Benefit of adjuvant chemotherapy in lymph node-negative, T1b and T1c triple-negative breast cancer.

INTRODUCTION: Current guidelines recommendations regarding chemotherapy in small (T1b and T1c), node-negative triple-negative breast cancer (TNBC) differ due to lack of high-quality data. Our study aimed to assess the benefit of adjuvant chemotherapy in patients with T1bN0M0 and T1cN0M0 TNBC. METHODS: We obtained data from the Surveillance, Epidemiology, and End Results database for patients with node-negative, T1b/T1c TNBC diagnosed between 2010 and 2020. Logistic regresion models assessed variables associated with chemotherapy administration. We evaluated the effect of chemotherapy on overall survival (OS) and breast cancer specific survival (BCSS) with Kaplan-Meier methods and Cox proportional hazards methods. RESULTS: We included 11,510 patients: 3,388 with T1b and 8,122 with T1c TNBC. During a median follow-up of 66 months, 305 patients with T1b and 995 with T1c died. After adjusting for clinicopathological, demographic and treatment factors, adjuvant chemotherapy improved OS in T1b TNBC (HR, 0.52; 95% CI, 0.41-0.68 p < 0.001) but did not improve BCSS (HR, 0.70; 95% CI, 0.45-1.07; p = 0.10); the association between chemotherapy and BCSS was not statistically significant in any subgroup. In T1c TNBC, adjuvant chemotherapy improved OS (HR, 0.54; 95% CI, 0.47-0.62; p < 0.001) and BCSS (HR, 0.79; 95% CI, 0.63-0.99; p = 0.043); the benefit of chemotherapy in OS varied by age (Pinteraction=0.024); moreover, the benefit in BCSS was similar in all subgroups. CONCLUSIONS: Our study results support the use of adjuvant chemotherapy in patients with node-negative, T1c TNBC. Patients with node-negative, T1b TNBC had excellent long-term outcomes; furthermore, chemotherapy was not associated with improved BCSS in these patients.

Secondary uncovered versus fully-covered metal stents for the management of occluded stent in unresectable distal malignant biliary obstruction.

INTRODUCTION: Self-expandable metallic stents (SEMS) have been widely placed for unresectable distal malignant biliary obstruction (UDMBO). However, the dysfunction rate is 19-40% and its treatment is controversial. We aimed asses the efficacy and safety of a secondary biliary stents (uncovered (UC) versus fully-covered (FC) stent) for the management of occluded SEMS. PATIENTS AND METHODS: Between 2015 and June 2023, 41 patients with UDMBO underwent secondary biliary stent placement as "stent-in-stent" (20 FCSEMS and 21 UCSEMS). The primary outcomes were technical and clinical success of SEMS placement. Secondary outcomes included adverse events (AEs), patency and survival. Patients were prospectively followed until death or loss of follow-up. RESULTS: Technical (100% vs 85.5%) and clinical (100% vs 95.2%) success rates were similar in FCSEMS and UCSEMS groups. The median follow-up period was 510 days (range 290-630). The median duration of stent patency of FCSEMS (220 days, IQR 137.5-442.5) was longer than UCSEMS (150 days, IQR 110-362.5) (P=0.395), although stent dysfunction within 6 months was not different between groups. Multivariate analysis indicated that sex (HR=0.909, 0.852-0.970), antitumor treatment (HR=0.248, 0.032-0.441), stent patency (HR=0.992, 0.986-0.998) and clinical success (HR=0.133, 0.026-0.690) were significant factors for overall survival. There were no remarkable differences in AEs. CONCLUSIONS: The placement of additional biliary stent using the stent-in-stent method is an effective and safe rescue treatment for patients with UDMBO and occluded stent. In addition, the use of FCSEMS compared UCSEMS has unclear benefits regarding stent patency and overall survival.

