Mitochondrial targeting is a promising approach for solving current issues in clinical application of chemotherapy and diagnosis of several disorders. Here, we discuss direct conjugation of ...mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium (TPP), which is a delocalized cationic lipid that readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential. Other moieties, including short peptides, dequalinium, guanidine, rhodamine, and F16, are also known to be promising mitochondrial targeting agents. Direct conjugation of mitochondrial targeting moieties to anticancer drugs, antioxidants and sensors results in increased cytotoxicity, anti-oxidizing activity and sensing activity, respectively, compared with their non-targeting counterparts, especially in drug-resistant cells. Although many mitochondria-targeted anticancer drug conjugates have been investigated
and
, further clinical studies are still needed. On the other hand, several mitochondria-targeting antioxidants have been analyzed in clinical phases I, II and III trials, and one conjugate has been approved for treating eye disease in Russia. There are numerous ongoing studies of mitochondria-targeted sensors.
There is increasing evidence of a relationship between blood DNA methylation and body mass index (BMI). We aimed to assess associations of BMI with individual methylation measures (CpGs) through a ...cross-sectional genome-wide DNA methylation association study and a longitudinal analysis of repeated measurements over time.
Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined in baseline peripheral blood samples from 5361 adults recruited to the Melbourne Collaborative Cohort Study (MCCS) and selected for nested case-control studies, 2586 because they were subsequently diagnosed with cancer (cases) and 2775 as controls. For a subset of 1088 controls, these measures were repeated using blood samples collected at wave 2 follow-up, a median of 11 years later; weight was measured at both time points. Associations between BMI and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. These were applied to cases and controls separately, with results combined through fixed-effects meta-analysis.
Cross-sectional analysis identified 310 CpGs associated with BMI with P<1.0 × 10
, 225 of which had not been reported previously. Of these 225 novel associations, 172 were replicated (P<0.05) using the Atherosclerosis Risk in Communities (ARIC) study. We also replicated using MCCS data (P<0.05) 335 of 392 associations previously reported with P<1.0 × 10
, including 60 that had not been replicated before. Associations between change in BMI and change in methylation were observed for 34 of the 310 strongest signals in our cross-sectional analysis, including 7 that had not been replicated using the ARIC study.
Together, these findings suggest that BMI is associated with blood DNA methylation at a large number of CpGs across the genome, several of which are located in or near genes involved in ATP-binding cassette transportation, tumour necrosis factor signalling, insulin resistance and lipid metabolism.
The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ ...systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
Background
The number of persons who are substance abusing has been increasing globally. A majority of them remain in their communities, untreated. Empirical studies have shown some positive impacts ...of case management on substance abuse. However, studies that systematically synthesize the effectiveness of community‐based case management with populations that abuse substances are limited.
Aim
To review evidence of the impact of case management in improving treatment of substance abuse among adults in community settings.
Methods
The Cochrane processes guided this systematic review. PubMed, CINAHL, PsycINFO, Ovid and the Web of Science were searched to retrieve primary studies published from 2000 to 2013. All randomized controlled trials were considered for review. The methodological quality of the studies was assessed.
Results
The initial unfiltered search identified 506 references. A total of seven randomized controlled trials were selected for review. Findings show that, compared with clinical case management and usual care, community‐based case management services significantly improved clients' ability to abstain from drug use, reduced social problems, supported unmet service needs and improved satisfaction. Studies also showed reduced use of healthcare services, but results were mixed.
Conclusions
There is an evidence base for practicing case management among adults who are substance abusing. In general, studies concluded that case management is an active and assertive method of care coordination for formal substance abuse treatment. Further research is needed to assess case management's cost‐effectiveness and the impact of dosage on client outcomes.
Implications for Nursing Policy
Because of the complexity of population health management across settings and over long time frames, evidence‐based strategies are required to achieve health improvements. Because it provides continuous and timely care, healthcare leaders and policymakers should consider community‐based case management as an important strategy for coordinating the care in populations that are substance abusing.
Background
Accountable, continuous and patient‐centred care in community‐based settings is increasingly needed to reduce fragmented care, especially to reduce patient readmission rates. Case ...management has been proven effective in reducing healthcare costs and in increasing continuity of care, but its effectiveness in community‐based settings is not clear.
