Pituitary Abscess Causing Panhypopituitarism in a Patient With Neurobrucellosis: Case Report.

Background/Objective: Pituitary abscess is an uncommon life-threatening disease that could lead to panhypopituitarism. It is important to suspect its prevalence in regions with endemic infectious diseases. Case Report: A 55-year-old man, a farmer, with a background of consumption of unpasteurized dairy products, presented with headache, impaired consciousness, and fever that started in February 2023. Initial test results were consistent with neuroinfection. Brain MRI showed ventriculitis; the pituitary gland was heterogeneous with the presence of an 8 × 8 mm abscess. The pituitary hormone axis was evaluated, and it showed results compatible with the results of panhypopituitarism with central hypothyroidism, central hypocortisolism, central hypogonadism, and growth hormone deficiency. Hormone replacement treatment with hydrocortisone and levothyroxine was started. The Rose Bengal test for Brucella spp. and 2-mercaptoethanol Brucella agglutination test showed positive results. After neurobrucellosis (NB) was diagnosed, antibiotic treatment was commenced. The patient was discharged 6 weeks later and treatment with prednisone, levothyroxine, recombinant somatropin, testosterone, as well as doxycycline, and rifampin was continued for another 4 months. Discussion: NB and pituitary abscess are rare manifestations of brucellosis and are challenging to diagnose due to their nonspecific clinical presentation and cerebrospinal fluid (CSF) findings. NB diagnosis relies on neurologic symptoms and serological evidence of Brucella infection. Magnetic resonance imaging is the preferred diagnostic tool for pituitary abscesses. Medical management may be sufficient, while transsphenoidal drainage is not always necessary. Hormonal deficits typically remain permanent. Conclusion: Pituitary abscess could be suspected in patients presenting with symptoms of neuroinfection, panhypopituitarism, and heterogenous image in the magnetic resonance imaging differential diagnosis. Opportune management can lead to reduced mortality and improved recovery of the pituitary hormone function.

Synthesis, Herbicidal Activity, and Structure-Activity Relationships of O-Alkyl Analogues of Khellin and Visnagin.

Khellin and visnagin furanochromones were recently reported as potential new bioherbicides with phytotoxic activities comparable to those of some commercially available herbicides. In this study, we examined the effect of O-alkylation and O-arylalkylation of both khellin and visnagin on its effect on herbicidal and antifungal activity. Synthetic analogues included O-demethyl khellin and visnagin, acetylated O-demethyl khellin and visnagin, O-benzylated demethyl khellin and visnagin, four O-demethyl alkylated khellin analogues, and six O-demethyl alkylated visnagin analogues, many of which are reported here for the first time. Both acetate analogues of khellin and visnagin indicated more activity as herbicides on Lemna pausicostata than visnagin, with IC50 values of 71.7 and 77.6 µM, respectively. Complete loss of activity for all O-alkyl analogues with a carbon chain length of greater than 14 carbons was observed. The O-demethyl butylated visnagin analogue was the most active compound with an IC50 of 47.2 µM against L. pausicostata. O-Demethyl ethylated analogues of both khellin and visnagin were as effective as khellin. In the antifungal bioautography bioassay against Colletotrichum fragariae at 100 µg, the only active O-alkyl and O-arylalkyl analogues were O-ethylated, O-butylated, and O-benzylated visnagin analogues with zones of inhibition of 10, 9, and 9 mm, respectively, an effect comparable to that of visnagin and khellin.

The metabolic phenotype of the patient influences the reduction in carotid intima-media thickness achieved following metabolic surgery.

OBJECTIVES: To determine whether metabolic phenotype is associated with the change in carotid intima-media thickness (CIMT) in patients undergoing bariatric /metabolic surgery (BMS). METHODS: We performed a case-control study of BMS candidates who had metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO). We measured the change in CIMT during the 9 months following BMS. The plasma tumor necrosis factor-α, interleukin-1ß, adiponectin, leptin, nitric oxide (NO), vascular endothelial growth factor A (VEGF-A), and malondialdehyde concentrations were determined, adipocyte area was measured histologically, and adipose tissue area was estimated using computed tomography. RESULTS: Fifty-six patients (mean age 44.5 years, mean body mass index 44.9 kg/m2, 53% women, and 53% had MUO) were studied. Nine months following BMS, the MUO phenotype was not associated with a significant reduction in CIMT, and that of the MHO group was larger. In addition, fewer participants achieved a 10% reduction in CIMT in the MUO group. A CIMT reduction was associated with lower VEGF-A and NO in the MUO group, while that in the MHO group was associated with a higher NO concentration. CONCLUSION: The metabolic phenotype of patients may influence their change in CIMT following BMS, probably through circulating vasodilatory and pro-inflammatory molecules.