Racial disparities in overall survival after the introduction of cyclin-dependent kinase 4/6 inhibitors for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

PURPOSE: CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy have improved HR + /HER2- metastatic breast cancer (MBC) outcomes. However, it is still unclear whether the response to CDK4/6i is similar for all races. Therefore, we aimed to assess overall survival (OS) trends stratified by race in patients with HR + /HER2- MBC after the approval of CDK4/6i, as part of the standard of care, in 2015. METHODS: We performed a population-based study using the SEER database. Patients with HR + /HER2- MBC were divided into two time-based cohorts: 1) pre-CDK4/6i era (diagnosed in 2011-2013) and 2) post-CDK4/6i era (diagnosed in 2015-2017). We used propensity score matching and identified 2,684 patients in each cohort that matched in several characteristics. Kaplan-Meier methods were used to estimate 2-year OS. Association between cohort and OS was evaluated using marginal Cox proportional hazards models with robust sandwich variance estimator. We conducted competing risk analysis to estimate the risk of breast cancer death in both cohorts. RESULTS: The 2-year OS rate was 65% for the post-CDK4/6i era and 62% for the pre-CDK4/6i era (stratified log-rank p = 0.025). The 2-year OS for non-Hispanic White (NHW) patients improved in the post-CDK4/6i era compared to the pre-CDK4/6i era (67% vs. 63%, p = 0.033). However, OS did not improve for non-Hispanic Black (NHB) (54% vs. 54%, p = 0.876) or Hispanic (67% vs. 65%, p = 0.617) groups. The risk of breast cancer death decreased in the post-CDK4/6i era as compared to the pre-CDK4/6i era (2-year risk of breast cancer death: 33% vs. 30%, p = 0.015); however, this effect was observed only in NHW (sHR 0.84, p = 0.005) women, but not in NHB (sHR 0.94, p = 0.630) or Hispanic (sHR 0.91, p = 0.550) women. CONCLUSIONS: Our study confirms that outcomes for HR + /HER2- MBC have improved after CDK4/6i were introduced in 2015. However, this effect is primarily driven by the improved OS in NHW patients, without significant improvement in OS in NHB or Hispanics.

Racial disparities in treatment and outcomes between non-Hispanic Black and non-Hispanic White women with nonmetastatic inflammatory breast cancer.

PURPOSE: The incidence rate of inflammatory breast cancer (IBC) is higher among non-Hispanic Black (NHB) than non-Hispanic White (NHW) women. We examined the differences in treatment and outcomes between NHB and NHW women with IBC, accounting for demographic, clinicopathological, and socioeconomic factors. METHODS: We collected data from the Surveillance, Epidemiology, and End Results database for NHB and NHW women with IBC diagnosed between 2010-2016. We analyzed the odds of receiving chemotherapy, radiation, and surgery between NHB and NHW women. We evaluated overall survival (OS) with Kaplan-Meier methods and Cox proportional hazards methods. Competing risk analysis was used to compare the risk of breast cancer death between NHB and NHW women. We also evaluated the magnitude of survival disparities within the strata of demographic, socioeconomic, and treatment factors. RESULTS: Among 1,652 NHW and 371 NHB women with IBC, the odds of receiving chemotherapy, surgery, and radiation were similar for NHB and NHW. After 39-month follow-up, the median OS was 40 and 81 months for NHB and NHW, respectively (p < 0.0001). The risk of breast cancer death was higher for NHB than NHW women (5-year risk of breast cancer death, 51% vs. 35%, p < 0.0001). CONCLUSION: After adjustment for demographic, clinicopathological, and socioeconomic factors; NHB women with IBC had similar odds of receiving surgery, chemotherapy, and radiation therapy, but were more likely to die of the disease compared to their NHW counterparts. Our findings suggest the presence of masked tumor biology, treatment, or socioeconomic factors associated with race that can lead to worse IBC outcomes.

Clinical, diagnostic and epidemiological implications of Hepatozoon spp., Babesia spp. and Leishmania infantum infection in cats and dogs in a Mediterranean periurban setting.

