Firearm-Related Lead Exposure and Child Lead Levels in the United States, 2012-2018.

OBJECTIVE: To determine if firearm ownership is positively related to elevated child lead levels at a state-level, even when accounting for other sources of lead. STUDY DESIGN: For this cross-sectional ecological study, we investigated whether household firearm ownership rates (a proxy for firearm-related lead exposure) was associated with the prevalence of elevated child blood lead levels in 44 US States between 2012 and 2018. To account for potential confounding, we adjusted for other known lead exposures, poverty rate, population density, race, and calendar year. To address missing data, we used multiple imputation by chained equations. RESULTS: Prevalence of elevated child blood lead positively correlated with household firearm ownership and established predictors of lead exposure. In fully adjusted negative binomial regression models, child blood lead was positively associated with household firearm ownership and older housing; each IQR (14%) increase in household firearm ownership rate was associated with a 41% higher prevalence of childhood elevated blood lead (prevalence ratio: 1.41, 95% CI: 1.11-1.79). CONCLUSION: These data provide state-level evidence that firearms may be an important source of child lead exposure. More research is needed to substantiate this relationship and identify modifiable pathways of exposure at the individual level.

Increased response to immune checkpoint inhibitors with dietary methionine restriction.

Dietary methionine restriction, defined as reduction of methionine intake by around 80%, reproducibly decreases tumor growth and synergizes with cancer therapies. Here, we combined dietary methionine restriction with immune checkpoint inhibitors in a model of colon adenocarcinoma. In vitro , we observed that methionine restriction increased the expression of MHC-I and PD-L1 in both mouse and human colorectal cancer cells. We also saw an increase in the gene expression of STING, a known inducer of type I interferon signaling. Inhibition of the cGAS-STING pathway, pharmacologically or with siRNA, blunted the increase in MHC-I and PD-L1 surface and gene expression following methionine restriction. PD-L1 expression was also This indicated that the cGAS-STING pathway in particular, and interferon in general, is playing a role in the immune response to methionine restriction. We then combined dietary methionine restriction with immune checkpoint inhibitors targeted against CTLA-4 and PD-1 in a MC38 colorectal cancer tumor model in C57BL/6 mice. The combination treatment was five times more effective at reducing tumor size than immune checkpoint inhibition alone in males. We noted sex differences in the response to dietary methionine restriction for the MC38 tumor model in C57BL/6 mice. Finally, we observed an increase in PD-L1 protein expression in MC38 tumors from animals who were fed a methionine-restricted diet. Furthermore, the distribution of CD8 staining changed from mostly peripheric in the controls, to intratumoral in the methionine-restricted tumors. MHC-I, which has a high basal expression in MC38 cells, was highly expressed in all tumors. These results indicate that methionine restriction improves the response to immune checkpoint inhibitors in mice, and that this improvement is associated with the cGAS-STING pathway and interferon signaling.

Engineering of Chinese hamster ovary cells for co-overexpressing MYC and XBP1s increased cell proliferation and recombinant EPO production.

Improving the cellular capacity of Chinese hamster ovary (CHO) cells to produce large amounts of therapeutic proteins remains a major challenge for the biopharmaceutical industry. In previous studies, we observed strong correlations between the performance of CHO cells and expression of two transcription factors (TFs), MYC and XBP1s. Here, we have evaluated the effective of overexpression of these two TFs on CHO cell productivity. To address this goal, we generated an EPO-producing cell line (CHOEPO) using a targeted integration approach, and subsequently engineered it to co-overexpress MYC and XBP1s (a cell line referred to as CHOCXEPO). Cells overexpressing MYC and XBP1s increased simultaneously viable cell densities and EPO production, leading to an enhanced overall performance in cultures. These improvements resulted from the individual effect of each TF in the cell behaviour (i.e., MYC-growth and XBP1s-productivity). An evaluation of the CHOCXEPO cells under different environmental conditions (temperature and media glucose concentration) indicated that CHOCXEPO cells increased cell productivity in high glucose concentration. This study showed the potential of combining TF-based cell engineering and process optimisation for increasing CHO cell productivity.

Representation Matters: One Urology Residency Program's Approach to Increasing Workforce Diversity.

