Development and Feasibility of a Prehabilitation Protocol for Patients Diagnosed with Head and Neck Cancer.

BACKGROUND:  Head and neck (H&N) cancers account for 4% of total cancers diagnosed. However, quality of life (QoL) implications are more severe for this patient population due to the complexity, extent, and deformities resulting from treatment interventions. Principally debilitating complications include diminished functional walking capacity, reduced cervical range of motion (ROM), and scapular strength. An extensive literature search revealed a paucity of evidence utilizing physical therapy assessment and intervention for this population. The purpose of this study was to describe the development and clinical feasibility of a prehabilitation program aimed to thwart these complications for patients diagnosed with H&N cancer.  Methods: Inclusion criteria: male or female, 18+ years, speak and read the English language, ambulate independently, diagnosed with H&N cancer, and scheduled for surgical intervention. Institutional Review Board approval was obtained. Pre- and post-surgical measurements included the six-minute walk test (6MWT), cervical ROM, manual muscle testing for scapular strength, and three questionnaires: physical activity history, health behaviors questionnaire, and the Functional Assessment Cancer Therapy H&N QoL survey.  Results: Three participants were enrolled (two males and one female) all identifying as Caucasian and between 60-90 years of age. Pre- to post-cervical ROM demonstrated decline in extension/bilateral rotation for two of three participants. Two participants demonstrated decreased 6MWT distance while one increased. No participants experienced any adverse effects of the prehabilitation program.  Conclusion: This is the first study protocol to describe a physical therapist-administered H&N cancer prehabilitation program. Professionally administered education and exercise has potential to prevent, manage, and mitigate the adverse effects of cancer treatment. Additional research is needed to define the importance of prehabilitation relative to improved clinical outcomes and improved QoL. Patients with a cancer diagnosis are susceptible to impairments and functional limitations as a result of treatments and this prehabilitation program demonstrates potential to positively impact outcomes across the survivorship continuum. Due to their education and integration within the medical system, physical therapists are well-positioned to lead the effort to unify theory and clearly define parameters for oncology prehabilitation.

Effects of Aerobic Exercise on Oxidative Stress in Patients Diagnosed with Cancer: A Narrative Review.

BACKGROUND: Oxidative stress (OS) can bring about an imbalance between the production of free radicals (pro-oxidants) and their elimination by protective mechanisms (antioxidants). Exercise and/or physical activity (PA) may provide a mechanism to control the variation and equilibrium between pro-oxidants and antioxidants. PURPOSE:  The purpose of this narrative review is to investigate the evidence regarding the effect of exercise and/or PA on OS among individuals diagnosed with cancer.  Methods: A narrative review study design involved a literature search (August 2016) across the databases: Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane, Excerpta Medica database (Embase), and PubMed. Articles included those published from January 2000 - August 2016; inclusive of the search terms "cancer" AND "neoplasm" AND "oncology" AND "oxidative stress" AND "exercise" AND "physical activity"; written in the English language; and utilizing human subjects. The references of the selected articles were then reviewed to identify any qualifying articles. A modified Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) review of each article was completed by two investigators. RESULTS:  Eight articles met the final inclusion criteria. Moderate exercise may provide protective mechanisms against OS via increased antioxidant activity, while exhaustive exercise may be responsible for increased levels of OS, increasing the risk for malignancy. While increased OS levels are utilized by current oncologic therapies to damage malignant and premalignant cells, they also damage healthy cells (cardiac, nerve, and lymphatic). CONCLUSION: Moderate levels of exercise and/or PA may provide preventative and protective qualities against the negative side effects associated with increased OS from cancer treatment.

Implementation and Preliminary Analysis of FACT-G Quality of Life Questionnaire within an Oncology Survivorship Clinic.

PURPOSE: To conduct a descriptive analysis of the results from the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QOL) questionnaire, describe the outcomes from the FACT-G to drive treatment recommendations within the breast survivorship clinic and to quantify the severity of QOL issues experienced. METHODS: A retrospective analysis utilizing medical records of participants in a breast cancer survivorship clinic. Measurement data included demographics and FACT-G results. Descriptive analysis of demographics and trends in referral recommendations and FACT-G scores was completed. RESULTS: All 30 participants were females diagnosed with breast cancer of various stages, ages 28 to 81 years. Approximately 1.5 years elapsed between cancer diagnosis and completion of the FACT-G. Participants received surgery (100%), radiation (76%), and chemotherapy and/or hormonal therapy (43%). Results demonstrated that participants reported having a lack of energy (24%) and were bothered by side effects of their treatment (20%). The greatest impact on functional well-being was difficulty sleeping (50%). LIMITATIONS: Decreased ability to generalize the data to breast cancer survivors due to small sample size from one institution and potential referral bias. CONCLUSIONS: Cancer survivors experience QOL issues throughout the continuum of their care, which can result in long-term effects on their physical, functional, social and emotional well-being. QOL is a major focus for cancer survivors and many times determines a survivor's healthcare decisions. QOL measurements can be utilized at multiple points during survivorship to identify the need for referrals and to guide interventions.

Unfolding of in planta activity of anti-rep ribozyme in presence of a RNA silencing suppressor.

Antisense RNA ribozymes have intrinsic endonucleolytic activity to effect cleavage of the target RNA. However, this activity in vivo is often controlled by the dominance of antisense or other double-stranded RNA mechanism. In this work, we demonstrate the in planta activity of a hammerhead ribozyme designed to target rep-mRNA of a phytopathogen Mungbean Yellow Mosaic India virus (MYMIV) as an antiviral agent. We also found RNA-silencing is induced on introduction of catalytically active as well as inactive ribozymes. Using RNA-silencing suppressors (RSS), we demonstrate that the endonucleolytic activity of ribozymes is a true phenomenon, even while a mutated version may demonstrate a similar down-regulation of the target RNA. This helps to ease the confusion over the action mechanism of ribozymes in vivo.

A rare case of primary adenoid cystic carcinoma of lung.

A 33-year-old male presented with repeated episodes of blood-streaked sputum for last one-and half-year. Chest radiograph showed consolidation in the right lower zone. