Cryo-EM structure of antibacterial efflux transporter QacA from Staphylococcus aureus reveals a novel extracellular loop with allosteric role.

Efflux of antibacterial compounds is a major mechanism for developing antimicrobial resistance. In the Gram-positive pathogen Staphylococcus aureus, QacA, a 14 transmembrane helix containing major facilitator superfamily antiporter, mediates proton-coupled efflux of mono and divalent cationic antibacterial compounds. In this study, we report the cryo-EM structure of QacA, with a single mutation D411N that improves homogeneity and retains efflux activity against divalent cationic compounds like dequalinium and chlorhexidine. The structure of substrate-free QacA, complexed to two single-domain camelid antibodies, was elucidated to a resolution of 3.6 Å. The structure displays an outward-open conformation with an extracellular helical hairpin loop (EL7) between transmembrane helices 13 and 14, which is conserved in a subset of DHA2 transporters. Removal of the EL7 hairpin loop or disrupting the interface formed between EL7 and EL1 compromises efflux activity. Chimeric constructs of QacA with a helical hairpin and EL1 grafted from other DHA2 members, LfrA and SmvA, restore activity in the EL7 deleted QacA revealing the allosteric and vital role of EL7 hairpin in antibacterial efflux in QacA and related members.

Measuring long-term exposure to wildfire PM2.5 in California: Time-varying inequities in environmental burden.

Wildfires have become more frequent and intense due to climate change and outdoor wildfire fine particulate matter (PM2.5) concentrations differ from relatively smoothly varying total PM2.5. Thus, we introduced a conceptual model for computing long-term wildfire PM2.5 and assessed disproportionate exposures among marginalized communities. We used monitoring data and statistical techniques to characterize annual wildfire PM2.5 exposure based on intermittent and extreme daily wildfire PM2.5 concentrations in California census tracts (2006 to 2020). Metrics included: 1) weeks with wildfire PM2.5 < 5 µg/m3; 2) days with non-zero wildfire PM2.5; 3) mean wildfire PM2.5 during peak exposure week; 4) smoke waves (≥2 consecutive days with <15 µg/m3 wildfire PM2.5); and 5) mean annual wildfire PM2.5 concentration. We classified tracts by their racial/ethnic composition and CalEnviroScreen (CES) score, an environmental and social vulnerability composite measure. We examined associations of CES and racial/ethnic composition with the wildfire PM2.5 metrics using mixed-effects models. Averaged 2006 to 2020, we detected little difference in exposure by CES score or racial/ethnic composition, except for non-Hispanic American Indian and Alaska Native populations, where a 1-SD increase was associated with higher exposure for 4/5 metrics. CES or racial/ethnic × year interaction term models revealed exposure disparities in some years. Compared to their California-wide representation, the exposed populations of non-Hispanic American Indian and Alaska Native (1.68×, 95% CI: 1.01 to 2.81), white (1.13×, 95% CI: 0.99 to 1.32), and multiracial (1.06×, 95% CI: 0.97 to 1.23) people were over-represented from 2006 to 2020. In conclusion, during our study period in California, we detected disproportionate long-term wildfire PM2.5 exposure for several racial/ethnic groups.

Early warning of the Indian Ocean Dipole using climate network analysis.

SignificanceThe Indian Ocean Dipole (IOD), an air-sea coupled phenomenon over the tropical Indian Ocean, has substantial impacts on the climate, ecosystems, and society. Due to the winter predictability barrier, however, a reliable prediction of the IOD has been limited to 3 or 4 mo in advance. Our work approaches this problem from a new data-driven perspective: the climate network analysis. Using this network-based method, an efficient early warning signal for the IOD event was revealed in boreal winter. Our approach can correctly predict the IOD events one calendar year in advance (from December of the previous year) with a hit rate of higher than 70%, which strongly outperforms current dynamic models.

Protracted Indian monsoon droughts of the past millennium and their societal impacts.