Hepatozoon spp., Babesia spp. and Leishmania infantum are common parasites of dogs in Mediterranean countries and are less frequent in cats, particularly Babesia spp. and L. infantum. Moreover, there is limited information on coinfections between these parasites and on L. infantum's distribution in blood, skin and lymphoid tissue in cats. We used PCR and DNA sequencing to investigate the prevalence of these parasites and the aetiology of Hepatozoon spp. and Babesia spp., in blood, skin, spleen and lymph node samples from up to 212 stray cats and 82 abandoned dogs in southeast Spain. All except 2 dogs were healthy; instead, 112 cats had clinical signs. The estimated PCR prevalences (95% confidence interval) were 25% (19-31%) Hepatozoon felis in cats, 13% (6-21%) Hepatozoon canis in dogs, 1% (0-4%) Babesia vogeli in dogs, 0% Babesia spp. in cats and 21% (15-26%) and 44% (33-55%) L. infantum in cats and dogs, respectively, and infections were not associated with each other. Leishmania infantum prevalence in lymphoid tissue was significantly higher in dogs than in cats (p < 0.001), and dogs had higher parasite loads than cats (p = 0.012). Moreover, L. infantum prevalence was significantly higher in the skin and lymphoid tissue compared to blood in infected, asymptomatic animals but it was similar in cats with clinical signs, which also had higher parasite loads compared to infected, asymptomatic cats (p < 0.05). The study highlights significant differences between sympatric dogs and cats with respect to the parasite infections investigated, as well as the need to examine both lymphoid tissue and skin samples to maximise the sensitivity of L. infantum infection diagnosis.

Microorganisms and Antibiotic Resistance of Bacterial Keratitis at a Rural County Hospital in Seville.

PURPOSE: To review the incidence, resistance patterns, and management of bacterial keratitis during the past 4 years. METHODS: We retrospectively reviewed the clinical records of microbiological isolates from patients with a clinical diagnosis of bacterial keratitis. RESULTS: A total of 159 patients were analyzed, and 102 microorganisms were isolated from 129 cultures. In these cultures, 23.7% of the microorganisms were gram positive, 60.8% were gram negative, and 15.5% were fungi. Pseudomonas aeruginosa was the most common bacteria (9.2%), followed by Serratia marcescens (4.4%) and Staphylococcus aureus (4%). Resistance to fluoroquinolones and aminoglycosides was found to be 23.1% and 53.1% in gram-positive and 2.8% and 13.9% in gram-negative bacteria, respectively. Resistance to ceftazidime against gram-negative bacteria was 13.9%. No resistance to vancomycin was observed. CONCLUSIONS: A high resistance rate to aminoglycosides and fluoroquinolones was observed in gram-positive bacteria. We concluded that fluoroquinolones or aminoglycosides may not be suitable for initial monotherapy in patients with severe bacterial keratitis.

The effect of an online exercise programme on bone health in paediatric cancer survivors (iBoneFIT): study protocol of a multi-centre randomized controlled trial.

BACKGROUND: New approaches on paediatric cancer treatment aim to maintain long-term health. As a result of radiotherapy, chemotherapy or surgery, paediatric cancer survivors tend to suffer from any chronic health condition. Endocrine dysfunction represents one of the most common issues and affects bone health. Exercise is key for bone mass accrual during growth, specifically plyometric jump training. The iBoneFIT study will investigate the effect of a 9-month online exercise programme on bone health in paediatric cancer survivors. This study will also examine the effect of the intervention on body composition, physical fitness, physical activity, calcium intake, vitamin D, blood samples quality of life and mental health. METHODS: A minimum of 116 participants aged 6 to 18 years will be randomized into an intervention (n = 58) or control group (n = 58). The intervention group will receive an online exercise programme and diet counselling on calcium and vitamin D. In addition, five behaviour change techniques and a gamification design will be implemented in order to increase the interest of this non-game programme. The control group will only receive diet counselling. Participants will be assessed on 3 occasions: 1) at baseline; 2) after the 9 months of the intervention; 3) 4 months following the intervention. The primary outcome will be determined by dual energy X-ray absorptiometry (DXA) and the hip structural analysis, trabecular bone score and 3D-DXA softwares. Secondary outcomes will include anthropometry, body composition, physical fitness, physical activity, calcium and vitamin D intake, blood samples, quality of life and mental health. DISCUSSION: Whether a simple, feasible and short in duration exercise programme can improve bone health has not been examined in paediatric cancer survivors. This article describes the design, rationale and methods of a study intended to test the effect of a rigorous online exercise programme on bone health in paediatric cancer survivors. If successful, the iBoneFIT study will contribute to decrease chronic health conditions in this population and will have a positive impact in the society. TRIAL REGISTRATION: Prospectively registered in isrctn.com: isrctn61195625 . Registered 2 April 2020.

Report of an unsual case of anophthalmia and craniofacial cleft in a newborn with Toxoplasma gondii congenital infection.

BACKGROUND: We present one unusual case of anophthalmia and craniofacial cleft, probably due to congenital toxoplasmosis only. CASE PRESENTATION: A two-month-old male had a twin in utero who disappeared between the 7th and the 14th week of gestation. At birth, the baby presented anophthalmia and craniofacial cleft, and no sign compatible with genetic or exposition/deficiency problems, like the Wolf-Hirschhorn syndrome or maternal vitamin A deficiency. Congenital toxoplasmosis was confirmed by the presence of IgM abs and IgG neo-antibodies in western blot, as well as by real time PCR in blood. CMV infection was also discarded by PCR and IgM negative results. Structures suggestive of T. gondii pseudocysts were observed in a biopsy taken during the first functional/esthetic surgery. CONCLUSIONS: We conclude that this is a rare case of anophthalmia combined with craniofacial cleft due to congenital toxoplasmosis, that must be considered by physicians. This has not been reported before.

Translation and Initial Psychometric Evaluation of Spanish Versions of Three Psychedelic Acute Effects Measures: Mystical, Challenging, and Insight Experiences.

This study translated and tested the psychometric properties of acute psychedelic effects measures among Spanish-speaking people. The Psychological Insight Questionnaire (PIQ), Challenging Experiences Questionnaire (CEQ), and Mystical Experiences Questionnaire (MEQ) were translated before being incorporated into a web-based survey. We recruited native Spanish-speakers (N = 442; Mage = 30.8, SD = 10.9; Latino/Latina = 62%; Hispanic = 91.4%; male = 71.5%) to assess their previous experience with one of two psychedelics (LSD = 58.4%; Psilocybin = 41.6%) and their acute and enduring effects. Confirmatory factor analysis (confirming factor structure based on the English version) revealed a good fit for the MEQ, PIQ and the CEQ. Repeating our analysis in each drug subsample revealed consistency in factor structure for each assessment tool. Construct validity was supported by significant positive associations between the PIQ and MEQ, and between the PIQ and MEQ and changes in cognitive fusion and negative associations between changes in prosocial behaviors. As a signal of predictive validity, persisting effects (PEQ) were strongly related to scores on the MEQ and PIQ. Findings demonstrate that the Spanish versions of these measures can be reliably employed in studies of psychedelic use or administration in Spanish-speaking populations.

Reactivations after 5-methoxy-N,N-dimethyltryptamine use in naturalistic settings: An initial exploratory analysis of the phenomenon's predictors and its emotional valence.

