Rollet's mixed chancre in an adult woman diagnosed in the state of Amazonas, Brazil: A case report.

Rollet's Mixed Chancre is a clinical presentation of sexually transmitted infections (STI), involving the coexistence of Haemophilus ducreyi and Treponema pallidum at the same site of infection. Here, we report a case of Rollet's Mixed Chancre in a 32-year-old Brazilian woman. On physical examination she presented with a unilateral bubo measuring approximately 5 × 3 centimeters in diameter, in association with an ulcerated lesion that evolved for 10 days at the inguinal region. She was successfully treated at a health unit with antibiotics. Rollet's Mixed Chancre, though uncommon, poses diagnostic challenges. This case highlights the importance of considering rare STI manifestations. Moreover, comprehensive STI screening and adherence to treatment guidelines are essential for effective management and prevention of further transmission.

Host metabolomic responses in recurrent P. vivax malaria.

Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC-MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate ß-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax.

Temporal and spatial variation in hydrogen sulfide (H2S) emissions during holopelagic Sargassum spp. decomposition on beaches.

BACKGROUND: Since 2011, over 30 tropical Atlantic nations have experienced substantial landings of holopelagic Sargassum spp. Its decomposition results in the production of hydrogen sulfide (H2S), which, in elevated concentrations, can pose a threat to human health. This study aims to enhance our understanding of the temporal and spatial variability in H2S emissions during the decomposition of Sargassum on beaches. The primary objective is to assess potential exposure risks for local populations, tourists, and cleanup workers. METHODS: H2S levels were monitored using a SENKO sensor (SGTP-H2S; limit of detection 0.1-100 ppm; resolution 0.1 ppm) at four distances from Sargassum accumulation points of (0, 10, 30, and 40 m) in Puerto Morelos, Mexico, during 2022 and 2023. RESULTS: Elevated concentrations of H2S were detected beneath the Sargassum piles, with 23.5% of readings exceeding 5 ppm and occasional spikes above 100 ppm. Above the piles, 87.3% of the measurements remained below 2 ppm, and the remainder fell between 2.1 and 5.2 ppm. At 10 m from the shoreline, 90% of measurements registered below 0.1 ppm, and the remaining 10% were below 2 ppm. Readings at 30 and 40 m consistently recorded levels below 0.1 ppm. H2S concentrations positively correlated with Sargassum pile height, the temperature beneath the piles, and wind speed. CONCLUSIONS: Our findings suggest no immediate and significant exposure risk for residents or tourists. However, Sargassum cleanup workers face a higher exposure risk, potentially encountering concentrations above 5 ppm for nearly one-fourth of the working time.

Methylprednisolone therapy induces differential metabolic trajectories in severe COVID-19 patients.

IMPORTANCE: The SARS-CoV-2 virus infection in humans induces significant inflammatory and systemic reactions and complications of which corticosteroids like methylprednisolone have been recommended as treatment. Our understanding of the metabolic and metabolomic pathway dysregulations while using intravenous corticosteroids in COVID-19 is limited. This study will help enlighten the metabolic and metabolomic pathway dysregulations underlying high daily doses of intravenous methylprednisolone in COVID-19 patients compared to those receiving placebo. The information on key metabolites and pathways identified in this study together with the crosstalk with the inflammation and biochemistry components may be used, in the future, to leverage the use of methylprednisolone in any future pandemics from the coronavirus family.

Understanding and combatting misinformation across 16 countries on six continents.

The spread of misinformation online is a global problem that requires global solutions. To that end, we conducted an experiment in 16 countries across 6 continents (N = 34,286; 676,605 observations) to investigate predictors of susceptibility to misinformation about COVID-19, and interventions to combat the spread of this misinformation. In every country, participants with a more analytic cognitive style and stronger accuracy-related motivations were better at discerning truth from falsehood; valuing democracy was also associated with greater truth discernment, whereas endorsement of individual responsibility over government support was negatively associated with truth discernment in most countries. Subtly prompting people to think about accuracy had a generally positive effect on the veracity of news that people were willing to share across countries, as did minimal digital literacy tips. Finally, aggregating the ratings of our non-expert participants was able to differentiate true from false headlines with high accuracy in all countries via the 'wisdom of crowds'. The consistent patterns we observe suggest that the psychological factors underlying the misinformation challenge are similar across different regional settings, and that similar solutions may be broadly effective.

Chemistry and Pharmacology of Bergenin or Its Derivatives: A Promising Molecule.

Bergenin is a glycosidic derivative of trihydroxybenzoic acid that was discovered in 1880 by Garreau and Machelart from the rhizomes of the medicinal plant Bergenia crassifolia (currently: Saxifraga crassifolia-Saxifragaceae), though was later isolated from several other plant sources. Since its first report, it has aroused interest because it has several pharmacological activities, mainly antioxidant and anti-inflammatory. In addition to this, bergenin has shown potential antimalarial, antileishmanial, trypanocidal, antiviral, antibacterial, antifungal, antinociceptive, antiarthritic, antiulcerogenic, antidiabetic/antiobesity, antiarrhythmic, anticancer, hepatoprotective, neuroprotective and cardioprotective activities. Thus, this review aimed to describe the sources of isolation of bergenin and its in vitro and in vivo biological and pharmacological activities. Bergenin is distributed in many plant species (at least 112 species belonging to 34 families). Both its derivatives (natural and semisynthetic) and extracts with phytochemical proof of its highest concentration are well studied, and none of the studies showed cytotoxicity for healthy cells.

Effectiveness of elbasvir/grazoprevir plus ribavirin for hepatitis C virus genotype 1a infection and baseline NS5A resistance.

INTRODUCTION AND OBJECTIVES: In clinical trials, patients with hepatitis C virus (HCV) genotype (GT)1a infection and baseline resistance-associated substitutions (RASs) at amino acid positions 28, 30, 31, or 93 receiving elbasvir/grazoprevir for 12 weeks achieved lower rates of sustained virologic response (SVR) than those without baseline RASs. SVR rates in patients with RASs were improved when elbasvir/grazoprevir treatment duration was extended from 12 to 16 weeks and administered concomitantly with ribavirin. MATERIALS AND METHODS: This was a retrospective, observational analysis using electronic health record abstraction. Patients with HCV GT1a infection and RASs at positions 28, 30, 31, or 93 who were prescribed 16 weeks of elbasvir/grazoprevir and ≥ 1 prescription for ribavirin were included. SVR was defined as HCV RNA below the lower limit of quantification ≥ 70 days after end of treatment. RESULTS: The primary analysis included patients with baseline RASs at positions 30, 31, or 93 (n = 76); a secondary analysis included patients with RASs at positions 28, 30, 31, or 93 (n = 93). SVR was achieved by 77.6% (59/76) of patients in the primary analysis and 80.6% (75/93) of those in the secondary analysis. Of the 18 (19.4%) patients in the secondary cohort who failed to achieve SVR, 8 relapsed (4 with treatment-emergent NS5A substitutions) and 10 did not have viral sequencing to distinguish relapse from reinfection. CONCLUSIONS: This analysis highlights the opportunities in leveraging real-world data to further understand treatment outcomes in smaller, discrete subgroups of patients with HCV infection who cannot be thoroughly evaluated in clinical trials.

Electrocardiogram as a Lyme Disease Screening Test.

OBJECTIVE: To examine the association between electrocardiographic (ECG) evidence of carditis at the time of Lyme disease evaluation and a diagnosis of Lyme disease. STUDY DESIGN: We performed an 8-center prospective cohort study of children undergoing emergency department evaluation for Lyme disease limited to those who had an ECG obtained by their treating clinicians. The study cardiologist reviewed all ECGs flagged as abnormal by the study sites to assess for ECG evidence of carditis. We defined Lyme disease as the presence of an erythema migrans lesion or a positive 2-tier Lyme disease serology. We used logistic regression to measure the association between Lyme disease and atrioventricular (AV) block or any ECG evidence of carditis. RESULTS: Of the 546 children who had an ECG obtained, 214 (39%) had Lyme disease. Overall, 42 children had ECG evidence of carditis, of whom 24 had AV block (20 first-degree). Of the patients with ECG evidence of carditis, only 21 (50%) had any cardiac symptoms. The presence of AV block (OR 4.7, 95% CI 1.8-12.1) and any ECG evidence of carditis (OR 2.3, 95% CI 1.2-4.3) were both associated with diagnosis of Lyme disease. CONCLUSIONS: ECG evidence of carditis, especially AV block, was associated with a diagnosis of Lyme disease. ECG evidence of carditis can be used as a diagnostic biomarker for Lyme disease to guide initial management while awaiting Lyme disease test results.

Growth performance, carcass traits and meat quality of lambs fed increasing level of Macadamia nut cake.

