A high-resolution δ18O record and Mediterranean climate variability

A high-resolution, well-dated foraminiferal δ18O record from a shallow-water core drilled from the Gallipoli Terrace in the Gulf of Taranto (Ionian Sea), previously measured over the last two millennia, has been extended to cover 707 BC–1979 AD. Spectral analysis of this series, performed by Singular Spectrum Analysis (SSA) and other classical and advanced methods, strengthens the results obtained analysing the shorter δ18O profile, detecting the same highly significant oscillations of about 600 yr, 380 yr, 170 yr, 130 yr, and 11 yr, respectively explaining about 12%, 7%, 5%, 2% and 2% of the time series total variance, plus a millennial trend (18% of the variance). The comparison with the results of Multi-channel Singular Spectrum Analysis (MSSA) applied to a data set of 26 Northern Hemisphere (NH) temperature-proxy records shows that NH temperature anomalies share with our local record a long-term trend and a bicentennial cycle. These two variability modes, previously identified as temperature-driven, are the most powerful modes in the NH temperature data set. Both the long-term trends and the bicentennial oscillations, when reconstructed locally and hemispherically, show coherent phases. Also the corresponding local and hemispheric amplitudes are comparable, if changes in the precipitation-evaporation balance of the Ionian sea, presumably associated with temperature changes, are taken into account

A high-resolution δ18O record and Mediterranean climate variability

A high-resolution, well-dated foraminiferal δ¹⁸O record from a shallow-water core drilled from the Gallipoli Terrace in the Gulf of Taranto (Ionian Sea), previously measured over the last two millennia, has been extended to cover 707 BC–AD 1979. Spectral analysis of this series, performed using singular-spectrum analysis (SSA) and other classical and advanced methods, strengthens the results obtained analysing the shorter δ¹⁸O profile, detecting the same highly significant oscillations of about 600, 380, 170, 130 and 11 years, respectively explaining about 12, 7, 5, 2 and 2% of the time series total variance, plus a millennial trend (18% of the variance). The comparison with the results of multi-channel singular-spectrum analysis (MSSA) applied to a data set of 26 Northern Hemisphere (NH) temperature-proxy records shows that NH temperature anomalies share with our local record a~long-term trend and a bicentennial (170-year period) cycle. These two variability modes, previously identified as temperature-driven, are the most powerful modes in the NH temperature data set. Both the long-term trends and the bicentennial oscillations, when reconstructed locally and hemispherically, show coherent phases. Furthermore, the corresponding local and hemispheric amplitudes are comparable if changes in the precipitation–evaporation balance of the Ionian sea, presumably associated with temperature changes, are taken into account

Diagénesis de los carbonatos continentales del margen flexural de la subcuenca Sorocayense-Hilario, Argentina

Las unidades litoestratigráficas que conforman el Grupo Sorocayense y que constituyen el relleno de la subcuenca Sorocayense-Hilario representan sistemas aluviales-fluviales-lacustres con aporte volcánico significativo durante su depositación. Estas unidades corresponden a las formaciones: Cerro Colorado del Cementerio, Agua de los Pajaritos, Monina, Hilario y El Alcázar y cada una de ellas contiene niveles carbonáticos. Estos carbonatos continentales constituyen un medio útil para entender la evolución de la subcuenca a través del estudio petrográfico complementado con técnicas de catodoluminiscencia. Estos estudios han permitido entender la génesis y diagénesis carbonática e inferir qué factores principales la controlaron. Se identificaron seis microfacies: a) micrita homogénea, b) micrita bioclástica, c) dolomicrita, d) micrita laminada, e) packstone oncolítico, y f) carbonato esparítico. En tales microfacies, se identificaron seis fases de cementación y alteración: a) micritización, b) compactación mecánica, c) cementación calcítica, d) cementación esparítica, e) cementación microesparítica, y f) compactación química. Estos análisis permitieron establecer una cronología diagenética y apoyan la hipótesis de que la diagénesis fue controlada por la tectónica, con mayor impacto en las facies carbonáticas asociadas al margen flexural de la subcuenca. El principal efecto habría sido por medio de la acción paleohidrológica, lo que favoreció la migración lateral de agua meteórica a través de los fallamientos. La presencia de dolomita en algunas microfacies se vincula con la composición predominantemente montmorillonítica de los ensambles de arcillas que habría aportado el Mg. A su vez, en los carbonatos, el Mg tiende a ser fácilmente reemplazado por Mn, lo que causa incremento de la luminiscencia.The units that conform the Sorocayense Group and infill the Sorocayense-Hilario subbasin represent an alluvial-fluvial-lacustrine succession with significant volcanic supply during its deposition. They are namely the Cerro Colorado del Cementerio, Agua de los Pajaritos, Monina, Hilario and El Alcázar formations and present several carbonate levels. These continental carbonates present a means to understand basin evolution through the study of their petrography and chemical elemental composition trough cathodoluminescence techniques in order to understand their genesis and diagenesis and which main factors controlled them.Fil: Benavente, Cecilia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Matheos, Sergio Daniel. YPF - Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Barredo, Silvia. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto del Gas y del Petróleo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Abarzúa, Fernando. No especifíca;Fil: Mancuso, Adriana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentin

Diagénesis de los carbonatos continentales del margen flexural de la subcuenca Sorocayense-Hilario, Argentina

Las unidades litoestratigráficas que conforman el Grupo Sorocayense y que constituyen el relleno de la subcuenca Sorocayense-Hilario representan sistemas aluviales-fluviales-lacustres con aporte volcánico significativo durante su depositación. Estas unidades corresponden a las formaciones: Cerro Colorado del Cementerio, Agua de los Pajaritos, Monina, Hilario y El Alcázar y cada una de ellas contiene niveles carbonáticos. Estos carbonatos continentales constituyen un medio útil para entender la evolución de la subcuenca a través del estudio petrográfico complementado con técnicas de catodoluminiscencia. Estos estudios han permitido entender la génesis y diagénesis carbonática e inferir qué factores principales la controlaron. Se identificaron seis microfacies: a) micrita homogénea, b) micrita bioclástica, c) dolomicrita, d) micrita laminada, e) packstone oncolítico, y f) carbonato esparítico. En tales microfacies, se identificaron seis fases de cementación y alteración: a) micritización, b) compactación mecánica, c) cementación calcítica, d) cementación esparítica, e) cementación microesparítica, y f) compactación química. Estos análisis permitieron establecer una cronología diagenética y apoyan la hipótesis de que la diagénesis fue controlada por la tectónica, con mayor impacto en las facies carbonáticas asociadas al margen flexural de la subcuenca. El principal efecto habría sido por medio de la acción paleohidrológica, lo que favoreció la migración lateral de agua meteórica a través de los fallamientos. La presencia de dolomita en algunas microfacies se vincula con la composición predominantemente montmorillonítica de los ensambles de arcillas que habría aportado el Mg. A su vez, en los carbonatos, el Mg tiende a ser fácilmente reemplazado por Mn, lo que causa incremento de la luminiscencia.The units that conform the Sorocayense Group and infill the Sorocayense-Hilario subbasin represent an alluvial-fluvial-lacustrine succession with significant volcanic supply during its deposition. They are namely the Cerro Colorado del Cementerio, Agua de los Pajaritos, Monina, Hilario and El Alcázar formations and present several carbonate levels. These continental carbonates present a means to understand basin evolution through the study of their petrography and chemical elemental composition trough cathodoluminescence techniques in order to understand their genesis and diagenesis and which main factors controlled them.Fil: Benavente, Cecilia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Matheos, Sergio Daniel. YPF - Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Barredo, Silvia. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto del Gas y del Petróleo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Abarzúa, Fernando. No especifíca;Fil: Mancuso, Adriana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentin

Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma.

SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the transmembrane activator Smoothened (Smo), have shown the rapid development of drug resistance and tumor relapse due to novel Smo mutations. Moreover, a subset of patients did not respond to vismodegib because mutations were localized downstream of Smo. Thus, targeting downstream Hh components is now considered a preferable approach. We show here that selective inhibition of the downstream Hh effectors HDAC1 and HDAC2 robustly counteracts SHH-MB growth in mouse models. These two deacetylases are upregulated in tumor and their knockdown inhibits Hh signaling and decreases tumor growth. We demonstrate that mocetinostat (MGCD0103), a selective HDAC1/HDAC2 inhibitor, is a potent Hh inhibitor and that its effect is linked to Gli1 acetylation at K518. Of note, we demonstrate that administration of mocetinostat to mouse models of SHH-MB drastically reduces tumor growth, by reducing proliferation and increasing apoptosis of tumor cells and prolongs mouse survival rate. Collectively, these data demonstrate the preclinical efficacy of targeting the downstream HDAC1/2-Gli1 acetylation in the treatment of SHH-MB

increased mean corpuscular volume of red blood cells predicts response to metronomic capecitabine and cyclophosphamide in combination with bevacizumab

