Zarit burden interview among caregivers of community-dwelling older adults in a caribbean setting (Jamaica): Reliability and factor structure

The Zarit Burden Interview has been the most popularly used tool for measuring caregiver burden and with the 60 years and over population in Jamaica and developing countries expected to increase, caregiver burden and its assessment assume increased importance. Establishing the reliability and underlying factor structure of instruments such as the ZBI is critical. This study sought to determine the reliability of the Zarit Burden Interview and to assess its underlying factor structure. The ZBI was administered to 180 caregivers of community dwelling older persons in Jamaica in a nationally representative sample across four geographic health regions in 2016. The factor structure was identified using exploratory factor analysis (EFA) with Varimax rotation. Cronbach's alpha was used to assess internal consistency/reliability of the instrument. The internal consistency/reliability of the ZBI instrument was high (Cronbach's α = 0.859) and the corrected item-total correlations ranged from 0.134 to 0.730. The ZBI mean score was found to be 16.92 ± 12.04. EFA produced a six-factor model comprised of 19 items which explained 48.97% of total variance, and was subsequently reduced to four (37.27% of total variance) via the use of parallel analysis and scrutiny of confidence intervals. The four factors identified were ‘personal strain’, ‘social relations disruption’, ‘resource strain/imbalance’ and ‘role intensity’. The ZBI-22 tool is a reliable instrument for evaluating caregiver burden among community dwelling older persons in Jamaica. A four factor model has emerged providing greater insights on the underlying constructs of the ZBI, the most widely used caregiver burden assessment tool.     

A comparison of the in vitro and in vivo activities of IgG and F(ab')2 fragments of a mixture of three monoclonal anti-Her-2 antibodies.

PURPOSE: We have demonstrated previously that a mixture of three anti-Her-2 monoclonal antibodies (MAbs) that bind to different epitopes on the extracellular domain of Her-2 expressed on a human breast cancer cell line has more potent antitumor activity than the individual MAbs both in vitro and in xenografted severe combined immunodeficient mice. Because the activity of Herceptin is Fc dependent, we determined whether this would also be the case when a mixture of these three anti-Her-2 MAbs was used. EXPERIMENTAL DESIGN: IgG and highly purified F(ab')(2) fragments of the anti-Her-2 MAbs and Herceptin were prepared and evaluated for their ability to induce cell death, inhibit vascular endothelial growth factor secretion, and mediate antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity in vitro. They were also compared for their abilities to induce regression of large BT474 tumors in severe combined immunodeficient mice. RESULTS: All of the F(ab')(2) fragments were >95% pure and, as expected, did not mediate antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity in vitro. The in vitro antiproliferative and proapoptotic effects of the IgGs and F(ab')(2) fragments were similar. In contrast, the IgGs had significant antitumor activity in vivo, whereas their F(ab')(2) fragments were only marginally effective even at 5-fold higher doses to offset their shorter half-lives. CONCLUSIONS: These results confirm the importance of the Fc portion of Herceptin for optimal in vivo activity and demonstrate that even a mixture of three anti-Her-2 MAbs that are highly effective at inducing cell death in vitro requires Fc-mediated effector function for optimal in vivo activity.     

The challenges of androgen insensitivity syndrome

Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic syndrome that occurs as result of an androgen receptor mutation; it affects the normal masculinization process in chromosomal male patients. More than 900 androgen receptor mutations that can lead to AIS have been identified. The complete androgen insensitivity is characterized by a total lack of response to androgens, usually in patients with 46XY karyotype but with feminine phenotype. Primary amenorrhoea and inguinal swellings in female patients are the main signs that could raise suspicion for this syndrome. Patients with partial androgen insensitivity have ambiguous genitalia at birth and gynecomastia during puberty, whereas those with mild androgen insensitivity present a normal male phenotype but altered spermatogenesis during adulthood and pubertal gynecomastia. The diagnosis of AIS often proves to be a challenge; its management is complex and requires a multidisciplinary approach to meet decision-making challenges in sex assignment, fertility and timing of gonadectomy, psychological outcomes and genetic counselling.     

Metallic and Metal Oxides Nanoparticles for Sensing Food Pathogens—An Overview of Recent Findings and Future Prospects

Nowadays, special importance is given to quality control and food safety. Food quality currently creates significant problems for the industry and implicitly for consumers and society. The effects materialize in economic losses, alterations of the quality and organoleptic properties of the commercial products, and, last but not least, they constitute risk factors for the consumer’s health. In this context, the development of analytical systems for the rapid determination of the sanitary quality of food products by detecting possible pathogenic microorganisms (such as Escherichia coli or Salmonella due to the important digestive disorders that they can cause in many consumers) is of major importance. Using efficient and environmentally friendly detection systems for identification of various pathogens that modify food matrices and turn them into food waste faster will also improve agri-food quality throughout the food chain. This paper reviews the use of metal nanoparticles used to obtain bio nanosensors for the purpose mentioned above. Metallic nanoparticles (Au, Ag, etc.) and their oxides can be synthesized by several methods, such as chemical, physical, physico-chemical, and biological, each bringing advantages and disadvantages in their use for developing nanosensors. In the “green chemistry” approach, a particular importance is given to the metal nanoparticles obtained by phytosynthesis. This method can lead to the development of good quality nanoparticles, at the same time being able to use secondary metabolites from vegetal wastes, as such providing a circular economy character. Considering these aspects, the use of phytosynthesized nanoparticles in other biosensing applications is also presented as a glimpse of their potential, which should be further explored.     

