BMI in early adolescence, using causal inference methods. METHODS: Data from the Avon Longitudinal Study of Parents and Children were used to estimate an interventional disparity measure for a child polygenic score for BMI (PGS-BMI) on BMI at 12 years. The approach compares counterfactual outcomes for different hypothetical interventions on parental-feeding styles applied when children are 10-11 years (n = 4248). Results are presented as adjusted total association (Adj-Ta) between genetic liability (PGS-BMI) and BMI at 12 years, versus the interventional disparity measure-direct effect (IDM-DE), which represents the association that would remain, had we intervened on parental-feeding under different scenarios. RESULTS: For children in the top quintile of genetic liability, an intervention shifting parental feeding to the levels of children with lowest genetic risk, resulted in a difference of 0.81 kg/m2 in BMI at 12 years (Adj-Ta = 3.27, 95% CI: 3.04, 3.49; versus IDM-DE = 2.46, 95% CI: 2.24, 2.67). CONCLUSIONS: Findings suggest that parental-feeding interventions have the potential to buffer some of the genetic liability for childhood obesity. Further, we highlight a novel way to analyze potential interventions for health conditions only using secondary data analyses, by combining methodology from statistical genetics and social epidemiology.

Whole-exome sequencing identifies genes associated with Tourette's disorder in multiplex families.

Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein-protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.

Patterns and associated factors of electrocardiographic abnormality among type 2 diabetic patients in Amhara National Regional State Referral Hospitals, Ethiopia: a multicenter institution-based cross-sectional study.

BACKGROUND: Cardiovascular diseases are the most causes of mortality and morbidity among diabetes mellitus (DM) patients. Electrocardiographic (ECG) changes are common in the early course of the disease. Little is known about the electrocardiographic abnormalities among type 2 DM patients in Ethiopia. This study determined the overall prevalence, its patterns, and the associated factors of ECG abnormalities among people living with T2DM in Amhara National Regional State referral hospitals, Ethiopia. METHODS: A multicenter institution-based cross-sectional study was conducted from 01 April to 30 May 2021. A simple random sampling and systematic sampling techniques were employed to select the referral hospitals and study participants, respectively. A digital electrocardiograph was used to measure the ECG parameters and the other data were collected using an interviewer-administered questionnaire. Epi-data version-4.6 and Stata-14 were used for data entry and statistical analysis, respectively. The descriptive statistics were presented with tables and graphs. A binary logistic regression model was fitted to identify associated factors of ECG abnormality. In the final model, statistical significance was decided at p≤0.05, and the strength of association was indicated using an adjusted odds ratio with 95% CI. RESULTS: Two-hundred and fifty-eight participants (response rate = 99.6%) were included for the analysis. The prevalence of overall ECG abnormality was 45% (95% CI: 39, 51%). On the basis of the electrocardiographic patterns, 57 (21.1%; 95% CI: 14.6, 32.6%) were presented with T-wave abnormality, 36 (14%; 95% CI: 10.1, 18.8%) left axis deviation, and 24 (9.3% [6.3, 13.5%]) sinus tachycardia. Higher monthly income (> 90$) (AOR = 0.51 [0.31, 0.83]), over 10 years duration of DM (AOR = 4.5[1.05, 18.94]), hypertension (AOR = 3.9 [1.6, 9.40]), fasting blood sugar of ≥ 130 mg/dl (AOR = 5.01[2.13, 12.20]), and overweight (AOR = 2.65[1.17, 5.98]) were statistically significant factors of overall ECG abnormality. CONCLUSIONS: Nearly, half of the participants had at least one ECG abnormality. Higher-income, prolonged disease duration, hypertension, higher fasting blood sugar, and overweight were significantly associated with ECG abnormality. The findings of this study suggest the need to institute routine ECG screening for all T2DM patients to reduce ECG abnormalities and further complications.

Eating disorder symptoms and their associations with anthropometric and psychiatric polygenic scores.

BACKGROUND: Eating disorder (ED) symptoms are prevalent in the general population, but their shared genetic underpinnings with psychiatric, metabolic, and anthropometric traits are not known. Here, we examined if polygenic scores (PGSs) of traits associated with anorexia nervosa are also associated with adolescent ED symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC). METHODS: A total of 8654 participants with genotype data and at least one phenotypic measure were included from the ALSPAC study. We associated PGS from 25 traits (16 psychiatric, 4 metabolic, and 5 anthropometric) with eight ED symptoms, including behaviours such as fasting for weight loss and cognitions such as body dissatisfaction. RESULTS: Higher attention deficit hyperactivity disorder PGS and lower educational attainment PGS were associated with fasting for weight loss. Higher insomnia PGS was associated with increased body dissatisfaction. We found no evidence of an association between metabolic trait PGS and any ED symptom. Fat-free mass, fat mass, and body fat percentage PGSs, were positively associated with binge eating, excessive exercise, fasting for weight loss, body dissatisfaction, and weight and shape concern. CONCLUSIONS: ED symptoms are genetically associated with psychiatric and anthropometric, but not with metabolic traits. Our findings provide insights for future genetic research investigating on why some individuals with ED symptoms progress to develop threshold EDs while others do not.

Investigation of gene-environment interactions in relation to tic severity.

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies.

One size does not fit all. Genomics differentiates among anorexia nervosa, bulimia nervosa, and binge-eating disorder.

OBJECTIVE: Genome-wide association studies have identified multiple genomic regions associated with anorexia nervosa. No genome-wide studies of other eating disorders, such as bulimia nervosa and binge-eating disorder, have been performed, despite their substantial heritability. Exploratively, we aimed to identify traits that are genetically associated with binge-type eating disorders. METHOD: We calculated genome-wide polygenic scores for 269 trait and disease outcomes using PRSice v2.2 and their association with anorexia nervosa, bulimia nervosa, and binge-eating disorder in up to 640 cases and 17,050 controls from the UK Biobank. Significant associations were tested for replication in the Avon Longitudinal Study of Parents and Children (up to 217 cases and 3,018 controls). RESULTS: Individuals with binge-type eating disorders had higher polygenic scores than controls for other psychiatric disorders, including depression, schizophrenia, and attention deficit hyperactivity disorder, and higher polygenic scores for body mass index. DISCUSSION: Our findings replicate some of the known comorbidities of eating disorders on a genomic level and motivate a deeper investigation of shared and unique genomic factors across the three primary eating disorders.

Eating behavior trajectories in the first 10 years of life and their relationship with BMI.

BACKGROUND: Child eating behaviors are highly heterogeneous and their longitudinal impact on childhood weight is unclear. The objective of this study was to characterize eating behaviors during the first 10 years of life and evaluate associations with BMI at age 11 years. METHOD: Data were parental reports of eating behaviors from 15 months to age 10 years (n = 12,048) and standardized body mass index (zBMI) at age 11 years (n = 4884) from the Avon Longitudinal Study of Parents and Children. Latent class growth analysis was used to derive latent classes of over-, under-, and fussy-eating. Linear regression models for zBMI at 11 years on each set of classes were fitted to assess associations with eating behavior trajectories. RESULTS: We identified four classes of overeating; "low stable" (70%), "low transient" (15%), "late increasing" (11%), and "early increasing" (6%). The "early increasing" class was associated with higher zBMI (boys: ß = 0.83, 95% CI: 0.65, 1.02; girls: ß = 1.1; 0.92, 1.28) compared with "low stable." Six classes were found for undereating; "low stable" (25%), "low transient" (37%), "low decreasing" (21%), "high transient" (11%), "high decreasing" (4%), and "high stable" (2%). The latter was associated with lower zBMI (boys: ß = -0.79; -1.15, -0.42; girls: ß = -0.76; -1.06, -0.45). Six classes were found for fussy eating; "low stable" (23%), "low transient" (15%), "low increasing" (28%), "high decreasing" (14%), "low increasing" (13%), and "high stable" (8%). The "high stable" class was associated with lower zBMI (boys: ß = -0.49; -0.68-0.30; girls: ß = -0.35; -0.52, -0.18). CONCLUSIONS: Early increasing overeating during childhood is associated with higher zBMI at age 11. High persistent levels of undereating and fussy eating are associated with lower zBMI. Longitudinal trajectories of eating behaviors may help identify children potentially at risk of adverse weight outcomes.

A longitudinal study of eating behaviours in childhood and later eating disorder behaviours and diagnoses.

BACKGROUND: Eating behaviours in childhood are considered as risk factors for eating disorder behaviours and diagnoses in adolescence. However, few longitudinal studies have examined this association. AIMS: We investigated associations between childhood eating behaviours during the first ten years of life and eating disorder behaviours (binge eating, purging, fasting and excessive exercise) and diagnoses (anorexia nervosa, binge eating disorder, purging disorder and bulimia nervosa) at 16 years. METHOD: Data on 4760 participants from the Avon Longitudinal Study of Parents and Children were included. Longitudinal trajectories of parent-rated childhood eating behaviours (8 time points, 1.3-9 years) were derived by latent class growth analyses. Eating disorder diagnoses were derived from self-reported, parent-reported and objectively measured anthropometric data at age 16 years. We estimated associations between childhood eating behaviours and eating disorder behaviours and diagnoses, using multivariable logistic regression models. RESULTS: Childhood overeating was associated with increased risk of adolescent binge eating (risk difference, 7%; 95% CI 2 to 12) and binge eating disorder (risk difference, 1%; 95% CI 0.2 to 3). Persistent undereating was associated with higher anorexia nervosa risk in adolescent girls only (risk difference, 6%; 95% CI, 0 to 12). Persistent fussy eating was associated with greater anorexia nervosa risk (risk difference, 2%; 95% CI 0 to 4). CONCLUSIONS: Our results suggest continuities of eating behaviours into eating disorders from early life to adolescence. It remains to be determined whether childhood eating behaviours are an early manifestation of a specific phenotype or whether the mechanisms underlying this continuity are more complex. Findings have the potential to inform preventative strategies for eating disorders.

Identifying typical trajectories in longitudinal data: modelling strategies and interpretations.

Individual-level longitudinal data on biological, behavioural, and social dimensions are becoming increasingly available. Typically, these data are analysed using mixed effects models, with the result summarised in terms of an average trajectory plus measures of the individual variations around this average. However, public health investigations would benefit from finer modelling of these individual variations which identify not just one average trajectory, but several typical trajectories. If evidence of heterogeneity in the development of these variables is found, the role played by temporally preceding (explanatory) variables as well as the potential impact of differential trajectories may have on later outcomes is often of interest. A wide choice of methods for uncovering typical trajectories and relating them to precursors and later outcomes exists. However, despite their increasing use, no practical overview of these methods targeted at epidemiological applications exists. Hence we provide: (a) a review of the three most commonly used methods for the identification of latent trajectories (growth mixture models, latent class growth analysis, and longitudinal latent class analysis); and (b) recommendations for the identification and interpretation of these trajectories and of their relationship with other variables. For illustration, we use longitudinal data on childhood body mass index and parental reports of fussy eating, collected in the Avon Longitudinal Study of Parents and Children.

Appropriate use of anti-thrombotic therapy in patients with atrial fibrillation at single-center experience, Northwest Ethiopia.

BACKGROUND: Atrial fibrillation (AF) is the commonest clinically significant ECG-evidenced sustained cardiac arrhythmia in clinical practice. Disability and mortality attributed to AF is high in low-income regions like sub-Saharan Africa. The risk of stroke/TIA in patients with AF can be significantly reduced with anti-thrombotic therapy. Despite the existing evidence of its benefit, significant percentages of AF patients eligible for anti-thrombotic therapy are undertreated in the region. METHODS: A hospital-based cross-sectional study was conducted to determine the appropriate use of anti-thrombotic therapy in patients with AF between December 1, 2018 and September 30, 2019 at Cardiac Clinic, University of Gondar hospital, Northwest Ethiopia. Consecutive sampling method was used to recruit 210 study subjects. Patients were interviewed to obtain socio-demographic data. Relevant medical history and laboratory parameters were obtained from patients' records. Diagnosis of atrial fibrillation was based on detection of irregular arterial pulse and presence of 'f' waves on 12-lead ECG tracing. Clinical evaluation, echocardiography, chest X-ray and blood chemistry were used to diagnose underlying causes of AF. Data was entered into EPI Info version 4.4.1 and analyzed using SPSS version 20. Bi-variate and multi-variate logistic regression analyses were used to identify associated factors with appropriate use of anti-thrombotic therapy in patients with atrial fibrillation. P-values < 0.05 were used to declare significant association. RESULTS: A total of 210 patients were included in the study. The mean age of patients was 51.29 ± 17.2 years. Two-thirds (145/210) of participants were females. Seventy-four (35%) had valvular AF, while 136/210 (65%) had non-valvular AF. Sixty-six percent (139/210) of study subjects were appropriately treated with anti-thrombotic therapy. Appropriately treated subjects in valvular AF group and non-valvular AF group were 58/74 (78%) and 81/136 (60%) respectively. On multi-variate analysis, 'can afford for regular INR monitoring' (AOR = 2.60 95% CI: 1.10-6.10, P = 0.001) was significantly associated with appropriate use of anti-thrombotic therapy. CONCLUSION: Sixty-six percent of AF patients eligible for anti-thrombotic therapy were appropriately treated. Intervention program to access 'regular INR monitoring' should be practiced to escalate utilization rate of anti-thrombotic therapy (warfarin) in eligible AF patients.

