Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells.

Self-renewal of spermatogonial stem cells is vital to lifelong production of male gametes and thus fertility. However, the underlying mechanisms remain enigmatic. Here, we show that DOT1L, the sole H3K79 methyltransferase, is required for spermatogonial stem cell self-renewal. Mice lacking DOT1L fail to maintain spermatogonial stem cells, characterized by a sequential loss of germ cells from spermatogonia to spermatids and ultimately a Sertoli cell only syndrome. Inhibition of DOT1L reduces the stem cell activity after transplantation. DOT1L promotes expression of the fate-determining HoxC transcription factors in spermatogonial stem cells. Furthermore, H3K79me2 accumulates at HoxC9 and HoxC10 genes. Our findings identify an essential function for DOT1L in adult stem cells and provide an epigenetic paradigm for regulation of spermatogonial stem cells.

Intrinsically disordered Meningioma-1 stabilizes the BAF complex to cause AML.

Meningioma-1 (MN1) overexpression in AML is associated with poor prognosis, and forced expression of MN1 induces leukemia in mice. We sought to determine how MN1 causes AML. We found that overexpression of MN1 can be induced by translocations that result in hijacking of a downstream enhancer. Structure predictions revealed that the entire MN1 coding frame is disordered. We identified the myeloid progenitor-specific BAF complex as the key interaction partner of MN1. MN1 over-stabilizes BAF on enhancer chromatin, a function directly linked to the presence of a long polyQ-stretch within MN1. BAF over-stabilization at binding sites of transcription factors regulating a hematopoietic stem/progenitor program prevents the developmentally appropriate decommissioning of these enhancers and results in impaired myeloid differentiation and leukemia. Beyond AML, our data detail how the overexpression of a polyQ protein, in the absence of any coding sequence mutation, can be sufficient to cause malignant transformation.

Tracking Li atoms in real-time with ultra-fast NMR simulations.

We present for the first time a multiscale machine learning approach to jointly simulate atomic structure and dynamics with the corresponding solid state Nuclear Magnetic Resonance (ssNMR) observables. We study the use-case of spin-alignment echo (SAE) NMR for exploring Li-ion diffusion within the solid state electrolyte material Li3PS4 (LPS) by calculating quadrupolar frequencies of 7Li. SAE NMR probes long-range dynamics down to microsecond-timescale hopping processes. Therefore only a few machine learning force field schemes are able to capture the time- and length scales required for accurate comparison with experimental results. By using a new class of machine learning interatomic potentials, known as ultra-fast potentials (UFPs), we are able to efficiently access timescales beyond the microsecond regime. In tandem, we have developed a machine learning model for predicting the full 7Li electric field gradient (EFG) tensors in LPS. By combining the long timescale trajectories from the UFP with our model for 7Li EFG tensors, we are able to extract the autocorrelation function (ACF) for 7Li quadrupolar frequencies during Li diffusion. We extract the decay constants from the ACF for both crystalline ß-LPS and amorphous LPS, and find that the predicted Li hopping rates are on the same order of magnitude as those predicted from the Li dynamics. This demonstrates the potential for machine learning to finally make predictions on experimentally relevant timescales and temperatures, and opens a new avenue of NMR crystallography: using machine learning dynamical NMR simulations for accessing polycrystalline and glass ceramic materials.

The EFG Rosetta Stone: translating between DFT calculations and solid state NMR experiments.