A total of 40 lambs were divided into four different treatments according to the inclusion level of the macadamia nut cake: C-control (0%), M1 (6.5%), M2 (12%) and M3 (20%). Feed was provided twice a day; animal weighing along with body condition scoring occurred within a 14-day interval. The lambs were slaughtered at the end of the performance test. Analysis of variance was performed through the Mixed procedure of the SAS, as well as linear and quadratic regression analysis. The groups presented differences between the treatments (P <0.05) for dry matter intake (DMI), ethereal extract intake (EEI), consumption in relation to live weight percentage and feed conversion ratio (FCR). The lowest mean DMI was obtained by the animals that received the M2 and differed from the C treatment, whose average was the highest. The EEI was highest for the M3 group and the FCR was also better for this group. There was a linear effect for EEI and FCR, and quadratic for crude protein intake. There was no effect for carcass characteristics, and only initial pH had a decreasing linear effect. The macadamia nut cake was effective in promoting the performance of the animals, since there was an improvement in feed conversion.

Food Entrainment, Arousal, and Motivation in the Neonatal Rabbit Pup.

In the newborn rabbit, the light entrainable circadian system is immature and once a day nursing provides the primary timing cue for entrainment. In advance of the mother's arrival, pups display food anticipatory activity (FAA), and metabolic and physiological parameters are synchronized to this daily event. Central structures in the brain are also entrained as indicated by expression of Fos and Per1 proteins, GFAP, a glial marker, and cytochrome oxidase activity. Under fasting conditions, several of these rhythmic parameters persist in the periphery and brain, including rhythms in the olfactory bulb (OB). Here we provide an overview of these physiological and neurobiological changes and focus on three issues, just beginning to be examined in the rabbit. First, we review evidence supporting roles for the organum vasculosum of lamina terminalis (OVLT) and median preoptic nucleus (MnPO) in homeostasis of fluid ingestion and the neural basis of arousal, the latter which also includes the role of the orexigenic system. Second, since FAA in association with the daily visit of the mother is an example of conditioned learning, we review evidence for changes in the corticolimbic system and identified nuclei in the amygdala and extended amygdala as part of the neural substrate responsible for FAA. Third, we review recent evidence supporting the role of oxytocinergic cells of the paraventricular hypothalamic nucleus (PVN) as a link to the autonomic system that underlies physiological events, which occur in preparation for the upcoming next daily meal. We conclude that the rabbit model has contributed to an overall understanding of food entrainment.

Nonparametric Population Pharmacokinetic Modeling of Isoniazid in Colombian Patients With Tuberculosis.

BACKGROUND: Isoniazid (INH) is a first-line antituberculosis (TB) agent with a pharmacokinetic profile characterized by high interindividual variation; however, population pharmacokinetic studies in patients with TB are scarce. The aim was to develop a population model for INH in Colombian patients with TB suitable for predicting drug exposure and assessing the probability of target attainment of pharmacodynamic goals. METHODS: Ten hospitalized adult patients with TB undergoing INH treatment were recruited. After an 8-hour fasting, subjects took 300 mg of INH, and 10 samples were taken from 0 to 12 hours. INH was quantified by high-performance liquid chromatography-UV, and data were analyzed with the Pmetrics R package software. A Monte Carlo simulation with the model parameters was run to determine the probability of target attainment for optimal efficacy. RESULTS: The best model included 2 compartments, first-order absorption (Ka), delayed absorption (Tlag), and linear clearance (CL). Median Tlag was 0.25 hours, 5.54 hour for Ka, (Equation is included in full-text article.)for CL, (Equation is included in full-text article.)for the volume of the central compartment (Vc), 1.04 L/h for intercompartmental clearance (Q), and 788 L for the volume of the peripheral compartment (Vp). CL and Vc were allometrically scaled on basis of the normalized body weight. CONCLUSIONS: The Monte Carlo simulation indicated that 300 mg of INH per day is appropriate for Mycobacterium tuberculosis strains with minimal inhibitory concentration (MIC) up to 0.03 mg/L (target: area under the concentration-time curve/MIC >597); however, to cover strains with MIC up to 0.125 mg/L (80% of clinical isolates), a dose of 900 mg per day would be required.

KAE1 Allelic Variants Affect TORC1 Activation and Fermentation Kinetics in Saccharomyces cerevisiae.