OBJECTIVE: To address the challenge in urology in recruiting physicians from backgrounds racially and ethnically underrepresented in medicine (URiM), we sought to design, implement, and evaluate methods for recruiting URiM candidates to our urology residency program. METHODS: We developed a 3-pronged approach aimed at increasing the number of interviewed applicants, and subsequently number of URiM residents recruited to our program. The 3 facets included: (1) funded visiting student rotation, (2) holistic evaluation of applications, (3) implemented targeted outreach. Statistical analysis of the applicants interviewed and matched into our residency program, as well as traditional metrics used for residency recruitment, were performed from 2015 to 2022. RESULTS: The number of URiM interviewees significantly increased from 6.1% in 2015 to its peak, 40%, in 2020. In 2015, there were no URiM residents in our urology residency program. By 2022, the total URiM complement increased to 35%. In evaluating traditional metrics of residency recruitment, there was no significant difference in mean USMLE Step 1 score before compared with after the implementation of our recruitment approach. The maximum rank number reached to fill the urology residency positions also remained relatively stable throughout the study period, with a range from 5 to 38. CONCLUSION: We demonstrate that the implementation of our innovative and intentional 3-pronged recruitment approach effectively increased the number of URiM interviewees and residents in our residency program. The diversification of our urology workforce depends on the implementation of such efforts, and we encourage urologists to lead the way on such initiatives.

Production and quality of sorghum silage intercropped with marandu grass and pigeonpea / Produção e qualidade de silagem de sorgo consorciado com capim marandu e feijão guandu

Lack of forage in the winter dry season is a concern for cattle production in tropical Brazil. Pasture renovation with silage production might solve an immediate concern for forage production and help develop an improved pasture condition after cropping. The present study was focused to compare the production and quality of monocropped sorghum and sorghum intercropped with Marandu grass and/or pigeonpea in two row spacings. The experiment was carried out on a sandy Oxisol in São Paulo state in Brazil with an experimental design of a 2 x 4 factorial arrangement with four replications. Treatments were: monocropped sorghum,sorghum intercropped with Urochloa brizantha, sorghum intercropped with Cajanus cajan(cv. BRS Mandarim), and sorghum intercropped with Urochloa+ pigeonpea with 0.45 and 0.90 m row spacings. Greatest forage production was with 0.45-m spacing for monocropped sorghum and dual-species intercropping. With 0.90-m spacing, greatest production was for Sorghum+Urochloa. Sorghum+Urochloa+Cajanusintercropping provided the highest concentrations of crude protein in silage, regardless of row spacing. An increase in ensiling time reduced quality of the silage due to a decline in crude protein and TDN and an increase in fibers. However, the reduced spacing between lines with the inclusion of legumes resulted in a greater amount of silage with a higher concentration of protein.(AU)

A falta de forragem na estação seca é uma preocupação para os produtores de carne bovina no Brasil. A renovação de pastagens com produção de silagem pode se constituir emuma alternativa para a produção de alimento para o período seco do ano e, ao mesmo tempo, porporcionar a formação de pastagem de melhorar qualidade. O presente estudo teve como objetivo comparar a produção e a qualidade da silage de sorgo em monocultivo e consorciado com capim-marandu e/ou feijão-guandu em dois espaçamentos entre linhas. O experimento foi conduzido em Latossolo arenoso no estado de São Paulo com delineamento experimental em arranjo fatorial 2 x 4, com quatro repetições. Os tratamentos foram: sorgo em monocultivo, sorgo consorciado com Urochloa brizantha, sorgo consorciado com Cajanus cajan(cv. BRS Mandarim) e sorgo consorciadocom U. brizantha +C. cajancom espaçamento de 0,45 e 0,90 m. A maior produção de forragem foi obtida com espaçamento de 0,45 m para sorgo monocultivo eno consórico de duas espécies. Com espaçamento de 0,90 m, a maior produção foi para sorgo+U. brizantha. O consórcio sorgoU. brizantha+C. cajanproporcionou as maiores concentrações de proteína bruta na silagem, independentemente do espaçamento entre linhas. O aumento do tempo de ensilagem reduziu a qualidade da silagem devido à queda de proteína bruta e NDT e aumento de fibras. Oespaçamento reduzido entre linhas,com a inclusão de leguminosas resultou em maior quantidade de silage,e maior concentração de proteína.(AU)

Enhanced recombinant protein production in CHO cell continuous cultures under growth-inhibiting conditions is associated with an arrested cell cycle in G1/G0 phase.

Low temperature and sodium butyrate (NaBu) are two of the most used productivity-enhancing strategies in CHO cell cultures during biopharmaceutical manufacturing. While these two approaches alter the balance in the reciprocal relationship between cell growth and productivity, we do not fully understand their mechanisms of action beyond a gross cell growth inhibition. Here, we used continuous culture to evaluate the differential effect of low temperature and NaBu supplementation on CHO cell performance and gene expression profile. We found that an increase in cell-productivity under growth-inhibiting conditions was associated with the arrest of cells in the G1/G0 phase. A transcriptome analysis revealed that the molecular mechanisms by which low temperature and NaBu arrested cell cycle in G1/G0 differed from each other through the deregulation of different cell cycle checkpoints and regulators. The individual transcriptome changes in pattern observed in response to low temperature and NaBu were retained when these two strategies were combined, leading to an additive effect in arresting the cell cycle in G1/G0 phase. The findings presented here offer novel molecular insights about the cell cycle regulation during the CHO cell bioprocessing and its implications for increased recombinant protein production. This data provides a background for engineering productivity-enhanced CHO cell lines for continuous manufacturing.

Challenges for the development of a universal vaccine against leptospirosis revealed by the evaluation of 22 vaccine candidates.

Leptospirosis is a neglected disease of man and animals that affects nearly half a million people annually and causes considerable economic losses. Current human vaccines are inactivated whole-cell preparations (bacterins) of Leptospira spp. that provide strong homologous protection yet fail to induce a cross-protective immune response. Yearly boosters are required, and serious side-effects are frequently reported so the vaccine is licensed for use in humans in only a handful of countries. Novel universal vaccines require identification of conserved surface-exposed epitopes of leptospiral antigens. Outer membrane ß-barrel proteins (ßb-OMPs) meet these requirements and have been successfully used as vaccines for other diseases. We report the evaluation of 22 constructs containing protein fragments from 33 leptospiral ßb-OMPs, previously identified by reverse and structural vaccinology and cell-surface immunoprecipitation. Three-dimensional structures for each leptospiral ßb-OMP were predicted by I-TASSER. The surface-exposed epitopes were predicted using NetMHCII 2.2 and BepiPred 2.0. Recombinant constructs containing regions from one or more ßb-OMPs were cloned and expressed in Escherichia coli. IMAC-purified recombinant proteins were adsorbed to an aluminium hydroxide adjuvant to produce the vaccine formulations. Hamsters (4-6 weeks old) were vaccinated with 2 doses containing 50 - 125 µg of recombinant protein, with a 14-day interval between doses. Immunoprotection was evaluated in the hamster model of leptospirosis against a homologous challenge (10 - 20× ED50) with L. interrogans serogroup Icterohaemorrhagiae serovar Copenhageni strain Fiocruz L1-130. Of the vaccine formulations, 20/22 were immunogenic and induced significant humoral immune responses (IgG) prior to challenge. Four constructs induced significant protection (100%, P < 0.001) and sterilizing immunity in two independent experiments, however, this was not reproducible in subsequent evaluations (0 - 33.3% protection, P > 0.05). The lack of reproducibility seen in these challenge experiments and in other reports in the literature, together with the lack of immune correlates and commercially available reagents to characterize the immune response, suggest that the hamster may not be the ideal model for evaluation of leptospirosis vaccines and highlight the need for evaluation of alternative models, such as the mouse.

Electrospinning-Generated Nanofiber Scaffolds Suitable for Integration of Primary Human Circulating Endothelial Progenitor Cells.

The extracellular matrix is fundamental in order to maintain normal function in many organs such as the blood vessels, heart, liver, or bones. When organs fail or experience injury, tissue engineering and regenerative medicine elicit the production of constructs resembling the native extracellular matrix, supporting organ restoration and function. In this regard, is it possible to optimize structural characteristics of nanofiber scaffolds obtained by the electrospinning technique? This study aimed to produce partially degraded collagen (gelatin) nanofiber scaffolds, using the electrospinning technique, with optimized parameters rendering different morphological characteristics of nanofibers, as well as assessing whether the resulting scaffolds are suitable to integrate primary human endothelial progenitor cells, obtained from peripheral blood with further in vitro cell expansion. After different assay conditions, the best nanofiber morphology was obtained with the following electrospinning parameters: 15 kV, 0.06 mL/h, 1000 rpm and 12 cm needle-to-collector distance, yielding an average nanofiber thickness of 333 ± 130 nm. Nanofiber scaffolds rendered through such electrospinning conditions were suitable for the integration and proliferation of human endothelial progenitor cells.

The impact of perioperative stroke and delirium on outcomes after surgical aortic valve replacement.

