Genome-wide association studies of salinity tolerance in local aman rice.

The present study aimed to identify and characterize new sources of salt tolerance among 94 rice varieties from varied geographic origins. The genotypes were divided into five groups based on their morphological characteristics at both vegetative and reproductive stages using salinity scores from the Standard Evaluation System (SES). The experiment was designed as per CRD (Completely Randomized Design) with 2 sets of salinity treatments for 8 dS/meter and 12 dS/meter, respectively compared with one non-salinized control set. Using a Soil Plant Analysis Development (SPAD) meter, assessments of the apparent chlorophyll content (greenness) of the genotypes were done to comprehend the mechanism underlying their salt tolerance.  To evaluate molecular genetic diversity, a panel of 1 K RiCA SNP markers was employed. Utilizing TASSEL 5.0 software, 598 filtered SNPs were used for molecular analysis. Whole-genome association studies (GWAS) were also used to investigate panicle number per plant (pn, tiller number per plant (till), SPAD value (spad), sterility (percent) (str), plant height (ph) and panicle length (pl. It is noteworthy that these characteristics oversee conveying the visible signs of salt damage in rice. Based on genotype data, diversity analysis divided the germplasm groups into four distinct clusters (I, II, III and IV). For the traits studied, thirteen significant marker-trait associations were discovered. According to the phenotypic screening, seven germplasm genotypes namely Koijuri, Asha, Kajal, Kaliboro, Hanumanjata, Akundi and Dular, are highly tolerant to salinity stress. The greenness of these genotypes was found to be more stable over time, indicating that these genotypes are more resistant to stress. Regarding their tolerance levels, the GWAS analysis produced comparable results, supporting that salinity-tolerant genotypes having minor alleles in significant SNP positions showed more greenness during the stress period. The Manhattan plot demonstrated that at the designated significant SNP position, the highly tolerant genotypes shared common alleles. These genotypes could therefore be seen as important genomic resources for accelerating the development and release of rice varieties that are tolerant to salinity.

Assessment and report of individual symptoms in studies of delirium in postoperative populations: a systematic review.

OBJECTIVES: Delirium is most often reported as present or absent. Patients with symptoms falling short of the diagnostic criteria for delirium fall into 'no delirium' or 'control' groups. This binary classification neglects individual symptoms and may be hindering identification of the pathophysiology underlying delirium. This systematic review investigates which individual symptoms of delirium are reported by studies of postoperative delirium in adults. METHODS: Medline, EMBASE and Web of Science databases were searched on 03 June 2021 and 06 April 2023. Two reviewers independently examined titles and abstracts. Each paper was screened in duplicate and conflicting decisions settled by consensus discussion. Data were extracted, qualitatively synthesised and narratively reported. All included studies were quality assessed. RESULTS: These searches yielded 4,367 results. After title and abstract screening, 694 full-text studies were reviewed, and 62 deemed eligible for inclusion. This review details 11,377 patients including 2,049 patients with delirium. In total, 78 differently described delirium symptoms were reported. The most reported symptoms were inattention (N = 29), disorientation (N = 27), psychomotor agitation/retardation (N = 22), hallucination (N = 22) and memory impairment (N = 18). Notably, psychomotor agitation and hallucinations are not listed in the current Diagnostic and Statistical Manual for Mental Disorders-5-Text Revision delirium definition. CONCLUSIONS: The 78 symptoms reported in this systematic review cover domains of attention, awareness, disorientation and other cognitive changes. There is a lack of standardisation of terms, and many recorded symptoms are synonyms of each other. This systematic review provides a library of individual delirium symptoms, which may be used to inform future reporting.

Leveraging deep neural networks to uncover unprecedented levels of precision in the diagnosis of hair and scalp disorders.

BACKGROUND: Hair and scalp disorders present a significant challenge in dermatology due to their clinical diversity and overlapping symptoms, often leading to misdiagnoses. Traditional diagnostic methods rely heavily on clinical expertise and are limited by subjectivity and accessibility, necessitating more advanced and accessible diagnostic tools. Artificial intelligence (AI) and deep learning offer a promising solution for more accurate and efficient diagnosis. METHODS: The research employs a modified Xception model incorporating ReLU activation, dense layers, global average pooling, regularization and dropout layers. This deep learning approach is evaluated against existing models like VGG19, Inception, ResNet, and DenseNet for its efficacy in accurately diagnosing various hair and scalp disorders. RESULTS: The model achieved a 92% accuracy rate, significantly outperforming the comparative models, with accuracies ranging from 50% to 80%. Explainable AI techniques like Gradient-weighted Class Activation Mapping (Grad-CAM) and Saliency Map provided deeper insights into the model's decision-making process. CONCLUSION: This study emphasizes the potential of AI in dermatology, particularly in accurately diagnosing hair and scalp disorders. The superior accuracy and interpretability of the model represents a significant advancement in dermatological diagnostics, promising more reliable and accessible diagnostic methods.

Dishevelled 2 regulates cancer cell proliferation and T cell mediated immunity in HER2-positive breast cancer.

BACKGROUND: Dishevelled paralogs (DVL1, 2, 3) are key mediators of Wnt pathway playing a role in constitutive oncogenic signaling influencing the tumor microenvironment. While previous studies showed correlation of ß-catenin with T cell gene expression, little is known about the role of DVL2 in modulating tumor immunity. This study aimed to uncover the novel interaction between DVL2 and HER2-positive (HER2+) breast cancer (BC) in regulating tumor immunity and disease progression. METHODS: DVL2 loss of function studies were performed with or without a clinically approved HER2 inhibitor, Neratinib in two different HER2+ BC cell lines. We analyzed RNA (RT-qPCR) and protein (western blot) expression of classic Wnt markers and performed cell proliferation and cell cycle analyses by live cell imaging and flow cytometry, respectively. A pilot study in 24 HER2+ BC patients was performed to dissect the role of DVL2 in tumor immunity. Retrospective chart review on patient records and banked tissue histology were performed. Data were analyzed in SPSS (version 25) and GraphPad Prism (version 7) at a significance p < 0.05. RESULTS: DVL2 regulates the transcription of immune modulatory genes involved in antigen presentation and T cell maintenance. DVL2 loss of function down regulated mRNA expression of Wnt target genes involved in cell proliferation, migration, invasion in HER2+ BC cell lines (±Neratinib). Similarly, live cell proliferation and cell cycle analyses reveal that DVL2 knockdown (±Neratinib) resulted in reduced proliferation, higher growth arrest (G1), limited mitosis (G2/M) compared to non-targeted control in one of the two cell lines used. Analyses on patient tissues who received neoadjuvant chemotherapy (n = 14) further demonstrate that higher DVL2 expression at baseline biopsy pose a significant negative correlation with % CD8α levels (r = - 0.67, p < 0.05) while have a positive correlation with NLR (r = 0.58, p < 0.05), where high NLR denotes worse cancer prognosis. These results from our pilot study reveal interesting roles of DVL2 proteins in regulating tumor immune microenvironment and clinical predictors of survival in HER2+ BC. CONCLUSION: Our study demonstrates potential immune regulatory role of DVL2 proteins in HER2+ BC. More in-depth mechanistic studies of DVL paralogs and their influence on anti-tumor immunity may provide insight into DVLs as potential therapeutic targets benefiting BC patients.

Sequence variability of CatSper1 and TNP2 gene in indigenous and crossbred cattle in Bangladesh.

CatSper1 and TNP2 genes are known to affect semen quality and fertility parameters, including sperm motility and maturation. However, studies are yet to examine the genes in indigenous and crossbred cattle in Bangladesh. Therefore, this study was conducted to determine the genetic variants of CatSper1 and TNP2 in indigenous and crossbred cattle in Bangladesh. Blood samples were collected from 130 indigenous and 70 crossbred (Holstein Friesian × indigenous) cattle. Nucleotide variation was evaluated by PCR-RFLP and sequencing. The results of the study showed that the indigenous cattle possessed only TT genotype (1.0), whereas the crossbreds possessed both TT (0.91) and CT (0.09) genotypes, which was validated by gene sequencing. Additionally, the CatSper1 was conserved in both the indigenous and crossbred cattle, suggesting good semen quality and fertility. However, the TNP2 was conserved in the indigenous breeds and mostly conserved in the crossbreds. The findings of this study reveal the diversity of CatSper1 and TNP2 genes in indigenous and crossbred cattle.

Newborn behavioral observations system in rural Pakistan: A feasibility and acceptability study.

The Newborn Behavioral Observations (NBO) system is a relationship-based tool that helps parents recognize their infant's competencies and learn their behavioral cues, with the goals of enhancing parental responsiveness and satisfaction in the infant-parent relationship. In our study, a pediatrician integrated the NBO into 44 pediatric health care visits of infants in rural Pakistan villages, under the remote guidance of two U.S.-based child psychiatrists. A clinician then gave the mothers a survey about their experience of the NBO and found that the mothers were highly satisfied, reporting greater appreciation of their infant's strengths, greater understanding of their infant's behavioral cues, stronger attachment to their infant, and greater self-confidence as a mother. In their consideration of these results, the authors explore cultural reasons for the mothers' responses and generate hypotheses to inform an outcome study of a similar intervention. This was a feasibility and acceptability study and was not randomized, had no control group, and did not use objective measures of outcome.

El sistema de Observaciones de Comportamiento del Recién Nacido (NBO)™ es una herramienta basada en la relación que se enfoca en ayudar a los padres a reconocer las competencias de su infante y aprender sus señales de comportamiento, con el propósito de mejorar la sensibilidad y satisfacción del progenitor en la relación infante-progenitor. En este estudio de probabilidad y aceptabilidad, un clínico pediatra integró el NBO dentro de 44 visitas de cuidado de salud pediátricas a infantes en aldeas rurales en Pakistán, bajo la guía remota de dos siquiatras infantiles con base en los Estados Unidos. Entonces, un clínico les dio a las madres una encuesta acerca de su experiencia con el NBO y se encontró que las madres estaban altamente satisfechas, reportando un mayor aprecio por los puntos fuertes de sus infantes, una mayor comprensión de las señalas de comportamiento de sus infantes, una más fuerte afectividad hacia sus infantes, así como una mayor auto confianza como madre. En sus consideraciones de estos resultados, los autores exploran razones culturales para las respuestas de las madres y generan hipótesis como información para un estudio de resultado de una intervención similar.

Le système d'observation comportementale du nouveau-né (Newborn Behavioral Observations, abrégé selon l'anglais NBO system™) est un outil basé sur la relation se concentrant sur l'aide aux parents à reconnaître les compétences de leur nourrisson et à comprendre leurs signaux de comportement, se donnant pour but de mettre en valeur la réaction parentale et la satisfaction dans la relation nourrisson-parent. Dans cette étude de faisabilité et d'acceptabilité un clinicien en pédiatrie a intégré le NBO dans 44 visites de santé pédiatrique de nourrissons dans des villages du Pakistan rural, sous l'orientation professionnelle à distance de deux psychiatres de l'enfance basés aux Etats-Unis d'Amérique. Un clinicien a ensuite donné aux mères un questionnaires sur leur expérience du NBO et a trouvé que les mères étaient très satisfaites, faisant état d'une plus grande appréciation des forces de leurs nourrissons, d'une plus grande compréhension des signaux de comportement de leur nourrisson, d'un attachement plus fort à leur nourrisson et d'une plus grande confiance en soi en tant que mère. Dans leur considération de ces résultats les auteurs explorent les raisons culturelles expliquant les réponses des mères et génèrent des hypothèses pour informer une étude d'une intervention similaire.

Scrutinizing Deleterious Nonsynonymous SNPs and Their Effect on Human POLD1 Gene.

POLD1 (DNA polymerase delta 1, catalytic subunit) is a protein-coding gene that encodes the large catalytic subunit (POLD1/p125) of the DNA polymerase delta (Polδ) complex. The consequence of missense or nonsynonymous SNPs (nsSNPs), which occur in the coding region of a specific gene, is the replacement of single amino acid. It may also change the structure, stability, and/or functions of the protein. Mutation in the POLD1 gene is associated with autosomal dominant predisposition to colonic adenomatous polyps, colon cancer, endometrial cancer (EDMC), breast cancer, and brain tumors. These de novo mutations in the POLD1 gene also result in autosomal dominant MDPL syndrome (mandibular hypoplasia, deafness, progeroid features, and lipodystrophy). In this study, genetic variations of POLD1 which may affect the structure and/or function were analyzed using different types of bioinformatics tools. A total of 17038 nsSNPs for POLD1 were collected from the NCBI database, among which 1317 were missense variants. Out of all missense nsSNPs, 28 were found to be deleterious functionally and structurally. Among these deleterious nsSNPs, 23 showed a conservation scale of >5, 2 were predicted to be associated with binding site formation, and one acted as a posttranslational modification site. All of them were involved in coil, extracellular structures, or helix formation, and some cause the change in size, charge, and hydrophobicity.

Heterogeneity in prevalence of subclinical Plasmodium falciparum and Plasmodium vivax infections but no parasite genomic clustering in the Chittagong Hill Tracts, Bangladesh.

BACKGROUND: Malaria remains endemic in Bangladesh, with the majority of cases occurring in forested, mountainous region in the Chittagong Hill Tracts (CHT). This area is home to Bengali and diverse groups of indigenous people (Pahari) residing largely in mono-ethnic villages. METHODS: 1002 individuals of the 9 most prominent Pahari and the Bengali population were randomly selected and screened by RDT and qPCR. Parasites were genotyped by msp2 and deep sequencing of 5 amplicons (ama1-D3, cpmp, cpp, csp, and msp7) for Plasmodium falciparum (n = 20), and by microsatellite (MS) typing of ten loci and amplicon sequencing of msp1 for Plasmodium vivax (n = 21). Population structure was analysed using STRUCTURE software. Identity-by-state (IBS) was calculated as a measure of parasite relatedness and used to generate relatedness networks. RESULTS: The prevalence of P. falciparum and P. vivax infection was 0.7% by RDT (P. falciparum 6/1002; P. vivax 0/1002, mixed: 1/1002) and 4% by qPCR (P. falciparum 21/1002; P. vivax 16/1002, mixed: 5/1002). Infections were highly clustered, with 64% (27/42) of infections occurring in only two Pahari groups, the Khumi and Mro. Diversity was high; expected heterozygosity was 0.93 for P. falciparum and 0.81 for P. vivax. 85.7% (18/21) of P. vivax and 25% (5/20) of P. falciparum infections were polyclonal. No population structure was evident for either species, suggesting high transmission and gene flow among Pahari groups. CONCLUSIONS: High subclinical infection prevalence and genetic diversity mirror ongoing transmission. Control activities should be specifically directed to Pahari groups at greatest risk.

Adverse childhood experiences and risk factors associated with asthma among children in the United States: the intersection of sex and race/ethnicity.

OBJECTIVE: The objectives of this cross-sectional study were to examine: 1) the association between adverse childhood experiences (ACEs) and asthma among children, and 2) the interaction between sex and race/ethnicity on asthma. METHODS: Data for this study were obtained from the 2017-2018 National Survey of Children's Health. Binary logistic regression was conducted on an analytic sample of 49,000 children ages 0-17 years with asthma as the outcome variable and ACEs as the main explanatory variable. RESULTS: Based on parent reports, we found that 11.5% of children had asthma and about 42% had at least one ACE, with 9.7% having ≥3 ACEs. Controlling for other factors, children with ≥3 ACEs had 1.45 times higher odds of having asthma when compared to children with no ACEs. Non-Hispanic Black males and females were more likely to have asthma when compared to non-Hispanic White males. CONCLUSIONS: The findings of this study demonstrate an association between ACEs and asthma with children exposed to ≥3 ACEs more likely to have asthma underscoring the importance of cumulative effect of ACEs on asthma. Our study also revealed an interaction between sex and race/ethnicity on asthma among children. Additional studies are needed to understand the mechanisms through which ACEs is associated with asthma among children.

Seasonal influenza vaccine uptake among healthcare workers in tertiary care hospitals, Bangladesh: Study protocol for influenza vaccine supply and awareness intervention.

BACKGROUND: Healthcare workers (HCWs), such as doctors, nurses, and support staffs involved in direct or indirect patient care, are at increased risk of influenza virus infections due to occupational exposures. Vaccination is the most effective way to prevent influenza. Despite the World Health Organization (WHO) recommendations, Bangladesh lacks a seasonal influenza vaccination policy for HCWs, and thus vaccination rates remain low. The current project aims to investigate the effect of interventions on influenza vaccine awareness and availability of vaccine supply, explore HCWs' knowledge and perceptions about influenza vaccination, understand the barriers and motivators for influenza vaccine uptake, and understand policymakers' views on the practicality of influenza vaccination among HCWs. METHOD: We will conduct the study at four tertiary care teaching hospitals in Bangladesh, using a cluster randomized controlled trial approach, with the hospital as the unit of randomization and intervention. The study population will include all types of HCWs.The four different types of intervention will be randomly allocated and implemented in four study hospitals separately. The four interventions will be: i) ensuring the availability of influenza vaccine supply; ii) developing influenza vaccine awareness; iii) both ensuring influenza vaccine supply and developing influenza vaccine awareness and iv) control arm with no intervention. Both quantitative and qualitative approaches will be applied to assess the intervention effect. We will estimate the Difference in Differences (DID) with 95% CI of the proportion of vaccine uptake between each intervention and control (non-intervention) arm, adjusting for the clustering effect. The qualitative data will be summarised using a framework matrix method. DISCUSSION: The results of this study will inform the development and implementation of a context-specific strategy to enhance influenza vaccination rates among Bangladeshi HCWs. TRIAL REGISTRATION: Clinicaltrials.gov NCT05521763. Version 2.0 was registered in September 2022, and the first participant enrolled in March 2022. Retrospectively registered.

Genotyping of κ-casein and ß-lactoglobulin genes in native cattle from Barishal region of Bangladesh.

The study was conducted to determine the genetic variants of κ-casein and ß-lactoglobulin genes in native cattle. DNA was extracted from blood samples (n = 80) collected from Babuganj, Barishal followed by PCR with gene-specific primers. Genotyping was done by RFLP with HindIII, and HaeIII restriction enzymes. Allelic and genotypic frequencies, genetic diversity, heterozygosity and Hardy-Weinberg equilibrium were estimated using the Popgen32 software. A total 80 samples were genotyped and three genotypes, namely AA, AB and BB, were detected for both the genes. In case of κ-casein gene, higher frequency was observed for AA genotype (0.73) followed by AB (0.23) and BB (0.04) genotype. A allele (0.84) was found to dominate over B allele (0.16). For ß-lactoglobulin gene, BB genotype (0.66) was found more frequently than AB (0.18) and AA (0.16) genotypes. Highest frequency was found for B (0.75) followed by A (0.25) allele. The average genetic diversity (He) was 0.38. The result indicated differences between observed (Ho) and expected (He) heterozygosity and it was out of equilibrium genetics, assumed that selection pressure was in population. To the best of our knowledge, this is the first reported study on κ-casein and ß-lactoglobulin gene variants analysis in cattle in Bangladesh.

Livelihood challenges and healthcare-seeking behavior of fishermen amidst the COVID-19 pandemic in the Sundarbans mangrove forest of Bangladesh.

The outbreak of coronavirus disease (COVID-19) has posed significant challenges to human wellbeing and survival, particularly among groups of people such as the Sundarbans mangrove forest resource-dependent communities (SMFRDCs), and especially the fishermen in these communities, in developing countries like Bangladesh. It is therefore essential to explore the livelihood conditions, health status and care-seeking behavior of the fishermen in these communities during the ongoing pandemic. This study was carried out by applying mixed methods, including interviews and focus group discussion (FGD), in the three sub-districts of Khulna, Satkhira, and Bagerhat, which are in the southwestern region adjacent to the Sundarbans mangrove forest (SMF) of Bangladesh. Quantitative data were collected from 76 fishermen through telephone interviews, while 24 fishermen participated in three distinct focus group discussions. The findings suggest that the fishermen have experienced a reduction of income, as they have been barred from entering the SMF during the pandemic, which has gradually affected their number of trips to and stays at the forest as well as their catch of fisheries resources. The decline in demand in both regional and international markets has left the fishermen with only a handful of alternative ways to adjust to these unprecedented circumstances, such as borrowing money, selling household assets, and in some extreme cases marrying off young children to reduce the financial burden, as many are now jobless. Their financial hardship during the pandemic has affected their households' capacity to afford basic household necessities, including food, fuel, education, and health expenses. Subsequently, when these fishermen suffer ailments such as fever, cough, headache, and cold - the general symptoms of COVID-19 - they cannot seek medical assistance from trained doctors. Their financial constraints have compelled them to rely on indigenous knowledge, in particular village quack doctors, or in some cases to seek help from local pharmacies for modern medicine. Thus, the government should provide financial support and strengthen the local market value chain so that disadvantaged fishermen in SMFRDCs can adopt alternative livelihood opportunities. Furthermore, longitudinal research on the impacts of COVID-19 on livelihood, local adaptation strategies, health status, and care-seeking behavior is also strongly recommended.

Characterization and survival of broad-spectrum biocontrol agents against phytopathogenic fungi.

The current study intended to isolate, characterize and identify biocontrol bacteria possessing broad-spectrum antifungal activity from the phyllosphere of different crops including maize, wheat and potato and to assess their growth-promoting activity. In this study 14/113 biocontrol bacteria showed antifungal activity. Bacterial isolates M11 and M33 from maize out of 113 were re-selected on the basis of their strong (more than 50%) broad spectrum antifungal activity after their assessment against four economically important phytopathogenic fungi including Alternaria alternata, Rhizoctonia solani, Fusarium oxysporum and Fusarium verticillioides. The isolates were further assessed for plant growth promoting traits, i.e., indole-3-acetic acid production, phosphate solubilization, production of cellulase, microbial volatile compounds, hydrogen cyanide and siderophores. All fourteen isolates showed positive results for the production of indole-3-acetic acid hormone and cellulase enzyme, 10 isolates were positive for hydrogen cyanide production; siderophores production was observed in 7 isolates while 5 isolates showed ability to solubilize inorganic phosphate. Microbial volatile compounds were only synthesized by M11 and M33, which were identified as Bacillus amyloliquefaciens and Bacillus subtilis respectively by 16S rRNA gene sequencing. The survival study revealed that biocontrol bacteria B. amyloliquefaciens and B. subtilis have the ability to survive in cost effective molasses containing carrier material up to a three-month period.

Gut Microbiota and Development of Vibrio cholerae-Specific Long-Term Memory B Cells in Adults after Whole-Cell Killed Oral Cholera Vaccine.

Cholera is a diarrheal disease caused by Vibrio cholerae that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the V. cholerae O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to V. cholerae and may be a major determinant of long-term protection against cholera. Shanchol, a widely used oral cholera vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype or OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower abundance of Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1ß and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may "prime" the mucosal immune response to vaccine antigens. Our results suggest the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential vaccine adjuvants is warranted.

Glucose-6-phosphate dehydrogenase activity in individuals with and without malaria: Analysis of clinical trial, cross-sectional and case-control data from Bangladesh.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) activity is dependent upon G6PD genotype and age of the red blood cell (RBC) population, with younger RBCs having higher activity. Peripheral parasitemia with Plasmodium spp. induces hemolysis, replacing older RBCs with younger cells with higher G6PD activity. This study aimed to assess whether G6PD activity varies between individuals with and without malaria or a history of malaria. METHODS AND FINDINGS: Individuals living in the Chittagong Hill Tracts of Bangladesh were enrolled into 3 complementary studies: (i) a prospective, single-arm clinical efficacy trial of patients (n = 175) with uncomplicated malaria done between 2014 and 2015, (ii) a cross-sectional survey done between 2015 and 2016 (n = 999), and (iii) a matched case-control study of aparasitemic individuals with and without a history of malaria done in 2020 (n = 506). G6PD activity was compared between individuals with and without malaria diagnosed by microscopy, rapid diagnostic test (RDT), or polymerase chain reaction (PCR), and in aparasitemic participants with and without a history of malaria. In the cross-sectional survey and clinical trial, 15.5% (182/1,174) of participants had peripheral parasitemia detected by microscopy or RDT, 3.1% (36/1,174) were positive by PCR only, and 81.4% (956/1,174) were aparasitemic. Aparasitemic individuals had significantly lower G6PD activity (median 6.9 U/g Hb, IQR 5.2-8.6) than those with peripheral parasitemia detected by microscopy or RDT (7.9 U/g Hb, IQR 6.6-9.8, p < 0.001), but G6PD activity similar to those with parasitemia detected by PCR alone (submicroscopic parasitemia) (6.1 U/g Hb, IQR 4.8-8.6, p = 0.312). In total, 7.7% (14/182) of patients with malaria had G6PD activity < 70% compared to 25.0% (248/992) of participants with submicroscopic or no parasitemia (odds ratio [OR] 0.25, 95% CI 0.14-0.44, p < 0.001). In the case-control study, the median G6PD activity was 10.3 U/g Hb (IQR 8.8-12.2) in 253 patients with a history of malaria and 10.2 U/g Hb (IQR 8.7-11.8) in 253 individuals without a history of malaria (p = 0.323). The proportion of individuals with G6PD activity < 70% was 11.5% (29/253) in the cases and 15.4% (39/253) in the controls (OR 0.7, 95% CI 0.41-1.23, p = 0.192). Limitations of the study included the non-contemporaneous nature of the clinical trial and cross-sectional survey. CONCLUSIONS: Patients with acute malaria had significantly higher G6PD activity than individuals without malaria, and this could not be accounted for by a protective effect of G6PD deficiency. G6PD-deficient patients with malaria may have higher than expected G6PD enzyme activity and an attenuated risk of primaquine-induced hemolysis compared to the risk when not infected.

The impact of cognitive impairment on self-regulatory styles in breast cancer survivors.

OBJECTIVE: Cognitive impairment (CI) is highly prevalent in breast cancer survivors (BCS), and can be a barrier to health-promoting behaviours. However, the ways in which CI may affect self-regulation or motivation to perform such behaviours have not been explored. We assessed if BCS with CI report greater extrinsic self-regulation compared to those without CI and if this relationship persists after controlling for depression. METHODS: We recruited BCS with diabetes and assessed cognition and motivation to perform healthy diabetes management behaviours (e.g., diet and exercise). Participants completed a cognitive battery evaluating attention, working memory, executive functioning (EF), processing speed (PS), language and memory. The Treatment Self-Regulation Questionnaire (TSRQ) assessed intrinsic versus extrinsic motivation. Depression was determined by a score ≥16 on the Center for Epidemiological Studies Depression Scale. Wilcoxon rank-sum test compared associations between CI and TSRQ scores. RESULTS: Participants were 118 older adults (mean age 65 years). Participants with CI in the following domains had higher extrinsic self-regulation scores compared to those without CI: attention (p < 0.01), PS (p = 0.01), EF (p < 0.01), language (p = 0.02; p = 0.04) and memory (p = 0.04; p = 0.03). After adjusting for depression, the relationship between CI and higher extrinsic self-regulation scores remained significant. CONCLUSIONS: BCS with CI appear to rely more on external sources of motivation to perform health behaviours, regardless of depression. Future studies and interventions to improve health behaviours should consider screening for CI and involving caregivers for those with CI to improve outcomes.

Genetic architecture of Al3+ toxicity tolerance in rice F2:3 populations determined through QTL mapping.

Aluminum (Al3+) toxicity is one of the factors limiting crop production in acidic soils. Identifying quantitative trait loci (QTLs)/genes for tolerance to Al3+ toxicity at seed germination can aid the development of new tolerant cultivars. The segregating population derived from Pak Basmati (Indica) × Pokkali (Indica) was used for mapping QTLs linked with tolerance to Al3+ toxicity ranging from 0 to 20 mM at pH 4 ± 0.2 at germination. The favorable alleles for all new QTLs were analyzed based on germination traits, i.e., final germination percentage (FG%), germination energy (GE), germination speed (GS), germination index (GI), mean germination time (MGT), germination value (GV), germination velocity (GVe), peak value of germination (GPV), and germination capacity (GC), and growth traits, such as root length (RL), shoot length (SL), total dry biomass (TDB) and germination vigor index (GVI). The phenotypic evolution showed transgressive variations. For genome-wide mapping, 90 polymorphic SSRs with 4 gene-specific markers and Win QTL Cart were used for QTL analysis. In all, 35 QTLs for germination and 11 QTLs for seedling growth were detected in distinct chromosomal regions by composite interval mapping (CIM), and multiple interval mapping (MIM) confirmed the pleiotropy at region RM128 on chromosome 1. Based on our genetic mapping studies, the genes/QTLs underlying tolerance to Al3+ toxicity could differ for both the germination and seedling stages in segregated populations. The QTLs identified in this study could be a source of new alleles for improving tolerance to Al3+ toxicity in rice.

Evaluation of circulating leukocyte transcriptome and its relationship with immune function and blood markers in dairy cows during the transition period.

Dairy cows during the transition period are faced with important physiological changes which include a dysfunctional immune system and an increased inflammatory state. New data are necessary to understand the key factors involved in the immune system regulation. Six dairy cows were sampled during transition period to investigate the leukocyte transcriptome changes and its relationship with blood biomarkers. Blood samples were collected at - 20 ± 2, - 3 ± 1, 3, and 7 days from parturition (DFP). Leukocyte transcriptome was analyzed by deep sequencing technology (Hiseq1000 Illumina, USA). Plasma was analyzed for metabolic biomarkers. Differentially expressed genes (DEG) were used to run an enrichment analysis through the Dynamic Impact Approach (DIA). Considering - 20 DFP as references time, the main KEGG impacted pathways were activated before calving (- 3 DFP) and were connected to lipid metabolism, lipid transport in plasma, and phagosome. The greatest differences were found after parturition with 281 DEG (179 upregulated and 102 downregulated). The activated pathways were mainly related to immunity and endocrine aspects, while metabolic pathways related to lipid and amino acid metabolism were inhibited. Plasma BHBA had a substantial inhibitory impact on KEGG pathways related to DNA replication and cell cycle, while plasma IL-1ß had an inhibitory impact on fatty acid elongation in mitochondria and an activated impact in several pathways related to cellular energy metabolism. Overall, this study confirmed that many changes in lipid metabolism and immune competence of the circulating leukocytes occurred in dairy cow around calving. Interestingly, BHBA and IL-1ß connected with the transcriptome.

Therapeutic Advances in the Management of Smoldering Myeloma.

BACKGROUND: The International Myeloma Working Group has defined smoldering multiple myeloma (SMM) as the presence of 10%-60% plasma cells in the bone marrow and M-protein (IgG, IgA) ≥3 g/dL without end-organ damage (an increased calcium level, renal failure, anemia, and destructive bone lesions). AREAS OF UNCERTAINTY: Patients considered to have SMM should not have any myeloma-defining events or amyloidosis. Different risks factors classify SMM into low-, intermediate-, or high-risk categories. The rate of progression from SMM to symptomatic myeloma is ∼10% per year during the first 5 years of diagnosis. SMM requires frequent follow-up ∼every 3 months during the first 5 years as compared to monoclonal gammopathy of undermined significance, which usually requires follow-up every 6-12 months after the first year of diagnosis. DATA SOURCES: A literature search was performed from electronic bibliographic databases: MEDLINE (Ovid SP/PubMed), EMBASE, the Cochrane Library (Cochrane Database of Systematic Reviews), and Cochrane Central Register of Controlled Trials and from annual meeting abstracts from inception to May 2017. THERAPEUTIC ADVANCES: This review presents the literature and available data that support or do not support early treatment of high-risk SMM (HR-SMM) and provides evidence-based recommendations for management of SMM patients. Despite emerging data recommending early treatment of HR-SMM, we predict the SMM category may disappear in the near future and patients will be diagnosed with either multiple myeloma or monoclonal gammopathy of undermined significance. CONCLUSIONS: Success with early therapy trials for HR-SMM is largely due to patients meeting current criteria for multiple myeloma that may have been classified as SMM and, therefore, benefitted from therapy. Based on current practices and the literature, SMM should be managed with close follow-up. Based on available data, we suggest SMM to only be treated in clinical trial settings.

Cdc2-like kinase 2 (Clk2) promotes early neural development in Xenopus embryos.

Neural induction and patterning in vertebrates are regulated during early development by several morphogens, such as bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs). Ventral ectoderm differentiates into epidermis in response to BMPs, whereas BMP signaling is tightly inhibited in the dorsal ectoderm which develops into neural tissues. Here, we show that Cdc2-like kinase 2 (Clk2) promotes early neural development and inhibits epidermis differentiation in Xenopus embryos. clk2 is specifically expressed in neural tissues along the anterior-posterior axis during early Xenopus embryogenesis. When overexpressed in ectodermal explants, Clk2 induces the expression of both anterior and posterior neural marker genes. In agreement with this observation, overexpression of Clk2 in whole embryos expands the neural plate at the expense of epidermal ectoderm. Interestingly, the neural-inducing activity of Clk2 is increased following BMP inhibition and activation of the FGF signaling pathway in ectodermal explants. Clk2 also downregulates the level of p-Smad1/5/8 in cooperation with BMP inhibition, in addition to increasing the level of activated MAPK together with FGF. These results suggest that Clk2 plays a role in early neural development of Xenopus possibly via modulation of morphogen signals such as the BMP and FGF pathways.