Prefrontal cortex neurons in adult rats exposed to early life stress fail to appropriately signal the consequences of motivated actions.

Early life stress (ELS) can set the stage for susceptibility to cognitive and emotional dysfunction in adulthood by disrupting typical neural development. The prefrontal cortex (PFC) continues to mature during early life, making this region particularly vulnerable to disruption for animals who experience ELS. Despite this, the effects of ELS experience on in vivo PFC function in awake and behaving adult animals are currently poorly understood. To assess this, we employed an instrumental conflict task to assess how hungry adult rats, either ELS (wet bedding) or unstressed Controls, were able to flexibly alter their motivation for food reward seeking (lever presses) in situations that were either threatening or safe. During this task, in vivo electrophysiological recordings (both single unit and local field potentials [LFPs]) were made in the rats' ventral-medial PFC (vmPFC). We found that ELS rats were less motivated to lever press for rewards than Controls in the threat situations during repeated extinction sessions. In recordings taken during this suppression task, Control vmPFC neurons displayed reliable differences between motivated actions, such as between rewarded and unrewarded presses, but ELS neurons failed to differentiate these action-outcome differences. We also found differences in task-related LFP activity between groups; in particular, prior ELS experience appears to induce abnormal changes in low-frequency oscillations during shock-associated threat stimuli prior to presses, as well as diminished higher-frequency oscillations following rewarded presses. Collectively, we demonstrate that ELS experience produces persistent impairment in motivational regulation that is associated with significant changes in in vivo PFC signals. Specifically, ELS-experienced adults fail to appropriately update motivated action strategies under threat conditions, and likewise fail to appropriately monitor and update action/outcome relationships in motivated behavior. These ELS-related changes may therefore lay the foundation for heightened susceptibility to mental-health disorders in adults such as substance abuse and post-traumatic stress disorder.

Subtype-specific expression of MELK is partly due to copy number alterations in breast cancer.

Maternal embryonic leucine-zipper kinase (MELK) regulates cell cycle progression and is highly expressed in many cancers. The molecular mechanism of MELK dysregulation has not been determined in aggressive forms of breast cancer, such as triple negative breast cancer (TNBC). To evaluate molecular markers of MELK aberrations in aggressive breast cancer, we assessed MELK gene amplification and expression in breast tumors. MELK mRNA expression is highly up-regulated in basal-like breast cancer (BLBC), the major molecular subtype of TNBC, compared to luminal or other subtypes of breast tumors. MELK copy number (CN) gains are significantly associated with BLBC, whereas no significant association of CpG site methylation or histone modifications with breast cancer subtypes was observed. Accordingly, the CN gains appear to contribute to an increase in MELK expression, with a significant correlation between mRNA expression and CN in breast tumors and cell lines. Furthermore, immunohistochemistry (IHC) assays revealed that both nuclear and cytoplasmic staining scores of MELK were significantly higher in invasive ductal carcinoma (IDC) tumors compared to ductal carcinoma in situ (DCIS) and normal breast tissues. Our data showed that upregulation of MELK in BLBC may be in part driven by CN gains, rather than epigenetic modifications, indicating a potential for overexpression and CN gains of MELK to be developed as a diagnostic and prognostic marker to identify patients who have more aggressive breast cancer.

Effects of Slide Storage on Detection of Molecular Markers by IHC and FISH in Endometrial Cancer Tissues From a Clinical Trial: An NRG Oncology/GOG Pilot Study.

