Fundus Autofluorescence in Posterior and Panuveitis-An Under-Estimated Imaging Technique: A Review and Case Series.

Fundus autofluorescence (FAF) is a prompt and non-invasive imaging modality helpful in detecting pathological abnormalities within the retina and the choroid. This narrative review and case series provides an overview on the current application of FAF in posterior and panuveitis. The literature was reviewed for articles on lesion characteristics on FAF of specific posterior and panuveitis entities as well as benefits and limitations of FAF for diagnosing and monitoring disease. FAF characteristics are described for non-infectious and infectious uveitis forms as well as masquerade syndromes. Dependent on the uveitis entity, FAF is of diagnostic value in detecting disease and following the clinical course. Currently available FAF modalities which differ in excitation wavelengths can provide different pathological insights depending on disease entity and activity. Further studies on the comparison of FAF modalities and their individual value for uveitis diagnosis and monitoring are warranted.

HYPERREFLECTIVE FOCI NOT SEEN AS HYPERPIGMENTARY ABNORMALITIES ON COLOR FUNDUS PHOTOGRAPHS IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the prognostic value of quantifying optical coherence tomography (OCT)-defined hyperreflective foci (HRF) that do not correspond to hyperpigmentary abnormalities (HPAs) on color fundus photographs (CFPs)-HRF (OCT+/CFP-) -when considered in addition to HPA extent, for predicting late age-related macular degeneration development. This study sought to understand the impact of HRF (OCT+/CFP-) extent on visual sensitivity. METHODS: Two hundred eighty eyes from 140 participants with bilateral large drusen underwent imaging and microperimetry at baseline, and then 6-monthly for 3-years. The extent of HPAs on CFPs and HRF (OCT+/CFP-) on OCT was quantified at baseline. Predictive models for progression to late age-related macular degeneration, accounting for drusen volume and age, were developed using HPA extent, with and without HRF (OCT+/CFP-) extent. The association between HPA and HRF (OCT+/CFP-) extent with sector-based visual sensitivity was also evaluated. RESULTS: Incorporating HRF (OCT+/CFP-) extent did not improve the predictive performance for late age-related macular degeneration development ( P ≥ 0.32). Increasing HPA and HRF (OCT+/CFP-) extent in each sector were independently and significantly associated with reduced sector-based visual sensitivity ( P ≤ 0.004). CONCLUSION: The addition of HRF (OCT+/CFP-) extent to HPA extent did not improve the prediction of late age-related macular degeneration development. HRF (OCT+/CFP-) extent was also independently associated with local reductions in visual sensitivity, after accounting for HPAs.

Inter-Rater Reliability of Proliferative Diabetic Retinopathy Assessment on Wide-Field OCT-Angiography and Fluorescein Angiography.

Purpose: To assess inter-rater reliability in the detection of proliferative diabetic retinopathy (PDR) changes using wide-field optical coherence tomography angiography (WF-OCTA) versus fluorescein angiography (FA). Methods: This retrospective, cross-sectional study included patients with severe nonproliferative and PDR. Images were acquired with 12 × 12 mm WF-OCTA and FA with a 55° lens. Images were cropped to represent the exact same field of view. Qualitative (detection of neovascularization at the disc [NVD] and elsewhere [NVE], enlarged foveal avascular zone [FAZ], vitreous hemorrhage [VH]) and quantitative analyses (FAZ area, horizontal, vertical, and maximum FAZ diameter) were performed by 2 masked graders using ImageJ. Inter-rater reliability was calculated using unweighted Cohen's kappa coefficient (κ) for qualitative analyses and intraclass correlation coefficients (ICC) for quantitative analyses. Results: Twenty-three eyes of 17 patients were included. Inter-rater reliability was higher for FA than for WF-OCTA in qualitative analyses: κ values were 0.65 and 0.78 for detection of extended FAZ, 0.83 and 1.0 for NVD, 0.78 and 1.0 for NVE, and 0.19 and 1 for VH for WF-OCTA and FA, respectively. In contrast, inter-rater reliability was higher for WF-OCTA than for FA in the quantitative analyses: ICC values were 0.94 and 0.76 for FAZ size, 0.92 and 0.79 for horizontal FAZ diameter, 0.82 and 0.72 for vertical FAZ diameter, and 0.88 and 0.82 for maximum FAZ diameter on WF-OCTA and FA, respectively. Conclusions: Inter-rater reliability of FA is superior to WF-OCTA for qualitative analyses whereas inter-rater reliability of WF-OCTA is superior to FA for quantitative analyses. Translational Relevance: The study highlights the specific merits of both imaging modalities in terms of reliability. FA should be preferred for qualitative parameters, whereas WF-OCTA should be preferred for quantitative parameters.

Alcohol use and motives for drinking across the menstrual cycle in a psychiatric outpatient sample.

BACKGROUND: Females who misuse alcohol experience high rates of negative physical and mental health consequences. Existing findings are inconsistent but suggest a relationship between ovarian hormones and alcohol use. We aim to clarify how alcohol use and drinking motives vary across the menstrual cycle in female psychiatric outpatients using the luteinizing hormone (LH)-confirmed cycle phase. METHODS: Daily self-reports (n = 3721) were collected from 94 naturally cycling females, recruited for past-month suicidal ideation, during the baseline phase of three parent clinical trials between February 2017 and May 2022. Multilevel logistic and linear models estimated the relationship between the cycle phase (with LH-surge confirmed ovulation) and daily alcohol use or drinking motives, moderated by the weekend. Models were adjusted for age, legal drinking status, substance use disorder, and the COVID-19 pandemic, and included random effects. RESULTS: Participants were generally more likely to drink in the midluteal (vs. perimenstrual) phase, but more likely to drink heavily on weekends in periovulatory and perimenstrual (vs. midluteal) phases. Social motives for drinking were significantly higher on weekends in the periovulatory, mid-follicular, and midluteal phases (vs. weekdays), but this finding was non-significant in the perimenstrual phase. Participants rated drinking to cope higher in the perimenstrual phase (vs. midluteal phase), regardless of the weekend. CONCLUSION: In a psychiatric sample with LH-surge-confirmed ovulation, we find an increased likelihood to drink heavily in periovulatory and perimenstrual phases on weekends. We also find that the perimenstrual phase is associated with increased drinking to cope, and relatively lower weekend social drinking. Finally, random effects across models suggest individual differences in the extent to which the cycle influences drinking. Our findings stress (1) predictable phases of increased high-risk alcohol use across the menstrual cycle, and (2) the importance of individual assessment of cyclical changes in alcohol use to predict and prevent ovulation- and menses-related surges in heavy drinking.

Diagnóstico antenatal de cardiopatías congénitas por telemedicina: experiencia en CERPO, 2017-2022 / Antenatal diagnosis of congenital heart disease by telemedicine: experience in CERPO, 2017-2022

Introducción: Las cardiopatías congénitas son las anomalías más frecuentes y la principal causa de muerte infantil y neonatal. El diagnóstico prenatal mejora el resultado perinatal determinando el lugar de nacimiento y el nivel de cuidado neonata. La telemedicina mediante videoconferencia en tiempo real permite mejorar la precisión diagnóstica y planificar el nacimiento. Objetivo: Determinar el diagnóstico y manejo perinatal de fetos con sospecha de cardiopatía congénitas, evaluadas a través de telemedicina en tiempo real atendidas en CERPO en el periodo 2017-2022. Material y métodos: Estudio retrospectivo de las evaluaciones mediante telemedicina en tiempo real realizadas en CERPO entre los años 2017 a 2022. Se revisó el resultado perinatal y se compararon los diagnósticos pre y postnatales, extraídos de la base de datos CERPO y Unidad de Neonatología del Hospital Luis Tisné Brousse. Resultados: La correlación del diagnóstico de cardiopatía congénita mediante telemedicina es de un 81,8% y de 89,8% con el diagnostico posnatal. Conclusiones: La evaluación por medio de telemedicina permite mejorar la precisión diagnostica de la cardiopatía congénita en áreas con escaso acceso a operadores experimentados en evaluación cardiaca fetal. Esto minimiza el impacto económico y social asociado al manejo perinatal de un feto con cardiopatía congénita en nuestro país.

