Genetically Determined Research Articles

Spatio-temporal human snow leopard (Panthera uncia) conflicts and mitigation measures in Baltistan - free-livestock grazing pastoral areas

Apex predators are essential for maintaining ecosystem balance by controlling biotic communities. The spatio-temporal grazing of livestock in pastoral areas can pose threats to endangered carnivores and their prey resulting in resource competition, conflicts and increased disease transmission. Our research aimed to assess the spatio-temporal distribution of snow leopards and livestock determine factors causing snow leopard-livestock conflicts identify seasonal conflict zones through public claims and interviews and evaluate conservation benefits and challenges. In this study, camera traps were used in 20 villages of Baltistan from November to April resulting in 720 snow leopard sightings and 8277 livestock events. Snow leopards preyed on 195 livestock in the 2022–2023 period resulting in an estimated loss of $225,004.51 USD including sheeps, goats, cows and yaks.We utilized the Generalized Linear Regression Model to examine snow leopard attacks finding that the timing of attacks was not significant. Proximity to predator-proofed corrals, traditional corrals, bite marks and distance to the nearest village or shepherd huts were positively correlated with attacks, while small stock body size was not significant. Through 110 public interviews we discovered that awareness campaigns and avoidance strategies successfully mitigated human-snow leopard conflicts. In conclusion, our results found that livestock attacks occur in pastures during both day and night with the size and sex of the livestock affecting the likelihood of attacks. Snow leopard attacks were linked to increased grazing and poorly constructed corrals. Snow leopards targeted vulnerable areas of their prey including the neck, mouth, ears and anal region. Compensation claims and field visits were used to identify conflict areas and public perception. In the future research should prioritize the use of camera traps to study prey and snow leopard density, grazing effects, food habits using genetic tools and sex determination.

Prevalence of Trehalase Enzymopathy Genetic Determinants in Siberian and Russian Far East Populations.

. Using the Infinium iSelect HD Custom BeadChip biochip (Illumina, United States) on the iScan platform and real-time polymerase chain reaction on a Bio-Rad CFX96 Touch amplifier, genotyping of 1068 DNA samples was carried out, of which 667 represent 10 ethnic groups of the indigenous people of the North of Siberia and the Far East of the Russian Federation. Two reference groups (357 samples) of Russians (n=311) and Yakuts (n = 46) represent the "Caucasoid" and "Mongoloid" poles of the Russian population. : The reduced trehalase activity that the heterozygous GA*TREH genotype determines can manifest itself in 19.8-53.7% of indigenous northerners. An additional 1.0 to 19.7% of the population are carriers of the AA*TREH genotype, which is associated with apparent trehalose malabsorption. The carriers may experience nausea, abdominal pain, and other dyspeptic symptoms after eating trehalose containing foods. The total risk of trehalase enzymopathy among the indigenous northerners in the Asian part of the Russian Federation is very high and can reach 60-70%. There is a gradient in the A*TREH allele frequencies in the small-numbered indigenous northern groups of Russia from the west (Khanty, Mansi, Nenets) to the east (peoples of the Far East). : The results are consistent with previously reported data on the higher carriage of the A*TREH mutant allele in Mongoloid populations compared to Caucasoid groups. It was hypothesized that, while the initial A*TREH allele prevalence in Mongoloid groups was moderately high, an adaptation to a low-sugar protein-lipid "high-latitude" diet led to a weaker control over the maintenance of the carriage of the ancestral G* allele. Trehalose malabsorption requires special attention of specialists in the field of nutrition, gastroenterology, public health, and medical genetics working in high-latitude regions.

Identification of the genetic determinants and clinical implications of bone marrow adiposity using deep learning in the uk biobank

Identification of the genetic determinants and clinical implications of bone marrow adiposity using deep learning in the uk biobank

Sex differences in shared genetic determinants between severe mental disorders and metabolic traits

High rates of metabolic risk factors contribute to premature mortality in patients with severe mental disorders, but the molecular underpinnings of this association are largely unknown. We performed the first analysis on shared genetic factors between severe mental disorders and metabolic traits considering the effect of sex. We applied an integrated analytical pipeline on the largest sex-stratified genome-wide association datasets available for bipolar disorder (BD), major depressive disorder (MDD), schizophrenia (SZ), and for body mass index (BMI) and waist-to-hip ratio (WHR) (all including participants of European origin). We observed extensive genetic overlap between all severe mental disorders and variants associated with BMI in women or men and identified several genetic loci shared between BD, or SZ and BMI in women (24 and 91, respectively) or men (13 and 208, respectively), with mixed directions of effect. A large part of the identified genetic variants showed sex differences in terms of location, genes modulated in adipose tissue and/or brain regions, and druggable targets. By providing a complete picture of disorder specific and cross-disorder shared genetic determinants, our results highlight potential sex differences in the genetic liability to metabolic comorbidities in patients with severe mental disorders.

Employing genome-wide association studies to investigate acid adaptation mechanisms in Listeria monocytogenes

Listeria monocytogenes is a critical foodborne pathogen known to develop adaptation traits in mildly acidic food processing environments. This study analyzed the genomic data of 49 strains derived from clinical and food sources, utilizing genome-wide association studies (GWAS) to explore the correlation between the genotypic and phenotypic traits of L. monocytogenes, thereby identifying the genetic determinants of its acid adaptation capability. The findings revealed no significant association between the collected acid adaptation genes and the bacterial growth parameters. The GWAS results indicated that numerous single nucleotide polymorphism (SNP) sites were significantly correlated with the growth parameters of L. monocytogenes in a pH = 5.0 acidic environment, whereas the associations diminished as the pH approached neutrality at pH = 6.7. Analysis and annotation of synonymous mutation loci revealed that non-synonymous mutations primarily impact function. The phenotypes pH = 5.0, ΔpH (5.0–5.5), SNPλ, and SNPμmax show the strongest associations with non-synonymous mutation loci. The genes lmo0017, lmo1173, lmo0794, and lmo2783 are significant non-synonymous mutation loci influencing acid adaptation. These genes play critical roles in intracellular pH regulation, cell wall synthesis and environmental response control, directly or indirectly affecting bacterial acid tolerance. Future research could leverage existing data combined with machine learning and causal inference methods to further dissect the genotype-phenotype causal relationships, identifying causative genetic factors that govern the acid adaptation in L. monocytogenes, providing insights for risk assessment and management strategies in food safety.

Leveraging Evolutionary Psychology for Tourism Research: Identifying and Addressing Key Challenges

Evolutionary psychology has led to an increasing number of important and novel findings on tourist and resident attitudes and behaviors. However, in parallel with such advances, several challenges hinder the further application of evolutionary psychology in tourism studies. In this letter to the editor, we therefore identify and address six key challenges to the use of evolutionary psychology in tourism. These challenges are: (1) a difficulty in distinguishing proximate from ultimate explanations, (2) a belief that evolutionary psychology focuses on nature, and ignores nurture, (3) a belief in human exceptionalism, (4) an impression that evolutionary psychology overemphasizes gender differences, (5) a view of evolutionary psychology as a single, unified theory, and (6) a belief that evolutionary psychology can be used to justify genetic determinism, sexism, and racism. In identifying and responding to these challenges, we hope to inspire scholars to consider adopting an evolutionary psychology lens in their future research.

Prevalence and Mortality of Malaria among Children under Five in Sub-Saharan Africa: A Review

Malaria had been a significant public health challenge in sub-Saharan Africa, particularly affecting children under five years of age, who accounted for over two-thirds of all malaria-related deaths globally. This review examined the prevalence and mortality rates of malaria among this vulnerable population, highlighting key determinants such as socioeconomic status, maternal education, environmental conditions, and access to healthcare. Recent data indicated that approximately 24.2% of children under five in the region are affected by malaria, with socioeconomic disparities exacerbating the risk. The review also discussed the effectiveness of various preventive interventions, including insecticide-treated nets (ITNs), indoor residual spraying (IRS), and seasonal malaria chemoprevention (SMC), emphasizing the need for multifaceted approaches that address both biological and social determinants of health. A comprehensive literature review was conducted to synthesize current research findings and provide insights into the challenges and opportunities for reducing malaria incidence and mortality in this demographic. Ultimately, addressing the complex interplay of risk factors is essential for developing targeted strategies to mitigate the impact of malaria on young children in sub-Saharan Africa. Keywords: Malaria, Children under five, Prevalence, Mortality, Sub-Saharan Africa.

Socioeconomic and Environmental Risk Factors for Malaria in Young Children: A Review

Malaria remained a significant public health challenge in sub-Saharan Africa, disproportionately affecting children under five years of age. Understanding the socioeconomic and environmental risk factors associated with malaria in this vulnerable population was crucial for developing targeted interventions to reduce transmission and improve health outcomes. This review examined the complex interplay between socioeconomic status, housing conditions, environmental factors, and malaria risk among young children. A comprehensive literature search was conducted to synthesize current research findings on the topic. Key socioeconomic determinants included household income, maternal education, and access to preventive measures. Children from low-income families were at higher risk due to limited resources for malaria prevention and treatment, as well as poorer living conditions that facilitate mosquito breeding. Environmental factors such as proximity to stagnant water bodies, inadequate sanitation, and climate variability further exacerbated malaria transmission. The review highlighted the need for multifaceted approaches that address both biological and social determinants of health to effectively reduce the burden of malaria among children under five in sub-Saharan Africa. Keywords: Malaria, Socioeconomic factors, Environmental factors, young children, Sub-Saharan Africa

The “Latines Lideres En Salud (LaLiSa)” study: Rationale and design

BackgroundLatines suffer from breast cancer (BC), due to elevated biological and social determinants of health (SDOH) risks. This study compares the effects of different strategies on uptake of cancer genetic services, specifically hereditary cancer risk assessment, genetic counseling, and genetic testing, and risk-based BC care. Design/methodsIn Chicago, Illinois, Aim 1 participants are recruited from a federally qualified health center (FQHC) and community venues. For Aim 1, eligible participants: (1) are female; (2) are Latine; (3) are 30+ years old; (4) have personal or family history of BC or cancers with shared hereditary mutations; (5) have at least one SDOH risk; and (6) have not received any cancer genetic services. Participants are randomly assigned to different study arms. Both arms include phone-based sessions, FQHC-based navigation for SDOH, and low- or no-cost cancer genetic services. The educate sessions focus on risk assessment and prevention. The empower sessions focus on risk assessment and equip participants with the skills to share information about FQHC-based cancer genetic services. For Aim 2, eligible participants are: (1) female; (2) network members of Aim 1 participants; and (3) eligible for BC screening based on guidelines recommended by the American Cancer Society (ACS). Primary outcomes include uptake of any cancer genetic services. Analyses will also explore intervention differences by neighborhood context. DiscussionThis is one of the first trials focused on Latines' participation in cancer genetic services and risk-based BC care within the context of SDOH - which has major implications for equity in precision cancer prevention.

In vitro efficacy of aquaculture antimicrobials and genetic determinants of resistance in bacterial isolates from tropical aquaculture disease outbreaks.

Understanding the efficacy of antimicrobials against pathogens from clinical samples is critical for their responsible use. The manuscript presents in vitro efficacy and antimicrobial resistance (AMR) genes in seven species of fish pathogens from the disease outbreaks of Indian aquaculture against oxytetracycline, florfenicol, oxolinic acid, and enrofloxacin. In vitro efficacy was evaluated by minimum inhibitory concentration and minimum bactericidal concentration. The gene-specific PCR screened AMR genes against quinolones (qnrA, qnrB, and qnrS) and tetracyclines (tetM, tetS, tetA, tetC, tetB, tetD, tetE, tetH, tetJ, tetG, and tetY). The results showed that Aeromonas veronii (45%) showed the maximum resistance phenotype, followed by Streptococcus agalactiae (40%), Photobacterium damselae (15%), Vibrio parahaemolyticus (10%), and Vibrio vulnificus (5%). There was no resistance among Vibrio harveyi and Vibrio alginolyticus against the tested antimicrobials. The positive association between tetA, tetB, tetC, tetM, or a combination of these genes to oxytetracycline resistance and qnrS to quinolone resistance indicated their potential in surveillance studies. The prevalence of resistance phenotypes (16.43%) and evaluated AMR genes (2.65%) against aquaculture antimicrobials was low. The resistance phenotype pattern abundance was 0.143. All the isolates showed susceptibility to florfenicol. The results help with the appropriate drug selection against each species in aquaculture practices.

Genome-wide association studies of thyroid-related hormones, dysfunction, and autoimmunity among 85,421 Chinese pregnancies

Maintaining normal thyroid function is crucial in pregnancy, yet thyroid dysfunction and the presence of thyroid peroxidase antibodies (TPOAb) affect 0.5% to 18% of pregnant women. Here, we conducted a genome-wide association study (GWAS) of eight thyroid traits, including two thyroid-related hormones, four thyroid dysfunctions, and two thyroid autoimmunity measurements among 85,421 Chinese pregnant women to investigate the genetic basis of thyroid function during pregnancy. Our study identified 176 genetic loci, including 125 previously unknown genome-wide associations. Joint epidemiological and Mendelian randomization analyses revealed significant associations between the gestational thyroid phenotypes and gestational complications, birth outcomes, and later-age health outcomes. Specifically, genetically elevated thyroid-stimulating hormone (TSH) levels during pregnancy correlated with lower glycemic levels, reduced blood pressure, and longer gestational duration. Additionally, TPOAb and thyroid functions during pregnancy share genetic correlations with later-age thyroid and cardiac disorders. These findings provide insights into the genetic determinants of thyroid traits during pregnancy, which may lead to new therapeutics, early pre-diagnosis and preventive strategies starting from early adulthood.

B - 22 Self-Reported Traumatic Brain Injury and its Biopsychosocial Risk Factors in Siblings of Individuals with Neurodevelopmental Conditions

Abstract Objective Siblings of individuals with neurodevelopmental conditions (NDCs) are situated within a complex system of transdiagnostic risk and resilience factors for poor psychosocial, cognitive and behavioral outcomes. Many such factors experienced by NDC siblings overlap with risk for traumatic brain injury (TBI) and correlate with poorer recovery trajectories. Method With data from an online self-report survey, the present study used Bayesian analyses to characterize and compare TBI and biopsychosocial risk factors amongst 632 siblings (207 NDC, 425 controls; mean age 20.54 years, range 10–30, 78.48% female), and examine correlations between clinical, biological, and social determinant of health variables. Results NDC siblings had a higher self-reported lifetime history of TBI compared to controls (14.98% versus 6.35%), with most NDC siblings reporting more than one TBI, and at an earlier mean age. TBI history was associated with psychiatric diagnoses and subclinical NDC features, including hyperactivity and impulsivity, inattention, conduct problems, and autistic traits. Family and structural factors related to TBI included poorer parent–child relationship, NDC diagnoses of autism or fetal alcohol spectrum disorder, minority ethnicity and lower income. Conclusions Findings have important clinical and policy implications for health literacy, TBI education and screening, development of prevention and intervention strategies, and implementation of family support to target social and structural determinants of health impacting NDC sibling wellbeing.

Revealing genetic causality between blood-based biomarkers and major depression in east Asian ancestry.

Major Depression (MD) is a common mental disorder. In East Asian ancestry, the association, causality, and shared genetic basis between blood-based biomarkers and MD remain unclear. We investigated the relationships between blood-based biomarkers and MD through a cross-sectional study and Mendelian randomization (MR) analysis. Cross-trait analysis and enrichment analyses were used to highlight the shared genetic determinants and biological pathways. We conducted summary data-based MR to identify shared genes, which were then validated using a transcriptome dataset from drug-naïve patients with MD. In the cross-sectional study, C-Reactive Protein showed the significantly positive correlation with depressive symptoms, while hematocrit, hemoglobin, and uric acid exhibited significantly negative correlations. In MR analysis, basophil count (BASO) and low-density lipoprotein cholesterol (LDLc) had a significant causal effect on MD. The enrichment analysis indicated a significant role of inflammatory cytokines and oxidative stress. The shared genes MFN2, FAM55C, GCC2, and SCAPER were validated, with MFN2 identified as a pleiotropic gene involved in MD, BASO, and LDLc. This study highlighted that BASO and LDLc have a causal effect on MD in East Asian ancestry. The pathological mechanisms of MD are related not only to inflammatory cytokines and oxidative stress but also to down regulation of MFN2 expression and mitochondrial dysfunction.

Identification of the genetic determinants of shovel-shaped incisors and Carabelli’s cusp

Shovel-shaped incisors (SSI) and Carabelli’s cusp (CC) are noteworthy human dental non-metric traits which presence and degree of expression have been reported to cluster within distinct populations. Recent advances in developmental biology suggest that SSI and CC are likely under polygenic developmental control; therefore, genetic variation in multiple genes is likely to contribute to differential SSI and CC expression. The exact genetic mechanisms underlying variation in SSI and CC development, however, remain mostly unknown. This study aims to identify whether variation in the basal DNA sequences of six candidate genes, NKX2-3, SOSTDC1, BMP4, FGF3, FGF4, and WNT10A, has any impact on SSI and/or CC expression. Study methods involve collection of saliva samples and dental data from 36 participants. The Arizona State University Dental Anthropology System (ASUDAS) has been used to score SSI and CC expression. Next-generation sequencing (NGS) methods were utilized to sequence the entire gene region of the candidate genes. Spearman’s correlation test was used to score the relationship between the genotype and degree of trait expression of participants. Fifteen SNPs/INDELs belonging to SOSTDC1, FGF3, FGF4 and WNT10A were significantly associated with SSI and/or CC expression. No SNPs/INDELs were detected in the genes BMP4 and NKX2-3 that significantly contributes to observed phenotypes. FGF3, FGF4, SOSTDC1 and WNT10A were possibly involved in the formation of shoveling and Carabelli’s cusp. However, because of the small sample size, more studies are needed to confirm their role and rule out any potential role of NKX2-3 and BMP4 in the production of SSI and CC.

Lack of a genetic risk continuum between pubertal timing in the general population and idiopathic hypogonadotropic hypogonadism.

Pubertal timing is a highly heritable trait in the general population. Recently, a large-scale exome-wide association study has implicated rare variants in six genes (KDM4C, MC3R, MKRN3, PDE10A, TACR3, and ZNF483) as genetic determinants of pubertal timing within the general population. Two of the genes (TACR3, MKRN3) are already implicated in extreme disorders of pubertal timing. This observation suggests that there may be a pervasive "genetic risk continuum" wherein genes that govern pubertal timing in the general population, by extension, may also be causal for rare Mendelian disorders of pubertal timing. Hence, we hypothesized that the four novel genes linked to pubertal timing in the population will also contribute to idiopathic hypogonadotropic hypogonadism (IHH), a genetic disorder characterized by absent puberty. Exome sequencing data from 1322 unrelated IHH probands were reviewed for rare sequence variants (RSVs) (minor allele frequency bins: <1%; <0.1%; <0.01%) in the six genes linked to puberty in the general population. A gene-based rare variant association testing (RVAT) was performed between the IHH cohort and a reference public genomic sequences repository-the Genome Aggregation Database (gnomAD). As expected, RVAT analysis showed that RSVs in TACR3, a known IHH gene, were significantly enriched in the IHH cohort compared to gnomAD cohort across all three MAF bins. However, RVAT analysis of the remaining five genes failed to show any RSV enrichment in the IHH cohort across all MAF bins. Our findings argue strongly against a pervasive genetic risk continuum between pubertal timing in the general population and extreme pubertal phenotypes. The biologic basis of such distinct genetic architectures' merits further evaluation.

Genomic insights into mRNA COVID-19 vaccines efficacy: Linking genetic polymorphisms to waning immunity

ABSTRACT Genetic polymorphisms have been linked to the differential waning of vaccine-induced immunity against COVID-19 following vaccination. Despite this, evidence on the mechanisms behind this waning and its implications for vaccination policy remains limited. We hypothesize that specific gene variants may modulate the development of vaccine-initiated immunity, leading to impaired immune function. This study investigates genetic determinants influencing the sustainability of immunity post-mRNA vaccination through a genome-wide association study (GWAS). Utilizing a hospital-based, test negative case-control design, we enrolled 1,119 participants from the Taiwan Precision Medicine Initiative (TPMI) cohort, all of whom completed a full mRNA COVID-19 vaccination regimen and underwent PCR testing during the Omicron outbreak. Participants were classified into breakthrough and protected groups based on PCR results. Genetic samples were analyzed using SNP arrays with rigorous quality control. Cox regression identified significant single nucleotide polymorphisms (SNPs) associated with breakthrough infections, affecting 743 genes involved in processes such as antigenic protein translation, B cell activation, and T cell function. Key genes identified include CD247, TRPV1, MYH9, CCL16, and RPTOR, which are vital for immune responses. Polygenic risk score (PRS) analysis revealed that individuals with higher PRS are at greater risk of breakthrough infections post-vaccination, demonstrating a high predictability (AUC = 0.787) in validating population. This finding confirms the significant influence of genetic variations on the durability of immune responses and vaccine effectiveness. This study highlights the importance of considering genetic polymorphisms in evaluating vaccine-induced immunity and proposes potential personalized vaccination strategies by tailoring regimens to individual genetic profiles.

Pathophysiology and Treatment of Prediabetes and Type 2 Diabetes in Youth.

Youth-onset type 2 diabetes is a heterogeneous disease with increasing prevalence in relation to increased rates of obesity in children. It has genetic, epigenetic, social, and environmental determinants. Youth-onset type 2 diabetes is alarming given a rapidly progressive course compared with the course of adult-onset disease, early-onset vascular complications, and long-term exposure to hyperglycemia and associated complications. It is often preceded by "prediabetes," a disease phase where defects in β-cell function relative to insulin sensitivity emerge. Herein, we review the current understanding of the pathophysiology of prediabetes and type 2 diabetes in youth. We describe the mechanisms underlying insulin resistance, the precipitous decline of β-cell function, and the role of other hormonal abnormalities in the pathogenesis of the disease. We discuss the critical importance of social determinants of health in the predisposition and progression of these conditions and present current management strategies and the advances in therapeutic approaches. These must adapt to meet the unique needs of the individual patient and family. Significant knowledge gaps remain that need to be addressed in future research.

Evolutionary dynamics in gut-colonizing Candida glabrata during caspofungin therapy: Emergence of clinically important mutations in sphingolipid biosynthesis.

Invasive fungal infections are associated with high mortality, which is exacerbated by the limited antifungal drug armamentarium and increasing antifungal drug resistance. Echinocandins are a frontline antifungal drug class targeting β-glucan synthase (GS), a fungal cell wall biosynthetic enzyme. Echinocandin resistance is generally low but increasing in species like Candida glabrata, an opportunistic yeast pathogen colonizing human mucosal surfaces. Mutations in GS-encoding genes (FKS1 and FKS2 in C. glabrata) are strongly associated with clinical echinocandin failure, but epidemiological studies show that other, as yet unidentified factors also influence echinocandin susceptibility. Furthermore, although the gut is known to be an important reservoir for emergence of drug-resistant strains, the evolution of resistance is not well understood. Here, we studied the evolutionary dynamics of C. glabrata colonizing the gut of immunocompetent mice during treatment with caspofungin, a widely-used echinocandin. Whole genome and amplicon sequencing revealed rapid genetic diversification of this C. glabrata population during treatment and the emergence of both drug target (FKS2) and non-drug target mutations, the latter predominantly in the FEN1 gene encoding a fatty acid elongase functioning in sphingolipid biosynthesis. The fen1 mutants displayed high fitness in the gut specifically during caspofungin treatment and contained high levels of phytosphingosine, whereas genetic depletion of phytosphingosine by deletion of YPC1 gene hypersensitized the wild type strain to caspofungin and was epistatic to fen1Δ. Furthermore, high resolution imaging and mass spectrometry showed that reduced caspofungin susceptibility in fen1Δ cells was associated with reduced caspofungin binding to the plasma membrane. Finally, we identified several different fen1 mutations in clinical C. glabrata isolates, which phenocopied the fen1Δ mutant, causing reduced caspofungin susceptibility. These studies reveal new genetic and molecular determinants of clinical caspofungin susceptibility and illuminate the dynamic evolution of drug target and non-drug target mutations reducing echinocandin efficacy in patients colonized with C. glabrata.

Biological and ecological determinants of Hand Foot and Mouth Disease (HFMD) in Coastal District of Northeastern Peninsular Malaysia: A 5-Year retrospective study

Hand, foot, and mouth disease (HFMD) is a common viral communicable disease in Malaysia, characterized by its self-limiting nature, yet it leads to numerous outbreaks and fatalities, particularly among young children. The current study aimed to determine the prevalence, geographic distribution, temporal patterns, and associated factors of HFMD cases within the Bachok District of Kelantan, spanning the years 2018 to 2022. A retrospective cohort study analysed extract data on independent factors and notification status from the Communicable Disease Control Information System (CDCIS). Simple and multiple logistic regression analyses were employed on a cohort of 1351 HFMD’s notifications. The retrospective analysis reveals a predominant HFMD’s notification were males (56.7%). Outpatient care was common (98.4%), with primary health care being the main choice. Logistic regression indicates higher odds for HFMD in those attending primary health care or private practitioners, daycare attendees, during the Southwest Monsoon season, and before the Movement Control Order (MCO) implementation, emphasizing key risk factors for HFMD. This study’s integrative approach recognizes that health and disease are often influenced by a combination of factors spanning the ecological, biological, and clinical domains. Thus, emphasizing the need for a comprehensive understanding when formulating public health strategies particularly in primary healthcare settings and daycare facilities during the Southwest Monsoon season.

A plasmid-mediated type III secretion system associated with invasiveness and diarrheagenicity of Providencia rustigianii.

We have recently described a clinical isolate of Providencia rustigianii strain JH-1 carrying the genes for cytolethal distending toxin (CDT) in a conjugative plasmid. A cdtB mutant of strain JH-1, which lost CDT activity, was still found to retain invasiveness and diarrheagenicity. The strain was subjected to phenotypic and genetic analyses including whole genome sequencing (WGS) to explore the genetic determinants of the observed invasiveness and diarrheagenic properties. Analysis and annotation of WGS data revealed the presence of two distinct type III secretion systems (T3SS) in strain JH-1, one of which was located on the chromosome designated as cT3SS (3,992,833 bp) and the other on a mega-plasmid designated as pT3SS (168,819 bp). Comparative genomic analysis revealed that cT3SS is generally conserved in Providencia spp. but pT3SS was limited to a subset of Providencia spp., carrying cdt genes. Strain JH-1 was found to invade HeLa cells and induce fluid accumulation with characteristic pathological lesions in rabbit ileal loops. Remarkably, these phenomena were associated with the pT3SS but not cT3SS. The plasmid could be transferred by conjugation from strain JH-1 to other strains of P. rustigianii, Providencia rettgeri, and Escherichia coli with concomitant transfer of these virulence properties. This is the first report of a functional and mobile T3SS in P. rustigianii and its association with invasiveness and diarrheagenicity of this bacterium. These data suggest that P. rustigianii and other CDT-producing Providencia strains might carry T3SS and exert their diarrheagenic effect by exploiting the T3SS nano-machinery.IMPORTANCEThe precise mechanism of virulence of Providencia rustigianii is unclear, although some strains produce cytolethal distending toxin as a putative virulence factor. We have detected the presence of a type III secretion system (T3SS) for the first time on a plasmid in a P. rustigianii strain. Plasmid-mediated T3SS seems to be directly involved in virulence of P. rustigianii and may serve as a means of horizontal transfer of T3SS genes. Our results may have implication in understanding the mechanism of emergence of new pathogenic strains of P. rustigianii.