We performed a pilot study in anticipation of using long-aged precut formalin-fixed paraffin-embedded tissue sections stored in real-world conditions for translational biomarker studies of topoisomerase 2A (TOP2A), Ki67, and human epidermal growth factor receptor 2 (HER2) in endometrial cancer. Formalin-fixed paraffin-embedded tissue blocks or unstained slides or both from GOG-0177 were collected centrally (1999-2000) and stored at room temperature. During 2004 to 2011 specimens were stored at 4°C. Matched pairs of stored slides and freshly cut slides from stored blocks were analyzed for TOP2A (KiS1), Ki67 (MIB1), and HER2 (HercepTest) proteins. To assess DNA stability (HER2 PathVision), fluorescence in situ hybridization (FISH) was repeated on stored slides from 21 cases previously shown to be HER2 amplified. Immunohistochemistry (IHC) staining intensity and extent, mean FISH copies/cell, and copy number ratios were compared using the κ statistic for concordance or signed rank test for differences in old cut versus new cut slides. IHC results reflected some protein degradation in stored slides. The proportion of cells with TOP2A staining was lower on average by 12% in older sections (P=0.03). The proportion of Ki67-positive cells was lower in stored slides by an average of 10% (P<0.01). Too few cases in the IHC cohort were FISH positive for any conclusions. HER2 amplification by FISH was unaffected by slide storage. We conclude that use of aged stored slides for proliferation markers TOP2A and Ki67 is feasible but may modestly underestimate true values in endometrial cancer. Pilot studies for particular storage conditions/durations/antigens to be used in translational studies are warranted.

Elevated fear responses to threatening cues in rats with early life stress is associated with greater excitability and loss of gamma oscillations in ventral-medial prefrontal cortex.

Stress experienced early in development can have profound influences on developmental trajectories and ultimately behaviors in adulthood. Potent stressors during brain maturation can profoundly disrupt prefrontal cortical areas in particular, which can set the stage for prefrontal-dependent alterations in fear regulation and risk of drug abuse in adulthood. Despite these observations, few studies have investigated in vivo signaling in prefrontal signals in animals with a history of early life stress (ELS). Here, rats with ELS experienced during the first post-natal week were then tested on a conditioned suppression paradigm during adulthood. During conditioned suppression, electrophysiological recordings were made in the ventral medial prefrontal cortex (vmPFC) during presentations of a fear-associated cue that resolved both single-unit activity and local field potentials (LFPs). Relative to unstressed controls, ELS-experienced rats showed greater fear-related suppression of lever pressing. During presentations of the fear-associated cue (CS+), neurons in the vmPFC of ELS animals showed a significant increase in the probability of excitatory encoding relative to controls, and excitatory phasic responses in the ELS animals were reliably of higher magnitude than Controls. In contrast, vmPFC neurons in ELS subjects better discriminated between the shock-associated CS+ and the neutral ("safe") CS- cue than Controls. LFPs recorded in the same locations revealed that high gamma band (65-95 Hz) oscillations were strongly potentiated in Controls during presentation of the fear-associated CS+ cue, but this potentiation was abolished in ELS subjects. Notably, no other LFP spectra differed between ELS and Controls for either the CS+ or CS-. Collectively, these data suggest that ELS experience alters the neurobehavioral functions of PFC in adulthood that are critical for processing fear regulation. As such, these alterations may also provide insight into increased susceptibility to other PFC-dependent processes such as risk-based choice, motivation, and regulation of drug use and relapse in ELS populations.

Autoinstrucción para la búsqueda eficiente de información para alumnos de pregrado de odontología en una universidad chilena / Self-instruction for the efficient search of information for undergraduate students of Dentistry at a Chilean university

INTRODUCCIÓN: Para realizar una práctica clínica basada en la evidencia es fundamental que los profesionales de la salud sepan reconocer sus brechas de conocimiento y posean las herramientas necesarias para realizar búsquedas de información. Con el objetivo de mejorar la metodología de enseñanza-aprendizaje para la búsqueda eficiente, se diseñaron tres cápsulas de autoaprendizaje. SUJETOS Y MÉTODOS: Las cápsulas se aplicaron en cursos del primer, quinto y octavo semestre de la carrera de odontología y se analizaron sus resultados en los niveles 1 y 2 del modelo de evaluación de programas Kirkpatrick. Cada cápsula se evaluó en modalidad online mediante una tarea de aplicación y un cuestionario de cumplimiento de objetivos. RESULTADOS: Las cápsulas se aplicaron el primer y segundo semestre de 2018 a un total de 218 alumnos. Tanto alumnos como profesores se manifestaron satisfechos con la metodología y los contenidos, destacando la modalidad b-learning y la calidad del material instruccional. El 100% de los alumnos aprobó la evaluación asociada a cada cápsula. El promedio de percepción de alcance de objetivos fue del 72% para la cápsula 1, 80% para la cápsula 2 y 84% para la cápsula 3, con una mayor proporción de diferencias positivas (p = 0,00). CONCLUSIÓN: Las cápsulas de autoinstrucción para la enseñanza de búsqueda de evidencia son una metodología efectiva, en términos de reacción y aprendizaje

