Is serum C-terminal telopeptide cross-link of type 1 collagen a reliable parameter for predicting the risk of medication-related osteonecrosis of the jaws? A systematic review and meta-analysis of diagnostic test accuracy

Clinical Oral Investigations - To determine the usefulness of Serum C-terminal telopeptide cross-link of type 1 collagen (sCTX) as a preoperative marker for predicting the risk of developing...     

Gender assessment of job stress in healthcare workers. Implications for practice

Background:Work-related stress (WRS) in the healthcare sector is a major issue for both workers and organizations. To date, no consensus exists regarding differences in gender susceptibility to WRS in healthcare workers (HCWs).Objectives:The purpose of this study was to analyze how male and female HCWs employed in emergency departments experienced WRS.Methods:A cross-sectional study was conducted regarding the perception of WRS in registered nurses employed in emergency departments. The Italian version of the Job Content Questionnaire and the Rapid Stress Assessment scale were administrated to 710 registered nurses.Results:The WRS assessment showed that significantly more females than males were in a situation of isostrain (18.5% vs 9.8% p<0,05). In females, low social support was associated with high levels of job strain (18,5% vs 4,4% p<0,05).Conclusion:This study reflects the need for a gender-specific approach in the evaluation of WRS in the healthcare sector, and is consistent with literature that evidenced gender differences in the perception of WRS. Lack of social support proved to be a determinant of WRS in female HCWs. Organizational interventions aimed at providing a more suitable workgroup design are required in order to minimize WRS in female HCWs.Key words: Stress, risk assessment, nurses, emergency department, social support     

The risk of fractures,acute myocardial infarction,atrial fibrillation and ventricular arrhythmia in geriatric patients exposed to promethazine

ABSTRACT

Objectives: This study aimed to compare the risk of fractures, acute myocardial infarction, atrial fibrillation, and ventricular arrhythmia among Danish citizens aged ≥ 65 which were new users of promethazine or domperidone, triazolam, loratadine, and betahistine. Secondly, the study aimed to perform a risk stratification to identify the most relevant predictors for the study outcomes.

Methods: The study period was 01/01/2015 to 31/12/2016. The data sources were the Danish registers. Each patient was followed for 90 days. A logistic regression model was used to compute the unadjusted and adjusted odds ratios (OR), and a conditional inference tree was used to identify the most relevant predictors for the study outcomes.

Results: Promethazine had a higher risk of hospitalization for atrial fibrillation than loratadine and betahistine (OR 1.58; 95% CI 1.07–2.63 and OR 3.22; 95% CI 1.69–7.14, respectively). For fractures, acute myocardial infarction, and ventricular arrhythmia hospitalizations, no statistically significant differences were found among drugs under investigation. The medical history of cardiac arrhythmia (OR 4.14; 95% CI 2.94–5.78, p < 0.0001) was the most relevant predictor for atrial fibrillation hospitalizations.

Conclusion: This study found an increased risk of atrial fibrillation hospitalization among promethazine users, and the risk was higher among patients with prior cardiac arrhythmia.     

The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury

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Measurement errors in control risk regression: A comparison of correction techniques

Control risk regression is a diffuse approach for meta-analysis about the effectiveness of a treatment, relating the measure of risk with which the outcome occurs in the treated group to that in the control group. The severity of illness is a source of between-study heterogeneity that can be difficult to measure. It can be approximated by the rate of events in the control group. Since the estimate is a surrogate for the underlying risk, it is prone to measurement error. Correction methods are necessary to provide reliable inference. This article illustrates the extent of measurement error effects under different scenarios, including departures from the classical normality assumption for the control risk distribution. The performance of different measurement error corrections is examined. Attention will be paid to likelihood-based structural methods assuming a distribution for the control risk measure and to functional methods avoiding the assumption, namely, a simulation-based method and two score function methods. Advantages and limits of the approaches are evaluated through simulation. In case of large heterogeneity, structural approaches are preferable to score methods, while score methods perform better for small heterogeneity and small sample size. The simulation-based approach has a satisfactory behavior whichever the examined scenario, with no convergence issues. The methods are applied to a meta-analysis about the association between diabetes and risk of Parkinson disease. The study intends to make researchers aware of the measurement error problem occurring in control risk regression and lead them to the use of appropriate correction techniques to prevent fallacious conclusions.     

Sealing materials for post-extraction site: a systematic review and network meta-analysis

Clinical Oral Investigations - By means of a systematic review and network meta-analysis, this study aims to answer the following questions: (a) does the placement of a biomaterial over an...     

A specific basal body linker protein provides the connection function for basal body inheritance in trypanosomes

Centrioles and basal bodies (CBBs) are found in physically linked pairs, and in mammalian cells intercentriole connections (G1–G2 tether and S–M linker) regulate centriole duplication and function. In trypanosomes BBs are not associated with the spindle and function in flagellum/cilia nucleation with an additional role in mitochondrial genome (kinetoplast DNA [kDNA]) segregation. Here, we describe BBLP, a BB/pro-BB (pBB) linker protein in Trypanosoma brucei predicted to be a large coiled-coil protein conserved in the kinetoplastida. Colocalization with the centriole marker SAS6 showed that BBLP localizes between the BB/pBB pair, throughout the cell cycle, with a stronger signal in the old flagellum BB/pBB pair. Importantly, RNA interference (RNAi) depletion of BBLP leads to a conspicuous splitting of the BB/pBB pair associated only with the new flagellum. BBLP RNAi is lethal in the bloodstream form of the parasite and perturbs mitochondrial kDNA inheritance. Immunogold labeling confirmed that BBLP is localized to a cytoskeletal component of the BB/pBB linker, and tagged protein induction showed that BBLP is incorporated de novo in both new and old flagella BB pairs of dividing cells. We show that the two aspects of CBB disengagement—loss of orthogonal orientation and ability to separate and move apart—are consistent but separable events in evolutionarily diverse cells and we provide a unifying model explaining centriole/BB linkage differences between such cells.