High therapeutic efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Somalia.

BACKGROUND: Artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA/PPQ) are the recommended first- and second-line treatments, respectively, for uncomplicated falciparum malaria in Somalia. The studies reported here were conducted to assess the efficacy of these artemisinin-based combinations and the mutations in Plasmodium falciparum K13-propeller (Pfk13) domain and amplification in Pfplasmepsin 2 (Pfpm2) gene in Somalia. METHODS: One-arm prospective studies were conducted to assess the clinical and parasitological responses to DHA/PPQ and AL at two sites in 2016 and 2017, respectively, using the standard WHO protocol. The patterns of molecular markers associated with artemisinin and PPQ resistance were investigated for the first time in Somalia. RESULTS: A total of 339 patients were enrolled with 139 for AL and 200 for DHA/PPQ. With AL, no parasite recurrence was observed among patients treated at either site, corresponding to 100% clinical and parasitological responses. For DHA-PPQ, an adequate clinical and parasitological response rate > 97% was observed. All study patients on both treatments at both sites were parasite-free on day 3. Of the 138 samples with interpretable results for the polymorphism in Pfk13, only one (0.7%), from Bosaso, contained a non-synonymous mutation (R622I), which is not one of the known markers of artemisinin resistance. No Pfpm2 amplification was observed among the 135 samples with interpretable results. CONCLUSIONS: AL and DHA/PPQ were highly effective in the treatment of uncomplicated falciparum malaria, and there was no evidence of resistance to artemisinin or PPQ. These two combinations are thus relevant in the chemotherapeutic strategy for malaria control in Somalia. Trial registration ACTRN12616001005448 (Jowhar DP study), ACTRN12616000553471 (Bosaso DP study), ACTRN12617001055392 (AL study in Bosaso and Jowhar).

Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach.

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.

Efficacy of artesunate + sulphadoxine/pyrimethamine and artemether + lumefantrine and dhfr and dhps mutations in Somalia: evidence for updating the malaria treatment policy.

OBJECTIVE: To determine the therapeutic efficacy of artesunate + sulphadoxine/pyrimethamine (AS + SP) and artemether + lumefantrine (AL), and to investigate the presence of molecular mutations associated with resistance, to inform national malaria treatment policy. METHODS: One-arm prospective studies were conducted in three study sites in Somalia in 2013 and 2015 to evaluate the efficacy of AS + SP and AL among patients with uncomplicated falciparum malaria. Outcomes included clinical and parasitological response over 28 days, and the presence of dihydrofolate reductase (dfhr) and dihydropteroate synthase (dhps) and mutations. RESULTS: Among patients treated with AS + SP, the PCR-corrected treatment failure rate was 12.3%. The majority of patients (89%) carried either the quintuple mutations (51I/108N + 437G/540E/581G or 51I/59R/108N + 437G/540E) or the quadruple mutation (51I/108N + 437G/540E). All patients who failed treatment with AS + SP carried the quintuple mutation (51I/108N + 437G/540E/581G). In the studies of AL, the PCR-corrected treatment failure rate was <6%. All patients in both treatment groups cleared their parasitaemia by day 3. CONCLUSIONS: The findings demonstrate a failing first-line treatment (AS + SP), with a failure rate above the threshold (10%) for policy change, and a high prevalence of quintuple mutations. In contrast, AL was highly efficacious. Based on these findings and the results from a previous AS + SP study, AL was selected to replace AS + SP as the first-line treatment for uncomplicated malaria in Somalia in 2016. Dihydroartemisinin + piperaquine (DHA + PPQ) has been recommended as the second-line treatment. Routine monitoring of recommended ACTs should continue to inform treatment policy.

A Modified Wrapping-internal Shunt Method for Hemostasis in Bentall Procedure.

INTRODUCTION: Blindly punching between aorta and right atrium is dangerous. In that case, there is concerned about leakage between the two referred isolate parts. Besides, as the routine imaging techniques (echocardiography or computer tomography) are incompetent to detect this particular anatomic structure preoperatively, the intraoperative inspection appears necessary. Our method is useful for identifying this innate fusion plane. CASE REPORT: The thrombosis surrounding prosthesis was detected in the first ultrasound examination after the operation, which was considered to be an indication of successful hemostasis. As the innate fusion between aorta and right atrium appears no rare, the selective creation of left-to-right internal shunt is a valuable maneuver for controlling bleeding in appropriate cases.

Treatment of uncomplicated malaria with artesunate plus sulfadoxine-pyrimethamine is failing in Somalia: evidence from therapeutic efficacy studies and Pfdhfr and Pfdhps mutant alleles.

OBJECTIVE: Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been Somalia's national treatment policy since 2006. Routine monitoring of first-line malaria treatment is needed to ensure appropriate national malaria treatment policy and early detection of drug resistance. For this purpose, we conducted therapeutic efficacy studies of AS + SP for the treatment of uncomplicated malaria in Somalia in 2011. METHODS: Studies were conducted in three sentinel sites. Eligible patients were evaluated for clinical and parasitological outcomes according to the WHO standard protocol. Molecular surveillance was conducted on resistance conferring mutations in the P.falciparum dihydrofolate reductase (dfhr) and dihydropteroate synthase (dhps) genes. RESULTS: The proportion of PCR-corrected treatment failures was high in Jamame (22%, 95% CI: 13.7-32.8%) and low (<5%) in Janale and Jowhar. All patients cleared parasites by day 3. Molecular markers associated with SP resistance were detected in all three sites. Treatment failure was associated with the presence of the double mutant dhps A437G/K540E (OR = 22.4, 95% CI: 5.1-98.1), quadruple mutant dhfr N51I/S108N+dhps A437G/K540E (OR = 5.5, 95% CI: 2.3-13.6), quintuple mutant dhfr N51I/C59R/S108N+dhps A437G/K540E (OR = 3.5, 95% CI: 1.4-8.8) and younger age (OR=0.86, 95% CI: 0.76-0.96). CONCLUSIONS: The high treatment failure rate observed in Jamame, together with the presence of molecular mutations associated with SP resistance, indicates P. falciparum resistance to SP. In Jowhar, high treatment failure rates were absent despite the presence of molecular mutations; signs of resistance in vivo may have been masked by the stronger immunity of the older study population. The study underscores the need to update Somalia's national malaria treatment policy.

Global respiratory health priorities at the beginning of the 21st century.

Respiratory health has become a prevailing priority amid the diverse global health challenges that the 21st century brings, due to its substantial impact on individuals and communities on a global scale. Due to rapid advances in medicine, emerging knowledge gaps appear along with new challenges and ethical considerations. While breakthroughs in medical science can bring about encouraging possibilities for better treatments and interventions, they also lead to unanswered questions and areas where further research is warranted. A PubMed search on the topic "global respiratory health priorities" between the years 2000 and 2023 was conducted, which returned 236 articles. Of these, 55 were relevant and selected for inclusion in this article. The selection process took into account literature reviews, opinions from expert groups and careful analysis of existing gaps and challenges within the field; our selection encompasses specific infectious and noninfectious respiratory conditions in both adults and children. The global respiratory health priorities identified were selected on the basis that they have been recognised as critical areas of investigation and potential advancement and they span across clinical, translational, epidemiological and population health domains. Implementing these priorities will require a commitment to fostering collaboration and knowledge-sharing among experts in different fields with the ultimate aim to improve respiratory health outcomes for individuals and communities alike.