INTRODUCTION: To carry out an evidence-based clinical practice, health professionals must know how to recognize their knowledge gaps and have the necessary tools to search for information in order to improve their teaching methodology. Three self-learning capsules were designed to search efficiently for information. SUBJECTS AND METHODS: The capsules were applied in courses of the 1st, 5th and 8th semesters of the dentistry degree. The results were analyzed at levels 1 and 2 of the Kirkpatrick program evaluation model. Each capsule was evaluated in online mode through an application task and a and a fulfilling objectives questionnaire. RESULTS: The self-instruction capsules were applied to a total of 218 students. The satisfaction survey showed high values for students and teachers considering the methodology and content, highlighting the b-learning modality and the quality of the instructional material. All of the students approved the evaluation associated with each capsule. The average perception of goal achievement was 72% for capsule 1, 80% for capsule 2 and 84% for capsule 3, with a higher proportion of positive differences (p = 0.00). CONCLUSION: In terms of reaction and learning, it is an effective methodology to use self-instruction capsules for teaching evidence seeking

Impaired Tubular Reabsorption Is the Main Mechanism Explaining Increases in Urinary NGAL Excretion Following Acute Kidney Injury in Rats.

Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted low-molecular weight iron-siderophore-binding protein. NGAL overexpression in injured tubular epithelia partly explains its utility as a sensitive and early urinary biomarker of acute kidney injury (AKI). Herein, we extend mechanistic insights into the source and kinetics of urinary NGAL excretion in experimental AKI. Three models of experimental AKI were undertaken in adult male Wistar rats; renal ischemia-reperfusion injury (IRI) and gentamicin (G) and cisplatin (Cisp) nephrotoxicity. Alongside standard histological and biochemical assessment of AKI, urinary NGAL excretion rate, plasma NGAL concentration, and renal NGAL mRNA/protein expression were assessed. In situ renal perfusion studies were undertaken to discriminate direct shedding of NGAL to the urine from addition of NGAL to the urine secondary to alterations in the tubular handling of glomerular filtrate-derived protein. Renal NGAL expression and urinary excretion increased in experimental AKI. In acute studies in both the IRI and G models, direct renal perfusion with Kreb's buffer eliminated urinary NGAL excretion. Addition of exogenous NGAL to the Kreb's buffer circuit, reestablishment of perfusion with systemic blood or reperfusion with renal vein effluent restored high levels of urinary NGAL excretion. Urinary NGAL excretion in AKI arises in large proportion from reduced reabsorption from the glomerular filtrate. Hence, subclinical cellular dysfunction could increase urinary NGAL, particularly in concert with elevations in circulating prerenal NGAL and/or pharmacological inhibition of tubular reabsorption. More granular interpretation of urinary NGAL measurements could optimize the scope of its clinical utility as a biomarker of AKI.

Sex differences in the peripubertal response to a short-term, high-fat diet intake.

Obesity is one of the most important health problems facing developed countries because being overweight is associated with a higher incidence of type 2 diabetes, cardiovascular disease and cancer, as well as other comorbidities. Although increased weight gain results from a combination of poor dietary habits and decreased energy expenditure, not all individuals have equal propensities to gain weight or to develop secondary complications of obesity. This is partially a result not only of genetics, including sex, but also the time during which an individual is exposed to an obesogenic environment. In the present study, we have compared the response of male and female mice to short-term exposure to a high-fat diet (HFD) or a low-fat diet during the peripubertal period (starting at 42 days of age) because this is a stage of dramatic hormonal and metabolic modifications. After 1 week on a HFD, there was no significant increase in body weight, although females significantly increased their energy intake. Serum leptin levels increased in both sexes, even though no change in fat mass was detected. Glyceamia and homeostasis model assessment increased in males, suggesting a rapid change in glucose metabolism. Hypothalamic pro-opiomelanocortin mRNA levels were significantly higher in females on a HFD compared to all other groups, which may be an attempt to reduce their increased energy intake. Hypothalamic inflammation and gliosis have been implicated in the development of secondary complications of obesity; however, no indication of activation of inflammatory processes or gliosis was found in response to 1 week of HFD in the hypothalamus, hippocampus or cerebellum of these young mice. These results indicate that there are both sex and age effects in the response to poor dietary intake because peripubertal male and female mice respond differently to short-term dietary changes and this response is different from that reported in adult rodents.

No laughing matter: Latinas' high quality of conversations relate to behavioral laughter.

Latinx in the United States have greater life expectancy than other groups, in spite of their socioeconomic and psychosocial disadvantage. This phenomenon has been described as the Latinx health paradox. This investigation observed the interplay of cultural processes and social networks to shed light on this paradox. Latina (N = 26) and White-European (N = 24) mothers wore a digital recorder as they went about their daily lives. Four conversation styles were characterized from the recordings to measure the mothers' quality of their conversations (small talk and substantive conversations) within different social networks (with the father vs. other adults). As a positive indicator of well-being, laughter was assessed during the conversations. Results demonstrated that Latina mothers tend to laugh more than White-European mothers; and that this relation is mediated by substantive conversations with others. This suggests that Latinas' cultural processes afford meaningful conversations, which relates to more behavioral laughter, a process that may have positive implications on well-being.

Pediatric Eosinophilic Esophagitis: Results of the European Retrospective Pediatric Eosinophilic Esophagitis Registry (RetroPEER).

OBJECTIVES: Recommendations for diagnosing and treating eosinophilic esophagitis (EoE) are evolving; however, information on real world clinical practice is lacking. To assess the practices of pediatric gastroenterologists diagnosing and treating EoE and to identify the triggering allergens in European children. METHODS: Retrospective anonymized data were collected from 26 European pediatric gastroenterology centers in 13 countries. Inclusion criteria were: Patients diagnosis with EoE, completed investigations prescribed by the treating physician, and were on stable medical or dietary interventions. RESULTS: In total, 410 patients diagnosed between December 1999 and June 2016 were analyzed, 76.3% boys. The time from symptoms to diagnosis was 12 ±â€Š33.5 months and age at diagnosis was 8.9 ±â€Š4.75 years. The most frequent indications for endoscopy were: dysphagia (38%), gastroesophageal reflux (31.2%), bolus impaction (24.4%), and failure to thrive (10.5%). Approximately 70.3% had failed proton pump inhibitor treatment. The foods found to be causative of EoE by elimination and rechallenge were milk (42%), egg (21.5%), wheat/gluten (10.9%), and peanut (9.9%). Elimination diets were used exclusively in 154 of 410 (37.5%), topical steroids without elimination diets in 52 of 410 (12.6%), both diet and steroids in 183 of 410 (44.6%), systemic steroids in 22 of 410 (5.3%), and esophageal dilation in 7 of 410 (1.7%). Patient refusal, shortage of endoscopy time, and reluctance to perform multiple endoscopies per patient were noted as factors justifying deviation from guidelines. CONCLUSIONS: In this "real world" pediatric European cohort, milk and egg were the most common allergens triggering EoE. Although high-dose proton pump inhibitor trials have increased, attempted PPI treatment is not universal.

Effectiveness and safety of ertapenem used in hospital-at-home units: data from Spanish Outpatient Parenteral Antimicrobial Therapy Registry.

AIM: To evaluate the effectiveness and safety of ertapenem in patients hospitalized at home. PATIENTS & METHODS: Retrospective analysis of data from Spanish Outpatient Parenteral Antimicrobial Therapy (OPAT) registry. RESULTS: Data from 1428 patients (median age 70 years; 5.4% institutionalized) and 1547 infectious processes (24% self-administration) were analyzed. Clinical cure or improvement was achieved in 93.8% of cases. Rate of related readmissions was 4.2%, of clinically important complications -3.9%, and of adverse drug reactions -3.2%. High comorbidity burden, contagion in nursing home and certain types of infection were associated with worse prognosis. Self-administration was effective and safe, except in case of nursing home-acquired infections. CONCLUSION: Ertapenem OPAT was effective and safe. Caregivers in nursing homes should be better trained in OPAT-related procedures.