Combination of Bempegaldesleukin and Anti-CTLA-4 Prevents Metastatic Dissemination After Primary Resection or Radiotherapy in a Preclinical Model of Non-Small Cell Lung Cancer.

Surgical resection or hypo-fractionated radiation therapy (RT) in early-stage non-small cell lung cancer (NSCLC) achieves local tumor control, but metastatic relapse remains a challenge. We hypothesized that immunotherapy with anti-CTLA-4 and bempegaldesleukin (BEMPEG; NKTR-214), a CD122-preferential IL2 pathway agonist, after primary tumor RT or resection would reduce metastases in a syngeneic murine NSCLC model. Mice bearing Lewis Lung Carcinoma (LLC) tumors were treated with combinations of BEMPEG, anti-CTLA-4, and primary tumor treatment (surgical resection or RT). Primary tumor size, mouse survival, and metastatic disease at the time of death were assessed. Flow cytometry, qRT-PCR, and cytokine analyses were performed on tumor specimens. All mice treated with RT or surgical resection of primary tumor alone succumbed to metastatic disease, and all mice treated with BEMPEG and/or anti-CTLA-4 succumbed to primary tumor local progression. The combination of primary tumor RT or resection and BEMPEG and anti-CTLA-4 reduced spontaneous metastasis and improved survival without any noted toxicity. Flow cytometric immunoprofiling of primary tumors revealed increased CD8 T and NK cells and decreased T-regulatory cells with the combination of BEMPEG, anti-CTLA-4, and RT compared to RT alone. Increased expression of genes associated with tumor cell immune susceptibility, immune cell recruitment, and cytotoxic T lymphocyte activation were observed in tumors of mice treated with BEMPEG, anti-CTLA-4, and RT. The combination of BEMPEG and anti-CTLA-4 with primary tumor RT or resection enabled effective control of local and metastatic disease in a preclinical murine NSCLC model. This therapeutic combination has important translational potential for patients with early-stage NSCLC and other cancers.

Identification of adipose tissue-related predictors of the reduction in cardiovascular risk induced by metabolic surgery.

OBJECTIVES: We aimed to determine whether parameters associated with adipose tissue (adipocyte density and the circulating concentrations of markers of adipose tissue pathology) predict cardiovascular risk (CVR) modification after metabolic surgery (MS). METHODS: We performed a case-control study of patients with morbid obesity who were candidates for MS. CVR was defined using flow-mediated dilation (FMD) and carotid intima media thickness (CIMT), which were measured during the 9 months following MS. Subgroups of CVR reduction were defined using the following cut-offs: CIMT 10% and/or a two-fold increase in FMD. RESULTS: We studied 40 patients with morbid obesity (mean age 44.5 years, 75% women, mean body mass index 46.4 kg/m2) and high prevalences of the metabolically unhealthy obesity phenotype, hypertension, and diabetes mellitus. A significant reduction in CVR was associated with lower vascular endothelial growth factor-A concentration (6.20 vs. 1.59 pg/mL, respectively), low adipocyte density in visceral adipose tissue (100 vs. 80 cells/field), low infiltration with CD68+ cells (18 vs. 8 cells/field) and higher concentrations of lipid peroxidation markers and malondialdehyde (313.7 vs. 405.7 ng/mL). CONCLUSION: The characteristics of adipose tissue and the circulating concentrations of markers of adipose pathology might represent useful predictors of the reduction in CVR following MS.Clinical trial registration number: NCT0356198 (https://clinicaltrials.gov).

Intra-abdominal hypertension and hypoxic respiratory failure together predict adverse outcome - A sub-analysis of a prospective cohort.

PURPOSE: To assess whether the combination of intra-abdominal hypertension (IAH, intra-abdominal pressure ≥ 12 mmHg) and hypoxic respiratory failure (HRF, PaO2/FiO2 ratio < 300 mmHg) in patients receiving invasive ventilation is an independent risk factor for 90- and 28-day mortality as well as ICU- and ventilation-free days. METHODS: Mechanically ventilated patients who had blood gas analyses performed and intra-abdominal pressure measured, were included from a prospective cohort. Subgroups were defined by the absence (Group 1) or the presence of either IAH (Group 2) or HRF (Group 3) or both (Group 4). Mixed-effects regression analysis was performed. RESULTS: Ninety-day mortality increased from 16% (Group 1, n = 50) to 30% (Group 2, n = 20) and 27% (Group 3, n = 100) to 49% (Group 4, n = 142), log-rank test p < 0.001. The combination of IAH and HRF was associated with increased 90- and 28-day mortality as well as with fewer ICU- and ventilation-free days. The association with 90-day mortality was no longer present after adjustment for independent variables. However, the association with 28-day mortality, ICU- and ventilation-free days persisted after adjusting for independent variables. CONCLUSIONS: In our sub-analysis, the combination of IAH and HRF was not independently associated with 90-day mortality but independently increased the odds of 28-day mortality, and reduced the number of ICU- and ventilation-free days.

Asociación entre interleuquinas inflamatorias y la presencia de trastornos intraventriculares de la conducción en pacientes con serología positiva para enfermedad de Chagas y función ventricular conservada / Association between inflammatory interleukins and intraventricular conduction disturbances in patients with positive serology for Chagas disease and preserved ventricular function

RESUMEN Introducción: Los trastornos intraventriculares de la conducción constituyen una manifestación habitual en los pacientes con enfermedad de Chagas con función ventricular izquierda conservada. Se desconoce si su presencia puede estar asociada a una mayor actividad inflamatoria. Objetivos: Determinar si existe una correlación entre los niveles de interleuquinas y la presencia de trastornos intraventriculares de la conducción en pacientes con serología positiva para enfermedad de Chagas y fracción de eyección ventricular izquierda conservada. Material y métodos: Se evaluó a 22 pacientes con edades comprendidas entre 21 y 80 años, seropositivos para enfermedad de Chagas, de más de 20 años de evolución y fracción de eyección ventricular izquierda mayor del 50%. Se analizó, además, un grupo control de 14 individuos sanos. Se determinaron las concentraciones en plasma de IFN-γ, IL-1β, IL-6, IL-10, IL-12 (p70), IL-15, IL-17A, MCP-1/CCL2, MIP-1 a/CCL3, TNF-a e IL-2. Se consideró trastornos intraventriculares de la conducción a la presencia de bloqueo de rama derecha, hemibloqueo anterior izquierdo o bloqueo de rama izquierda. Resultados: De los 22 pacientes con serología positiva para enfermedad de Chagas, 10 presentaron trastornos de la intraventriculares de la conducción (45,4%). En el grupo con trastornos intraventriculares de la conducción, se observaron niveles elevados de interleuquinas de alto efecto inflamatorio como INF-γ, IL-15, IL-2 (p70), IL-12, MP1-a, en comparación al grupo control, además de presentar altos valores de IL-10 como mecanismo modulador de una respuesta inmunitaria excesiva. Conclusiones: La asociación entre niveles elevados de interleuquinas y la presencia de trastornos intraventriculares de la conducción plantea un posible proceso inflamatorio crónico para su desarrollo en pacientes chagásicos con fracción de eyección ventricular izquierda conservada.

ABSTRACT Background: Intraventricular conduction disturbances are common in patients with Chagas disease and preserved left ventricular ejection fraction, but their association with higher inflammatory activity is unknown. Objectives: The aim of this study was to determine the presence of an association between interleukin levels and intraventricular conduction disturbances in patients with positive serology for Chagas disease and preserved left ventricular function. Methods: Twenty-two patients between 22 and 80 years of age with positive serology test for Chagas disease with more than 20 years progression and left ventricular ejection fraction ≥50% were included in the study and compared with a control group of 14 healthy individuals. Plasma levels of IFN-γ, IL-1β, IL-6, IL-10, IL-12 (p70), IL-15, IL-17A, MCP-1/CCL2, MIP-1 a/CCL3, TNF-a and IL-2 were measured in patients and controls. Right bundle branch block, left anterior hemiblock or left bundle branch block were considered intraventricular conduction disturbances. Results: Among the 22 patients with positive serology for Chagas disease, 10 presented intraventricular conduction disturbances (45.4%). This group had elevated levels of interleukins with high inflammatory effect such as INF-γ, IL-15, IL-2, IL-12, MIP-1 a, compared with the control group, and high levels of IL-10 as a regulatory mechanism of an excessive immune response. Conclusions: The association between elevated levels of inflammatory interleukins and intraventricular conduction disturbances suggests that chronic inflammation may play a role in the development of these abnormalities in patients with positive serology for Chagas disease and preserved left ventricular ejection function.

Enlarged adipocytes from subcutaneous vs. visceral adipose tissue differentially contribute to metabolic dysfunction and atherogenic risk of patients with obesity.

