Physical activity and quality of life in head and neck cancer survivors

Purpose To examine the prevalence of exercise in head and neck cancer survivors and determine preliminary associations with quality of life (QoL), fatigue, and depression.Materials and methods Fifty-nine of 65 (91%) eligible head and neck cancer survivors recruited from an academic oncology clinic completed a self-administered survey including the modified Godin Leisure-Time Exercise Questionnaire and Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N), which includes physical, social, emotional and functional well-being (FWB) as well as additional concerns, and the FACT-General (FACT-G). Medical variables were obtained by medical record review.Results The majority of participants were men (83%) and were Caucasian (92%), with mean age of 58±12.8. Cancer sites were primarily the oral cavity (24%), oropharynx (37%), or larynx (25%), with 20% being stage I, 7% stage II, 19% stage III, and 54% stage IV disease. Chemotherapy and/or radiation were ongoing in 14% of the participants. Half of the participants (51%) were diagnosed <6 months ago. Only three (5%) participants reported any vigorous exercise minutes (M=7.3±35.4), and only seven (12%) participants reported any moderate exercise minutes (M=19.5±70.6). Light exercise was reported by 26 (44%) (M=83.4±147.1). Only five (8.5%) participants were meeting current public health exercise guidelines. Partial correlations adjusting for age, medical comorbidity, and alcohol use showed that the total exercise minutes (i.e., light + moderate + vigorous) was positively associated with FWB (r=0.30, p=0.027), FACT-G (r=0.25, p=0.071), and FACT-H&N (r=0.26, p=0.064), was negatively associated with fatigue (r=−0.27, p=0.051), and had no association with depression (r=0.10, p=0.500).Conclusions Few head and neck cancer survivors are participating in any moderate or vigorous exercise, and over half are completely sedentary. Meaningful and potentially beneficial associations between total exercise minutes, QoL, and fatigue were demonstrated. An exercise intervention may have utility in this understudied cancer survivor group. Further research is warranted.     

Sphingolipids Mediate Differential Echinocandin Susceptibility in Candida albicans and Aspergillus nidulans

The cell wall synthesis-inhibiting echinocandins, including caspofungin and micafungin, play important roles in the treatment of candidiasis and aspergillosis. Previous studies revealed that, in the haploid yeast Candida glabrata, sphingolipid biosynthesis pathway mutations confer caspofungin reduced susceptibility (CRS) but micafungin increased susceptibility (MIS). Here, we describe one Candida albicans strain (of 10 tested) that similarly yields CRS-MIS mutants at relatively high frequency. Mutants demonstrated increased levels of long-chain bases (sphingolipid pathway intermediates) and, unique to this strain, loss of His104/Pro104 heterozygosity in the TSC13-encoded enoyl reductase. CRS-MIS was similarly observed in a C. albicans homozygous fen1Δ fen12Δ laboratory strain and in diverse wild-type strains following exogenous long-chain-base treatment. Analogous to these results, CRS-MIS was demonstrated in an Aspergillus nidulans basA mutant encoding defective sphingolipid C₄-hydroxylase and in its wild-type parent exposed to long-chain bases. Sphingolipids likely modulate echinocandin interaction with their Fks membrane target in all susceptible fungi, with potential implications for optimizing therapy with existing antifungals and the development of novel agents.     

A Competent and Commercially Viable Process for the Synthesis of the Anti-Hypertensive Drug Olmesartan Medoxomil

Drug product purity and potency are of most significance in the regulatory market as we notice many recalled batches worldwide, particularly in the US and Japan. Olmesartan Medoxomil is an anti-hypertensive drug. The present invention relates to a process for the preparation of Olmesartan Medoxomil with 99.9% purity in an overall 62% yield. The synthesis includes three isolations and one purification with easy plant operations. This process describes the formation and control of each individual impurity in all stages. This process for Olmesartan Medoxomil and its intermediates is competent for industrial production in very short reaction time intervals with an appreciable yield and high purity.     

Refining Measurement of Social Cognitive Theory Factors Associated with Exercise Adherence in Head and Neck Cancer Patients

Social cognitive theory (SCT) measures related to exercise adherence in head and neck cancer (HNCa) patients were developed. Enrolling 101 HNCa patients, psychometric properties and associations with exercise behavior were examined for barriers self-efficacy, perceived barriers interference, outcome expectations, enjoyment, and goal setting. Cronbach's alpha ranged from.84 to.95; only enjoyment demonstrated limited test-retest reliability. Subscales for barriers self-efficacy (motivational, physical health) and barriers interference (motivational, physical health, time, environment) were identified. Multiple SCT constructs were cross-sectional correlates and prospective predictors of exercise behavior. These measures can improve the application of the SCT to exercise adherence in HNCa patients.     

Extracellular vesicles from bone marrow mesenchymal stem/stromal cells transport tumor regulatory microRNA,proteins, and metabolites

Human mesenchymal stem/stromal cells (hMSCs) have been shown to support breast cancer cell proliferation and metastasis, partly through their secretome. hMSCs have a remarkable ability to survive for long periods under stress, and their secretome is tumor supportive. In this study, we have characterized the cargo of extracellular vesicular (EV) fraction (that is in the size range of 40-150nm) of serum deprived hMSCs (SD-MSCs). Next Generation Sequencing assays were used to identify small RNA secreted in the EVs, which indicated presence of tumor supportive miRNA. Further assays demonstrated the role of miRNA-21 and 34a as tumor supportive miRNAs. Next, proteomic assays revealed the presence of ≈150 different proteins, most of which are known tumor supportive factors such as PDGFR-β, TIMP-1, and TIMP-2. Lipidomic assays verified presence of bioactive lipids such as sphingomyelin. Furthermore, metabolite assays identified the presence of lactic acid and glutamic acid in EVs. The co-injection xenograft assays using MCF-7 breast cancer cells demonstrated the tumor supportive function of these EVs. To our knowledge this is the first comprehensive -omics based study that characterized the complex cargo of extracellular vesicles secreted by hMSCs and their role in supporting breast cancers.     

Rapid diagnosis of acute bacterial meningitis: role of a broad range 16S rRNA polymerase chain reaction

Background: Acute bacterial meningitis is a significant cause of morbidity and mortality throughout the world. It can be difficult to diagnose, as the symptoms and signs are often non-specific. Study Objective: To evaluate the performance of an in-house semi-nested polymerase chain reaction (PCR) assay targeting the 16S rRNA gene of Eubacteria for the rapid diagnosis of acute bacterial meningitis using cerebrospinal fluid (CSF) specimens. Methods: A total of 112 CSF samples from 112 patients were used in the study. Among these, 32 samples were obtained from confirmed cases of Streptococcus pneumoniae, six samples were obtained from confirmed cases of Haemophilus influenzae, one sample from a confirmed case of Neisseria meningitidis, and 10 cases of clinically suspected acute bacterial meningitis. The remaining 63 CSF samples were obtained from patients with non-infectious illnesses (n = 47) of the central nervous system (CNS) and autopsy-confirmed tuberculous meningitis (n = 16). Results: The assay had an overall sensitivity of 93% (95% confidence interval [CI] 0.81–0.98, negative predictive value = 95%) and a specificity of 98% (95% CI 0.92–1.0, positive predictive value = 98%). Conclusion: These preliminary findings suggest that the semi-nested PCR assay targeting the 16S rRNA gene may be used as a rapid test for the diagnosis of acute bacterial meningitis.