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Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research. [ABSTRACT FROM AUTHOR]

Studies conducted nationally found that students with Matric Accounting knowledge performed significantly better than students without it in university-level Accounting modules (Baard, Steenkamp, and Kidd 2010; Papageorgiou 2017; Steenkamp, Baard, and Frick 2009). However, the reality at South African universities is that Accounting as a school subject is not always a requirement to pursue BCom Accounting studies. This situation means that at certain universities, Accounting as a school subject is not taken into consideration for this degree, while this is the case at some universities. This study focuses on two cohorts of students enrolled for the mainstream programme in 2017-2019 at a South African university. The reason for focusing on these two cohorts was to establish the throughput rate of students with or without Matric Accounting knowledge. Two most significant findings of this study are that firstly, students who obtained at least 70 per cent for Matric Accounting completed the degree within the minimum three-year time frame, while students who obtained at least 80 per cent had a higher throughput rate of 48.8 per cent. Secondly, students who achieved lower than 70 per cent for Mathematics and did not complete Matric Accounting were unable to complete the degree in the minimum timeframe. The research methodology includes both quantitative and qualitative methods. The results can inform the selection and admission criteria at tertiary institutions and inform other stakeholders in higher education on how school subjects and grades influence students' throughput rate. [ABSTRACT FROM AUTHOR]

South African higher education institutions have been grappling with the high dropout rate, specifically at first year level. Despite universities' attempts to implement various strategies to increase student retention, there is very little or no empirical warrant to validate these attempts of research in the South African context. Hence, the aim of this study is to explore how disciplinespecific peer mentoring impacts first year students' academic performance. The two most significant findings of this study are that firstly, the mean continuous assessment mark of the mentees (73.6) is significantly higher compared to students who were not mentees and, secondly, the mentees' final examination performance was also higher (60.9 versus 52.9). This study highlights the possibilities of using peer mentoring to improve first years' academic performance. The evidence as revealed in the study provides insights into these possibilities. For example, the peer mentees indicated that they the peer mentors weekly motivational messages inspired them to continue with their studies and the continuous support from the peer mentors assisted them to understand the difficult concepts of Economics. While this study did not focus on the peer mentors, we also found that they were willing to participate voluntarily in this programme, as they believed that there are multiple benefits to being a peer mentor. We argue that the implementation of discipline-specific peer mentoring programmes across all disciplines could facilitate student retention and increase the overall pass rate of first year students. [ABSTRACT FROM AUTHOR]

Dental biocorrosion can produce a devastating impact on oral health. The restorative phase of the treatment should not cause additional damage of the remaining sound tooth structure. Ultrathin occlusal veneers are a conservative alternative to traditional onlays and complete crowns for the treatment of severe biocorrosive lesions. This strategy is explained in the present case report through a full-mouth rehabilitation of a patient with moderate biocorrosion. Maxillary anterior teeth were restored using the bilaminar technique (lingual direct composite veneers with labial ceramic veneers) and posterior teeth using ultrathin CAD-CAM ceramic occlusal veneers. The technical aspects required for the implementation of this new restorative design are presented with a special emphasis on the control of tooth preparation based on diagnostic wax-up, provisionalization, and the use of CAD-CAM technology. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a chitosan/cellulose nanofibril (CNF) nanocomposite and evaluate its effect on strawberry’s postharvest quality after coating. From the results of color, thickness, and scanning electron microscopy (SEM) and permeability to water vapor analyses, the best film formulation for coating strawberries was determined. Three coating formulations were prepared: 1% chitosan, 1% chitosan + 3% CNF, and 1% chitosan + 5% CNF. The strawberries were immersed in the filmogenic solutions and kept under cold storage (1 ± 1°C). The color of the film was not affected by increased concentration of cellulose nanofibrils; however, the thickness and water vapor permeability were affected by the CNF addition. The coating with the highest CNF concentration performed better in reducing fruit mass and firmness loss. The color was positively influenced by the addition of the coating, regardless of formulation, as well as soluble solid content, PG enzymatic activity, and the fruit appearance. The pH and titratable acidity showed no significant difference among treatments. It was observed that the vitamin C, phenolic compounds, and anthocyanin content, as well as the PAL activity and the antioxidant activity (except for % protection), were affected by chitosan coating, however not by the addition of CNFs. [ABSTRACT FROM AUTHOR]