Centrioles and basal bodies (CBBs) are microtubule structures found in many major eukaryotic groups; where present, they are vital for cilia and flagella formation (1) and play important roles in cell division and developmental events. CBB assembly pathways share a common set of key regulatory proteins, indicating that these structures are variations of a common pattern (2).Faithful centriole duplication and segregation in proliferative eukaryotic cells is a well-orchestrated process (albeit with variations of pattern in different cell types across evolution) under strict temporal and spatial control and usually involve “templating”’ from a previously formed CBB (3). Two particular conceptual themes, a linker and a tether (4), have been rehearsed to explain number control, inheritance patterns, and centriole properties in mammalian cells. In interphase G1, each cell has a single centriole pair, and the duplication cycle starts in the G1/S transition and is very well described in its temporal sequence (5). During the centriole duplication and segregation cycle, centrioles are connected by the two different types of structures—the “tether” and “linker”—whose presence and disassembly at specific stages of the cell cycle are important for faithful cell-cycle progression (4, 6). The tether connects the proximal ends of the two parental centrioles from G1 to late G2 and appears important in providing a single cytoplasmic microtubule organizing center in organisms with a centrosomal architecture. Some significant studies have revealed essential components of the tether, for example CNAP and Rootletin (7, 8), Cep68 (9), LRRC45 (10), Centlein (11), and CCDC102B (12). The linker forms during S phase and connects the proximal end of the nascent procentriole to the side of the parental centriole in the orthogonal orientation. In the centriole cycle this link is described as being removed in late M phase when centriole disengagement occurs. There are two iconic features of centriole disengagement: a reorientation resulting in the loss of the original orthogonal orientation of the two paired centrioles and, second, an ability to transiently move apart (4). There is an expectation that there will be molecular components specific to each structure, but other components of the centrosome as a wider concept might play a role in both structures (4). The literature has seen a variety of terms used to describe these conceptual structures: centriole linker, centrosome linker, and so on. Here, for clarity in discussing cross-evolutionary fundamental concepts we will use the simple terms “tether” and “linker” as defined by Nigg and Stearns (4).Current knowledge on the composition of the linker is limited, but studies in Drosophila suggest that the SAS6–ANA2 complex may play a role in centriole engagement (13). Interestingly, linker cleavage in disengagement in human cells requires the activity of the polo-like kinases and of separase, the protease responsible for sister chromatid separation (14, 15).Many eukaryotic cells do not exhibit a centrosomally organized cytoplasm—particularly those that proliferate with assembled flagella or cilia. Although essential for cilia/flagella assembly, in such systems CBBs are often not directly involved in mitotic spindle architecture since mitosis is closed (i.e., without nuclear envelope disassembly), and anaphase and CBB separation are not concurrent. Further, in systems such as trypanosomes (16) and Leishmania (17) CBBs perform a central role in the segregation of the single mitochondrial DNA network (the kinetoplast) (18). Cell division in these organisms, where microtubule organizing centers are dispersed and do not cluster into a centrosome, involves the coordinated duplication and segregation of the nucleus (N) and the kinetoplast (K) (16). Trypanosome cells in G1 have a “1K1N” configuration, characterized by the presence of a single nucleus and a single kinetoplast, physically associated with a BB pair containing a mature BB, which subtends the flagellar axoneme, and a probasal body (pBB). At the start of S phase the pBB matures and elongates forming the new flagellum, and a new pBB forms next to each mature BB (19). The kinetoplast is divided during S/G2 (19, 20) via movement apart of the BB pairs, resulting in a characteristic “2K1N” cell, with two kinetoplasts and one nucleus. The intranuclear mitotic spindle then forms and mitosis gives rise to a cell with a “2K2N” configuration with widely separated BB pairs and associated new and old flagella. Subsequently, a mainly longitudinal cleavage furrow separates the nascent cell daughters (19).In this study, we describe the BB linker protein (BBLP) that localizes between the BB and the pBB throughout the cell cycle. BBLP is a critical component of the linker connection between the BB and pBB, marking its initial construction at S phase and its modulation throughout that and subsequent cell cycles. This functional linker connection is compromised when RNA interference (RNAi) ablation of BBLP expression is induced and, in such knockdowns, the newly matured BB (subtending the new flagellum) becomes detached from its newly formed pBB. BBLP represents an initial insight into components that provide a cell-cycle-modulated connection between a paired mature and an immature CBB. We have analyzed our results in the light of the linker concept in mammalian cells and show that the two aspects of CBB disengagement—loss of orthogonal orientation and ability to separate and move apart—are consistent but separable events in evolutionarily diverse cells. Further, we provide a unifying model explaining linkage differences between the two distinct centriole/BB pairs in proliferating eukaryotic cells.     

Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases

Background

In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response.