We present a comprehensive study on the best practices for integrating first principles simulations in experimental quadrupolar solid-state nuclear magnetic resonance (SS-NMR), exploiting the synergies between theory and experiment for achieving the optimal interpretation of both. Most high performance materials (HPMs), such as battery electrodes, exhibit complex SS-NMR spectra due to dynamic effects or amorphous phases. NMR crystallography for such challenging materials requires reliable, accurate, efficient computational methods for calculating NMR observables from first principles for the transfer between theoretical material structure models and the interpretation of their experimental SS-NMR spectra. NMR-active nuclei within HPMs are routinely probed by their chemical shielding anisotropy (CSA). However, several nuclear isotopes of interest, e.g.7Li and 27Al, have a nuclear quadrupole and experience additional interactions with the surrounding electric field gradient (EFG). The quadrupolar interaction is a valuable source of information about atomistic structure, and in particular, local symmetry, complementing the CSA. As such, there is a range of different methods and codes to choose from for calculating EFGs, from all-electron to plane wave methods. We benchmark the accuracy of different simulation strategies for computing the EFG tensor of quadrupolar nuclei with plane wave density functional theory (DFT) and study the impact of the material structure as well as the details of the simulation strategy. Especially for small nuclei with few electrons, such as 7Li, we show that the choice of physical approximations and simulation parameters has a large effect on the transferability of the simulation results. To the best of our knowledge, we present the first comprehensive reference scale and literature survey for 7Li quadrupolar couplings. The results allow us to establish practical guidelines for developing the best simulation strategy for correlating DFT to experimental data extracting the maximum benefit and information from both, thereby advancing further research into HPMs.

Antifungal potential of the new copper(II)-theophylline/1,10-phenanthroline complex against drug-resistant Candida species.

Candida spp. are the commonest fungal pathogens worldwide. Antifungal resistance is a problem that has prompted the discovery of novel anti-Candida drugs. Herein, 25 compounds, some of them containing copper(II), cobalt(II) and manganese(II) ions, were initially evaluated for inhibiting the growth of reference strains of Candida albicans and Candida tropicalis. Eight (32%) of the compounds inhibited the proliferation of these yeasts, displaying minimum inhibitory concentrations (MICs) ranging from 31.25 to 250 µg/mL and minimum fungicidal concentration (MFCs) from 62.5 to 250 µg/mL. Drug-likeness/pharmacokinetic calculated by SwissADME indicated that the 8 selected compounds were suitable for use as topical drugs. The complex CTP, Cu(theo)2phen(H2O).5H2O (theo = theophylline; phen = 1,10-phenanthroline), was chosen for further testing against 10 medically relevant Candida species that were resistant to fluconazole/amphotericin B. CTP demonstrated a broad spectrum of action, inhibiting the growth of all 20 clinical fungal isolates, with MICs from 7.81 to 62.5 µg/mL and MFCs from 15.62 to 62.5 µg/mL. Conversely, CTP did not cause lysis in erythrocytes. The toxicity of CTP was evaluated in vivo using Galleria mellonella and Tenebrio molitor. CTP had no or low levels of toxicity at doses ranging from 31.25 to 250 µg/mL for 5 days. After 24 h of treatment, G. mellonella larvae exhibited high survival rates even when exposed to high doses of CTP (600 µg/mL), with the 50% cytotoxic concentration calculated as 776.2 µg/mL, generating selectivity indexes varying from 12.4 to 99.4 depending on each Candida species. These findings suggest that CTP could serve as a potential drug to treat infections caused by Candida species resistant to clinically available antifungals.

Unveiling the antifungal mechanisms of CTP, a new copper(II)-theophylline/1,10-phenanthroline complex, on drug-resistant non-albicans Candida species.

Candida species undeniably rank as the most prevalent opportunistic human fungal pathogens worldwide, with Candida albicans as the predominant representative. However, the emergence of non-albicans Candida species (NACs) has marked a significant shift, accompanied by rising incidence rates and concerning trends of antifungal resistance. The search for new strategies to combat antifungal-resistant Candida strains is of paramount importance. Recently, our research group reported the anti-Candida activity of a coordination compound containing copper(II) complexed with theophylline (theo) and 1,10-phenanthroline (phen), known as "CTP" - Cu(theo)2phen(H2O).5H2O. In the present work, we investigated the mechanisms of action of CTP against six medically relevant, antifungal-resistant NACs, including C. auris, C. glabrata, C. haemulonii, C. krusei, C. parapsilosis and C. tropicalis. CTP demonstrated significant efficacy in inhibiting mitochondrial dehydrogenases, leading to heightened intracellular reactive oxygen species production. CTP treatment resulted in substantial damage to the plasma membrane, as evidenced by the passive incorporation of propidium iodide, and induced DNA fragmentation as revealed by the TUNEL assay. Scanning electron microscopy images of post-CTP treatment NACs further illustrated profound alterations in the fungal surface morphology, including invaginations, cavitations and lysis. These surface modifications significantly impacted the ability of Candida cells to adhere to a polystyrene surface and to form robust biofilm structures. Moreover, CTP was effective in disassembling mature biofilms formed by these NACs. In conclusion, CTP represents a promising avenue for the development of novel antifungals with innovative mechanisms of action against clinically relevant NACs that are resistant to antifungals commonly used in clinical settings.

Chitosan/Virgin-Coconut-Oil-Based System Enriched with Cubosomes: A 3D Drug-Delivery Approach.

Emulsion-based systems that combine natural polymers with vegetable oils have been identified as a promising research avenue for developing structures with potential for biomedical applications. Herein, chitosan (CHT), a natural polymer, and virgin coconut oil (VCO), a resource obtained from coconut kernels, were combined to create an emulsion system. Phytantriol-based cubosomes encapsulating sodium diclofenac, an anti-inflammatory drug, were further dispersed into CHT/VCO- based emulsion. Then, the emulsions were frozen and freeze-dried to produce scaffolds. The scaffolds had a porous structure ranging from 20.4 to 73.4 µm, a high swelling ability (up to 900%) in PBS, and adequate stiffness, notably in the presence of cubosomes. Moreover, a well-sustained release of the entrapped diclofenac in the cubosomes into the CHT/VCO-based system, with an accumulated release of 45 ± 2%, was confirmed in PBS, compared to free diclofenac dispersed (80 ± 4%) into CHT/VCO-based structures. Overall, the present approach opens up new avenues for designing porous biomaterials for drug delivery through a sustainable pathway.

Building Fucoidan/Agarose-Based Hydrogels as a Platform for the Development of Therapeutic Approaches against Diabetes.

Current management for diabetes has stimulated the development of versatile 3D-based hydrogels as in vitro platforms for insulin release and as support for the encapsulation of pancreatic cells and islets of Langerhans. This work aimed to create agarose/fucoidan hydrogels to encapsulate pancreatic cells as a potential biomaterial for diabetes therapeutics. The hydrogels were produced by combining fucoidan (Fu) and agarose (Aga), marine polysaccharides derived from the cell wall of brown and red seaweeds, respectively, and a thermal gelation process. The agarose/fucoidan (AgaFu) blended hydrogels were obtained by dissolving Aga in 3 or 5 wt % Fu aqueous solutions to obtain different proportions (4:10; 5:10, and 7:10 wt). The rheological tests on hydrogels revealed a non-Newtonian and viscoelastic behavior, while the characterization confirmed the presence of the two polymers in the structure of the hydrogels. In addition, the mechanical behavior showed that increasing Aga concentrations resulted in hydrogels with higher Young's modulus. Further, the ability of the developed materials to sustain the viability of human pancreatic cells was assessed by encapsulation of the 1.1B4HP cell line for up to 7 days. The biological assessment of the hydrogels revealed that cultured pancreatic beta cells tended to self-organize and form pseudo-islets during the period studied.

Decoding the antifungal resistance mechanisms in biofilms of emerging, ubiquitous and multidrug-resistant species belonging to the Scedosporium/Lomentospora genera.

The opportunistic filamentous fungi belonging to the Scedosporium and Lomentospora genera are highly tolerant to all classes of available antifungal drugs. Moreover, the mature biofilm formed by these fungi presents higher antifungal resistance when compared to planktonic cells. Nevertheless, the resistance mechanisms developed by the biofilm lifestyle are not completely elucidated. In the current study, we have investigated the mainly known resistance mechanisms to azoles (voriconazole and fluconazole) and polyenes (amphotericin B [AMB]) in S. apiospermum, S. minutisporum, S. aurantiacum, and L. prolificans (formerly S. prolificans) biofilms. Both classes of antifungals can physically bind to the extracellular matrix of mature biofilms, preventing the drugs from reaching their targets on biofilm-forming cells, which precludes their activity and toxicity. In addition, the activity of efflux pumps, measured by Rhodamine 6 G, was increased along with the maturation of the biofilm. The efflux pump's inhibition by L-Phe-L-Arg-ß-naphthylamide culminated in a 2- to 16-fold increase in azole susceptibility in conidial cells, but not in mature biofilms. Finally, we demonstrated by using specific inhibitors that in conidia, but not in biofilms, AMB induced the production of reactive oxygen species through the activity of the oxidative phosphorylation system (complex I-IV and alternative oxidases). However, the cellular redox imbalance caused by AMB was well-coped with the high activity of antioxidative enzymes, such as superoxide dismutase and catalase. Altogether, our results revealed that Scedosporium/Lomentospora biofilm resistance occurs through various mechanisms that operate concomitantly, which could explain the huge challenge in the clinical treatment of scedosporiosis/lomentosporiosis. LAY SUMMARY: Scedosporium/Lomentospora spp. are multidrug-resistant pathogens able to cause diverse types of infections with typical biofilm characteristics, which makes the treatment a hard issue. We deciphered the resistance mechanisms to classical antifungals developed in the biofilm formed by these fungi.

Differences in Charge Distribution in Leishmania tarentolae Leishmanolysin Result in a Reduced Enzymatic Activity.

Leishmania tarentolae is a non-pathogenic trypanosomatid isolated from lizards widely used for heterologous protein expression and extensively studied to understand the pathogenic mechanisms of leishmaniasis. The repertoire of leishmanolysin genes was reported to be expanded in L. tarentolae genome, but no proteolytic activity was detected. Here, we analyzed L. tarentolae leishmanolysin proteins from the genome to the structural levels and evaluated the enzymatic activity of the wild-type and overexpressing mutants of leishmanolysin. A total of 61 leishmanolysin sequences were retrieved from the L. tarentolae genome. Five of them were selected for phylogenetic analysis, and for three of them, we built 3D models based on the crystallographic structure of L. major ortholog. Molecular dynamics simulations of these models disclosed a less negative electrostatic potential compared to the template. Subsequently, L. major LmjF.10.0460 and L. tarentolae LtaP10.0650 leishmanolysins were cloned in a pLEXSY expression system into L. tarentolae. Proteins from the wild-type and the overexpressing parasites were submitted to enzymatic analysis. Our results revealed that L. tarentolae leishmanolysins harbor a weak enzymatic activity about three times less abundant than L. major leishmanolysin. Our findings strongly suggest that the less negative electrostatic potential of L. tarentolae leishmanolysin can be the reason for the reduced proteolytic activity detected in this parasite.

Molecular Dereplication and In Vitro and In Silico Pharmacological Evaluation of Coriandrum sativum against Neuroblastoma Cells.

The aim of this study was to investigate the cytotoxic activity of the Coriandrum sativum (C. sativum) ethanolic extract (CSEE) in neuroblastoma cells, chemically characterize the compounds present in the CSEE, and predict the molecular interactions and properties of ADME. Thus, after obtaining the CSEE and performing its chemical characterization through dereplication methods using UPLC/DAD-ESI/HRMS/MS, PM6 methods and the SwissADME drug design platform were used in order to predict molecular interactions and ADME properties. The CSEE was tested for 24 h in neuroblastoma cells to the establishment of the IC50 dose. Then, the cell death was evaluated, using annexin-PI, as well as the activity of the effector caspase 3, and the protein and mRNA levels of Bax and Bcl-2 were analyzed by ELISA and RT-PCR, respectively. By UHPLC/DAD/HRMS-MS/MS analysis, the CSEE showed a high content of isocoumarins-dihydrocoriandrin, coriandrin, and coriandrones A and B, as well as nitrogenated compounds (adenine, adenosine, and tryptophan). Flavonoids (apigenin, hyperoside, and rutin), phospholipids (PAF C-16 and LysoPC (16:0)), and acylglicerol were also identified in lower amount as important compounds with antioxidant activity. The in silico approach results showed that the compounds 1 to 6, which are found mostly in the C. sativum extract, obey the "Five Rules" of Lipinski, suggesting a good pharmacokinetic activity of these compounds when administered orally. The IC50 dose of CSEE (20 µg/mL) inhibited cell proliferation and promoted cell death by the accumulation of cleaved caspase-3 and the externalization of phosphatidylserine. Furthermore, CSEE decreased Bcl-2 and increased Bax, both protein and mRNA levels, suggesting an apoptotic mechanism. CSEE presents cytotoxic effects, promoting cell death. In addition to the promising results predicted through the in silico approach for all compounds, the compound 6 showed the best results in relation to stability due to its GAP value.

Indexes to assess feeding practices of children under 2 years old: a systematic review.

OBJECTIVE: To systematically review studies that used indexes to assess feeding practices of children under 2 years. DESIGN: Seven databases were searched with no limit on language or publication date. SETTING: The reviewed studies included thirteen Asian, ten Latin American, four European, four North American, three Oceanian and three African. PARTICIPANTS: Children under 2 years. RESULTS: We analysed thirty-six studies: twenty-two presenting original indexes and fourteen using adapted indexes. Among the original indexes, thirteen assess breast-feeding, fourteen food consumption, ten food groups, and ten other feeding practices. Original indexes were mainly adapted to fit the data available in the study, to update for current nutritional recommendations or to add components not present in the original indexes. Seven studies evaluated the associations between the indexes and nutrient intake or nutritional status. The main limitations cited by the authors were: flaws in the definition of the index components, criteria for cut-off points and weighting of the evaluated index components. CONCLUSIONS: The assessment of feeding practices for young children and its comparison across countries remains a challenge, especially due to the lack of consensus on the construction of indexes and regional differences in dietary recommendations and practices. Lack of validation for some indexes also makes it difficult to choose the most appropriate index for a given objective. Adapting existing indexes is a viable option. We point out relevant recommendations that may contribute to future research. Validation and longitudinal studies in diverse populations are favourable to qualify the assessment of feeding practices in this group.

Prevalence of overweight and obesity and associated factors among women of childbearing age in Brazil.

OBJECTIVE: To assess the factors associated with overweight and obesity among women of childbearing age in Brazil. DESIGN: Cross-sectional study. SETTING: Using the National Health Survey (PNS) database, from the year 2013. The socio-economic and demographic factors analysed were age, race/skin colour, region, marital status, education level, employment and family income. Concerning health history, diagnoses of hypertension, diabetes mellitus, high cholesterol, heart attack, stroke, chronic kidney disease, menarche, parity and depression were evaluated. For lifestyle information, health status, alcoholic beverage consumption, smoking and physical activity were included. The outcomes were obesity and overweight. The association of excess weight with socio-economic and demographic factors, health history and lifestyle characteristics was investigated according to the appropriate theoretical-conceptual model for the topic. PARTICIPANTS: The sample size was 17 109 women aged 18-49 years. RESULTS: The prevalence of women with excess weight was 55·20 %, with 33·26 % being overweight and 21·94 % with obesity. The factors associated with excess weight were age, non-white skin colour, having a partner, family income of up to two minimum wages, menarche before the age of 12, multiparity, diabetes mellitus, depression, hypertension, high cholesterol, stroke and heart attack. CONCLUSION: The results showed an association between excess weight and socio-demographic factors, both determinants of general and reproductive health history. Implementation of effective public health policies is necessary to prevent unfavourable outcomes related to the health of women of childbearing age with excess weight.

Anti-Leishmania braziliensis activity of 1,10-phenanthroline-5,6-dione and its Cu(II) and Ag(I) complexes.