Protracted droughts lasting years to decades constitute severe threats to human welfare across the Indian subcontinent. Such events are, however, rare during the instrumental period (ca. since 1871 CE). In contrast, the historic documentary evidence indicates the repeated occurrences of protracted droughts in the region during the preinstrumental period implying that either the instrumental observations underestimate the full spectrum of monsoon variability or the historic accounts overestimate the severity and duration of the past droughts. Here we present a temporally precise speleothem-based oxygen isotope reconstruction of the Indian summer monsoon precipitation variability from Mawmluh cave located in northeast India. Our data reveal that protracted droughts, embedded within multidecadal intervals of reduced monsoon rainfall, frequently occurred over the past millennium. These extreme events are in striking temporal synchrony with the historically documented droughts, famines, mass mortality events, and geopolitical changes in the Indian subcontinent. Our findings necessitate reconsideration of the region's current water resources, sustainability, and mitigation policies that discount the possibility of protracted droughts in the future.

Limited underthrusting of India below Tibet: 3He/4He analysis of thermal springs locates the mantle suture in continental collision.

During continent­continent collision, does the downgoing continental plate underplate far inboard of the collisional boundary or does it subduct steeply into the mantle, and how is this geometry manifested in the mantle flow field? We test conflicting models for these questions for Earth's archetypal continental collision forming the Himalaya and Tibetan Plateau. Air-corrected helium isotope data (3He/4He) from 225 geothermal springs (196 from our group, 29 from the literature) delineate a boundary separating a Himalayan domain of only crustal helium from a Tibetan domain with significant mantle helium. This 1,000-km-long boundary is located close to the Yarlung-Zangbo Suture (YZS) in southern Tibet from 80 to 92°E and is interpreted to overlie the "mantle suture" where cold underplated Indian lithosphere is juxtaposed at >80 km depth against a sub-Tibetan incipiently molten asthenospheric mantle wedge. In southeastern Tibet, the mantle suture lies 100 km south of the YZS, implying delamination of the mantle lithosphere from the Indian crust. This helium-isotopic boundary helps resolve multiple, mutually conflicting seismological interpretations. Our synthesis of the combined data locates the northern limit of Indian underplating beneath Tibet, where the Indian plate bends to steeper dips or breaks off beneath a (likely thin) asthenospheric wedge below Tibetan crust, thereby defining limited underthrusting for the Tibetan continental collision.

Higher sea surface temperature in the Indian Ocean during the Last Interglacial weakened the South Asian monsoon.

SignificanceUnderstanding the drivers of South Asian monsoon intensity is pivotal for improving climate forecasting under global warming scenarios. Solar insolation is assumed to be the dominant driver of monsoon variability in warm climate regimes, but this has not been verified by proxy data. We report a South Asian monsoon rainfall record spanning the last ∼130 kyr in the Ganges-Brahmaputra-Meghna river catchment. Our multiproxy data reveal that the South Asian monsoon was weaker during the Last Interglacial (130 to 115 ka)-despite higher insolation-than during the Holocene (11.6 ka to present), thus questioning the widely accepted model assumption. Our work implies that Indian Ocean warming may increase the occurrence of severe monsoon failures in South Asia.

Characterizing the etiology of recurrent tuberculosis using whole genome sequencing-Alaska, USA, 2008-2020.

BACKGROUND: Understanding the etiology of recurrent tuberculosis (rTB) is important for effective TB control. Prior to the advent of whole genome sequencing (WGS), attributing rTB to relapse or reinfection using genetic information was complicated by the limited resolution of conventional genotyping methods. METHODS: We applied a systematic method of evaluating whole genome single nucleotide polymorphism (wgSNP) distances and results of phylogenetic analyses to characterize the etiology of rTB in American Indian and Alaska Native (AIAN) persons in Alaska during 2008-2020. We contextualized our findings through descriptive analyses of surveillance data and results of a literature search for investigations that characterized rTB etiology using WGS. RESULTS: The percentage of TB cases in AIAN persons in Alaska classified as recurrent episodes (11.8%) was three times the national percentage (3.9%). Of 38 recurrent episodes included in genetic analyses, we attributed 25 (65.8%) to reinfection based on wgSNP distances and phylogenetic analyses; this proportion was the highest among 16 published point estimates identified through the literature search. By comparison, we attributed 11 of 38 (28.9%) and 6 of 38 (15.8%) recurrent episodes to reinfection based on wgSNP distances alone and on conventional genotyping methods, respectively. CONCLUSIONS: WGS and attribution criteria involving genetic distances and patterns of relatedness can provide an effective means of elucidating rTB etiology. Our findings indicate that rTB occurs at high proportions among AIAN persons in Alaska and is frequently attributable to reinfection, reinforcing the importance of active surveillance and control measures to limit the spread of TB disease in Alaskan AIAN communities.