Background: The psychedelic 5-MeO-DMT has shown clinical potential due to its short duration and ability to induce mystical experiences. However, a phenomenon known as "reactivations" (similar to "flashbacks") is a poorly understood and frequently reported phenomenon which appears associated with 5-MeO-DMT use and warranted further investigation. Aims: This study examined whether differences in age, gender, education, lifetime use, use location, and preparation strategies predict reactivations (primary outcome). Additionally, we explored how reactivations were perceived by survey respondents and whether demographic data predicted emotional valence (secondary outcome) of reported reactivations. Materials and methods: This study used secondary quantitative data from a survey assessing epidemiological and behavioral associations of 5-MeO-DMT use in non-clinical settings (N = 513). Descriptive statistics, chi-square tests, t-tests, and logistic regressions were utilized to explore aims. Results: Being female, older at the time of first 5-MeO-DMT dose, having higher educational attainment, and dosing in a structured group setting were associated with increased odds of reporting a reactivation event. Higher mystical experience scores, greater personal wellbeing and having had a non-dual awareness experience that was not substance-induced were associated with higher likelihood of reporting a neutral or positive emotional valence of a reactivation event. Conclusion: These findings suggest that reactivation phenomena, in this particular sample may most often represent a neutral or positive byproduct of the acute 5-MeO-DMT experience. More information is needed to best identify individuals most likely to experience a reactivation as a negative event to prevent such potential challenging outcomes.

2-Pyridone-stabilized iridium silylene/silyl complexes: structure and QTAIM analysis.

Iridium(iii) complexes of the general formula [Ir(X)(κ2-NSiiPr2)2] (NSiiPr2 = (4-methyl-pyridine-2-yloxy)diisopropylsilyl; X = Cl, 3; CF3SO3, 5; CF3CO2, 6) have been prepared and fully characterized, including X-ray diffraction studies and theoretical calculations. The presence of isopropyl substituents at the silicon atom favours the monomeric structure found in complexes 3 and 5. The short Ir-Si bond distances (2.25-2.28 Å) indicate some degree of base-stabilized silylene character of the Ir-Si bond in 3, 5 and 6 assisted by the 2-pyridone moiety. However, the shortening of these Ir-Si bonds might be a consequence of the constrained 2-pyridone geometry, and consequently the silyl character of these bonds can not be excluded. A DFT theoretical study on the nature of the Ir-Si bonds has been performed for complex 3 as well as for four other iridium complexes finding representative examples of different bonding situations between Ir and Si atoms: silylene, base-assisted silylene (both with an anionic base and with a neutral base), and silyl bonds, using the topological properties of the electron charge density. The results of these studies show that the Ir-Si bonds in Ir-NSiiPr2 complexes can be considered as an intermediate between the base-stabilized silylene and silyl cases, and therefore they have been proposed as 2-pyridone-stabilized iridium silylene/silyl bonds.

Insulin eye drops for treating corneal ulcer in a non-diabetic patient: regarding a case.

Corneal ulcers are included in a heterogeneous group of eye injuries. When  patients do not respond to treatment, including even corneal transplant, other  alternatives need to be explored.We present a case of a patient who suffered an accidental spillage from the  contents of a car battery. This corneal lesion was refractory to both surgical and  pharmacological treatment. After four years of a persistent ulcer, insulin topical  treatment 50 IU/mL was started. Improvement began to be observed and  currently the patient has completely recovered the corneal epithelium.Nowadays, evidence of the topical insulin use for the treatment of corneal ulcers  is higher in diabetic patients. In non-diabetic patients, evidence is restricted to a series of cases of neurotrophic corneal ulcers and a case report of a patient who  presented a persistent epithelial defect after resection of a neurinoma. This case  presents the experience of using an insulin drop formulation with effectiveness  and absence of toxicity in a patient nondiabetic with a post-caustic corneal ulcer.