Neonatal Overnutrition Increases Testicular Size and Expression of Luteinizing Hormone ß-Subunit in Peripubertal Male Rats.

Proper nutrition is important for growth and development. Maturation of the reproductive axis and the timing of pubertal onset can be delayed when insufficient nutrition is available, or possibly advanced with nutritional abundance. The childhood obesity epidemic has been linked to a secular trend in advanced puberty in some populations. The increase in circulating leptin that occurs in association with obesity has been suggested to act as a signal that an adequate nutritional status exists for puberty to occur, allowing activation of central mechanisms. However, obesity-associated hyperleptinemia is linked to decreased leptin sensitivity, at least in adults. Here, we analyzed whether neonatal overnutrition modifies the response to an increase in leptin in peripubertal male rats, as previously demonstrated in females. Wistar rats were raised in litters of 4 (neonatal overnutrition) or 12 pups (controls) per dam. Leptin was administered sc (3 µg/g body weight) at postnatal day 35 and the rats killed 45 min or 2 h later. Postnatal overfeeding resulted in increased body weight and circulating leptin levels; however, we found no overweight-related changes in the mRNA levels of neuropeptides involved in metabolism or reproduction. In contrast, pituitary expression of luteinizing hormone (LH) beta-subunit was increased in overweight rats, as was testicular weight. There were no basal differences between L4 and L12 males or in their response to leptin administration in pSTAT3 levels in the hypothalamus at either 45 min or 2 h. In contrast, pJAK2 was found to be higher at 45 min in L4 compared to L12 males regardless of leptin treatment, while at 2 h it was higher in L4 leptin-treated males compared to L12 leptin-treated males, as well as L4 vehicle-treated rats. There were no changes in response to leptin administration in the expression of the neuropeptides analyzed. However, serum LH levels rose only in L4 males in response to leptin, but with no change in testosterone levels. In conclusion, the advancement in pubertal onset in males with neonatal overnutrition does not appear to be related to overt modifications in the central response to exogenous leptin during the peripubertal period.

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.

In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation.

Equality in Educational Policy and the Heritability of Educational Attainment.

Secular variation in the heritability of educational attainment are proposed to be due to the implementation of more egalitarian educational policies leading to increased equality in educational opportunities in the second part of the 20th century. The action of effect is hypothesized to be a decrease of shared environmental (e.g., family socioeconomic status or parents' education) influences on educational attainment, giving more room for genetic differences between individuals to impact on the variation of the trait. However, this hypothesis has not yet found consistent evidence. Support for this effect relies mainly on comparisons between countries adopting different educational systems or between different time periods within a country reflecting changes in general policy. Using a population-based sample of 1271 pairs of adult twins, we analyzed the effect of the introduction of a specific educational policy in Spain in 1970. The shared-environmental variance decreased, leading to an increase in heritability in the post-reform cohort (44 vs. 67%) for males. Unstandardized estimates of genetic variance were of a similar magnitude (.56 vs. .57) between cohorts, while shared environmental variance decreased from .56 to .04. Heritability remained in the same range for women (40 vs. 34%). Our results support the role of educational policy in affecting the relative weight of genetic and environmental factors on educational attainment, such that increasing equality in educational opportunities increases heritability estimates by reducing variation of non-genetic familial origin.

Extra-nodal B-cell non-Hodgkin's lymphomas of the head and neck: a study of 68 cases.

OBJECTIVES: The objectives of this study are to describe the distinctive characteristics of extra-nodal B-cell non-Hodgkin's lymphomas (BNHLs) located in the head and neck in a series of patients, to discuss patient survival, and to compare the oral versus the non-oral locations of the extra-nodal BNHLs of the head and neck. MATERIAL AND METHODS: We studied 68 patients with BNHL of the head and neck. We analyzed the clinical and survival characteristics. Additionally, we performed Kaplan-Meier and Cox regression analyses to determine the influence of the different factors on survival. RESULTS: This study included 68 non-nodal lymphomas; 30 lymphomas (31.9%) were located intraorally, with the gingiva as the most frequent location. The oral lymphomas in stages 1 and 2 showed a prevalence of 60% (18/30). The Kaplan-Meier analysis showed that the stage of disease and the oral versus non-oral extranodal lymphomas were significant prognostic factors (p<0.05). However, the multivariate Cox analysis indicated that only complete remission and oral versus non-oral location were significant prognostic factors (p<0.01). CONCLUSIONS: The gingiva was the most common location of the intraoral lymphomas. Complete remission and non-oral location were the only significant survival factors in the multivariate Cox regression analysis.