Leishmaniasis, included in the priority list of the WHO, remains as a neglected disease caused by parasites of the Leishmania genus. There is no vaccine available for human leishmaniasis, and the current treatment is based on old drugs that cause serious side effects. Herein, we initially studied the cellular distribution of the virulence factor gp63, the major metallopeptidase, in a virulent strain of Leishmania braziliensis, and then we measured the inhibitory effects of 1,10-phenanthroline-5,6-dione (phendione), and its metal complexes, [Cu(phendione)3](ClO4)2.4H2O and [Ag(phendione)2]ClO4, on both cellular and extracellular metallopeptidases produced by promastigotes. The action of the three compounds on parasite viability and on parasite-macrophage interaction was also determined. Gp63 molecules were detected in several parasite compartments, including the cytoplasm, the membrane lining the cell body and flagellum, and in the flagellar pocket, which explains the presence of gp63 in the culture medium. The test compounds inhibited parasite metallopeptidases in a typical dose-dependent manner, and they also caused a significant and irreversible inhibition of parasite motility. Moreover, the pre-treatment of promastigotes with the test compounds induced a decrease in the association index with macrophages. Collectively, phendione and its Cu(II) and Ag(I) complexes are excellent prototypes for the development of new anti-L. braziliensis drugs.

A Method to Assess the Risk of Sun Coral Invasion in Marine Protected Areas.

The safest and most efficient method of avoiding costs and impacts associated with biological invasions is to prevent the introduction and establishment of non-native species. In Brazil, two invasive coral species have been causing ecological, economic and social impacts: Tubastraea coccinea and Tubastraea tagusensis. This work presents a protocol to analyze the risk of invasion in Marine Protected Areas (MPAs) in the State of Rio de Janeiro considering the main vector of these species on the Brazilian coast. This protocol takes five risk factors into account: environmental similarity between the donor area and the possible receiving area; available substrate for colonization; proximity to the donor region; proximity and quantity of oil platforms and drill ships that passed by the analyzed MPAs and proximity and quantity of oil platforms and drill ships that anchored near the MPAs. Results must be used by decision-makers for a better management of Marine Protected Areas. The protocol we present can be applied to analyze the relative risk of invasion throughout the Brazilian coast, in order to prioritize areas for early detection and monitoring of the presence of sun corals.

Post-seminal development and cryopreservation of endemic or endangered bromeliads.

Vriesea bahiana, Hohenbergia castellanosii and Encholirium spectabile are endemic Brazilian species that are considered endemic or endangered. Development of strategies to conserve these species is important to prevent irreversible genetic erosion. The objective of this study was to evaluate the post-seminal development and seed cryopreservation of three endemic or in danger of extinction bromeliad species in Brazil, to obtain a protocol that can safeguard the genetic variability of these species. In the seed cryopreservation assay, we evaluated five desiccation periods. The seeds in the cryotubes were taken from the desiccator and immediately plunged into liquid nitrogen. For the analysis of post-seminal development, seeds in different germination stages were collected and evaluated by light and scanning electron microscopy. Vriesea bahiana seeds frozen in liquid nitrogen presented almost 100% germination, indicating dormancy break of this species. Vriesea bahiana can be cryopreserved with 5.9% water content after being dried for 24 hours. Hohenbergia castellanosii and E. spectabile seeds did not need to be desiccated before being cryopreserved. The most relevant morphological traits for differentiation of genera and subfamilies of Bromeliaceae are the shape and type of seed appendages. In this study, all three species presented well-differentiated size and shape of their structures.

Exploring Innovative Leishmaniasis Treatment: Drug Targets from Pre-Clinical to Clinical Findings.

Leishmaniasis is a group of tropical diseases caused by parasitic protozoa belonging to the genus Leishmania. The disease is categorized in cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). The conventional treatment is complex and can present high toxicity and therapeutic failures. Thus, there is a continuing need to develop new treatments. In this review, we focus on the novel molecules described in the literature with potential leishmanicidal activity, categorizing them in pre-clinical (in vitro, in vivo), drug repurposing and clinical research.