The eukaryotic domain-conserved TORC1 signalling pathway connects growth with nutrient sufficiency, promoting anabolic processes such as ribosomal biogenesis and protein synthesis. In Saccharomyces cerevisiae, TORC1 is activated mainly by the nitrogen sources. Recently, this pathway has gotten renewed attention but now in the context of the alcoholic fermentation, due to its key role in nitrogen metabolism regulation. Although the distal and proximal effectors downstream TORC1 are well characterised in yeast, the mechanism by which TORC1 is activated by nitrogen sources is not fully understood. In this work, we took advantage of a previously developed microculture-based methodology, which indirectly evaluates TORC1 activation in a nitrogen upshift experiment, to identify genetic variants affecting the activation of this pathway. We used this method to phenotype a recombinant population derived from two strains (SA and WE) with different geographic origins, which show opposite phenotypes for TORC1 activation by glutamine. Using this phenotypic information, we performed a QTL mapping that allowed us to identify several QTLs for TORC1 activation. Using a reciprocal hemizygous analysis, we validated GUS1, KAE1, PIB2, and UTH1 as genes responsible for the natural variation in the TORC1 activation. We observed that reciprocal hemizygous strains for KAE1 (ATPase required for t6A tRNA modification) gene showed the greatest phenotypic differences for TORC1 activation, with the hemizygous strain carrying the SA allele (KAE1 SA ) showing the higher TORC1 activation. In addition, we evaluated the fermentative capacities of the hemizygous strains under low nitrogen conditions, observing an antagonistic effect for KAE1 SA allele, where the hemizygous strain containing this allele presented the lower fermentation rate. Altogether, these results highlight the importance of the tRNA processing in TORC1 activation and connects this pathway with the yeasts fermentation kinetics under nitrogen-limited conditions.

Effect of Bicarbonate and Oxidizing Conditions on U(IV) and U(VI) Reactivity in Mineralized Deposits of New Mexico.

We investigated the effect of bicarbonate and oxidizing agents on uranium (U) reactivity and subsequent dissolution of U(IV) and U(VI) mineral phases in the mineralized deposits from Jackpile mine, Laguna Pueblo, New Mexico, by integrating laboratory experiments with spectroscopy, microscopy and diffraction techniques. Uranium concentration in solid samples from mineralized deposit obtained for this study exceeded 7000 mg kg-1, as determined by X-ray fluorescence (XRF). Results from X-ray photoelectron spectroscopy (XPS) suggest the coexistence of U(VI) and U(IV) at a ratio of 19:1 at the near surface region of unreacted solid samples. Analyses made using X-ray diffraction (XRD) and electron microprobe detected the presence of coffinite (USiO4) and uranium-phosphorous-potassium (U-P-K) mineral phases. Imaging, mapping and spectroscopy results from scanning transmission electron microscopy (STEM) indicate that the U-P-K phases were encapsulated by carbon. Despite exposing the solid samples to strong oxidizing conditions, the highest aqueous U concentrations were measured from samples reacted with 100% air saturated 10 mM NaHCO3 solution, at pH 7.5. Analyses using X-ray absorption spectroscopy (XAS) indicate that all the U(IV) in these solid samples were oxidized to U(VI) after reaction with dissolved oxygen and hypochlorite (OCl-) in the presence of bicarbonate (HCO3 -). The reaction between these organic rich deposits, and 100% air saturated bicarbonate solution (containing dissolved oxygen), can result in considerable mobilization of U in water, which has relevance to the U concentrations observed at the Rio Paguate across the Jackpile mine. Results from this investigation provide insights on the reactivity of carbon encapsulated U-phases under mild and strong oxidizing conditions that have important implication in U recovery, remediation and risk exposure assessment of sites.