Morphological characteristics and source of adipose tissue as well as adipokines may increase cardiometabolic risk. This study aimed to explore whether adipose tissue characteristics may impact metabolic and atherogenic risks. Subcutaneous Adipose Tissue (SAT), Visceral Adipose Tissue (VAT) and peripheral blood were obtained from obese patients submitted to bariatric surgery. Adipose tissue (morphometry), plasma adiponectin, TNF-α, resistin (multiplexing) and biochemical chemistry were analyzed; as well as endothelial dysfunction (Flow Mediated Dilation, FMD) and atherogenesis (Carotid Intima Media Thickness, CIMT). Subgroups divided by adipocyte size and source were compared; as well as correlation and multivariate analysis. Sixty patients 36.6% males, aged 44 years-old, BMI 46.7 kg/m2 were included. SAT's adipocytes showed a lower range of size expandability than VAT's adipocytes. Independent from their source, larger adipocytes were associated with higher glucose, lower adiponectin and higher CIMT. Particularly, larger adipocytes from SAT were associated with higher blood pressure, lower insulin and HDL-cholesterol; and showed positive correlation with glucose, HbA1c, systolic/diastolic values, and negatively correlated with insulin and adiponectin. VAT's larger adipocytes particularly associated with lower resistin and lower FMD values. Gender and Diabetes Mellitus significantly impacted the relation of adipocyte size/source with the metabolic and atherogenic risk. Multivariable analysis suggested hypertension-resistin-HbA1c interactions associated with SAT's larger adipocytes; whereas potential insulin-adiponectin associations were observed for VAT's larger adipocytes. Adipocyte morphology and source are differentially related with cardiometabolic and atherogenic risk in population with obesity, which are potentially affected by gender and Diabetes Mellitus.

Toxicidad cardiovascular por parches transdérmicos de rivastigmina. A propósito de dos casos clínicos / Cardiovascular toxicity by rivastigmine transdermal patches. Two case report / Toxicidade cardiovascular por adesivos transdérmicos de rivastigmina. Relato de dois casos

Resumen: La rivastigmina, fármaco anticolinesterásico, mejora la neurotransmisión colinérgica y es utilizado en el tratamiento de las enfermedades de Alzheimer y de Parkinson. En el Centro de Información y Asesoramiento Toxicológico se han registrado casos de intoxicación por el uso de parches transdérmicos de rivastigmina, los cuales han aumentado en número en el último tiempo. Presentamos dos casos clínicos de intoxicación aguda por parches transdérmicos de rivastigmina en los que se constataron arritmias cardíacas graves, asociando un descenso de colinesterasa plasmática. Se destacan los riesgos del uso de esta medicación con el fin de estar atentos a los primeros síntomas de intoxicación, poder actuar en forma oportuna y prevenir nuevos eventos.

Summary: Rivastigmine, an anticholinesterase drug, improves cholinergic neurotransmission and is used in the treatment of Alzheimer's and Parkinson's diseases. In the Center for Information and Toxicological Advice there have been cases of intoxication due to the use of transdermal rivastigmine patches, which have increased in recent times. We present two clinical cases of acute intoxication by transdermal patches of rivastigmine in which serious cardiac arrhythmias were found, associating a decrease in plasma cholinesterase. The risks of the use of this medication are highlighted in order to be attentive to the first symptoms of intoxication, to be able to act timely and to prevent new events.

Resumo: A rivastigmina, um anticolinesterásico, melhora a neurotransmissão colinérgica e é usada no tratamento das doenças de Alzheimer e Parkinson. No Centro de Informação e Conselhos Toxicológicos, houve casos de intoxicação devido ao uso de adesivos transdérmicos de rivastigmina, que aumentaram nos últimos tempos. Se apresentam dois relatos de caso de intoxicação aguda por adesivos transdérmicos de rivastigmina. Em ambos os casos, foram encontradas arritmias cardíacas graves, associando uma diminuição na colinesterase plasmática. Os riscos do uso desse medicamento são destacados para estar atento aos primeiros sintomas de intoxicação, para poder atuar de forma oportuna e prevenir novos eventos.

Adicción Alimentaria: ¿Otro determinante asociado a la adhesión del tratamiento nutricional? / Dependência de Alimentos: Outro determinante associado à adesão de tratamento nutricional? / Food Addiction: Another determinant associated with the adhesion of nutritional treatment