Comparison of Patient Characteristics and Outcomes of Contralateral Prophylactic Mastectomy and Unilateral Total Mastectomy in Breast Cancer Patients

Background

There has been an increasing trend toward contralateral prophylactic mastectomy (CPM) in the management of breast cancer (BCa). This study??s objective was to compare clinicopathologic characteristics of BCa patients who elected CPM to those who elected unilateral total mastectomy (UTM) and to determine whether CPM improved survival.

Methods

Comparison was performed on 355 patients with stage 0?CIII BCa matched by age and stage who underwent mastectomy from 1995 to 2008: 177 patients had CPM; 178 patients had UTM. Clinicopathological characteristics and survival outcomes were analyzed.

Results

Women who underwent preoperative MRI were twice as likely to have CPM (40.9 vs. 19.7%, P?P?=?0.001; 64.3 vs. 41.4%, P?P?=?0.04, respectively). CPM patients elected nipple preservation (26 vs. 5.2%, P?P?P?=?0.01). CPM identified occult BCa in 11 patients (6.6%), and three UTM patients (1.7%) developed contralateral BCa. With median follow-up of 61?months, by univariable/multivariable analyses, CPM did not improve overall, disease-free, or distant metastases-free survival.

Conclusion

Factors that may influence choice of CPM included preoperative MRI, history of prior breast biopsies, immediate reconstruction, nipple preservation, family history, and BRCA status. Those who chose CPM did not have improved survival.     

Antibiotic prophylaxis in orthopedic prosthetic surgery

The problem of prophylaxis in orthopedic implant surgery will become increasingly important and complex as the population ages and requires more arthroplasty procedures, and the prevalence of antimicrobial-resistant bacteria meanwhile also continues to rise. Energy spent preventing prosthetic joint infection is more effective than that expended in treating the infection of a prosthetic joint, once established. Preventive measures encompass a wide array of variables related to host response, wound environment, and microorganisms. Prophylaxis should address these areas in the preoperative, intraoperative, and postoperative periods. Antimicrobial prophylaxis remains the single most effective method of reducing the prevalence of infection after total joint arthroplasty. In the postoperative period, prophylaxis aims to protect the prosthetic joint against hematogenous seeding from oral, urologic, skin, or gastrointestinal sources. Currently, dental and urologic advisory statements provide recommendations for antimicrobial prophylaxis for high-risk patients with total joint arthroplasty undergoing high-risk procedures. Close collaboration between the orthopedic surgeon, urologist, or dentist and the infectious disease specialist is crucial for providing recommendations regarding prophylaxis in special circumstances. In these particular circumstances, individual decisions should be made based on clinical judgment.     

The Use of Imputed Sibling Genotypes in Sibship-Based Association Analysis: On Modeling Alternatives, Power and Model Misspecification

When phenotypic, but no genotypic data are available for relatives of participants in genetic association studies, previous research has shown that family-based imputed genotypes can boost the statistical power when included in such studies. Here, using simulations, we compared the performance of two statistical approaches suitable to model imputed genotype data: the mixture approach, which involves the full distribution of the imputed genotypes and the dosage approach, where the mean of the conditional distribution features as the imputed genotype. Simulations were run by varying sibship size, size of the phenotypic correlations among siblings, imputation accuracy and minor allele frequency of the causal SNP. Furthermore, as imputing sibling data and extending the model to include sibships of size two or greater requires modeling the familial covariance matrix, we inquired whether model misspecification affects power. Finally, the results obtained via simulations were empirically verified in two datasets with continuous phenotype data (height) and with a dichotomous phenotype (smoking initiation). Across the settings considered, the mixture and the dosage approach are equally powerful and both produce unbiased parameter estimates. In addition, the likelihood-ratio test in the linear mixed model appears to be robust to the considered misspecification in the background covariance structure, given low to moderate phenotypic correlations among siblings. Empirical results show that the inclusion in association analysis of imputed sibling genotypes does not always result in larger test statistic. The actual test statistic may drop in value due to small effect sizes. That is, if the power benefit is small, that the change in distribution of the test statistic under the alternative is relatively small, the probability is greater of obtaining a smaller test statistic. As the genetic effects are typically hypothesized to be small, in practice, the decision on whether family-based imputation could be used as a means to increase power should be informed by prior power calculations and by the consideration of the background correlation.     

Panobinostat (LBH589)-induced acetylation of tubulin impairs megakaryocyte maturation and platelet formation

Drug-induced thrombocytopenia often results from dysregulation of normal megakaryocytopoiesis. In this study, we investigated the mechanisms responsible for thrombocytopenia associated with the use of Panobinostat (LBH589), a histone deacetylase inhibitor with promising anti-cancer activities. The effects of LBH589 were tested on the cellular and molecular aspects of megakaryocytopoiesis by utilizing an ex vivo system in which mature megakaryocytes (MK) and platelets were generated from human primary CD34(+) cells. We demonstrated that LBH589 did not affect MK proliferation or lineage commitment but inhibited MK maturation and platelet formation. Although LBH589 treatment of primary MK resulted in hyperacetylation of histones, it did not interfere with the expression of genes that play important roles during megakaryocytopoiesis. Instead, we found that LBH589 induced post-translational modifications of tubulin, a nonhistone protein that is the major component of the microtubule cytoskeleton. We then demonstrated that LBH589 treatment induced hyperacetylation of tubulin and alteration of microtubule dynamics and organization required for proper MK maturation and platelet formation. This study provides new insights into the mechanisms underlying LBH589-induced thrombocytopenia and provides a rationale for using tubulin as a target for selective histone deacetylase inhibitor therapies to treat thrombocytosis in patients with myeloproliferative neoplasms.