Introduction: Congenital heart disease is the most common anomaly and the leading cause of infant and neonatal death. Prenatal diagnosis improves perinatal outcomes by choosing the right place of birth and level of neonatal care. Telemedicine by videoconferencing in real-time allows for improved diagnostic accuracy and birth planning. Objective: To determine the diagnosis and perinatal management of fetuses with suspected congenital heart disease, evaluated by telemedicine at CERPO in the period 2017-2022. Material and Methods: Retrospective study of evaluations via real-time videoconferencing performed at CERPO between 2017-2022. The perinatal outcome was reviewed, and pre and postnatal diagnoses were compared. The data was extracted from the CERPO database and the Neonatology Unit of the Luis Tisné Brousse Hospital. Results: The correlation of congenital heart disease diagnosis by telemedicine was 81.8% and 89.8% with postnatal diagnosis. Conclusions: Telemedicine assessment improves the diagnostic accuracy of congenital heart disease in areas with poor access to an experienced fetal cardiac specialist. This minimizes the economic and social impact associated with our countrys perinatal management of a fetus with congenital heart disease.

Diagnóstico prenatal de enfermedad de canal atrio-ventricular, análisis epidemiológico y experiencia CERPO entre 2003 y 2021 / Prenatal diagnosis of atrio-ventricular canal disease, epidemiological analysis and CERPO experience between 2003 and 2021

Antecedentes: En Chile, la mitad de los casos de mortalidad perinatal son atribuibles a anomalías congénitas, y un tercio de estas corresponde a cardiopatías congénitas. Aproximadamente un 35% de estos últimos requerirán cirugía antes del año de vida, por lo que la pesquisa prenatal impacta profundamente en el pronóstico. Objetivo: Dar a conocer los resultados perinatales de pacientes con diagnóstico prenatal de canal atrio-ventricular controlados en el Centro de Referencia Perinatal Oriente (CERPO) entre los años 2003 y 2021, su asociación a otras anomalías, características demográficas y pronóstico a un año. Métodos: En este estudio se puede apreciar que tanto el pronóstico como el plan terapéutico posnatal dependerán de la presencia de otras alteraciones morfológicas y del estudio genético. De los factores estudiados, se puede concluir que tanto la presencia de anomalías cardiacas asociadas, como el grado de insuficiencia valvular y el tipo de canal no son predictores de la sobrevida perinatal. Conclusiones: Finalmente, en relación con la sobrevida posnatal, en este estudio, la sobrevida a un año de los recién nacidos vivos fue de un 52%, pero al desglosarlo en los niños con cariotipo euploide y trisomía 21, estos valores se tornan muy distintos, 44 y 81% respectivamente.

Background: In Chile, half of the perinatal mortality cases are attributable to congenital anomalies, and one third of these correspond to congenital heart disease. Approximately 35% of the later will require surgery before one year of life, so prenatal screening has a profound impact on the prognosis. Objective: To present the perinatal results of patients with a prenatal diagnosis of atrio-ventricular canal controlled at Centro de Referencia Perinatal Oriente CERPO) between 2003 and 2021, its association with other anomalies, demographic characteristics, and 1-year prognosis. Methods: In this study it can be seen that both the prognosis and the postnatal therapeutic plan will depend on the presence of other morphological alterations and the genetic study. From the factors studied, it can be concluded that the presence of associated cardiac anomalies, the degree of valvular insufficiency, and the type of canal are not predictors of perinatal survival. Conclusions: Finally, in relation to postnatal survival, in this study, the 1-year survival of live newborns was 52%, but when broken down into children with euploid karyotype and trisomy 21, these values become very different, 44 and 81% respectively.

Avocado Consumption for 12 Weeks and Cardiometabolic Risk Factors: A Randomized Controlled Trial in Adults with Overweight or Obesity and Insulin Resistance.