Moderate and severe periodontitis are positively associated with metabolic syndrome.

OBJECTIVE: This study investigated the association between periodontitis severity (exposure) and metabolic syndrome (MetS - outcome), using two criteria for diagnosis of the outcome, since this relationship remains unexplored. MATERIALS AND METHODS: A case-control study was conducted with 870 individuals: 408 with first MetS diagnosis (cases) and 462 without MetS (controls). Participants' general information was obtained using a questionnaire and laboratory data was collected from medical records. Periodontitis severity criteria followed the Center for Disease Control and Prevention: none, mild, moderate, and severe. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by logistic regression analysis. RESULTS: Findings showed a positive association between moderate and severe periodontitis and MetS: ORadjusted = 1.64 (95% CI: 1.01 to 2.68) and ORadjusted = 1.94 (95% CI: 1.19 to 3.16), respectively, after adjustment for age, sex, schooling level, smoking habit, and cardiovascular disease. The adjusted measurements showed that among individuals with moderate or severe periodontitis, the probability of having MetS was around two times greater than among those without periodontitis, and that the chance was greater among participants with severe periodontitis than those with moderate periodontitis. CONCLUSION: An association between the severity of periodontal status and MetS was found, suggesting a possible relationship between the two diseases. CLINICAL RELEVANCE: MetS influences the etiology of cardiovascular diseases, one of the leading causes of mortality worldwide. The findings suggest that the greater the severity of periodontitis, the greater is the association magnitude with MetS. The health professional needs to recognize that the importance of periodontal disease may play in MetS.

Health profile of pediatric Special Immigrant Visa holders arriving from Iraq and Afghanistan to the United States, 2009-2017: A cross-sectional analysis.

BACKGROUND: The United States has admitted over 80,000 Special Immigrant Visa holders (SIVH), which include children. Despite the increase in the proportion of SIVH admissions to the US over recent years, little is known about health conditions in SIV children. We report the frequency of selected diseases identified overseas and assess differences in selected conditions between SIV children from Iraq and Afghanistan. METHODS AND FINDINGS: We analyzed 15,729 overseas medical exam data in Centers for Disease Control and Prevention's Electronic Disease Notification system (EDN) for children less than 18 years of age from Iraq (29.1%) and Afghanistan (70.9%) who were admitted to the US from April 2009 through December 2017 in a cross-sectional analysis. Variables included age, sex, native language, measured height and weight, and results of the overseas medical examination. From our analysis, less than 1% of SIV children (Iraqi: 0.1%; Afghan: 0.12%) were reported to have abnormal tuberculosis test findings, less than 1% (Iraqi: 0.3%; Afghan: 0.7%) had hearing abnormalities, and about 4% (Iraqi: 6.0% Afghan: 2.9%) had vision abnormalities, with a greater prevalence of vision abnormalities noted in Iraqis (OR: 1.9, 95% CI 1.6-2.2, p <0.001). Seizure disorders were noted in 46 (0.3%) children, with Iraqis more likely to have a seizure disorder (OR: 7.6, 95% CI 3.8-15.0, p < 0.001). On average, children from Afghanistan had a lower mean height-for-age z-score (Iraqi: -0.28; Afghan: -0.68). Only the data quality assessment for height for age for children ≥5 years fell within WHO recommendations. Limitations included the inability to obtain all SIVH records and self-reported medical history of noncommunicable diseases. CONCLUSION: In this investigation, we found that less than 1% of SIV children were reported to have abnormal tuberculosis test findings and 4% of SIV children had reported vision abnormalities. Domestic providers caring for SIVH should follow the US Centers for Disease Control and Prevention (CDC) Guidelines for the US Domestic Medical Examination for Newly Arriving Refugees, including an evaluation for malnutrition. Measurement techniques and anthropometric equipment used in panel site clinics should be assessed, and additional training in measurement techniques should be considered. Future analyses could further explore the health of SIV children after resettlement in the US.