Complete chloroplast genome and comparison of herbicides toxicity on Aeschynomene indica (Leguminosae) in upland direct-seeding paddy field.

BACKGROUND: Indian jointvetch (Aeschynomene indica) is a common and pernicious weed found in the upland direct-seeding rice fields in the lower reaches of the Yangtze River in China. However, there are few reports on the degree of harm, genetic characteristics, and management methods of this weed. The purpose of this study is to clarify the harm of Indian jointvetch to upland direct-seeding rice, analyze the genetic characteristics of this weed based on chloroplast genomics and identify its related species, and screen herbicides that are effective in managing this weed in upland direct-seeding rice fields. RESULTS: In a field investigation in upland direct-seeding rice paddies in Shanghai and Jiangsu, we determined that the plant height and maximum lateral distance of Indian jointvetch reached approximately 134.2 cm and 57.9 cm, respectively. With Indian jointvetch present at a density of 4/m2 and 8/m2, the yield of rice decreased by approximately 50% and 70%, respectively. We further obtained the first assembly of the complete chloroplast (cp.) genome sequence of Indian jointvetch (163,613 bp). There were 161 simple sequence repeats, 166 long repeats, and 83 protein-encoding genes. The phylogenetic tree and inverted repeat region expansion and contraction analysis based on cp. genomes demonstrated that species with closer affinity to A. indica included Glycine soja, Glycine max, and Sesbania cannabina. Moreover, a total of 3281, 3840, and 3838 single nucleotide polymorphisms were detected in the coding sequence regions of the cp. genomes of S. cannabina voucher IBSC, G. soja, and G. max compared with the A. indica sequence, respectively. A greenhouse pot experiment indicated that two pre-emergence herbicides, saflufenacil and oxyfluorfen, and two post-emergence herbicides, florpyrauxifen-benzyl and penoxsulam, can more effectively manage Indian jointvetch than other common herbicides in paddy fields. The combination of these two types of herbicides is recommended for managing Indian jointvetch throughout the entire growth period of upland direct-seeding rice. CONCLUSIONS: This study provides molecular resources for future research focusing on the identification of the infrageneric taxa, phylogenetic resolution, and biodiversity of Leguminosae plants, along with recommendations for reliable management methods to control Indian jointvetch.

Source Tracing of Leishmania donovani in Emerging Foci of Visceral Leishmaniasis, Western Nepal.

We sequenced Leishmania donovani genomes in blood samples collected in emerging foci of visceral leishmaniasis in western Nepal. We detected lineages very different from the preelimination main parasite population, including a new lineage and a rare one previously reported in eastern Nepal. Our findings underscore the need for genomic surveillance.

Birth Cohort Colorectal Cancer (CRC): Implications for Research and Practice.

Colorectal cancer (CRC) epidemiology is changing due to a birth cohort effect, first recognized by increasing incidence of early onset CRC (EOCRC, age <50 years). In this paper, we define "birth cohort CRC" as the observed phenomenon, among individuals born 1960 and later, of increasing CRC risk across successive birth cohorts, rising EOCRC incidence, increasing incidence among individuals aged 50 to 54 years, and flattening of prior decreasing incidence among individuals aged 55 to 74 years. We demonstrate birth cohort CRC is associated with unique features, including increasing rectal cancer (greater than colon) and distant (greater than local) stage CRC diagnosis, and increasing EOCRC across all racial/ethnic groups. We review potential risk factors, etiologies, and mechanisms for birth cohort CRC, using EOCRC as a starting point and describing importance of viewing these through the lens of birth cohort. We also outline implications of birth cohort CRC for epidemiologic and translational research, as well as current clinical practice. We postulate that recognition of birth cohort CRC as an entity-including and extending beyond rising EOCRC-can advance understanding of risk factors, etiologies, and mechanisms, and address the public health consequences of changing CRC epidemiology.

Institutional complexity emerges from socioecological complexity in small-scale human societies.

Human lifestyles vary enormously over time and space and so understanding the origins of this diversity has always been a central focus of anthropology. A major source of this cultural variation is the variation in institutional complexity: the cultural packages of rules, norms, ontologies and expectations passed down through societies across generations. In this article, we study the emergence of institutions in small-scale societies. There are two primary schools of thought. The first is that institutions emerge top-down as rules are imposed by elites on their societies in order to gain asymmetrical access to power, resources and influence over others through coercion. The second is that institutions emerge bottom-up to facilitate interactions within populations as they seek collective solutions to adaptive problems. Here, we use Bayesian networks to infer the causal structure of institutional complexity in 172 small-scale societies across ethnohistoric western North America reflecting the wide diversity of indigenous lifestyles across this vast region immediately prior to European colonization. Our results suggest that institutional complexity emerges from underlying socioecological complexity because institutions are solutions to coordination problems in more complex environments where human-environment interactions require increased management.

Sickle cell disease in Indian tribal population: Findings of a multi-centre Indian SCD registry.

BACKGROUND: Sickle cell disease (SCD) registries provide crucial real-world data on demographics, epidemiology, healthcare, patient outcomes, and treatment efficacy. This paper presents findings from the Indian SCD Registry (ISCDR) on clinical manifestations, crisis episodes, disease management, and healthcare utilization in patients with SCD from 12 primary health centres (PHCs) in six tribal districts of India. METHODS: The ISCDR was introduced along with a three-tier screening process. Its Android-based application incorporates two electronic case report forms for patient data collection over one year. This paper presents a year's data from the ISCDR's 324 patients with SCD. RESULTS: Patients with SCD, aged one to 65 years, exhibited varied clinical manifestations. Most patients (85.2 %) were unaware of their SCD status before enrolling in ISCDR. Moderate to severe anaemia was prevalent (66.05 % and 30.56 %, respectively). Pain was a common complaint (80.86 %; CI: 76.17-85.00), while symptoms of stroke included sudden severe headaches (34.57 %; CI: 29.40-40.02). Common splenic sequestration symptoms included stomach pain (42.90 %; CI: 37.44-48.49) and abdominal tenderness (13.27 %; CI: 9.77-17.46), as a sign. Healthcare utilization was high, with 96.30 % receiving treatment and 83.64 % consuming hydroxyurea. Hospitalization occurred for 38.27 % (CI: 32.95-43.81), and 12.04 % (CI: 8.70-16.09) had blood transfusion during last year. CONCLUSIONS: ISCDR serves as a dynamic digital database on SCD epidemiology, clinical aspects, treatment and healthcare utilization. Notably, many patients lacked prior awareness of their SCD status, underscoring the need for improved awareness and care management. Integrating the registry into the national programme can streamline treatment implementation, prioritize management approaches, and optimize individual benefits.

Persistent cervical cancer disparities among American Indian/Alaska Native women: a systematic scoping review exploring the state of the science in this population.

PURPOSE: American Indian/Alaska Native (AI/AN) populations experience significantly higher incidence and mortality rates of cervical cancer. The objective of this systematic scoping review is to characterize the volume and nature of research being conducted specific to the AI/AN population regarding cervical cancer and related clinical themes. METHODS: This scoping review was conducted in collaboration with the Pacific Northwest Evidence-based Practice Center. Search strategies identified eligible publications from 1990 through 4 February 2022. Two reviewers independently abstracted study data, including clinical area, number of participants and percent inclusion of AI/AN, intervention or risk factor, outcomes reported, Indian Health Service (IHS) Region, and funding source. We used published algorithms to assess study design. RESULTS: Database searches identified 300 unique citations. After full-text evaluation of 129 articles, 78 studies and 9 secondary publications were included (total of 87). Approximately 74% of studies were observational in design, with cross-sectional methodology accounting for 42.7% of all included studies. The most common clinical theme was cervical cancer screening. The most common intervention/exposure was risk factor, typically race (AI/AN compared with other groups) (69%). For studies with documented funding sources, 67% were funded by the US Government. CONCLUSION: Of the small number of publications identified, the majority are funded through government agencies, are descriptive and/or cross-sectional studies that are hypothesis generating in nature, and fail to represent the diversity of the AI/AN populations in the US. This systematic scoping review highlights the paucity of rigorous research being conducted in a population suffering from a greater burden of disease.