Influencia de la reserva cognitiva en la calidad de vida en sujetos con enfermedad de Alzheimer / Influence of cognitive reserve on quality of life of patients with Alzheimer’s Disease

La calidad de vida (CV) se define como la percepción personal que un individuo tiene de su situación vital. Dentro de los factores que pueden influir en la CV, se encuentra la Reserva Cognitiva (RC), que podría entenderse como la capacidad del cerebro para hacer frente al daño cerebral generado por la patología, mediante procesos cognitivos preexistentes o compensatorios. El objetivo principal de este estudio, consiste en analizar, como influye la RC en la auto-percepción subjetiva de la CV en sujetos diagnosticados de Enfermedad de Alzheimer (EA) y comprobar si existen perfiles diferenciales en función de la sintomatología depresiva y el estado cognitivo de los mismos. La muestra utilizada estaba formada por 112 sujetos que se distribuyeron en dos grupos: uno de 74 sujetos diagnosticados de EA, y otro de 38 sujetos sanos. Se ha utilizado el cuestionario SF-36 para evaluar la CV. En relación a la variable RC, destacar que los sujetos con mayor RC, puntuaron más alto en cada una de las dimensiones del SF-36. La RC podría ser una fuente de influencia en la percepción de la CV de las personas con EA, en la medida en que sus diversos componentes conducirían a la consecución de una capacidad funcional más óptima y una aceptación del estado cognitivo (AU)

Quality of life (QL) is defined as the personal perception an individual has of his or her own life situation. Among the factors that can affect QL is Cognitive Reserve (CR) which can be understood as the brain’s capacity to resist the brain damage caused by pathology through preexisting or compensatory cognitive processes. The main objective of this study is to analyze how CR affects the subjective self-perception of QL in patients diagnosed with Alzheimer’s Disease (AD) and to determine the existence of different profiles in terms of depressive symptoms and cognitive state. The sample comprised 112 individuals divided into two groups: one group with 74 patients diagnosed with AD, and the other with 38 healthy participants. The SF-36 questionnaire was used to assess QL. As regards cognitive reserve, it was found that subjects with greater CR scored higher in each of the dimensions of the SF-36. CR could be a source of influence on perception of QL in persons with AD, to the extent that its different components would lead to a more optimal functional capability and a better acceptance of one's cognitive state (AU)

Anti-Bredt N-heterocyclic carbene: an efficient ligand for the gold(I)-catalyzed hydroamination of terminal alkynes with parent hydrazine.

An anti-Bredt N-heterocyclic carbene gold(I) chloride complex was synthesized by taking advantage of the reversible insertion of the free carbene into the NH bond of hexamethyldisilazane. This precatalyst promotes the parent hydrazine hydroamination of terminal alkynes at room temperature.

Impact of inadequate empirical therapy on the mortality of patients with bloodstream infections: a propensity score-based analysis.

The impact of the adequacy of empirical therapy on outcome for patients with bloodstream infections (BSI) is key for determining whether adequate empirical coverage should be prioritized over other, more conservative approaches. Recent systematic reviews outlined the need for new studies in the field, using improved methodologies. We assessed the impact of inadequate empirical treatment on the mortality of patients with BSI in the present-day context, incorporating recent methodological recommendations. A prospective multicenter cohort including all BSI episodes in adult patients was performed in 15 hospitals in Andalucía, Spain, over a 2-month period in 2006 to 2007. The main outcome variables were 14- and 30-day mortality. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Eight hundred one episodes were included. Inadequate empirical therapy was administered in 199 (24.8%) episodes; mortality at days 14 and 30 was 18.55% and 22.6%, respectively. After controlling for age, Charlson index, Pitt score, neutropenia, source, etiology, and presentation with severe sepsis or shock, inadequate empirical treatment was associated with increased mortality at days 14 and 30 (odds ratios [ORs], 2.12 and 1.56; 95% confidence intervals [95% CI], 1.34 to 3.34 and 1.01 to 2.40, respectively). The adjusted ORs after a propensity score-based matched analysis were 3.03 and 1.70 (95% CI, 1.60 to 5.74 and 0.98 to 2.98, respectively). In conclusion, inadequate empirical therapy is independently associated with increased mortality in patients with BSI. Programs to improve the quality of empirical therapy in patients with suspicion of BSI and optimization of definitive therapy should be implemented.

