Dental Caries Occurrence in Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis

Objective: The present review aimed to systematically evaluate the occurrence of caries in patients with inflammatory bowel disease (IBD), either Crohn's disease (CD) or ulcerative colitis (UC), compared to healthy controls. Materials and Methods: MEDLINE (PubMed), Embase, Google Scholar, LILACS, and Cochrane Library electronic databases were screened. Caries experience was measured through the Decayed, Missing, Filled Teeth (DMFT) index. The weighted mean difference (WMD) with 95% confidence interval was calculated between IBD patients and healthy controls. Results: Six studies were selected for the inclusion in the systematic review, 5 of which were also included in the quantitative synthesis of data. The WMD in the DMFT index between IBD and healthy subjects was 3.04 (1.52, 4.56) (p = 0.10). Subgroup analysis showed no difference (p = 0.31) between CD (2.52 [0.54, 4.49]) and UC (4.01 [1.52, 4.56]) subjects. Conclusions: There is a remarkably higher past and present occurrence of dental caries in subjects with IBD than healthy controls. This result should encourage clinicians to include oral health preventive programs in the overall treatment plan of IBD patients

RAPHAEL: recognition, periodicity and insertion assignment of solenoid protein structures.

Abstract Motivation: Repeat proteins form a distinct class of structures where folding is greatly simplified. Several classes have been defined, with solenoid repeats of periodicity between ca. 5 and 40 being the most challenging to detect. Such proteins evolve quickly and their periodicity may be rapidly hidden at sequence level. From a structural point of view, finding solenoids may be complicated by the presence of insertions or multiple domains. To the best of our knowledge, no automated methods are available to characterize solenoid repeats from structure. Results: Here we introduce RAPHAEL, a novel method for the detection of solenoids in protein structures. It reliably solves three problems of increasing difficulty: (1) recognition of solenoid domains, (2) determination of their periodicity and (3) assignment of insertions. RAPHAEL uses a geometric approach mimicking manual classification, producing several numeric parameters that are optimized for maximum performance. The resulting method is very accurate, with 89.5% of solenoid proteins and 97.2% of non-solenoid proteins correctly classified. RAPHAEL periodicities have a Spearman correlation coefficient of 0.877 against the manually established ones. A baseline algorithm for insertion detection in identified solenoids has a Q2 value of 79.8%, suggesting room for further improvement. RAPHAEL finds 1931 highly confident repeat structures not previously annotated as solenoids in the Protein Data Bank records. Availability: The RAPHAEL web server is available with additional data at http://protein.bio.unipd.it/raphael/ Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

Características geoquímicas de las cuñas de hielo en Puerto Deseado (Santa Cruz, Argentina): implicancias paleoambientales y cronológicas

Ground wedge structures of cryogenic origin are common in the Quaternary sediments along the coast of the Patagonia, and their formation is related to climatic cold events experienced by this area in the Late Quaternary. The infilling sediments of two wedges generations were analyzed in the area of Puerto Deseado. Bulk chemistry (major elements), X-ray diffraction (XRD), morphoscopic observations with Scanning Electronic Microscope (SEM) and chemical analyses of volcanic glass shards were undertaken to provide indications about infilling sediment provenience, along with chronological constraint for wedge formation. Bulk chemistry and XRD patterns indicate a significant SiO2- enriched composition of the sediment infilling compared to the most of the loess deposits of the North Argentina and the present day dust originated in Patagonia. This was interpreted as due to the nature of the bedrock present over the Deseado Massif. SEM morphoscopic characteristics of glass shards evidence typical aeolian reworking features, with impact structures and indented edges of the volcanic fragments. Chemical analyses of the glass shards indicate that they were probably generated by the H0 eruption (17,300-17,400 cal yr BP) of the Hudson volcano. Volcanological data indicate that H0 eruption dispersed toward NE, but volcanic glasses were available for reworking due to a WNW component in the western wind direction. Over the Deseado Massif structural high the glass shards mixed with sediments enriched in SiO2, and were eventually deflated further to SE reaching the present coastal area and infilling the frost cracks. The age of the glass shards (17,300-17,400 cal yr BP) and that of the sandy layer affected by cryogenic structures (14,670±750 yr BP) well constrain to the Late Glacial both wedge generations.Las cuñas de hielo son estructuras comunes en sedimentos cuaternarios a lo largo de la costa patagónica, y su formación está relacionada con eventos climáticos fríos experimentados en esta área en el Cuaternario Tardío. Se analizaron sedimentos que rellenan dos generaciones de cuñas de hielo en la zona de Puerto Deseado. Análisis químicos de elementos mayores, difractometría de rayos X (DRX), observaciones con microscopio electrónico de barrido (SEM) y análisis químico de fragmentos de vidrio volcánico contenidos en el sedimento que rellena las cuñas proporcionaron información sobre la precedencia del relleno, además de inferir antecedentes cronológicos sobre su formación. La composición química del sedimento y la difracción de rayos X indican una composición enriquecida en SiO2 en comparación con la mayoría de los depósitos de loess del norte de Argentina y el polvo actual originado en la Patagonia. Esto fue interpretado como producto de la influencia de las rocas que constituyen el macizo del Deseado. Las características morfológicas de los fragmentos de vidrio evidencian rasgos típicos de retrabajo eólico, con presencia de estructuras de impacto y bordes dentados. Los análisis químicos de los fragmentos de vidrio son compatibles con un origen en la erupción H0 (17.300-17.400 cal yr BP) del volcán Hudson. Datos volcanológicos indican que la erupción H0 originó una pluma de dispersión hacia el NE. El material volcánico dispersado por esta erupción quedó disponible para ser retrabajado por una componente WNW de los vientos del W dominantes en la zona. Sobre el macizo del Deseado, los fragmentos de vidrio se mezclaron con sedimentos ricos en SiO2 y fueron adicionalmente, enriquecidos en este elemento hasta alcanzar el área de costa actual, rellenando las cuñas de hielo. La edad de los fragmentos de vidrio (17.300-17.400 cal yr BP) y de la capa arenosa afectada por las estructuras criogénicas (14.670±750 años BP) limitan al glacial tardío la formación de ambas generaciones de cuñas.Centro de Estudios Integrales de la Dinámica Exógen