Breast cancer screening attitudes, beliefs, and behaviors of Zuni Pueblo women: identifying cornerstones for building effective mammogram screening intervention programs.

PURPOSE: Breast cancer is the leading form of cancer and has the second highest mortality rate of cancers for American Indian/Alaska Native (AI/AN) women. Early screening is critical. This study examines the breast cancer-related knowledge, beliefs, and behaviors of Zuni women in the Southwest United States (U.S.). METHODS: In 2020 and 2021, a survey was administered to better understand cancer screening patterns in Zuni Pueblo; 110 women from 50 to 75 years of age were recruited to respond to the breast cancer screening portion. Inclusion criteria included self-identifying as AI, a member of the Zuni tribe, or married to a Zuni tribal member, and meeting the age and gender requirements. Descriptive statistics and bivariate analyses were conducted examining the associations between measures of breast cancer knowledge, beliefs, and behaviors and breast cancer screening status (never, ever/non-compliant, and ever/compliant). RESULTS: Of survey participants, 47.3% have had a breast cancer screening and are up-to-date, 39.1% have had a screening in the past but are not up-to-date, and 13.6% have never been screened. Age was the only statistically significant socioeconomic predictor of breast cancer screening; the median (interquartile range) ages of each group are 62 (54, 68) ever/compliant, 56 (54, 68) ever/non-compliant, and 53 (51, 55) never (p-value < 0.001). Significant differences by health status and access to medical care include having a regular health care provider and going to see a provider for routine check-ups. The survey also shows differences in knowledge about breast cancer risk factors, beliefs, and behaviors. Women across all three screening statuses reported that they would get screened if encouraged by a health care provider. CONCLUSION: While survey respondents report a relatively high rate of ever having had a breast cancer screening, less than half are compliant with screening guidelines, which shows there is an opportunity to improve breast cancer screening rates. With culturally tailored interventions, providers have the potential to improve breast cancer screening for Zuni women.

Blood DNA methylation and liver cancer in American Indians: evidence from the Strong Heart Study.

PURPOSE: Liver cancer incidence among American Indians/Alaska Natives has risen over the past 20 years. Peripheral blood DNA methylation may be associated with liver cancer and could be used as a biomarker for cancer risk. We evaluated the association of blood DNA methylation with risk of liver cancer. METHODS: We conducted a prospective cohort study in 2324 American Indians, between age 45 and 75 years, from Arizona, Oklahoma, North Dakota and South Dakota who participated in the Strong Heart Study between 1989 and 1991. Liver cancer deaths (n = 21) were ascertained using death certificates obtained through 2017. The mean follow-up duration (SD) for non-cases was 25.1 (5.6) years and for cases, 11.0 (8.8) years. DNA methylation was assessed from blood samples collected at baseline using MethylationEPIC BeadChip 850 K arrays. We used Cox regression models adjusted for age, sex, center, body mass index, low-density lipoprotein cholesterol, smoking, alcohol consumption, and immune cell proportions to examine the associations. RESULTS: We identified 9 CpG sites associated with liver cancer. cg16057201 annotated to MRFAP1) was hypermethylated among cases vs. non-cases (hazard ratio (HR) for one standard deviation increase in methylation was 1.25 (95% CI 1.14, 1.37). The other eight CpGs were hypomethylated and the corresponding HRs (95% CI) ranged from 0.58 (0.44, 0.75) for cg04967787 (annotated to PPRC1) to 0.77 (0.67, 0.88) for cg08550308. We also assessed 7 differentially methylated CpG sites associated with liver cancer in previous studies. The adjusted HR for cg15079934 (annotated to LPS1) was 1.93 (95% CI 1.10, 3.39). CONCLUSIONS: Blood DNA methylation may be associated with liver cancer mortality and may be altered during the development of liver cancer.

