Gene arrays for diagnosis,prognosis and treatment of breast cancer metastasis

The advent of microarray tools has generated a massive amount of gene expression data. These data have greatly enhanced our understanding of the biology of breast cancer metastasis and provide a way to improve the prediction of the metastatic potential of breast tumours. Gene-expression profiling has highlighted the molecular heterogeneity of mammary tumours and contributed to the identification of a new molecular classification of breast cancers. In addition, several molecular signatures predicting the likelihood of distant metastases for breast cancer patients have been characterized. Further reports have described gene expression profiles associated with specific metastatic phenotypes, including the organ preference of breast cancer metastasis. Here we review the major studies that had important impacts on the understanding of breast cancer metastasis. We also discuss the future challenges in this research field and the special issues that still need to be examined.     

Enhancement of tioconazole ungual delivery: Combining nanocapsule formulation and nail poration approaches

This work investigated the impact of formulation including in vitro release profile, repeated dosing, and nail poration on the ex vivo nail delivery performance of antifungal formulations. Chitosan coated and uncoated tioconazole-loaded nanocapsules and a nano-based film-forming vehicle were assessed via in vitro release and in vitro permeation tests using an artificial membrane and human nail clippings, respectively. The later involved single and daily dosing experiments with intact and porated nails. Additional experiments with Nile Red-loaded formulations evaluated the depth of penetration of the fluorescent marker into the nail by laser scanning confocal microscopy. The nanocapsule formulations prolonged release of tioconazole for longer than the control solutions and this ability was related to an enhanced nail penetration of the drug. Further, the new film-forming formulation delivered its drug payload more efficiently than a marketed product. Daily dosing of the formulations doubled the amount of drug recovered from the nails. Porating the nails enhanced tioconazole delivery in single dose experiments only. The depth of penetration of Nile Red into the nails clippings ranged between 90–160?μm. This research suggests that ensuring prolonged release of a drug is fundamental to develop efficacious topical nail formulations.     

Globale und nationale Strategien gegen Antibiotikaresistenzen

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Die Ausbreitung von Antibiotikaresistenzen wurde in den letzten Jahren zunehmend als Problem im Bereich globale Gesundheit...     

Evaluation of reporting quality for observational studies using routinely collected health data in pharmacovigilance

Objectives: To appraise the reporting quality of studies which concerned linezolid-related thrombocytopenia referring to REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement.

Methods: Medline, Embase, Cochrane library and clinicaltrial.gov were searched for observational studies concerning linezolid-related thrombocytopenia using routinely collected health data from 2000 to 2017. Two reviewers screened potential eligible articles and extracted data independently. Finally, reporting quality assessment was performed by two senior researchers using RECORD statement.

Results: Of 25 included studies, 11 (44.0%) mentioned the type of data in the title and/or abstract. In 38 items derived from RECORD statement, the median number of items reported in the included studies was 22 (inter-quartile range 18–27). Inadequate reporting issues were discovered in the following aspects: validation studies of the codes or algorithms, study size estimation, quantitative variables, subgroup statistical methods, missing data, follow-up/matching or sampling strategy, sensitivity analysis and cleaning methods, funding and role of funders and accessibility of protocol, raw data.

Conclusion: This study provides the evidence that the reporting quality of post-marketing safety evaluation studies conducted using routinely collected health data was often insufficient. Future stakeholders are encouraged to endorse the RECORD guidelines in pharmacovigilance.     

Depression Treatment Enhances Adherence to Antiretroviral Therapy: a Meta-Analysis

Background

Depression is a risk factor for nonadherence to HIV/AIDS treatment.

Purpose

A meta-analysis was conducted to examine whether treatment of depression and psychological distress improves antiretroviral therapy adherence.

Methods

PubMed and PsycINFO databases were systematically searched for relevant articles. Studies that reported an association between depression treatment (or an intervention with a component addressing mental health) and antiretroviral adherence were included.

Results

Across 29 studies of 12,243 persons living with HIV/AIDS, treatment of depression and psychological distress improved antiretroviral adherence (p?<?0.001). The odds of a person adhering were 83 % better if he/she was treated for depression. Greater improvements in adherence were found for samples with lower CD4 counts or more severe depression, for interventions specifically targeting depression (versus addressing mental health as a secondary objective), longer treatments, and observational studies.

Conclusions

These findings support the need for detection and treatment of depression among persons living with HIV/AIDS.     

Early combination versus initial metformin monotherapy in the management of newly diagnosed type 2 diabetes: An East Asian perspective

Type 2 diabetes (T2D) in the East Asian population is characterized by phenotypes such as low body mass index, an index of β-cell dysfunction, and higher percentage of body fat, an index of insulin resistance. These phenotypes/pathologies may predispose people to early onset of diabetes with increased risk of stroke and renal disease. Less than 50% of patients with T2D in East Asia achieve glycaemic targets recommended by national or regional guidelines, which may be attributable to knowledge and/or implementation gaps. Herein, we review the latest evidence with special reference to East Asian patients with T2D and present arguments for the need to use early combination therapy to intensify glycaemic control. This strategy is supported by the 5-year worldwide VERIFY study, which reported better glycaemic durability in newly diagnosed patients with T2D with a mean HbA1c of 6.9% treated with early combination therapy of vildagliptin plus metformin versus those treated with initial metformin monotherapy followed by addition of vildagliptin only with worsening glycaemic control. This paradigm shift of early intensified treatment is now recommended by the American Diabetes Association and the European Association for the Study of Diabetes. In order to translate these evidence to practice, increased awareness and strengthening of the healthcare system are needed to diagnose and manage patients with T2D early for combination therapy.     

Viral genetic determinants for thrips transmission of Tomato spotted wilt virus

Tomato spotted wilt virus (TSWV) is transmitted exclusively by thrips in nature. A reassortment-based viral genetic system was used to map transmissibility by thrips to the medium (M) RNA of TSWV. To locate determinants of thrips transmission in the M RNA, 30 single-lesion isolates (SLIs) were generated from a single TSWV isolate that was inefficiently transmitted by thrips. Three of the 30 SLIs were transmitted by thrips, and 27 were not. Sequence analysis of the M RNA, thrips transmissibility assays, G(C) protein analysis, and transmission electron microscopic studies revealed that a specific nonsynonymous mutation (C1375A) in the G(N)/G(C) ORF of the M RNA resulted in the loss of thrips transmissibility without inhibition of virion assembly. This was in contrast to other nontransmissible SLIs, which had frameshift and/or nonsense mutations in the G(N)/G(C) ORF but were defective in virion assembly. The G(C) glycoprotein was detectable in the C1375A mutants but not in the frameshift or nonsense mutants. We report a specific viral determinant associated with virus transmission by thrips. In addition, the loss of transmissibility was associated with the accumulation of defective haplotypes in the population, which are not transmissible by thrips, rather than with the presence of a dominant haplotype that is inefficiently transmitted by thrips. These results also indicate that the glycoproteins may not be required for TSWV infection of plant hosts but are required for transmissibility by thrips.     

The Ultracor tilting disc heart valve prosthesis in the aortic position: mid-term follow up

BACKGROUND AND AIM OF THE STUDY: The Ultracor valve is a recent introduction in the evolution of the tilting disc valve. This report summarizes a single surgeon's experience with the valve in the aortic position over a nine-year period. METHODS: Between 1990 and 1999, 94 patients received an Ultracor heart valve prosthesis in the aortic position. Forty-five patients (48%) had associated procedures, of which 32 (34%) were coronary artery grafts. Mean follow up was 2.6 years; total follow up was 229 patient-years. Follow up was 100% complete. RESULTS: The actuarial survival rate, including operative mortality rate, at five years was 82%. Actuarial freedom from valve-related death was 96% at five years. The linearized complication rate was 1.7%/year for late valve-related mortality, 1.7%/year for thromboembolism, 2.2%/year for anticoagulant-related hemorrhage (ACH), 1.3%/year for prosthetic valve endocarditis (PVE), and 1.7%/year for reoperation. The estimates of actuarial freedom from complications at five years were thromboembolism 89%, ACH 90%, PVE 96% and reoperation 96%. No structural failure or valve thrombosis was observed. CONCLUSION: Our experience over nine years showed the Ultracor heart valve prosthesis in the aortic position to be comparable with other currently evaluated mechanical heart valves in terms of durability and clinical results. Further study in this area should concentrate on the impact of valve type on left ventricular recovery post-implantation to provide additional information to the surgeon when selecting a valve from the plethora of choices available.