Five-year Long-term Outcomes of Stereotactic Body Radiation Therapy for Operable Versus Medically Inoperable Stage I Non-small-cell Lung Cancer: Analysis by Operability, Fractionation Regimen, Tumor Size, and Tumor Location.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non-small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients. PATIENTS AND METHODS: All consecutive patients with stage I (cT1-2aN0M0) NSCLC treated with SBRT from June 2009 to July 2013 were assessed. Thoracic surgeon evaluation determined operability. Local failure was defined as growth following initial tumor shrinkage or progression on consecutive scans. LC, CSS, and OS were calculated using Cox proportional hazards regression. RESULTS: A total of 186 patients (204 lesions) were analyzed. Most patients were inoperable (82%) with Eastern Cooperative Oncology Group performance status of 1 (59%) or 2 (26%). All lesions received biological effective doses ≥ 100 Gy most commonly (94%) in 3 to 5 fractions. The median follow-up was 4.0 years. LC at 2 and 5 years were 95.6% (95% confidence interval, 92%-99%) and 93.7% (95% confidence interval, 90%-98%), respectively. Compared with operable patients, inoperable patients did not have significant differences in 5-year LC (93.1% vs. 96.7%; P = .49), nodal failure (31.4% vs. 11.0%; P = .12), distant failure (12.2% vs. 10.4%; P = .98), or CSS (80.6% vs. 91.0%; P = .45) but trended towards worse OS (34.2% vs. 45.3%; P = .068). Tumor size, location, and fractionation did not significantly influence outcomes. CONCLUSIONS: SBRT has excellent, durable LC and CSS rates for early-stage NSCLC, although inoperable patients had somewhat lower OS than operable patients, likely owing to greater comorbidities.

Indirect monitoring of TORC1 signalling pathway reveals molecular diversity among different yeast strains.

Saccharomyces cerevisiae is the main species responsible for the alcoholic fermentation in wine production. One of the main problems in this process is the deficiency of nitrogen sources in the grape must, which can lead to stuck or sluggish fermentations. Currently, yeast nitrogen consumption and metabolism are under active inquiry, with emphasis on the study of the TORC1 signalling pathway, given its central role responding to nitrogen availability and influencing growth and cell metabolism. However, the mechanism by which different nitrogen sources activates TORC1 is not completely understood. Existing methods to evaluate TORC1 activation by nitrogen sources are time-consuming, making difficult the analyses of large numbers of strains. In this work, a new indirect method for monitoring TORC1 pathway was developed on the basis of the luciferase reporter gene controlled by the promoter region of RPL26A gene, a gene known to be expressed upon TORC1 activation. The method was tested in strains representative of the clean lineages described so far in S. cerevisiae. The activation of the TORC1 pathway by a proline-to-glutamine upshift was indirectly evaluated using our system and the traditional direct methods based on immunoblot (Sch9 and Rps6 phosphorylation). Regardless of the different molecular readouts obtained with both methodologies, the general results showed a wide phenotypic variation between the representative strains analysed. Altogether, this easy-to-use assay opens the possibility to study the molecular basis for the differential TORC1 pathway activation, allowing to interrogate a larger number of strains in the context of nitrogen metabolism phenotypic differences.

The Vacuolar Pathway in Macrophages Plays a Major Role in Antigen Cross-Presentation Induced by the Pore-Forming Protein Sticholysin II Encapsulated Into Liposomes.

Cross-presentation is an important mechanism for the differentiation of effector cytotoxic T lymphocytes (CTL) from naïve CD8+ T-cells, a key response for the clearance of intracellular pathogens and tumors. The liposomal co-encapsulation of the pore-forming protein sticholysin II (StII) with ovalbumin (OVA) (Lp/OVA/StII) induces a powerful OVA-specific CTL activation and an anti-tumor response in vivo. However, the pathway through which the StII contained in this preparation is able to induce antigen cross-presentation and the type of professional antigen presenting cells (APCs) involved have not been elucidated. Here, the ability of mouse bone marrow-derived dendritic cells (BM-DCs) and macrophages (BM-MΦs) stimulated with Lp/OVA/StII to activate SIINFEKL-specific B3Z CD8+ T cells was evaluated in the presence of selected inhibitors. BM-MΦs, but not BM-DCs were able to induce SIINFEKL-specific B3Z CD8+ T cell activation upon stimulation with Lp/OVA/StII. The cross-presentation of OVA was markedly decreased by the lysosome protease inhibitors, leupeptin and cathepsin general inhibitor, while it was unaffected by the proteasome inhibitor epoxomicin. This process was also significantly reduced by phagocytosis and Golgi apparatus function inhibitors, cytochalasin D and brefeldin A, respectively. These results are consistent with the concept that BM-MΦs internalize these liposomes through a phagocytic mechanism resulting in the cross-presentation of the encapsulated OVA by the vacuolar pathway. The contribution of macrophages to the CTL response induced by Lp/OVA/StII in vivo was determined by depleting macrophages with clodronate-containing liposomes. CTL induction was almost completely abrogated in mice depleted of macrophages, demonstrating the relevance of these APCs in the antigen cross-presentation induced by this formulation.