Biogeographic patterns and community assembly mechanisms of bacterial community in the upper seawater of seamounts and non-seamounts in the Eastern Indian Ocean.

Seamounts are widespread underwater topographic features in the ocean that exert an influential role in shaping the microbial biogeographic distribution. Nevertheless, research on the differences in microbial biogeographic distribution between seamount and non-seamount upper water column is still lacking, particularly in the Indian Ocean where studies are limited. In the present study, a total of 45 seawater samples were collected from the water column (5-200 m) of seamounts (HS) and non-seamounts (E87 transect) regions in the Eastern Indian Ocean (EIO) for the analysis of microbial biogeographic patterns and community assembly processes. The results indicated that bacterial community diversity did not differ significantly between the HS and E87 transect regions; however, the community composition was significantly different. Additionally, bacterial community diversity, composition, as well as structure were more affected by depth than by region. Community diversity tended to increase with depth in E87 transect region, while it tended to decrease in HS region. A distance decay analysis also demonstrated that bacterial communities were more influenced by environmental and depth distances than geographic distances. In the assembly of bacterial communities on HS and E87 transect regions, as well as at different depths, stochastic processes, particularly dispersal limitation, were found to be predominant. These findings enhance our comprehension of bacterial community characteristics in the upper seawater of seamounts and non-seamounts regions in the EIO and offer insights into the assembly processes shaping microbial communities at varying depths. IMPORTANCE: By comparing the bacterial diversity, composition, and structure in the upper seawater of seamount and non-seamount areas, we provide valuable insights into the influential role of seamounts in shaping microbial biogeography. The finding that the depth had a more significant impact on bacterial community characteristics than region underscores the importance of considering vertical stratification when examining microbial distributions. Moreover, the dominance of stochastic processes, particularly dispersal limitation, in governing community assembly across both seamount and non-seamount areas offers critical implications for the mechanisms underlying microbial biogeographic patterns in these dynamic ocean environments. This study expands the current knowledge and lays the groundwork for further investigations into the complex interactions between oceanographic features, environmental gradients, and microbial community dynamics in the Indian Ocean.

Assessing the sensitivity and specificity of myositis-specific and associated autoantibodies: a sub-study from the MyoCite cohort.

OBJECTIVES: Myositis-specific and associated autoantibodies are important biomarkers in routine clinical use. We assessed local testing performance for myositis autoantibodies by comparing line immunoassay (LIA) to protein radio-immunoprecipitation and identifying clinical characteristics associated with each myositis autoantibody in the MyoCite cohort. METHODS: Serum samples from patients within the MyoCite cohort, a well-characterised retro-prospective dataset of adult and juvenile idiopathic inflammatory myopathy (IIM) patients in Lucknow, India (2017-2020), underwent LIA at Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGIMS), Lucknow. Immunoprecipitation of 147 IIM patient serum samples (125 adult-onset, 22 juvenile-onset) was conducted at the University of Bath, with researchers blind to LIA results. LIA performance was assessed against Immunoprecipitation as the reference standard, measuring sensitivity, specificity, and inter-rater agreement. Univariate and multivariate logistic regression determined clinical associations for specific MSA. RESULTS: Immunoprecipitation identified myositis autoantibodies in 56.5% (n = 83) of patient samples, with anti-Jo1 (n = 16; 10.9%) as the most common, followed by anti-MDA5 (n = 14, 9.5%). While LIA showed good agreement for anti-Jo1, anti-PL7 and anti-PL12 (Cohen's κ 0.79, 0.83, and 1, respectively), poor agreement was observed in other subgroups, notably anti-TIF1γ (Cohen's κ 0.21). Strongly positive samples, especially in myositis-specific autoantibodies, correlated more with immunoprecipitation results. Overall, 59 (40.1%) samples exhibited non-congruence on LIA and Immunoprecipitation, and κ values for LIA's for anti-TIF1γ, anti-Ku, anti-PmScl, anti-Mi2, and anti-SAE ranged between 0.21-0.60. CONCLUSION: While LIA reliably detected anti-Jo1, anti-PL7, anti-PL12, anti-MDA5, and anti-NXP-2, it also displayed false positives and negatives. Its effectiveness in detecting other autoantibodies, such as anti-TIF1γ, was poor.