Las úlceras corneales se incluyen dentro de un grupo heterogéneo de lesiones  oculares, las cuales pueden ser de gravedad variable. Cuando los pacientes no  responden al tratamiento, incluyendo incluso el trasplante corneal, se crea la  necesidad de explorar otras alternativas.Presentamos el caso de un paciente que sufrió una salpicadura ocular del  contenido de una batería de automóvil por accidente. Esta lesión corneal, fue  refractaria al tratamiento farmacológico e incluso quirúrgico. Tras cuatro años de persistencia de la úlcera corneal, se inició un tratamiento tópico con insulina 50  UI/ml. Se observó mejoría de forma evidente y actualmente el paciente ha  recuperado completamente el epitelio corneal.Hoy en día, las evidencias disponibles del uso tópico de la insulina para el  tratamiento de las úlceras corneales se centran en pacientes diabéticos. En los  pacientes no diabéticos, la evidencia se limita a una serie de casos de úlceras  neurotróficas corneales y al caso de un paciente que presentó un defecto  epitelial persistente después de la resección de un neurinoma. Este caso,  presenta la experiencia de uso de una formulación magistral de insulina  oftálmica con eficacia y ausencia de toxicidad en un paciente no diabético con  una úlcera corneal post-cáustica resistente al resto de tratamientos.

No Detectable Electroencephalographic Activity After Clinical Declaration of Death Among Tibetan Buddhist Meditators in Apparent Tukdam, a Putative Postmortem Meditation State.

Recent EEG studies on the early postmortem interval that suggest the persistence of electrophysiological coherence and connectivity in the brain of animals and humans reinforce the need for further investigation of the relationship between the brain's activity and the dying process. Neuroscience is now in a position to empirically evaluate the extended process of dying and, more specifically, to investigate the possibility of brain activity following the cessation of cardiac and respiratory function. Under the direction of the Center for Healthy Minds at the University of Wisconsin-Madison, research was conducted in India on a postmortem meditative state cultivated by some Tibetan Buddhist practitioners in which decomposition is putatively delayed. For all healthy baseline (HB) and postmortem (PM) subjects presented here, we collected resting state electroencephalographic data, mismatch negativity (MMN), and auditory brainstem response (ABR). In this study, we present HB data to demonstrate the feasibility of a sparse electrode EEG configuration to capture well-defined ERP waveforms from living subjects under very challenging field conditions. While living subjects displayed well-defined MMN and ABR responses, no recognizable EEG waveforms were discernable in any of the tukdam cases.

Selective reduction of formamides to O-silylated hemiaminals or methylamines with HSiMe2Ph catalyzed by iridium complexes.

The reaction of (4-methyl-pyridin-2-iloxy)ditertbutylsilane (NSitBu-H, 1) with [IrCl(coe)2]2 affords the iridium(iii) complex [Ir(H)(Cl)(κ2-NSitBu)(coe)] (2), which has been fully characterized including X-ray diffraction studies. The reaction of 2 with AgCF3SO3 leads to the formation of species [Ir(H)(CF3SO3)(κ2-NSitBu)(coe)] (3). The iridium complexes 2 and 3 are effective catalysts for the reduction of formamides with HSiMe2Ph. The selectivity of the reduction process depends on the catalyst. Thus, by using complex 2, with a chloride ancillary ligand, it has been possible to selectively obtain the corresponding O-silylated hemiaminal by reaction of formamides with one equivalent of HSiMe2Ph, while complex 3, with a triflate ligand instead of chloride, catalyzed the selective reduction of formamides to the corresponding methylamine.

Influence of stacked structure of carbons modified on its surface on n-pentane adsorption.

In this study, the microstructure of a series of activated carbons modified on its chemistry surface was evaluated from X-ray diffraction and porous structure analysis, and the effect of the stacked graphitic structure on the n-pentane adsorption capacity. The activated carbons were prepared modifying an activated carbon (obtained from coconut shell) by carbonization processes at 1073, 1173 and 1273 K and impregnation with 65% nitric acid solution, 60% phosphoric acid solution and reflux with 30% ammonium hydroxide solution. The activated carbons were characterized by N2 adsorption at 77 K. It was found that these are essentially microporous materials with surface areas between 469 and 1113 m2 g-1, and the evaluation of the microstructure was performed by determining the number of aromatic layers stacked from the analysis of the observed diffraction peak between 20-30° 2θ which corresponds to the 002 reflection in the plane of the coal using the STACK XRD technical. The results showed that impregnation as carbonization favours the development of the crystalline structure to the activated carbons, which is shown by the increase of the stacked structure at the same time; this favours the n-pentane adsorption.