A potential central role of Thaumarchaeota in N-Cycling in a semi-arid environment, Fort Stanton Cave, Snowy River passage, New Mexico, USA.

Low biomass and productivity of arid-land caves with limited availability of nitrogen (N) raises the question of how microbes acquire and cycle this essential element. Caves are ideal environments for investigating microbial functional capabilities, as they lack phototrophic activity and have near constant temperatures and high relative humidity. From the walls of Fort Stanton Cave (FSC), multicolored secondary mineral deposits of soil-like material low in fixed N, known as ferromanganese deposits (FMD), were collected. We hypothesized that within FMD samples we would find the presence of microbial N cycling genes and taxonomy related to N cycling microorganisms. Community DNA were sequenced using Illumina shotgun metagenomics and 16S rRNA gene sequencing. Results suggest a diverse N cycle encompassing several energetic pathways including nitrification, dissimilatory nitrate reduction and denitrification. N cycling genes associated with assimilatory nitrate reduction were also identified. Functional gene sequences and taxonomic findings suggest several bacterial and archaeal phyla potentially play a role in nitrification pathways in FSC and FMD. Thaumarchaeota, a deep-branching archaeal division, likely play an essential and possibly dominant role in the oxidation of ammonia. Our results provide genomic evidence for understanding how microbes are potentially able to acquire and cycle N in a low-nutrient subterranean environment.

Maternal residential pesticide use and risk of childhood leukemia in Costa Rica.

Evidence suggests that early-life exposure to pesticides inside the home may be associated with childhood leukemia, however data from Latin American countries are limited. We examined whether self-reported maternal residential pesticide use and nearby pesticide applications-before and after child's birth-were associated with acute lymphoblastic leukemia (ALL) in the Costa Rican Childhood Leukemia Study (CRCLS), a population-based case-control study (2001-2003). Cases (n = 251 ALL) were diagnosed between 1995 and 2000 (age <15 years at diagnosis) and were identified through the Costa Rican Cancer Registry and National Children's Hospital. Population controls (n = 577) were drawn from the National Birth Registry. We fitted unconditional logistic regression models adjusted for child sex, birth year, and socioeconomic status to estimate the exposure-outcome associations and also stratified by child sex. We observed that self-reported maternal insecticide use inside the home in the year before pregnancy, during pregnancy, and while breastfeeding was associated with increased odds of ALL among boys [adjusted Odds Ratio (aOR) = 1.63 (95% confidence interval [95% CI]: 1.05-2.53), 1.75 (1.13-2.73), and 1.75 (1.12-2.73), respectively. We also found evidence of exposure-response relationships between more frequent maternal insecticide use inside the home and increased odds of ALL among boys and girls combined. Maternal report of pesticide applications on farms or companies near the home during pregnancy and at any time period were also associated with ALL. Our study in Costa Rica highlights the need for education to minimize pesticide exposures inside and around the home, particularly during pregnancy and breastfeeding.

5000 Free Flaps and Counting: A 10-Year Review of a Single Academic Institution's Microsurgical Development and Outcomes.

BACKGROUND: The establishment of an effective clinical and academic culture within an institution is a multifactorial process. This process is cultivated by dynamic elements such as recruitment of an accomplished and diverse faculty, patient geographic outreach, clinical outcomes research, and fundamental support from all levels of an institution. This study reviews the academic evolution of a single academic plastic surgery practice, and summarizes a 10-year experience of microsurgical development, clinical outcomes, and academic productivity. METHODS: A 10-year retrospective institutional review was performed from fiscal years 2006 to 2016. Microsurgical flap type and operative volume were measured across all microsurgery faculty and participating hospitals. Microvascular compromise and flap salvage rates were noted for the six highest volume surgeons. Univariate and multivariable predictors of flap salvage were determined. RESULTS: The 5000th flap was performed in December of 2015 within this institutional study period. Looking at the six highest volume surgeons, free flaps were examined for microvascular compromise, with an institutional mean take-back rate of 1.53 percent and flap loss rate of 0.55 percent across all participating hospitals. Overall, 74.4 percent of cases were breast flaps, and the remaining cases were extremity and head and neck flaps. CONCLUSIONS: Focused faculty and trainee recruitment has resulted in an academically and clinically productive practice. Collaboration among faculty, staff, and residents contributes to continual learning, innovation, and quality patient care. This established framework, constructed based on experience, offers a workable and reproducible model for other academic plastic surgery institutions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.