BACKGROUND: Diets emphasizing unsaturated fat and high fiber are associated with reducing cardiometabolic risk factors. Avocados are rich in MUFA and PUFA fats and fiber. OBJECTIVES: Assess replacement of carbohydrate energy with avocado energy for 12 wk on glucose homeostasis and cardiometabolic risk factors in self-selecting free-living adults who are overweight or with obesity and have insulin resistance. METHODS: In a single-center, randomized, 2-arm, controlled, 12-wk parallel trial, adults [n = 93; male/female: 39/54; mean ± SD age: 42 ± 12 y; BMI: 32.6 ± 3.9 (in kg/m2);  HOMA-IR: 2.7 ± 1.7] were counseled to exchange avocado (AV) or control food (C; low fat, low fiber, energy matched) for carbohydrate food in their usual diet for 12 wk. The primary outcome was the change in Matsuda Insulin Sensitivity Index (MISI) after 12-wk interventions. Secondary outcomes were changes in fasting and post-oral glucose tolerance test glycemic variables, fasting lipids, endothelial activation and inflammation markers. Automated Self-Administered 24-h Dietary Assessment Tool captured weekly dietary intake. Intervention effects were mainly determined by ANCOVA using PC-SAS version 9.4. RESULTS: Dietary total, MUFA, and PUFA fat; fiber; and vegetable intake were higher in the AV group compared with the C group (P < 0.05), and no change in body weight or composition was observed (P > 0.05). Differences between the changes in MISI after AV compared with C were not different (Δ0-12 wk, P = 0.1092). Differences in fasting insulin (Δ0-12 wk, P = 0.0855) and improved glycated hemoglobin (Δ0-12 wk, P = 0.0632) after AV compared with C were suggested. C-reactive protein was significantly lower after AV compared with C at 12 wk (P = 0.0418). Select biomarkers of endothelial activation and lipoproteins by NMR were also influenced by AV compared with C food intake. CONCLUSIONS: Avocado intake was associated with a healthier dietary pattern and trends favoring improved glucose control and reduced biomarkers of cardiometabolic risk when replacing avocado energy for carbohydrate energy in free-living adults who are overweight or with obesity and have insulin resistance. This trial was registered at clinicaltrials.gov as NCT02695433.

Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits.

Objectives: To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS). Methods: A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] < 1.0 cm2) and normal left ventricular ejection fraction (LVEF). Patients were classified as: high-gradient (HG, mean gradient ≥ 40 mmHg), normal-flow low-gradient (NFLG, mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2). Results: Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3-30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12-0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13-0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20-0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively. Conclusions: Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.

Addition of Orange Pomace Attenuates the Acute Glycemic Response to Orange Juice in Healthy Adults.

BACKGROUND: Fiber is an important part of a healthy diet and is known to attenuate postprandial glycemia. Orange pomace (OP) is a by-product of orange juice (OJ) production and is a rich source of fiber. OBJECTIVE: Two separate studies determined the impact of added OP to 100% OJ on postprandial glycemic response compared with sugar-matched OJ or whole orange fruit (WOF). METHODS: Study 1 included 17 adults [65% female, age 39.3 ± 3.1 y, and BMI (in kg/m2) 24.6 ± 0.7], and study 2 included 45 different adults (47% female, age 25.1 ± 4.3 y, and BMI 22.5 ± 1.6). Studies were conducted at separate locations using a randomized, 3-arm, crossover design to test the glycemic response to sugar-matched OJ, OJ with 5 g fiber from OP (OPF), or WOF. The primary outcomes were 2-h glucose incremental area under the curve (iAUC) in study 1, analyzed by repeated measures ANOVA, and maximum glucose concentration (Cmax) in study 2, analyzed using PROC MIXED (ANCOVA). Glucose and insulin concentrations were measured at fasting and multiple time points over 2 h after test product consumption (study 1, serum; study 2, plasma). RESULTS: In study 1, glucose iAUC was not significantly lower in OPF compared to the OJ or WOF (825 ± 132 compared with 920 ± 132 and 760 ± 132 mg · min · dL-1, respectively, P = 0.57 for both). In study 2, glucose iAUC was significantly lower in WOF compared with OPF and OJ (689 ± 70.7 compared with 892 ± 70.7 and 974 ± 70.7 mg · min · dL-1, P = 0.02 and 0.001, respectively). Data from both studies indicated OPF reduced Cmax compared with OJ and that the reductions were comparable to WOF (study 1: OPF, 115 ± 4.06 compared with OJ, 124 ± 4.06 and WOF, 114 ± 4.06 mg · dL-¹, P = 0.002 and 0.75, respectively; study 2: OPF, 128 ± 1.92 compared with OJ, 136 ± 1.92 and WOF, 125 ± 1.92 mg · dL-¹, P = 0.001 and 0.28, respectively). CONCLUSION: Data from both studies demonstrated no significant effect of OPF on postprandial iAUC compared with OJ. However, adding OP into OJ attenuates the postprandial glucose Cmax, and the responses were comparable to WOF in healthy adults.

A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart.

Cardiomyocytes are subjected to the intense mechanical stress and metabolic demands of the beating heart. It is unclear whether these cells, which are long-lived and rarely renew, manage to preserve homeostasis on their own. While analyzing macrophages lodged within the healthy myocardium, we discovered that they actively took up material, including mitochondria, derived from cardiomyocytes. Cardiomyocytes ejected dysfunctional mitochondria and other cargo in dedicated membranous particles reminiscent of neural exophers, through a process driven by the cardiomyocyte's autophagy machinery that was enhanced during cardiac stress. Depletion of cardiac macrophages or deficiency in the phagocytic receptor Mertk resulted in defective elimination of mitochondria from the myocardial tissue, activation of the inflammasome, impaired autophagy, accumulation of anomalous mitochondria in cardiomyocytes, metabolic alterations, and ventricular dysfunction. Thus, we identify an immune-parenchymal pair in the murine heart that enables transfer of unfit material to preserve metabolic stability and organ function. VIDEO ABSTRACT.

Food prototype containing resistant starch type 4 on postprandial glycemic response in healthy adults.

Resistant starch (RS) is a variant of starch that is indigestible by human enzymes and has been acknowledged for multiple physiological benefits including attenuation of postprandial glycemia when incorporated into foods. Distarch phosphate is a RS type 4 (RS4) containing phosphodiester cross-links within and between starch molecules. Considering the importance of RS to human health, the present study aimed to investigate the dose response effect of a novel RS4 (potato-derived distarch phosphate - (VERSAFIBE 1490™) on acute postprandial glycemic responses compared with energy/available carbohydrate and sugar-matched control. The study was designed as a controlled, single-center randomized, single-blinded, cross-over trial, in which 31 healthy adults consumed a baked breakfast cereal bar containing 0, 10 or 20 g RS4 followed by serial blood samples over two hours to determine glucose and insulin concentrations and calculate the incremental area under the curve (iAUC). Results suggest that the addition of RS4 did not reduce iAUC glucose or insulin responses significantly (P > 0.05) at the doses provided. No significant changes in the glucose or insulin maximum concentration (Cmax) and time to reach maximal glucose and insulin concentrations (Tmax) were observed (P > 0.05). Overall, this particular RS4 did not affect measures of glycemia in healthy individuals at doses provided in ready-to-eat baked-good.

Enzyme promiscuity shapes adaptation to novel growth substrates.

Evidence suggests that novel enzyme functions evolved from low-level promiscuous activities in ancestral enzymes. Yet, the evolutionary dynamics and physiological mechanisms of how such side activities contribute to systems-level adaptations are not well characterized. Furthermore, it remains untested whether knowledge of an organism's promiscuous reaction set, or underground metabolism, can aid in forecasting the genetic basis of metabolic adaptations. Here, we employ a computational model of underground metabolism and laboratory evolution experiments to examine the role of enzyme promiscuity in the acquisition and optimization of growth on predicted non-native substrates in Escherichia coli K-12 MG1655. After as few as approximately 20 generations, evolved populations repeatedly acquired the capacity to grow on five predicted non-native substrates-D-lyxose, D-2-deoxyribose, D-arabinose, m-tartrate, and monomethyl succinate. Altered promiscuous activities were shown to be directly involved in establishing high-efficiency pathways. Structural mutations shifted enzyme substrate turnover rates toward the new substrate while retaining a preference for the primary substrate. Finally, genes underlying the phenotypic innovations were accurately predicted by genome-scale model simulations of metabolism with enzyme promiscuity.

Diferencias de género en la carrera profesional de los cardiólogos en 70 hospitales españoles / Gender differences in the professional lives of cardiologists in 70 Spanish hospitals

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Reframing gene essentiality in terms of adaptive flexibility.

BACKGROUND: Essentiality assays are important tools commonly utilized for the discovery of gene functions. Growth/no growth screens of single gene knockout strain collections are also often utilized to test the predictive power of genome-scale models. False positive predictions occur when computational analysis predicts a gene to be non-essential, however experimental screens deem the gene to be essential. One explanation for this inconsistency is that the model contains the wrong information, possibly an incorrectly annotated alternative pathway or isozyme reaction. Inconsistencies could also be attributed to experimental limitations, such as growth tests with arbitrary time cut-offs. The focus of this study was to resolve such inconsistencies to better understand isozyme activities and gene essentiality. RESULTS: In this study, we explored the definition of conditional essentiality from a phenotypic and genomic perspective. Gene-deletion strains associated with false positive predictions of gene essentiality on defined minimal medium for Escherichia coli were targeted for extended growth tests followed by population sequencing and transcriptome analysis. Of the twenty false positive strains available and confirmed from the Keio single gene knock-out collection, 11 strains were shown to grow with longer incubation periods making these actual true positives. These strains grew reproducibly with a diverse range of growth phenotypes. The lag phase observed for these strains ranged from less than one day to more than 7 days. It was found that 9 out of 11 of the false positive strains that grew acquired mutations in at least one replicate experiment and the types of mutations ranged from SNPs and small indels associated with regulatory or metabolic elements to large regions of genome duplication. Comparison of the detected adaptive mutations, modeling predictions of alternate pathways and isozymes, and transcriptome analysis of KO strains suggested agreement for the observed growth phenotype for 6 out of the 9 cases where mutations were observed. CONCLUSIONS: Longer-term growth experiments followed by whole genome sequencing and transcriptome analysis can provide a better understanding of conditional gene essentiality and mechanisms of adaptation to such perturbations. Compensatory mutations are largely reproducible mechanisms and are in agreement with genome-scale modeling predictions to loss of function gene deletion events.

Glabellar Botulinum Toxin Injections in Major Depressive Disorder: A Critical Review.

OBJECTIVE: To provide a critical appraisal of the primary clinical trials exploring the use of glabellar botulinum toxin type A (BTA) injections in the treatment of major depressive disorder (MDD) and propose future directions for research on this topic. DATA SOURCES: A search in PubMed, Scopus, and Google Scholar databases was performed in September 2017. Search terms included ("botulinum" OR "botox" OR "abobotulinumtoxin" OR "onabotulinum" OR "onabotulinumtoxin" OR "botulinumtoxin") AND ("antidepressant" OR "depression" OR "depressive" OR "depressed"). No other search parameters were utilized. STUDY SELECTION: Studies were selected for review if they were found to be a primary clinical trial on the use of BTA for the treatment of MDD. DATA EXTRACTION: Six studies were identified and scored by the authors using a 5-point Jadad scoring system. RESULTS: Three of the 6 studies were found to be of high quality with a Jadad score ≥ 3. The remainder had Jadad scores of 1. CONCLUSIONS: In general, the results from the reviewed studies suggest that BTA may be a promising treatment for MDD. However, these findings need to be interpreted with caution due to several limitations of the reviewed studies such as lack of a priori hypotheses, limited sample sizes, large gender bias, and significant difficulty in ensuring blinding.

Presence of organohalide-respiring bacteria in and around a permeable reactive barrier at a trichloroethylene-contaminated Superfund site.

Trichloroethylene (TCE) is one of the most common groundwater contaminants in the United States; however clean-up efforts are a challenge due to its physical and chemical properties. TCE and several of its degradation products were detected in the groundwater of the Beaver Dam Road Landfill site (Beltsville, MD) at concentrations above accepted maximum contaminant levels. A permeable reactive barrier (i.e., biowall) was installed to remediate the groundwater. Microbial infiltration and colonization of the biowall with native site bacteria was expected to occur. An array of molecular biological tools was applied to survey the microbial community for presence of organohalide-respiring microorganisms at the site. Microorganisms belonging to methanogens, acetogens, sulfate-reducing bacteria, and chlorinated aliphatic hydrocarbon-metabolizing bacteria were identified, thus making way for the application of the microbial populations in the biowall bioaugmentation efforts. In concomitant laboratory studies, molecular approaches were used to monitor continuously-fed column reactors containing saturated biowall material spiked with a commercially-available, Dehalococcoides-containing culture (SDC-9), with or without zero-valent iron (ZVI) shavings. The column without ZVI had the highest abundance of Dehalococcoides spp. (2.7 × 106 cells g-1 material, S.D. = 3.8 × 105 cells g-1 material), while the addition of ZVI did not affect the overall population. Although the addition of ZVI and biostimulation did change ratios of the Dehalococcoides strains, the results suggests that if ZVI would be applied as a biowall material amendment, biostimulation would not be required to maintain a Dehalococcoides population. These experimental results will be utilized in future remediation and/or biowall expansion plans to utilize the natural resources most effectively at the biowall site.

Systems assessment of transcriptional regulation on central carbon metabolism by Cra and CRP.

Two major transcriptional regulators of carbon metabolism in bacteria are Cra and CRP. CRP is considered to be the main mediator of catabolite repression. Unlike for CRP, in vivo DNA binding information of Cra is scarce. Here we generate and integrate ChIP-exo and RNA-seq data to identify 39 binding sites for Cra and 97 regulon genes that are regulated by Cra in Escherichia coli. An integrated metabolic-regulatory network was formed by including experimentally-derived regulatory information and a genome-scale metabolic network reconstruction. Applying analysis methods of systems biology to this integrated network showed that Cra enables optimal bacterial growth on poor carbon sources by redirecting and repressing glycolysis flux, by activating the glyoxylate shunt pathway, and by activating the respiratory pathway. In these regulatory mechanisms, the overriding regulatory activity of Cra over CRP is fundamental. Thus, elucidation of interacting transcriptional regulation of core carbon metabolism in bacteria by two key transcription factors was possible by combining genome-wide experimental measurement and simulation with a genome-scale metabolic model.

Using a high-organic matter biowall to treat a trichloroethylene plume at the Beaver Dam Road landfill.

Trichloroethylene (TCE) is a highly effective industrial degreasing agent and known carcinogen. It was frequently buried improperly in landfills and has subsequently become one of the most common groundwater and soil contaminants in the USA. A common strategy to remediate TCE-contaminated sites and to prevent movement of the TCE plumes into waterways is to construct biowalls which consist of biomaterials and amendments to enhance biodegradation. This approach was chosen to contain a TCE plume emanating from a closed landfill in Maryland. However, predicting the effectiveness of biowalls is often site specific. Therefore, we conducted an extensive series of batch reactor studies at 12 °C as opposed to the typical room temperature to examine biowall fill-material combinations including the effects of zero-valent iron (ZVI) and glycerol amendments. No detectable TCE was observed after several months in the laboratory study when using the unamended 4:3 mulch-to-compost combination. In the constructed biowall, this mixture reduced the upstream TCE concentration by approximately 90% and generated ethylene downstream, an indication of successful reductive dechlorination. However, the more toxic degradation product vinyl chloride (VC) was also detected downstream at levels approximately ten times greater than the maximum contaminant level. This indicates that incomplete degradation also occurred. In the laboratory, ZVI reduced VC formation. A hazard quotient was calculated for the landfill site with and without the biowall. The addition of the biowall decreased the hazard quotient by 88%.

Caso Clínico: Tumor de Askin / Clinical Case: Askin's Tumor

Introducción: El tumor neuroectodérmico primitivo (PNET) de la pared torácica también denominado tumor de Askin es una neoplasia rara y agresiva, que afecta mayoritariamente a niños y adolescente. Caso Clínico: Se reporta el caso de un joven de 17 años que presentó una gran tumoración subescapular derecha, acompañado de dolor y disnea a quien realizó previa quimioterapia neoadyuvante y dada buena repuesta, resección tumoral con márgenes oncológicos más reconstrucción plástica de hemitórax derecho. Constatándose como hallazgo intraoperatorio, no evidente en imágenes, metástasis pulmonar. Presenta evolución favorable posquirúrgica con posterior recurrencia local y metástasis a distancia, sin respuesta a la quimioterapia adyuvante con fallecimiento 7 meses luego de la cirugía. Conclusión: En el presente caso el TA tuvo una sobrevida corta a pesar el tratamiento neoadyuvante, resección quirúrgica y nuevo ciclo de tratamiento quimioterápico.

Introduction: The primitive neuroectodermal tumor (PNET) of the thoracic wall also called Askin's tumor is a rare and aggressive neoplasm, affecting mainly children and adolescents. Clinical case: We report the case of a 17-year-old boy who presented a large right subscapular tumor, accompanied by pain and dyspnea who underwent previous neoadjuvant chemotherapy and given good response, tumor resection with oncological margins plus plastic reconstruction of the right hemithorax. Being confirmed as an intraoperative finding, not evident in images, pulmonary metastasis. It presents favorable postoperative evolution with subsequent local recurrence and distant metastasis, without response to adjuvant chemotherapy with death 7 months after surgery. Conclusion: In the present case, the TA had a short survival despite neoadjuvant treatment, surgical resection and a new cycle of chemotherapy treatment.