The oxidative conversion of the N,S-bridged complexes [{RhLL'(µ-X)}2] to [(RhLL')3)(µ-X)2]+ (X = mt or taz): a comparison with the oxidation of N,N-bridged analogues.

The structures of [{RhLL'(µ-X)}(2)] [LL' = cod, (CO)(2), (CO)(PPh(3)) or {P(OPh)(3)}(2); X = mt or taz], prepared from [{RhLL'(µ-Cl)}(2)] and HX in the presence of NEt(3), depend on the auxiliary ligands LL'. The head-to-tail arrangement of the two N,S-bridges is accompanied by a rhodium-eclipsed conformation for the majority but the most hindered complex, [{Rh[P(OPh)(3)](2)(µ-taz)}(2)], uniquely adopts a sulfur-eclipsed structure. The least hindered complex, [{Rh(CO)(2)(µ-mt)}(2)], shows intermolecular stacking of mt rings in the solid state. The complexes [{RhLL'(µ-X)}(2)] are chemically oxidised to trinuclear cations, [(RhLL')(3)(µ-X)(2)](+), most probably via reaction of one molecule of the dimer, in the sulfur-eclipsed form, with the fragment [RhLL'](+) formed by oxidative cleavage of a second.

Relationship between level of education and breastfeeding duration depends on social context: breastfeeding trends over a 40-year period in Spain.

This article presents trends of breastfeeding in Spain from the 1960s to the end of the century, analyzing the relationship between level of education and breastfeeding duration. A sample of 666 adult women provided data about breastfeeding practices for children born between 1958 and 2002. Joinpoint regression models for breastfeeding duration for the firstborn child throughout these years show a U-shaped curve, with a sharp decrease at the beginning of the 1970s (-17.2%) and a gradual increase toward the end of the century (1.9%). However, the trend for women with primary studies shows a constant decrease throughout the whole period (-7.4%), while higher education levels relate to a positive trend from the 1970s onward (3.4%). The authors conclude that in the Spanish context, maternal level of education is not associated with breastfeeding duration in the same direction or with the same magnitude across time. Factors related to breastfeeding should be studied, taking into account social context.

Potassium S2N-heteroscorpionates: structure and iridaboratrane formation.

The potassium salts of the new S(2)N-heteroscorpionate ligand hydrobis(methimazolyl)(3,5-dimethylpyrazolyl)borate [HB(mt)(2)(pz(3,5-Me))](-) and its known analogue hydrobis(methimazolyl)(pyrazolyl)borate [HB(mt)(2)(pz)](-) (prepared from KTp' or KTp and methimazole, Hmt), and the adduct KTp·Hmt have polymeric structures in the solid state (the first a ladder and the other two chains). The iridaboratranes [IrHLL'{B(mt)(2)X}] (X = pz(3,5-Me) or pz), prepared from the heteroscorpionate anion and [{Ir(cod)(µ-Cl)}(2)] (LL' = cod), subsequent carbonylation [LL' = (CO)(2)] and then reaction with phosphine [LL' = (CO)(PR(3)), R = Ph or Cy], have a pendant pyrazolyl ring and a bicyclo-[3.3.0] cage formed by an S(2)-bound B(mt)(2) fragment. The binuclear species [(cod)HIr{µ-B(mt)(3)}IrCl(cod)], the only isolated product of the reaction of KTm with [{Ir(cod)(µ-Cl)}(2)], also has an S(2)-bound iridaboratrane unit but with the third mt ring linked to square planar iridium(I).