Short stature and dysmorphic features in Asian Indian siblings with DAAM2-associated steroid-resistant nephrotic syndrome: Expansion of the phenotypic spectrum or a blended phenotype?

Variants in more than 60 different genes, most of which code for podocyte-related proteins, have been found to be associated with monogenic forms of nephrotic syndrome (NS). Biallelic variants in DAAM2, a member of the formin family, were recently identified to cause autosomal recessive (AR) NS type 24 in four unrelated families with steroid-resistant nephrotic syndrome (SRNS). This case report represents only the fifth reported family of DAAM2-associated NS and the first from India, with two sibs who presented with a complex phenotype characterized by steroid-resistant nephrotic syndrome, short stature, dysmorphic facial features, deep-set toenails, myopia, increased thickness of the calvarium of the skull, and sloping ribs. Both sibs were found to have a homozygous likely pathogenic nonsense variant c.196C>T (p.Arg66Ter; NM_001201427.2) in exon 3 of the DAAM2 gene through whole exome sequencing. The dysmorphic features could possibly be part of the DAAM2-related phenotype which has hitherto not been reported or could represent a blended phenotype, with the extrarenal manifestations resulting from a yet to be identified coexisting genetic condition.

Federal Food Assistance Accessibility and Acceptability Among Indigenous Peoples in the United States: A Scoping Review.

The purpose of this scoping review was to determine the extent to which accessibility and acceptability of federal food assistance programs in the United States have been evaluated among indigenous peoples and to summarize what is currently known. Twelve publications were found that examine aspects of accessibility or acceptability by indigenous peoples of 1 or more federal food assistance programs, including the supplemental nutrition assistance program (SNAP) and/or the Food Distribution Program on Indian Reservations (n = 8), the Special Supplemental Nutrition Program for Women, infants, and children (WIC) (n = 3), and the national school lunch program (n = 1). No publications were found to include the commodity supplemental food program or the child and adult care food program. Publications ranged in time from 1990-2023, and all reported on findings from rural populations, whereas 3 also included urban settings. Program accessibility varied by program type and geographic location. Road conditions, transportation access, telephone and internet connectivity, and an overall number of food stores were identified as key access barriers to SNAP and WIC benefit redemption in rural areas. Program acceptability was attributed to factors such as being tribally administered, providing culturally sensitive services, and offering foods of cultural significance. For these reasons, Food Distribution Program on Indian Reservations and WIC were more frequently described as acceptable compared to SNAP and national school lunch programs. However, SNAP was occasionally described as more acceptable than other assistance programs because it allows participants autonomy to decide which foods to purchase and when. Overall, little attention has been paid to the accessibility and acceptability of federal food assistance programs among indigenous peoples in the United States. More research is needed to understand and improve the participation experiences and health trajectories of these priority populations.

Woodhouse-Sakati syndrome in an Indian patient with a novel pathogenic variant.

Woodhouse-Sakati syndrome consists of hypogonadism, diabetes mellitus, alopecia, ECG abnormalities, and dystonia. This condition is caused by the loss of function of the DCAF17 gene. Most of the patients have been reported from Greater Middle Eastern countries. We report a 38 male from southern India who presented with syncope and massive hemoptysis due to ruptured bronchopulmonary collaterals. He also had alopecia, cataracts, recently diagnosed diabetes and hypogonadism. Whole exome sequencing showed a novel homozygous truncating variant in the DCAF17 gene. Despite embolization of the aortopulmonary collaterals, the patient died of recurrent hemoptysis.