Abstract Background There is an urgent need for the identification of commonly assessable predictive factors in the treatment of patients with metastatic breast cancer. Methods During the course of a treatment including low dose metronomic oral cyclophosphamide and capecitabine plus i.v. bevacizumab (plus erlotinib in one third of the patients) for metastatic breast cancer, we observed that a relevant number of patients developed repeatedly elevated levels of mean corpuscular volume (MCV) of red blood cells without a significant fall in hemoglobin levels. We conducted a retrospective analysis on these 69 patients to evaluate if the increase in MCV could be associated to tumor response. Results During the course of treatment 42 out of 69 patients (61%) developed macrocytosis. Using Cox proportional hazards modeling that incorporated macrocytosis (MCV≥100 fl) as a time-dependent covariate, macrocytosis resulted in a halved risk of disease progression (HR 0.45; 95% CI, 0.22–0.92, p-value 0.028). In a landmark analysis limited to patients with no sign of progression after 24 weeks of treatment, median time to progression was 72 weeks (48 weeks after landmark) in patients who had developed macrocytosis, and 43 weeks (19 weeks after landmark) in patients who had not (p = 0.023). Conclusion Macrocytosis inversely related to risk of disease progression in patients treated with metronomic capecitabine plus cyclophosphamide and bevacizumab for metastatic breast cancer. This finding may be explained through thymidylate synthase inhibition by capecitabine. Whether bevacizumab has a role in determining macrocytosis, similarly to what happens with sunitinib, has to be further investigated. If other studies will confirm our findings, macrocytosis might be used as an early marker of response during metronomic treatment with capecitabine and cyclophosphamide with or without bevacizumab

Clostridioides difficile Infection in an Italian Tertiary Care University Hospital: A Retrospective Analysis

Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality, mostly in frail patients. Notification is not mandatory in Italy, and data on incidence, risk of death, and recurrence are lacking. The purpose of this study was to determine CDI incidence and risk factors for mortality and recurrence. The "ICD-9 00845" code in hospital-standardized discharged forms (H-SDF) and microbiology datasets were used to retrieve CDI cases at Policlinico Hospital, Palermo between 2013 and 2022. Incidence, ward distribution, recurrence rate, mortality, and coding rate were considered. The risk of death and recurrence was predicted through multivariable analysis. There were 275 CDIs, 75% hospital-acquired, the median time between admission and diagnosis was 13 days, and the median stay was 21 days. Incidence increased from 0.3 to 5.6% (an 18.7-fold increase) throughout the decade. Only 48.1% of cases were coded in H-SDF. The rate of severe/severe-complicated cases increased 1.9 times. Fidaxomicin was used in 17.1% and 24.7% of cases overall and since 2019. Overall and attributable mortalities were 11.3% and 4.7%, respectively. Median time between diagnosis and death was 11 days, and recurrence rate was 4%. Bezlotoxumab was administered in 64% of recurrences. Multivariable analysis revealed that only hemodialysis was associated with mortality. No statistically significant association in predicting recurrence risk emerged. We advocate for CDI notification to become mandatory and recommend coding CDI diagnosis in H-SDF to aid in infection rate monitoring. Maximum attention should be paid to preventing people on hemodialysis from getting CDI

Determinación de la angulación del conducto palatino posterior en cráneos humanos desdentados adultos

El conducto palatino posterior (CCP) comunica la fosa pterigomaxilar con la bóveda palatina con una dirección oblicua de atrás hacia adelante, de arriba hacia abajo y de afuera hacia adentro, dando paso a los elementos anatómicos que proveen inervación e irrigación al sector posterior del techo de la cavidad bucal. Figun y Garino establecieron parámetros para el acceso al CPP, tomando como referencia el eje del conducto en relación con el plano oclusal, en una angulación de 60 a 70 grados, no encontrándose en la bibliografía actual, datos de referencia para maxilares desdentados. Los objetivos fueron: a) determinar la angulación del CPP en cráneos desdentados; b) establecer parámetros de ubicación del orificio inferior del CPP; c) determinar si existe variabilidad significativa en relación a los maxilares dentados.Resumen publicado en Libro de resúmenes. Producción en Investigación, Docencia, Gestión, Extensión. Universidad Nacional de Rosario, Rosario, 2009.Facultad de Odontologí

Relationship between gender differences and clinical outcome in patients with the antiphospholipid syndrome

Antiphospholipid syndrome (APS), characterized by artherial and/or venous thrombosis, pregnancy morbidity and "antiphospholipid" antibodies (aPLs), is more common in women than in men, with a female to male ratio of about 3.5:1. Only few studies have investigated the clinical differences between male and female patients with APS. Therefore, this study was aimed to analyze the differences of clinical manifestations and laboratory tests, at diagnosis, between female and male APS patients and the clinical outcome. We enrolled 191 consecutive APS patients (125 with primary APS, PAPS, and 66 with secondary APS, SAPS) with a female predominant ratio of approximately 3:1 (142 vs 49). The prevalence of PAPS was higher in males than females (p<0.001). The analysis of aPL profile revealed that high IgM anti-cardiolipin (aCL) and high-medium IgG aCL titers were more frequent in males. In thrombotic APS peripheral arterial thrombosis was more common in male than female patients (p=0.049), as well as myocardial infarction (p=0.031). Multivariate analysis to correct for cardiovascular risk factors, high titer of aPLs and triple positivity for aPLs, revealed that the odds ratio for myocardial infarction in male was 3.77. Thus, APS may be considered as a disease in which serological (IgM titer) and clinical profiles are influenced by gender