Resumen: Los Programas de Prevención Secundaria Cardiovascular se han desarrollado para mejorar el proceso de atención de pacientes con cardiopatía isquémica y/o con alto riesgo cardiovascular. Sin embargo, la adherencia terapéutica en algunos aspectos es limitada, por lo que conocer la prevalencia de adicción alimentaria en esta población podría ser de utilidad para redireccionar la intervención nutricional. El objetivo de este trabajo es estudiar la prevalencia de adicción alimentaria de los pacientes que asisten al Programa de Prevención Secundaria Cardiovascular del Fondo nacional de Recursos en el período octubre a diciembre 2016 en el departamento de Montevideo, Uruguay. Se trata de un estudio descriptivo, observacional y de corte transversal. Se estudian 153 pacientes a los que se les aplicó el cuestionario estructurado YFAS de Gearhardt y valoración del estado nutricional a través del IMC extraído del Sistema Informático María del FNR. El 63% de la población fue del sexo masculino, 8 de cada 10 de los encuestados fueron adultos mayores (≥60 años), y predominó la malnutrición por exceso en el 70% de los encuestados, encontrándose obesidad en 4 de cada 10. La prevalencia de adicción alimentaria en el total de los encuestados fue del 5,9% (IC95%=2,7-10,9), siendo más prevalente en el rango etáreo de menores de 60 años. Dentro de la categoría de obesidad la prevalencia de adicción alimentaria fue 13,8% seguida por el sobrepeso. Se observa en un 10% de la población la presencia de 3 o más síntomas para adicción alimentaria sin tener aún la significación clínica que determine la presencia de la patología, predominando esto en la población del sexo masculino y en los menores de 60 años. Esta presencia dentro de la categoría de obesidad se puede ver en un 10%. Se concluye que casi el 6% de la población presentó adicción alimentaria y que un 10% tuvieron 3 o más síntomas propios de la patología. Incluir el test en la consulta de los pacientes pertenecientes al PPSCV permitiría derivar al equipo de psicología de la institución los pacientes que así lo requieran.

Resumo: Programas secundários de prevenção cardiovascular foram desenvolvidos para melhorar o processo de atendimento de pacientes com cardiopatia isquêmica e / ou com alto risco cardiovascular. No entanto, a adesão terapêutica em alguns aspectos é limitada, portanto, conhecer a prevalência de dependência alimentar nessa população pode ser útil para redirecionar a intervenção nutricional. O objetivo deste trabalho é estudar a prevalência de dependência alimentar de pacientes do Programa de Prevenção Secundária Cardiovascular do Fundo Nacional de Recursos no período de outubro a dezembro de 2016 no departamento de Montevidéu, Uruguai. Trata-se de um estudo descritivo, observacional e transversal. Foram estudados 153 pacientes aos quais foi aplicado o questionário estruturado YFAS de Gearhardt e a avaliação do estado nutricional por meio do IMC extraído do María Informatics System do FNR. 63% da população era do sexo masculino, 8 em cada 10 entrevistados eram adultos mais velhos (≥60 anos) e a supernutrição prevaleceu em 70% dos entrevistados, com obesidade em 4 em cada 10. a prevalência de dependência alimentar no total dos entrevistados foi de 5,9% (IC95% = 2,7-10,9), sendo mais prevalente na faixa etária de crianças menores de 60 anos. Na categoria obesidade, a prevalência de dependência alimentar foi de 13,8%, seguida pelo excesso de peso. Observa-se em 10% da população a presença de 3 ou mais sintomas de dependência alimentar sem ainda ter o significado clínico que determina a presença da patologia, predominantemente na população masculina e naqueles com menos de 60 anos. Essa presença na categoria obesidade pode ser vista em 10%. Conclui-se que quase 6% da população apresentava dependência alimentar e 10% apresentavam 3 ou mais sintomas da patologia. A inclusão do teste na consulta de pacientes pertencentes ao PPSCV permitiria que os pacientes que precisassem dele se referirem à equipe de psicologia da instituição.

Summary: The Cardiovascular Secondary Prevention Programs have been developed to improve the care process for patients with ischemic heart disease and / or with high cardiovascular risk. However, the therapeutic adherence in some aspects is limited, so knowing the prevalence of food addiction in this population could be useful to redirect the nutritional intervention. The objective of this study is to study the prevalence of food addiction in patients attending the Cardiovascular Secondary Prevention Program of the National Resources Fund from October to December 2016 in the department of Montevideo. It is a descriptive, observational and cross-sectional study. 153 patients were studied, the structured YFAS questionnaire of Gearhardt was applied and the nutritional status was assessed through the IMC extracted from the Maria IT System of the FNR. 63% of the population was male, 8 out of 10 of the respondents were elderly (≥60 years), and excess malnutrition predominated in 70% of respondents, with obesity in 4 out of 10. The prevalence of food addiction in the total of the respondents was 5.9% (95% CI = 2.7-10.9), being more prevalent in the age range of those under 60 years of age. Within the category of obesity, the prevalence of food addiction was 13.8%, followed by overweight. The presence of 3 or more symptoms for food addiction was observed in 10% of the population without having the clinical significance that determines the presence of the pathology, predominating in the male population and in those under 60 years of age. This presence within the category of obesity can be seen in 10%. It is concluded that almost 6% of the population had food addiction and 10% had 3 or more symptoms typical of the pathology. Including the test in the appointment of patients belonging to the CSPP would allow referral to the psychology team of the institution of those who require it.

Neutrophil-to-lymphocyte ratio and its relation with pro-inflammatory mediators, visceral adiposity and carotid intima-media thickness in population with obesity.

BACKGROUND: Atherosclerosis represents a cardiovascular risk. Chronic inflammation is a key factor for atherogenic progression. Neutrophil-to-lymphocyte ratio (NLR) has been proposed as a novel biomarker for cardiovascular risks. We aimed to explore whether NLR was related to surrogate pro-atherogenic promoters driving atherogenic progression, as measured by carotid intima-media thickness (CIMT). STUDY DESIGN: Thirty-one patients with obesity candidates for bariatric surgery were recruited from Centro Médico Nacional "20 de Noviembre", ISSSTE, Mexico City. The results are part of the "CROP" study (NCT03561987). NLR was calculated from routine complete blood count, and its relation with plasma pro-inflammatory mediators (hsCRP, TNF-α and IL-1ß), adipokines (adiponectin and leptin), adiposity markers (visceral adipose tissue [VAT] determined from CT scan image and VAT individual adipocyte area at histological sample) and CIMT were determined. RESULTS: Neutrophil-to-lymphocyte ratio correlated with hsCRP (Spearman's r = 0.70 [95% CI 0.46 to 0.85], P < 0.01), TNF-α (r = 0.69 [0.44 to 0.84], P < 0.0001) and adiponectin (r = -0.69 [-0.84 to -0.45], P < 0.03), as well as with VAT individual adipocyte area (r = 0.64 [0.37 to 0.81], P < 0.0001) and with VAT area (r = 0.43; [0.07 to 0.68], P < 0.01). Leptin and adiponectin showed further independent association with higher NLR (multivariate regression analysis OR 7.9 [95% CI 1.1 to 56.2] P = 0.03 and 0.1 [0.01 to 1.0] P = 0.05, respectively). Moreover, NLR distribution significantly varied between subgroups divided according to progressive CIMT (P = 0.05); whereas adiponectin and VAT adipocyte area associated with CIMT > 0.9 mm (univariate analysis OR 0.1 [0.01 to 1.0] P = 0.05 and 13.1 [1.4 to 126.3] P = 0.03, respectively). CONCLUSION: Neutrophil-to-lymphocyte ratio was related to pro-inflammatory, adiposity biomarkers and progressive subclinical atherogenesis.

Patient-Specific iPSC-Derived Endothelial Cells Uncover Pathways that Protect against Pulmonary Hypertension in BMPR2 Mutation Carriers.

In familial pulmonary arterial hypertension (FPAH), the autosomal dominant disease-causing BMPR2 mutation is only 20% penetrant, suggesting that genetic variation provides modifiers that alleviate the disease. Here, we used comparison of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from three families with unaffected mutation carriers (UMCs), FPAH patients, and gender-matched controls to investigate this variation. Our analysis identified features of UMC iPSC-ECs related to modifiers of BMPR2 signaling or to differentially expressed genes. FPAH-iPSC-ECs showed reduced adhesion, survival, migration, and angiogenesis compared to UMC-iPSC-ECs and control cells. The "rescued" phenotype of UMC cells was related to an increase in specific BMPR2 activators and/or a reduction in inhibitors, and the improved cell adhesion could be attributed to preservation of related signaling. The improved survival was related to increased BIRC3 and was independent of BMPR2. Our findings therefore highlight protective modifiers for FPAH that could help inform development of future treatment strategies.

Khellin and Visnagin, Furanochromones from Ammi visnaga (L.) Lam., as Potential Bioherbicides.

Plants constitute a source of novel phytotoxic compounds to be explored in searching for effective and environmentally safe herbicides. From a previous screening of plant extracts for their phytotoxicity, a dichloromethane extract of Ammi visnaga (L.) Lam. was selected for further study. Phytotoxicity-guided fractionation of this extract yielded two furanochromones, khellin and visnagin, for which herbicidal activity had not been described before. Khellin and visnagin were phytotoxic to model species lettuce (Lactuca sativa) and duckweed (Lemna paucicostata), with IC50 values ranging from 110 to 175 µM. These compounds also inhibited the growth and germination of a diverse group of weeds at 0.5 and 1 mM. These weeds included five grasses [ryegrass (Lolium multiflorum), barnyardgrass (Echinocloa crus-galli), crabgrass (Digitaria sanguinalis), foxtail (Setaria italica), and millet (Panicum sp.)] and two broadleaf species [morningglory (Ipomea sp.) and velvetleaf (Abutilon theophrasti)]. During greenhouse studies visnagin was the most active and showed significant contact postemergence herbicidal activity on velvetleaf and crabgrass at 2 kg active ingredient (ai) ha-1. Moreover, its effect at 4 kg ai ha-1 was comparable to the bioherbicide pelargonic acid at the same rate. The mode of action of khellin and visnagin was not a light-dependent process. Both compounds caused membrane destabilization, photosynthetic efficiency reduction, inhibition of cell division, and cell death. These results support the potential of visnagin and, possibly, khellin as bioherbicides or lead molecules for the development of new herbicides.