Genetic diversity and phylogenetic relationships between Leishmania infantum from dogs, humans and wildlife in south-east Spain.

Leishmania infantum causes human and canine leishmaniosis. The parasite, transmitted by phlebotomine sand flies, infects species other than dogs and people, including wildlife, although their role as reservoirs of infection remains unknown for most species. Molecular typing of parasites to investigate genetic variability and evolutionary proximity can help understand transmission cycles and designing control strategies. We investigated Leishmania DNA variability in kinetoplast (kDNA) and internal transcribed spacer 2 (ITS2) sequences in asymptomatically infected wildlife (n = 58) and symptomatically and asymptomatically infected humans (n = 38) and dogs (n = 15) from south-east Spain, using single nucleotide polymorphisms (SNPs) and in silico restriction fragment length polymorphism (RFLP) analyses. All ITS2 sequences (n = 76) displayed a 99%-100% nucleotide identity with a L. infantum reference sequence, except one with a 98% identity to a reference Leishmania panamensis sequence, from an Ecuadorian patient. No heterogeneity was recorded in the 73 L. infantum ITS2 sequences except for one SNP in a human parasite sequence. In contrast, kDNA analysis of 44 L. infantum sequences revealed 11 SNP genotypes (nucleotide variability up to 4.3%) and four RFLP genotypes including B, F and newly described S and T genotypes. Genotype frequency was significantly greater in symptomatic compared to asymptomatic individuals. Both methods similarly grouped parasites as predominantly or exclusively found in humans, in dogs, in wildlife or in all three of them. Accordingly, the phylogenetic analysis of kDNA sequences revealed three main clusters, two as a paraphyletic human parasites clade and a third including dogs, people and wildlife parasites. Results suggest that Leishmania infantum genetics is complex even in small geographical areas and that, probably, several independent transmission cycles take place simultaneously including some connecting animals and humans. Investigating these transmission networks may be useful in understanding the transmission dynamics, infection risk and therefore in planning L. infantum control strategies.

Real-time PCR assay for the diagnosis of pleural tuberculosis.

INTRODUCTION: The diagnosis of pleural tuberculosis requires an invasive and time-consuming reference method. Polymerase chain reaction (PCR) is rapid, but validation in pleural tuberculosis is still weak. OBJECTIVE: To establish the operating characteristics of real-time polymerase chain reaction (RT-PCR) hybridization probes for the diagnosis of pleural tuberculosis. METHODS: The validity of the RT-PCR hybridization probes was evaluated compared to a composite reference method by a cross-sectional study at the Hospital Universitario de la Samaritana. 40 adults with lymphocytic pleural effusion were included. Pleural tuberculosis was confirmed (in 9 patients) if the patient had at least one of three tests using the positive reference method: Ziehl-Neelsen or Mycobacterium tuberculosis culture in fluid or pleural tissue, or pleural biopsy with granulomas. Pleural tuberculosis was ruled out (in 31 patients) if all three tests were negative. The operating characteristics of the RT-PCR, using the Mid-P Exact Test, were determined using the OpenEpi 2.3 Software (2009). RESULTS: The RT-PCR hybridization probes showed a sensitivity of 66.7% (95% CI: 33.2%-90.7%) and a specificity of 93.5% (95% CI: 80.3%-98.9%). The PPV was 75.0% (95% CI: 38.8%-95.6%) and a NPV of 90.6% (95% CI: 76.6%-97.6%). Two false positives were found for the test, one with pleural mesothelioma and the other with chronic pleuritis with mesothelial hyperplasia. CONCLUSIONS: The RT-PCR hybridization probes had good specificity and acceptable sensitivity, but a negative value cannot rule out pleural tuberculosis.

INTRODUCCIÓN: El diagnóstico de tuberculosis pleural requiere un método de referencia invasivo y demorado. La reacción en cadena de la polimerasa es rápida, pero su validación en tuberculosis pleural aún es débil. OBJETIVO: Establecer las características operativas de la reacción en cadena de la polimerasa en tiempo real (RT-PCR) sondas de hibridación para el diagnóstico de tuberculosis pleural. MÉTODOS: Se evaluó la validez de la RT-PCR sondas de hibridación comparada con un método de referencia compuesto mediante un estudio transversal en el Hospital Universitario de la Samaritana. Se incluyeron 40 adultos con derrame pleural linfocitario. Tuberculosis pleural fue confirmada (en 9 pacientes) si el paciente tenía mínimo una de tres pruebas del método de referencia positiva: Ziehl-Neelsen o cultivo para Mycobacterium tuberculosis en líquido o tejido pleural, o biopsia pleural con granulomas; se descartó tuberculosis pleural (en 31 pacientes) si las tres pruebas eran negativas. Se determinaron las características operativas de la RT-PCR, mediante la Prueba Mid-P Exact, con el Software OpenEpi 2.3 (2009). RESULTADOS: La RT-PCR sondas de hibridación mostró una sensibilidad del 66.7% (IC 95%: 33.2%-90.7%) y una especificidad del 93.5% (IC 95%: 80.3%-98.9%). El VPP fue de 75.0% (IC 95%: 38.8%-95.6%) y un VPN de 90.6% (IC 95%: 76.6%-97.6%). Se encontraron dos falsos positivos para la prueba, uno con mesotelioma pleural y otro con pleuritis crónica con hiperplasia mesotelial. CONCLUSIONES: La RT-PCR sondas de hibridación tuvo una buena especificidad y una aceptable sensibilidad, pero un valor negativo no puede descartar tuberculosis pleural.

Clinical and Genetic Characterization and Biochemical Correlation at Presentation in 48 Patients Diagnosed with Urea Cycle Disorders at the Hospital Juan P Garrahan, Argentina

Abstract The clinical and biochemical findings in a cohort of 51 patients with urea cycle disorders followed at the Hospital Garrahan, Buenos Aires, Argentina were analyzed at the time of diagnosis (3 female patients were excluded). Of this cohort, 13/48 patients had early-onset (EO), 23/48 had late-onset (LO), and 12/48 had a different presentation because they had a family risk background (FRB) and had been diagnosed since they were born. The most frequent deficiency disorder was OTCD (65%). The initial ammonium value was evaluated, being higher in the EO group, with a statistically significant difference when compared with LO and FRB. 15/48 patients fell into a coma at the time of diagnosis, mean ammonia was 829.54 μmol / L, and 33/48 did not fell into a coma, the mean ammonium was of 159.3 μmol / L (p = 0.001). 15 patients died: 62% EO, 22% LO (p=0.0216), 17% FRB. A molecular study was performed on 35 patients. Patients with EO presentation suffer the most severe forms and still have high morbimortality. On the other hand, LO forms are forms of less severity that are finally diagnosed as a result of one or more acute episodes.

Determination of functional collective motions in a protein at atomic resolution using coherent neutron scattering.

Protein function often depends on global, collective internal motions. However, the simultaneous quantitative experimental determination of the forms, amplitudes, and time scales of these motions has remained elusive. We demonstrate that a complete description of these large-scale dynamic modes can be obtained using coherent neutron-scattering experiments on perdeuterated samples. With this approach, a microscopic relationship between the structure, dynamics, and function in a protein, cytochrome P450cam, is established. The approach developed here should be of general applicability to protein systems.