OBJECTIVE: The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days. METHODS: Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life. RESULTS: By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score >2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01). CONCLUSIONS: Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Characterization of Two Fusarium solani Species Complex Isolates from the Ambrosia Beetle Xylosandrus morigerus.

Ambrosia beetles are insect vectors of important plant diseases and have been considered as a threat to forest ecosystems, agriculture, and the timber industry. Several factors have been suggested as promoters of the pathogenic behavior of ambrosia beetles; one of them is the nature of the fungal mutualist and its ability to establish an infectious process. In Mexico, Xylosandrus morigerus is an invasive ambrosia beetle that damages many agroecosystems. Herein, two different isolates from the X. morigerus ambrosia beetle belonging to the Fusarium genus are reported. Both isolates belong to the Fusarium solani species complex (FSSC) but not to the Ambrosia Fusarium clade (AFC). The two closely related Fusarium isolates are pathogenic to different forest and agronomic species, and the morphological differences between them and the extracellular protease profile suggest intraspecific variability. This study shows the importance of considering these beetles as vectors of different species of fungal plant pathogens, with some of them even being phylogenetically closely related and having different pathogenic abilities, highlighting the relevance of the fungal mutualist as a factor for the ambrosia complex becoming a pest.

Novel 2-aryl-4-aryloxyquinoline-based fungistatics for Mucor circinelloides. Biological evaluation of activity, QSAR and docking study.

Zygomycetes are ubiquitous saprophytes in natural environments which transform organic matter. Some zygomycetes of gender Mucor have attracted interest in health sector. Due to its ability as opportunistic microorganisms infecting immuno-compromised people and to the few available pharmacological treatments, the mucormycosis is receiving worldwide attention. Concerning to the pharmacological treatments, some triazole-based compounds such as fluconazole are extensively used. Nevertheless, we focused in the quinolines since they are broadly used models for the design and development of new synthetic antifungal agents. In this study, the fungistatic activity on M. circinelloides of various 2-aryl-4-aryloxyquinoline-based compounds was discovered, and in some cases, it resulted better than reference compound fluconazole. These quinoline derivatives were synthesized via the Csp2-O bond formation using diaryliodonium(III) salts chemistry. A QSAR study was carried out to quantitatively correlate the chemical structure of the tested compounds with their biological activity. Also, a docking study to identify a plausible action target of our more active quinolines was carried out. The results highlighted an increased activity with the fluorine- and nitro-containing derivatives. In light of the few mucormycosis pharmacological treatments, herein we present some non-described molecules with excellent in vitro activities and potential use in the mucormycosis treatment.

TonB-dependent receptor epitopes expressed in M. bovis BCG induced significant protection in the hamster model of leptospirosis.

Leptospirosis is an emerging infectious disease caused by pathogenic Leptospira spp. A universal vaccine against leptospirosis is likely to require highly conserved epitopes from pathogenic leptospires that are exposed on the bacterial surface and that generate a protective and sterilizing immune response. Our group recently identified several genes predicted to encode TonB-dependent receptors (TBDR) in Leptospira interrogans using a reverse vaccinology approach. Three leptospiral TBDRs were previously described and partially characterized as ferric-citrate, hemin, and cobalamin transporters. In the current study, we designed a fusion protein composed of predicted surface-exposed epitopes from three conserved leptospiral TBDRs. Based on their three-dimensional structural models and the prediction of immunogenic regions, nine putative surface-exposed fragments were selected to compose a recombinant chimeric protein. A Mycobacterium bovis BCG strain expressing this chimeric antigen encoded in the pUP500/PpAN mycobacterial expression vector was used to immunize Syrian hamsters. All animals (20/20) vaccinated with recombinant BCG survived infection with an endpoint dose of L. interrogans (p < 0.001). No animal survived in the negative control group. Immunization with our recombinant BCG elicited a humoral immune response against leptospiral TBDRs, as demonstrated by ELISA and immunoblot. No leptospiral DNA was detected by lipL32 qPCR in the kidneys of vaccinated hamsters. Similarly, no growth was observed in macerated kidney cultures from the same animals, suggesting the induction of a sterilizing immune response. Design of new vaccine antigens based on the structure of outer membrane proteins is a promising approach to overcome the impact of leptospirosis by vaccination. KEY POINTS: • Predicted surface-exposed epitopes were identified in three leptospiral TBDRs. • An M. bovis BCG strain expressing a chimeric protein (rTBDRchi) was constructed. • Hamsters vaccinated with rBCG:TBDRchi were protected from lethal leptospirosis.

Are Grasses Really Useful for the Phytoremediation of Potentially Toxic Trace Elements? A Review.

The pollution of soil, water, and air by potentially toxic trace elements poses risks to environmental and human health. For this reason, many chemical, physical, and biological processes of remediation have been developed to reduce the (available) trace element concentrations in the environment. Among those technologies, phytoremediation is an environmentally friendly in situ and cost-effective approach to remediate sites with low-to-moderate pollution with trace elements. However, not all species have the potential to be used for phytoremediation of trace element-polluted sites due to their morpho-physiological characteristics and low tolerance to toxicity induced by the trace elements. Grasses are prospective candidates due to their high biomass yields, fast growth, adaptations to infertile soils, and successive shoot regrowth after harvest. A large number of studies evaluating the processes related to the uptake, transport, accumulation, and toxicity of trace elements in grasses assessed for phytoremediation have been conducted. The aim of this review is (i) to synthesize the available information on the mechanisms involved in uptake, transport, accumulation, toxicity, and tolerance to trace elements in grasses; (ii) to identify suitable grasses for trace element phytoextraction, phytostabilization, and phytofiltration; (iii) to describe the main strategies used to improve trace element phytoremediation efficiency by grasses; and (iv) to point out the advantages, disadvantages, and perspectives for the use of grasses for phytoremediation of trace element-polluted soils.

NDUFV1 mutations in complex I deficiency: Case reports and review of symptoms.

Mitochondrial complex I (CI) deficiency is the most common oxidative phosphorylation disorder described. It shows a wide range of phenotypes with poor correlation within genotypes. Herein we expand the clinics and genetics of CI deficiency in the brazilian population by reporting three patients with pathogenic (c.640G>A, c.1268C>T, c.1207dupG) and likely pathogenic (c.766C>T) variants in the NDUFV1 gene. We show the mutation c.766C>T associated with a childhood onset phenotype of hypotonia, muscle weakness, psychomotor regression, lethargy, dysphagia, and strabismus. Additionally, this mutation was found to be associated with headaches and exercise intolerance in adulthood. We also review reported pathogenic variants in NDUFV1 highlighting the wide phenotypic heterogeneity in CI deficiency.

The potential of Blepharidium guatemalense for nickel agromining in Mexico and Central America.

The aim of this study was to assess the potential of the woody nickel hyperaccumulator species Blepharidium guatemalense (Standl.) Standl. for agromining in southeastern Mexico. Pot trials consisting of nickel dosing (0, 20, 50, 100, and 250 mg Ni kg-1), and synthetic and organic fertilization were conducted. Field trials were also undertaken with different harvesting regimes of B. guatemalense. Foliar nickel concentrations increased significantly with rising nickel additions, with a 300-fold increase at 250 mg Ni kg-1 treatment relative to the control. Synthetic fertilization strongly increased nickel uptake without any change in plant growth or biomass, whereas organic fertilization enhanced plant shoot biomass with a negligible effect on foliar nickel concentrations. A 5-year-old stand which was subsequently harvested twice per year produced the maximum nickel yield tree-1 yr-1, with an estimated total nickel yield of 142 kg ha-1 yr-1. Blepharidium guatemalense is a prime candidate for nickel agromining on account of its high foliar Ni concentrations, high bioconcentration (180) and translocation factors (3.3), fast growth rate and high shoot biomass production. Future studies are needed to test the outcomes of the pot trials in the field. Extensive geochemical studies are needed to identify potential viable agromining locations. Novelty Statement Our research team is a pioneer in the discovery of metal hyperaccumulator plants in Mesoamerica with at least 13 species discovered in the last 2 years. This study is the first to assess the potential of nickel agromining (phytomining) in Mexico (and in all the American continent), using one of the strongest nickel hyperaccumulators reported so far. The promising results of this study are the basis for optimal agricultural management of Blepharidium guatemalense.

Effects of COVID-19 pandemic control measures on air pollution in Lima metropolitan area, Peru in South America.

The sanitary measures implemented to control and prevent an increase in infections due to the COVID-19 pandemic have produced an improvement in the air quality of many urban areas around the world. We assessed air quality during the COVID-19 pandemic for particulate matter (PM2.5 and PM10), NO2 and O3 in in metropolitan area of Lima, Peru between pre-lockdown period (February 1 and March 15 of 2020), historical period (March 16 to April 30 2017-2019) and lockdown period (March 16 to April 30, 2020). The complete national lockdown that was implemented in Peru produced statistically significant reductions in the in-air pollutant (PM10 (-40% and -58%), PM2.5 (-31% and -43%) and NO2 (-46% and -48%)), as recorded by the by the ground-based air quality monitoring network throughout the metropolitan area, compared with the corresponding concentrations for the previous weeks and over the same period for 2017-2019. Analysis of the spatial Distribution of satellite data also show decreases in the concentrations of PM10, PM2.5 and NO2 as a result of the containment measures and suspension of activities implemented by the Peruvian government. The concentrations of O3 significantly increased (11% and 170%) as a result of the decrease in the concentration of NO2, confirming that the study area is a hydrocarbon-limited system, as previously reported. The results obtained contribute to the assessment by the regulatory agencies of the possible strategies of control and monitoring of air pollution in the study area. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11869-021-00990-3.

Neurodevelopmental regression, severe generalized dystonia, and metabolic acidosis caused by POLR3A mutations.

OBJECTIVE: To expand the clinical phenotype of POLR3A mutations by assessing the functional consequences of a missense and a splicing acceptor mutation. METHODS: We performed whole-exome sequencing for identification of likely pathogenic mutations in a 9-year-old female patient with severe generalized dystonia, metabolic acidosis, leukocytosis, hypotonia, and dysphagia. Brain MRI showed basal ganglia atrophy and presence of lactate and lipid peaks by [1H]-magnetic resonance spectroscopy. Expression levels of Pol III target genes were measured by quantitative real-time (qRT)-PCR to study the pathogenicity of the biallelic mutations in patient fibroblasts. RESULTS: The patient is a compound heterozygous for a novel missense c.3721G>A (p.Val1241Met) and the splicing region c.1771-6C>G mutation in POLR3A, the gene coding for the catalytic subunit of RNA polymerase III (Pol III). Aberrant splicing was observed for the c.1771-6C>G mutation. Decreased RNA expression levels of Pol III targets (HNRNPH2, ubiquitin B, lactotransferrin, and HSP90AA1) were observed in patient fibroblasts with rescue to normal levels by overexpression of the wild-type protein but not by the p.Val1241Met variant. CONCLUSIONS: Mutations in the POLR3A gene cause POLR3A-related hypomyelinating leukodystrophy with or without oligodontia or hypogonadotropic hypogonadism (HLD7, OMIM: 607694) and neonatal progeroid syndrome (OMIM: 264090), both with high phenotypic variability. We demonstrated the pathogenicity of c.1771-6C>G and c.3721G>A mutations causing an early-onset disorder. The phenotype of our patient expands the clinical presentation of POLR3A-related mutations and suggests a new classification that we propose designating as Neurodevelopmental Disorder with Regression, Abnormal Movements, and Increased Lactate.

Management of complicated inflammatory fibroid polyp by partial laparoscopic esophagogastrectomy - A case report.

BACKGROUND: Inflammatory fibroid polyps (IFP), known as Vanek tumors, are benign neoplasms, usually located in the stomach and small bowel. The prognosis is good in long term. CLINICAL CASE: We report a 24-year-old woman, with 3 days history of abdominal pain located in the epigastrium, accompanied by melenic evacuations and weight loss since the last month, making the diagnosis of inflammatory fibroid gastric polyp by means of the upper endoscopy and biopsy. CONCLUSIONS: IFP are extremely rare neoplasms in the Mexican population. The symptoms range from asymptomatic, epigastralgia, anemia, and weight loss to intestinal obstruction. Its diagnosis is histopathological.

ANTECEDENTES: Los pólipos inflamatorios fibroideos, conocidos como tumores de Vanek, son neoplasias benignas localizadas en el antro gástrico y en el intestino delgado. El pronóstico es bueno a largo plazo. CASO CLÍNICO: Mujer de 24 años, ingre sada por 3 días de evolución con epigastralgia, acompañada de evacuaciones melénicas y pérdida de peso de 2 kg en el último mes. Se diagnostica, por endoscopía y biopsia, un pólipo inflamatorio fibroideo gástrico. CONCLUSIONES: Los pólipos inflamatorios fibroideos gástricos son neoplasias extremadamente raras en la población mexicana. Sus síntomas varían desde cuadros asintomáticos, epigastralgias, anemia y pérdida de peso hasta obstrucción intestinal. Su diagnóstico es histopatológico.