Aim
The aim of this integrative review is to examine the effectiveness of community‐based case management programmes in improving patient outcomes.
Methods
An integrative review of articles from PubMed, CINAHL and PsycInfo databases was undertaken to synthesize and analyse research about community‐based case management and its outcomes. Studies looking for patient outcomes and empirical studies published since 2000 were included. A total 18 articles were retrieved from 2000 to 2013.
Results
Most of the included studies were conducted in the USA, but international studies with quantitative approaches were reviewed (n = 6). The review revealed that community‐based case management significantly reduced hospital access outcomes, especially readmissions and increased cost effectiveness, patient clinical outcomes and patient satisfaction.
Limitations
This study did not isolate studies of patients with diseases or demographic characteristics in common, resulting in large variations in disease and demographic factors.
Conclusion
There is a base of evidence that community‐based case management is effective. Because it provides quality, patient‐centred care, case management should be used for major care coordination.
Implications for Nursing and Health Policy
The benefits of community‐based case management need to be announced to healthcare leaders and policymakers.
We report the first observation of the radiative decay of the ϒ(1S) into a charmonium state. The significance of the observed signal of ϒ(1S)→γχ_{c1} is 6.3 standard deviations including systematics. ...The branching fraction is calculated to be Bϒ(1S)→γχ_{c1}=4.7_{-1.8}^{+2.4}(stat)_{-0.5}^{+0.4}(sys)×10^{-5}. We also searched for ϒ(1S) radiative decays into χ_{c0,2} and η_{c}(1S,2S), and set upper limits on their branching fractions. These results are obtained from a 24.9 fb^{-1} data sample collected with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider at a center-of-mass energy equal to the ϒ(2S) mass using ϒ(1S) tagging by the ϒ(2S)→ϒ(1S)π^{+}π^{-} transitions.
The JSNS2 (J-PARC Sterile Neutrino Search at J-PARCSpallation Neutron Source) is an experiment designed for the searchfor sterile neutrinos. The experiment is currently at the stage ofthe second ...phase named JSNS2-II with two detectors at near andfar locations from the neutrino source. One of the key components ofthe experiment is an acrylic vessel, that is used for the targetvolume for the detection of the anti-neutrinos. The specifications,design, and measured properties of the acrylic vessel aredescribed.
To evaluate whether shear-wave velocity (SWV) can be used for predicting the prognoses of patients with colorectal cancer liver metastases (CRLMs) after chemotherapy.
Our institutional review board ...approved this prospective study, and written informed consent was obtained. SWV of CRLMs were obtained using point shear-wave elastography using acoustic radiation force impulse from 25 patients prior to and 2, 7, and 14 days after chemotherapy. Progression-free survival (PFS) after chemotherapy was estimated using the Kaplan–Meier method. The Cox proportional hazard regression model was used to determine significant predictive factors for PFS. For measurement reproducibility, an additional 37 patients with CRLMs were enrolled and assessed using intraclass correlation coefficients (ICCs).
After chemotherapy, 10 and 15 patients were classified into responder and non-responder groups, respectively. The estimated 1- and 3-year PFS values in the whole cohort were 36% and 8%, respectively. A decrease in the SWV value on day 2 relative to the initial value was a significant predictive factor for better PFS outcome (hazard ratio = 0.20, 95% confidence interval = 0.07–0.57, p=0.003). The estimated 1 and 3-year PFS rates were 66.7% and 22.2%, respectively, in nine patients with decreased SWV values on day 2 and significantly higher than 18.8% and 0% of 16 patients with increased SWV values on day 2. The ICC value of SWV of CRLMs in the additional 37 patients was 0.823 (95% CI = 0.685–0.905), indicating good agreement.
SWV values of CRLMs could provide prognostic information in patients with CRLMs treated with chemotherapy, as decreased SWV values on day 2 after chemotherapy was a significant predictive factor for better PFS.
•Almost perfect agreement for shear wave velocity (SWV) of metastasis was achieved.•The SWV of metastasis were not significantly associated with chemotherapy response.•Decreases in the SWV on day 2 were significant predicting factor for better PFS.
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