Crack-resistant Al2O3-SiO2 glasses.

Obtaining "hard" and "crack-resistant" glasses have always been of great important in glass science and glass technology. However, in most commercial glasses both properties are not compatible. In this work, colorless and transparent xAl2O3-(100-x)SiO2 glasses (30 ≤ x ≤ 60) were fabricated by the aerodynamic levitation technique. The elastic moduli and Vickers hardness monotonically increased with an increase in the atomic packing density as the Al2O3 content increased. Although a higher atomic packing density generally enhances crack formation in conventional oxide glasses, the indentation cracking resistance increased by approximately seven times with an increase in atomic packing density in binary Al2O3-SiO2 glasses. In particular, the composition of 60Al2O3 • 40SiO2 glass, which is identical to that of mullite, has extraordinary high cracking resistance with high elastic moduli and Vickers hardness. The results indicate that there exist aluminosilicate compositions that can produce hard and damage-tolerant glasses.

High Elastic Moduli of a 54Al2O3-46Ta2O5 Glass Fabricated via Containerless Processing.

Glasses with high elastic moduli have been in demand for many years because the thickness of such glasses can be reduced while maintaining its strength. Moreover, thinner and lighter glasses are desired for the fabrication of windows in buildings and cars, cover glasses for smart-phones and substrates in Thin-Film Transistor (TFT) displays. In this work, we report a 54Al2O3-46Ta2O5 glass fabricated by aerodynamic levitation which possesses one of the highest elastic moduli and hardness for oxide glasses also displaying excellent optical properties. The glass was colorless and transparent in the visible region, and its refractive index nd was as high as 1.94. The measured Young's modulus and Vickers hardness were 158.3 GPa and 9.1 GPa, respectively, which are comparable to the previously reported highest values for oxide glasses. Analysis made using (27)Al Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) spectroscopy revealed the presence of a significantly large fraction of high-coordinated Al in addition to four-coordinated Al in the glass. The high elastic modulus and hardness are attributed to both the large cationic field strength of Ta(5+) ions and the large dissociation energies per unit volume of Al2O3 and Ta2O5.

Femoral tunnel drilling angles for the posterolateral corner in multiligamentary knee reconstructions: computed tomography evaluation in a cadaveric model.

PURPOSE: The goal of this study was to determine the best angle at which to drill the femoral tunnels of the popliteus tendon (PT) and fibular collateral ligament (FCL) in combined reconstructive procedures so as to avoid either short tunnels or tunnel collisions with the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) femoral tunnels. METHODS: Eight cadaveric knees were studied. ACL/PCL femoral tunnels were arthroscopically drilled. PT and FCL tunnels were drilled at 0° and 30° axial and coronal angulations. They were scanned by computed tomography to document relations of the PT and FCL tunnels to the intercondylar notch and ACL/PCL tunnels. A minimum tunnel length of 25 mm was required. RESULTS: Drilling the PT tunnel at 0° axial angulation was associated with an increased risk of tunnel collision with the ACL (P < .001). Interference with the PCL tunnel can be avoided only if the K-wire guiding the PT tunnel is drilled with 30° coronal angulations (P < .001). The minimum tunnel length of the PT could be obtained only with both axial and coronal angulations of 30° (P = .003). Sufficient tunnel lengths of the FCL were obtained at all angulations evaluated (P = .036). However, only the tunnels drilled at 30° axial and 0° coronal angulations did not collapse with the ACL tunnels (P < .001). No intersections between FCL and PT tunnels were observed. CONCLUSIONS: When posterolateral reconstructions are performed in combination with concomitant anterior and posterior cruciate procedures, PT tunnels should be drilled at 30° axial and 30° coronal angulations. FCL tunnels should be drilled at 30° axial and 0° coronal angulations. These angulations should minimize such potential complications as short tunnels or collisions with the ACL/PCL tunnels. CLINICAL RELEVANCE: Specific drilling angles are necessary to avoid short tunnels or collisions between the drilled tunnels when FCL and PT femoral tunnels are performed in multiligament knee reconstructions.

Flow cytometric analysis of T-lymphocytes from nasopharynx-associated lymphoid tissue (NALT) in a model of secondary immunodeficiency in Wistar rats.

Nasopharynx-associated lymphoid tissue (NALT) is responsible for immune responses in the upper respiratory tract of rodents. In our model of protein malnutrition (R21 group), bronchus-associated lymphoid tissue (BALT), situated in the lower respiratory tract, showed a decrease of CD4(+), CD8alpha(+), and TCRalphabeta(+) lymphocytes but TCRgammadelta(+) cells were increased. Besides, there is no information regarding the frequencies of T-cell populations in 60-day-old Wistar rats (C60 group). So, the aim of the present study was to analyze by flow cytometry NALT T-cells from both groups. NALT lymphocytes were isolated from R21 and C60 groups and stained with different antibodies. Samples were run on a FACScalibur flow cytometer. Background staining was evaluated using isotype controls. Data analysis was performed using BD Cell Quest and WinMDI 2.9. In C60, the predominant population was CD4(+)TCRalphabeta(+), which was significantly diminished in the R21 group. However, CD8alpha(+), the majority expressing CD8alphabeta, and TCRgammadelta(+) cells were not affected. In our model of secondary immunodeficiency, there is a compartmentalization between NALT and BALT because they differ in the populations affected even though they are inductive sites of the respiratory tract in the common mucosal immune system.

Fine and coarse particulate matter chemical characterization in a heavily industrialized city in central Mexico during Winter 2003.

This paper presents the results of the first reported study on fine particulate matter (PM) chemical composition at Salamanca, a highly industrialized urban area of Central Mexico. Samples were collected at six sites within the urban area during February and March 2003. Several trace elements, organic carbon (OC), elemental carbon (EC), and six ions were analyzed to characterize aerosols. Average concentrations of PM with aerodynamic diameter of less than 10 microm (PM10) and fine PM with aerodynamic diameter of less than 2.5 microm (PM2.5) ranged from 32.2 to 76.6 [g m(-3) and 11.1 to 23.7 microg m(-3), respectively. OC (34%), SO4= (25.1%), EC (12.9%), and geological material (12.5%) were the major components of PM2.5. For PM10 geological material (57.9%), OC (17.3%), and SO4= (9.7%) were the major components. Coarse fraction (PM,, -PM2.5), geological material (81.7%), and OC (8.6%) were the dominant species, which amounted to 90.4%. Correlation analysis showed that sulfate in PM2.5 was present as ammonium sulfate. Sulfate showed a significant spatial variation with higher concentrations to the north resulting from predominantly southwesterly winds above the surface layer and by major SO2 sources that include a power plant and refinery. At the urban site of Cruz Roja it was observed that PM2.5 mass concentrations were similar to the submicron fraction concentrations. Furthermore, the correlation between EC in PM2.5 and EC measured from an aethalometer was r(2) = 0.710. Temporal variations of SO2 and nitrogen oxide were observed during a day when the maximum concentration of PM2.5 was measured, which was associated with emissions from the nearby refinery and power plant. From cascade impactor measurements, the three measured modes of airborne particles corresponded with diameters of 0.32, 1.8, and 5.6 microm.

Modeling inorganic aerosols and their response to changes in precursor concentration in Mexico City.

Based on data from the 1997 Investigación sobre Materia Particulada y Deterioro Atmosférico-Aerosol and Visibility Evaluation Research (IMADA-EVER) campaign and the inorganic aerosol model ISORROPIA, the response of inorganic aerosols to changes in precursor concentrations was calculated. The aerosol behavior is dominated by the abundance of ammonia and thus, changes in ammonia concentration are expected to have a small effect on particle concentrations. Changes in sulfate and nitrate are expected to lead to proportional reductions in inorganic fine particulate matter (PM2.5). Comparing the predictions of ISORROPIA with the observations, the lowest bias and error are achieved when the aerosols are assumed to be in the efflorescence branch. Including crustal species reduces the bias and error for nitrate but does not improve overall model performance. The estimated response of inorganic PM2.5 to changes in precursor concentrations is affected by the inclusion of crustal species in some cases, although average responses are comparable with and without crustal species. Observed concentrations of particle chloride suggest that gas phase concentrations of hydrogen chloride may not be negligible, and future measurement campaigns should include observations to test this hypothesis. Our ability to model aerosol behavior in Mexico City and, thus, design control strategies, is constrained primarily by a lack of observations of gas phase precursors. Future campaigns should focus in particular on better understanding the temporal and spatial distribution of ammonia concentrations. In addition, gas phase observations of nitric acid are needed, and a measure of particle water content will allow stable versus metastable aerosol behavior to be distinguished.