The aim of this study was to estimate the genetic diversity and structure of the only known population of minnow Astyanax xavante, which inhabits a stretch of river including several waterfalls. The FST values among the samples were not significant, except between two populations separated by a 30 m waterfall. Nevertheless, haplotype and nucleotide diversity increased in the downstream direction, indicating that gene flow is unidirectional, which indicates this genetic pattern as downstairs gene flow, as it has the effect of increasing genetic diversity in the downstream direction. [ABSTRACT FROM AUTHOR]

Abstract: We have demonstrated earlier that V717G-APP714–723, the membrane fragment of the V717G (“London”) familial Alzheimer’s disease (FAD) mutant of amyloid precursor protein (APP), is a potent stimulator of G-proteins in human brain membranes. In this study, we tested the hypothesis that Met-722 in the V717G-APP714–723 peptide (P2) plays a critical role in the P2-induced oxidative stimulation of G-proteins in the human temporal cortex membranes and in the neurotoxicity of the peptide in differentiated PC12 and cerebellar granular cells. We found that 10 μM P3, the Met-722 sulfoxide analog of P2, produced a twofold lower stimulation of G-proteins ([35S]-GTPγS binding) in control temporal cortex membranes compared with 10 μM P2. The stimulatory effect of 10 μM P4, the Met-722 sulfone analog of P2, was 2.5-fold lower than the effect of P2. In Alzheimer’s disease (AD) temporal cortex, the P3 and P4 stimulation of G-proteins was slightly weaker than the P2 stimulation. Substitution of the Met-722 S-atom in P2 by -CH2- group (P5) led to the disappearance of P2 stimulatory effect on G-proteins. Glutathione (GSH), melatonin (Mel), desferrioxamine (DFO) and 17-β-estradiol (17βE) significantly reduced P2 stimulatory effect on G-proteins in human brain. Only DFO and Mel were able to reduce the moderate stimulation of G-proteins by P3, whereas none of the tested antioxidants influenced the weak stimulation by P4. P2 at 100 μM induced a 40% decrease in PC12 cell viability as revealed by MTT assay, the effect being significantly higher than that of P3 or P4, whereas P1 (wild-type APP714–723) did not affect cell viability. Trypan Blue exclusion assay demonstrated that 10 μM P2 and P3 induced 3.8- and 3.5-fold death in the cerebellar granular cells as compared with the respective control values. P1 and P4 at 10 μM induced 1.7- and 2.3-fold increase in cell death, respectively. Treatment of the cerebellar granular cells with pertussis toxin decreased the high neurotoxicity of P2 and P3, whereas the low toxicity of P1 and P4 was not influenced. These results support the hypothesis that the G-protein stimulatory effect and neurotoxicity of “London”-mutated V717G-APP714–723 (P2) and its Met-722 oxidized analogs involve oxidative-dependent and oxidative-independent mechanisms and the oxidation state of Met-722 plays a critical role in determining the mechanism. [Copyright &y& Elsevier]

Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles in hypertension and progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients (47 males and 35 females; mean age 34.87±11.22 years). One hundred healthy subjects (54 males and 46 females; mean age 35.54±10.26 years) were also investigated for AGT polymorphism, and 80 healthy subjects (45 males and 35 females; mean age 36.54±12.41) for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction sequence-specific primers, and polymerase chain reaction followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than those without CAD. (P <0.05 and P <0.001, respectively) Presence of the MT genotype was significantly associated with CAD, and this genotype introduced a 3.5-fold risk of CAD compared with the MM genotype ( P <0.05; 95% confidence interval: 1.21–10.20). The transplant recipients with CAD also had significantly lower frequencies of the 5G/5G genotype and the 5G allele than those without CAD ( P <0.001 and P <0.05, respectively). Presence of the 4G allele introduced a 1.94-fold risk of CAD compared with the 5G allele (95% confidence interval: 1.05–3.66). Determination of AGT M235T and PAI-1 genotypes before transplantation may help identify patients who are at risk for chronic renal transplant dysfunction. [ABSTRACT FROM AUTHOR]

The expression and stability of receptors for the Fc region of human IgG on the surface of group A streptococci was studied. Two strains were sequentially passed in mice 22 times. The Fc-receptor expression on one group A strain, 529, was unaltered while the expression of Fc receptor on a second, 64, was enhanced and approached the level of Fc-receptor expression of the protein A-rich Staphylococcus aureus Cowan strain. The level of Fc-receptor expression on this organism remained stable for over 18 months of laboratory subculture. Mouse passage did not result in the production of a soluble Fc receptor from either of the streptococcal strains. Heat extraction of the Fc-receptor-positive group A strain resulted in solubilization of an Fc-receptor activity which was functionally distinct from either staphylococcal protein A or the Fc receptor isolated from a group C streptococcus. [ABSTRACT FROM AUTHOR]

Background: CAT employs 0.8-1% cells in a low ionic environment. In this study, the sensitivity of a CAT was assessed using manufactured ready-touse 0.8% antibody (Ab) screen (SC) and identification (ID) cells and a fully automated system (AutoVue™ [AV]). Study Design: AbSC and AbID tests using the indirect antiglobulin test were performed on AV. AbSCs were performed using 50 µL of a 0.8% RRBC 3-cell screen (0.8% Surgiscreen®) and 40 µL of serum/plasma in CAT-polyspecific anti-human globulin (PAHG) cassettes (Ortho BioVue™ [BV] PAHG) with a minimum incubation of 15 minutes at 37°C. AbIDs were performed manually using a ready-to-use panel (0.8% Resolve®) Panel A). The comparative gel test was performed using a PAHG gel card (DiaMed [DM] LISS/Coombs) and associated ready-to-use RRBC 3-cell screen and panel (ID-DiaCell and ID-DiaPanel) using a 15 minute incubation at 37°C. Four hundred forty three samples were evaluated, 363 random patient samples collected in EDTA and 80 non-random serum/plasma samples containing previously identified Abs. Repeat testing and/or Ab ID resolved samples that gave discrepant results. Abs to antigens present on only one manufacturer's AbSC cells were excluded from analysis. Results: AV/BV and DM antibody screen results agreed for 435 of 443 (98.2%) samples tested: 369 samples were negative and 66 samples were positive in both test systems. Overall, there were 27 RH, 12 KEL, 6 JK, 3 FY, 5 MNS, 2 LE, and 12 mixed blood group system antibodies, 1 auto antibody, 4 nonspecific and 2 false positives detected.The eight samples that did not agree (1.8%) were all positive in AV/BV and negative in DM. After repeat testing, 2 samples were identified as false positive (unable to repeat initial results). Ab detection of the remaining 6 samples revealed 4 specific antibodies, 1 antibody to red cell diluent and 1 unable to ID. The specific antibodies included 1 anti-Jk[sup a], 1 anti-K, 1 anti-Jk[sup a], -K and 1 anti-Le[sup a]. The sensitivity and specificity of the AV/ BV is 100% and 98.9% respectively, while DM is 94.3% and 100%. Conclusion: The use of a fully automated walk-away CAT test system AV/BV with ready- to-use RRBCs provides equivalent or better sensitivity than the manual DM gel test system. [ABSTRACT FROM AUTHOR]

The microbial remediation of 2,4,6-trinitrotoluene (TNT) contaminated soils is difficult because it is not possible to achieve mineralization of this substance. TNT can only be transformed via the sequence TNT yields 4-aminodinitrotoluene (4-ADNT) yields 2,4-diaminonitrotoluene (2,4-DANT) yields 2,4,6-triaminotoluene (TAT). TAT is formed whenredox potentials are below - 250 mV, otherwise 2,4-DANT is accumulated. If under in-situ conditions TNT or its metabolites are irreversibly incorporated into the humic matrix (humification) instead of beingsorbed, the humification might be used as a remediation technology. Equilibrium dialysis showed that TNT, 4-ADNT and 2,4-DANT did not adsorb on humic substances. However, in TNT- degradation studies under nitrogen limitation, the more humic substances were added the less metabolites were recovered proposing an efficient microorganism-mediatedincorporation (humification), probably based on stress-induced radical enzyme reactions. This assumption was supported by the observationthat 2,4-DANT but not TNT or 4-ADNT is attacked by the radicalic working enzyme peroxidase. Molar mass chromatography showed that 2,4-DANT is incorporated into the humic matrix by the peroxidase. The microbiologically formed 'bound residues' could not be released by drastic pH shifts to pH 2 or 12. Only methanolic saponification resulted in the release of about 10% of the bound residues. An in-situ remediationtechnology may include at first a stepwise microbial reduction of TNT to 2,4-DANT. Although under in-situ conditions TAT cannot be formedin a further step due to the redox potential higher than required, this is not necessary because the metabolite 2,4-DANT can be efficiently incorporated into humic substances. [ABSTRACT FROM AUTHOR]

Background:Many studies have shown that transforming growth factor(TGF)-beta has a major role in renal scarring in many renal diseases and hypertension.Objectives:The primary aim of this study was to investigate both the relationship between hypertension and serum and urinary levels of TGF-beta[2] (a more sensitive isoform for glomeruli than TGF-beta[1]), and the effects of combination therapy with perindopril + indapamide on microalbuminuria, which becomes an early indicator of hypertensive benign nephropathy, and serum and urinary TGF-beta[2] levels in patients with mild to moderate essential hypertension. In addition, we examined the possible relationship between TGF-beta[2] gene polymorphism and essential hypertension.Methods:This study was conducted at the Department of Nephrology, Medical Faculty, Gazi University, Ankara, Turkey. Patients aged >/=18 years with newly diagnosed mild to moderate essential hypertension (systolic/diastolic blood pressure [SBP/DBP] >120/>80 mm Hg) who had not previously received antihypertensive treatment were included in the study. Patients with stage I hypertension received perindopril 2 mg + indapamide 0.625 mg (tablet), and patients with stage lI hypertension received perindopril 4 mg + indapamide 1.125 mg (tablet). All study drugs were given OD (morning) PO with food for 6 months. Serum and urinary TGF-beta[2] and creatinine levels and serum and urinary albumin levels were measured before and after perindopril + indapamide administration. Amplified DNA fragments of the TGF-beta[2] primer region were screened using amplification refractory mutation system polymerase chain reaction analysis, and the number of ACA repeats was confirmed by DNA sequencing. Genetic studies were performed using a commercial TGF-beta[2] kit.Results:Forty patients were enrolled in the study, and 38 patients (27 women, 11 men; mean [SD] age, 46.3 [6.5] years) completed it. SBP and DBP were significantly decreased from baseline with perindopril/indapamide (both, P < 0.001). Microalbuminuria and urinary TGF-beta[2] levels also decreased significantly from baseline (P = 0.04 and P < 0.001, respectively), whereas the serum TGF-beta[2] level did not change significantly. Three patients, all of whom were found to have TGF-beta[2] gene mutations, had increased urinary TGF-beta[2] levels despite good blood pressure control.Conclusions:The results of this study in patients with mild to moderate hypertension suggest that, despite good clinical control of blood pressure, the persistence of microalbuminuria and high urinary TGF-beta[2] levels might predict renal impairment. When treating these patients, genetic tendencies and possible polymorphisms on the TGF-beta[2] locus should be kept in mind. [ABSTRACT FROM AUTHOR]

Suicidal ideation and depression are common in people living with HIV (PLWH) in sub-Saharan Africa, but longitudinal data on their persistence in the modern antiretroviral therapy era are lacking. We examined the prevalence of persistent suicidal ideation and depression symptoms using the PHQ-9 in a well-characterized cohort of PLWH and HIV-uninfected community controls. Multivariable logistic regression models were used to determine the relationship between HIV and persistent depression and suicidal ideation. Persistent suicidal ideation was more common in PLWH but there was no difference in persistent depression by HIV status. Approximately one out of five participants with depression at baseline had persistent depression after 12-24 months and only about one out of four participants reporting suicidal ideation at baseline had persistent suicidal ideation after 12-24 months. HIV was associated with suicidal ideation at baseline. Persistent suicidal ideation was significantly associated with HIV immune non-response (p = 0.022). These findings highlight the need for integration of mental health services into HIV care in sub-Saharan Africa with a focus on suicide prevention., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Psoriasis is an inflammatory skin disease with an estimated heritability of around 70%. Previous GWASs have detected several risk loci for psoriasis. To further improve the understanding of the genetic risk factors impacting the disease, we conducted a discovery GWAS in FinnGen and a subsequent replication and meta-analysis with data from the Estonian Biobank and the UK Biobank; the study sample included 925,649 individuals (22,659 cases and 902,990 controls), the largest sample for psoriasis yet. In addition, we conducted downstream analyses to find out more about psoriasis' cross-trait genetic correlations and causal relationships. We report 6 risk loci, which, to our knowledge, are previously unreported, most of which harbor genes related to NF-κB signaling pathway and overall immunity. Genetic correlations highlight the relationship between psoriasis and smoking, higher body weight, and lower education level. In addition, we report causal relationships between psoriasis and mood symptoms as well as 2-directioned causal relationship between psoriasis and lower education level. Our results provide further knowledge on psoriasis risk factors, which may be useful in the development of future treatment strategies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Gestational diabetes mellitus (GDM) is a common metabolic disorder affecting more than 16 million pregnancies annually worldwide 1,2 . GDM is related to an increased lifetime risk of type 2 diabetes (T2D) 1-3 , with over a third of women developing T2D within 15 years of their GDM diagnosis. The diseases are hypothesized to share a genetic predisposition 1-7 , but few studies have sought to uncover the genetic underpinnings of GDM. Most studies have evaluated the impact of T2D loci only 8-10 , and the three prior genome-wide association studies of GDM 11-13 have identified only five loci, limiting the power to assess to what extent variants or biological pathways are specific to GDM. We conducted the largest genome-wide association study of GDM to date in 12,332 cases and 131,109 parous female controls in the FinnGen study and identified 13 GDM-associated loci, including nine new loci. Genetic features distinct from T2D were identified both at the locus and genomic scale. Our results suggest that the genetics of GDM risk falls into the following two distinct categories: one part conventional T2D polygenic risk and one part predominantly influencing mechanisms disrupted in pregnancy. Loci with GDM-predominant effects map to genes related to islet cells, central glucose homeostasis, steroidogenesis and placental expression., (© 2024. The Author(s).)

Introduction: For people living with HIV/AIDS, care is commonly delivered through Differentiated Service Delivery (DSD). Although people with multidrug-resistant tuberculosis (MDR-TB) and HIV/AIDS experience severe treatment associated challenges, there is no DSD model to support their treatment. In this study, we defined patterns of medication adherence and characterized longitudinal barriers to inform development of an MDR-TB/HIV DSD framework., Methods: Adults with MDR-TB and HIV initiating bedaquiline (BDQ) and receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa, were enrolled and followed through the end of MDR-TB treatment. Electronic dose monitoring devices (EDM) measured BDQ and ART adherence. Longitudinal focus groups were conducted and transcripts analyzed thematically to describe discrete treatment stage-specific and cross-cutting treatment challenges., Results: 283 participants were enrolled and followed through treatment completion (median 17.8 months [IQR 16.5-20.2]). Thirteen focus groups were conducted. Most participants (82.7%, 234/283) maintained high adherence (mean BDQ adherence 95.3%; mean ART adherence 85.5%), but an adherence-challenged subpopulation with <85% cumulative adherence (17.3%, 49/283) had significant declines in mean weekly BDQ adherence from 94.9% to 39.9% (p<0.0001) and mean weekly ART adherence from 83.9% to 26.6% (p<0.0001) over 6 months. Psychosocial, behavioral, and structural obstacles identified in qualitative data were associated with adherence deficits in discrete treatment stages, and identified potential stage specific interventions., Conclusion: A DSD framework for MDR-TB/HIV should intensify support for adherence-challenged subpopulations, provide multi-modal support for adherence across the treatment course and account for psychosocial, behavioral, and structural challenges linked to discrete treatment stages., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This systematic and meta-analysis review evaluated the transcutaneous electrical nerve stimulation (TENS)-induced action mechanisms for animal analgesia., Materials and Methods: Two independent investigators identified relevant articles published until February 2021 through a literature review, and a random-effects meta-analysis was performed to synthesize the results., Results: Of the 6984 studies found in the data base search, 53 full-text articles were selected and used in the systematic review. Most studies used Sprague Dawley rats (66.03%). High-frequency TENS was applied to at least one group in 47 studies, and most applications were performed for 20 minutes (64.15%). Mechanical hyperalgesia was analyzed as the primary outcome in 52.83% of the studies and thermal hyperalgesia in 23.07% of studies using a heated surface. More than 50% of the studies showed a low risk of bias on allocation concealment, random housing, selective outcome reporting, and acclimatization before the behavioral tests. Blinding was not performed in only one study and random outcome assessment in another study; acclimatization before the behavioral tests was not performed in just one study. Many studies had an uncertain risk of bias. Meta-analyses indicated no difference between low-frequency and high-frequency TENS with variations among the pain models., Conclusions: This systematic review and meta-analysis suggests that TENS has presented a substantial scientific foundation for its hypoalgesic effect in preclinical studies for analgesia., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: Highly effective, short-course, bedaquiline-containing treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and integrase strand transfer inhibitor (INSTI)-containing fixed dose combination antiretroviral therapy (ART) have radically transformed treatment for MDR-TB and HIV. However, without advances in adherence support, we may not realize the full potential of these therapeutics. The primary objective of this study is to compare the effect of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform., Methods: This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of four adherence support strategies on a composite clinical outcome in adults with MDR-TB and HIV initiating bedaquiline-containing MDR-TB treatment regimens and receiving ART in KwaZulu-Natal, South Africa. Trial arms include (1) enhanced standard of care, (2) psychosocial support, (3) mHealth using cellular-enabled electronic dose monitoring, and (4) combined mHealth and psychosocial support. The level of support will be titrated using a differentiated service delivery (DSD)-informed assessment of treatment support needs. The composite primary outcome will include survival, negative TB culture, retention in care, and undetectable HIV viral load at month 12. Secondary outcomes will include individual components of the primary outcome and quantitative evaluation of adherence on TB and HIV treatment outcomes., Discussion: This trial will evaluate the contribution of different modes of adherence support on MDR-TB and HIV outcomes with WHO-recommended all-oral MDR-TB regimens and ART in a high-burden operational setting. We will also assess the utility of a DSD framework to pragmatically adjust levels of MDR-TB and HIV treatment support., Trial Registration: ClinicalTrials.gov NCT05633056. Registered on 1 December 2022., (© 2023. The Author(s).)

Red rot, caused by Colletotrichum falcatum , is an important constraint to sugarcane production. In Louisiana, red rot primarily affects planted seed-cane and is more severe when billets (stalk sections) are planted rather than whole stalks. At planting, application of seed-treatment pesticides, particularly a combination of a fungicide and the insecticide thiamethoxam, has improved stand establishment and increased yields in billet plantings in Louisiana. However, information on the effect of chemicals on disease development is lacking. Greenhouse experiments were conducted to evaluate stalk rot symptom severity and initial plant growth for billets dip-treated with a combination of the fungicides azoxystrobin and propiconazole, thiamethoxam, a combination of both fungicides and the insecticide, and, as a control, untreated billets. Reductions in disease severity recorded for different treatments were similar for billets inoculated with the fungus or exposed to natural inoculum. Disease severity was consistently reduced by the combination treatment, while reductions resulting from treatment with fungicides and insecticide alone were variable. Reductions occurred for both internode and node rot severity. The effects of pesticide treatments on plant growth after 6 weeks were minor; however, there was evidence of disease adversely affecting germination, particularly for nontreated billets exposed to natural inoculum, where germination was reduced by one third. The treatments that reduced disease severity prevented this reduction. The results provide evidence that reduction in disease severity is an important contributor to the stand establishment and yield improvements observed for treated billets in field experiments., Competing Interests: The author(s) declare no conflict of interest.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities., (© 2023. Springer Nature Limited.)

Objectives: A frequently suggested approach to reduce greenhouse gas emissions (GHGEs) caused by food production is to reduce the intake of animal products, which can create nutritional deficiencies. This study aimed to identify culturally acceptable nutritional solutions for German adults that are both climate friendly and health promoting., Methods: Linear programming was applied to optimize the food supply for omnivores, pescatarians, vegetarians, and vegans considering nutritional adequacy, health promotion, GHGEs, affordability, and cultural acceptability by approaching German national food consumption., Results: Implementing dietary reference values and omitting meat (products) reduced the GHGEs by ≤52%. The vegan diet was alone in staying below the Intergovernmental Panel on Climate Change (IPCC) threshold of 1.6 kg carbon dioxide equivalents per person per day. The optimized omnivorous diet constrained to meet this goal maintained ≥50% of each baseline food and, on average, deviated from baseline by 36% for women and 64% for men. Butter, milk, meat products, and cheese were reduced by half for both sexes, whereas bread, bakery goods, milk, and meat were reduced mainly for men. The intake of vegetables, cereals, pulses, mushrooms, and fish increased by between 63% and 260% for the omnivores, compared with baseline. Besides the vegan dietary pattern, all optimized diets cost less than the baseline diet., Conclusions: A linear programming approach for optimizing the German habitual diet to be healthy, affordable, and meet the IPCC GHGE threshold was possible for several dietary patterns and appears to be a feasible way forward toward including climate goals into food-based dietary guidelines., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A promising strategy for cocaine addiction treatment is the anti-drug vaccine. These vaccines induce the production of anticocaine antibodies, capable of linking to cocaine, and decrease the passage of cocaine throughout the blood-brain barrier, decreasing drug activity in the brain. Our research group developed a new vaccine candidate, the UFMG-V4N2, to treat cocaine use disorders (CUD) using an innovative carrier based on calixarenes. This study assessed the safety and immunogenicity of the anti-cocaine vaccine UFMG-VAC-V4N2 in a non-human primate toxicity study using single and multiple vaccine doses. The UFMG-VAC-V4N2 yielded only mild effects in the injection site and did not influence the general health, feeding behavior, or hematological, renal, hepatic, or metabolic parameters in the vaccinated marmosets. The anti-cocaine vaccine UFMG-VAC-V4N2 presented a favorable safety profile and induced the expected immune response in a non-human primate model of Callithrix penicillata. This preclinical UFMG-VAC-V4N2 study responds to the criteria required by international regulatory agencies contributing to future anticocaine clinical trials of this anti-cocaine vaccine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored 1,2 . FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10 -11 ) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants., (© 2023. The Author(s).)