Increased Serum Beta-Secretase 1 Activity is an Early Marker of Alzheimer's Disease

Background: Beta-site APP cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in amyloid-beta (A beta) plaques formation. BACE1 activity is increased in brains of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and plasma levels of BACE1 appears to reflect those in the brains.Objective: In this work, we investigated the role of serum BACE1 activity as biomarker for AD, estimating the diagnostic accuracy of the assay and assessing the correlation of BACE1 activity with levels of A beta(1-40), A beta(1-42), and A beta(40/42) ratio in serum, known biomarkers of brain amyloidosis.Methods: Serum BACE1 activity and levels of A beta(1-40), A beta(1-42), were assessed in 31 AD, 28 MCI, diagnosed as AD at follow-up (MCI-AD), and 30 controls. The BACE1 analysis was performed with a luciferase assay, where interpolation of relative fluorescence units with a standard curve of concentration reveals BACE1 activity. Serum levels of A beta(1-40), A beta(1-42) were measured with the ultrasensitive Single Molecule Array technology.Results: BACE1 was increased (higher than 60%) in AD and MCI-AD: a cut-off of 11.04 kU/L discriminated patients with high sensitivity (98.31%) and specificity (100%). Diagnostic accuracy was higher for BACE1 than A beta(40/42) ratio. High BACE1 levels were associated with worse cognitive performance and earlier disease onset, which was anticipated by 8 years in patients with BACE1 values above the median value (> 16.67 kU/L).Conclusion: Our results provide new evidence supporting serum/plasma BACE1 activity as an early biomarker of AD

MEK1/2 regulate normal BCR and ABL1 tumor-suppressor functions to dictate ATO response in TKI-resistant Ph+ leukemia

Resistance to tyrosine kinase inhibitors (TKIs) remains a clinical challenge in Ph-positive variants of chronic myeloid leukemia. We provide mechanistic insights into a previously undisclosed MEK1/2/BCR::ABL1/BCR/ABL1-driven signaling loop that may determine the efficacy of arsenic trioxide (ATO) in TKI-resistant leukemic patients. We find that activated MEK1/2 assemble into a pentameric complex with BCR::ABL1, BCR and ABL1 to induce phosphorylation of BCR and BCR::ABL1 at Tyr360 and Tyr177, and ABL1, at Thr735 and Tyr412 residues thus provoking loss of BCR's tumor-suppression functions, enhanced oncogenic activity of BCR::ABL1, cytoplasmic retention of ABL1 and consequently drug resistance. Coherently, pharmacological blockade of MEK1/2 induces dissociation of the pentameric MEK1/2/BCR::ABL1/BCR/ABL1 complex and causes a concurrent BCRY360/Y177, BCR::ABL1Y360/Y177 and cytoplasmic ABL1Y412/T735 dephosphorylation thereby provoking the rescue of the BCR's anti-oncogenic activities, nuclear accumulation of ABL1 with tumor-suppressive functions and consequently, growth inhibition of the leukemic cells and an ATO sensitization via BCR-MYC and ABL1-p73 signaling axes activation. Additionally, the allosteric activation of nuclear ABL1 was consistently found to enhance the anti-leukemic effects of the MEK1/2 inhibitor Mirdametinib, which when combined with ATO, significantly prolonged the survival of mice bearing BCR::ABL1-T315I-induced leukemia. These findings highlight the therapeutic potential of MEK1/2-inhibitors/ATO combination for the treatment of TKI-resistant leukemia

Risk factors for atrial fibrillation in dogs with dilated cardiomyopathy

IntroductionAtrial fibrillation secondary to dilated cardiomyopathy (DCM) frequently affects large-breed dogs. The aim of the present study was to identify risk factors for the development of atrial fibrillation in dogs of different breeds with an echocardiographic diagnosis of DCM.MethodsIn this multicenter retrospective study, we searched the electronic databases of five cardiology referral centers for dogs with an echocardiographic diagnosis of DCM. A comparison of clinical and echocardiographic variables was performed between dogs developing atrial fibrillation and those not developing atrial fibrillation and the ability to distinguish between these two groups of dogs was evaluated by receiver operating characteristic curve analysis. Univariate and multivariable logistic regression analysis estimated the odds ratio (OR) with 95% confidence interval (CI) of developing atrial fibrillation.ResultsWe included 89 client-owned dogs with occult and overt echocardiographic DCM. Of these, 39 dogs (43.8%) had atrial fibrillation, 29 dogs (32.6%) maintained a sinus rhythm, and 21 dogs (23.6%) showed other cardiac arrhythmias. Left atrial diameter had high accuracy (area under the curve = 0.816, 95% CI = 0.719–0.890) to predict the development of atrial fibrillation at the cut-off of >4.66 cm. After multivariable stepwise logistic regression analysis, only increased left atrial diameter (OR = 3.58, 95% CI = 1.87–6.87; p < 0.001) and presence of right atrial enlargement (OR = 4.02, 95% CI = 1.35–11.97; p = 0.013) were significant predictors of atrial fibrillation development.DiscussionAtrial fibrillation is a common complication of DCM in the dog and is significantly associated with increased absolute left atrial diameter and right atrial enlargement

Design and advancement status of the Beam Expander Testing X-ray facility (BEaTriX)

The BEaTriX (Beam Expander Testing X-ray facility) project is an X-ray apparatus under construction at INAF/OAB to generate a broad (200́60 mm2), uniform and low-divergent X-ray beam within a small lab (6́15 m2). BEaTriX will consist of an X-ray source in the focus a grazing incidence paraboloidal mirror to obtain a parallel beam, followed by a crystal monochromation system and by an asymmetrically-cut diffracting crystal to perform the beam expansion to the desired size. Once completed, BEaTriX will be used to directly perform the quality control of focusing modules of large X-ray optics such as those for the ATHENA X-ray observatory, based on either Silicon Pore Optics (baseline) or Slumped Glass Optics (alternative), and will thereby enable a direct quality control of angular resolution and effective area on a number of mirror modules in a short time, in full X-ray illumination and without being affected by the finite distance of the X-ray source. However, since the individual mirror modules for ATHENA will have an optical quality of 3-4 arcsec HEW or better, BEaTriX is required to produce a broad beam with divergence below 1-2 arcsec, and sufficient flux to quickly characterize the PSF of the module without being significantly affected by statistical uncertainties. Therefore, the optical components of BEaTriX have to be selected and/or manufactured with excellent optical properties in order to guarantee the final performance of the system. In this paper we report the final design of the facility and a detailed performance simulation

DICER1 Syndrome: A Multicenter Surgical Experience and Systematic Review

DICER1 syndrome is a rare genetic disorder that predisposes patients to the development of malignant and non-malignant diseases. Presently, DICER1 syndrome diagnosis still occurs late, usually following surgical operations, affecting patients' outcomes, especially for further neoplasms, which are entailed in this syndrome. For this reason, herein we present a multicenter report of DICER1 syndrome, with the prospective aim of enhancing post-surgical surveillance. A cohort of seven patients was collected among the surgical registries of Pediatric Surgery at the University of Pisa with the General and Oncologic Surgery of Federico II, University of Naples, and the Pediatric Surgery, Regina Margherita Hospital, University of Turin. In each case, the following data were analyzed: sex, age at diagnosis, age at first surgery, clinical features, familial, genetic investigations, and follow-up. A comprehensive literature review of DICER1 cases, including case reports and multicenter studies published from 1996 to June 2022, was performed. Eventually, the retrieved data from the literature were compared with the data emerging from our cohort of patients

Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia

INTRODUCTION: Casirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm. METHODS: This is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and β-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality. RESULTS: A total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data. CONCLUSION: The mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions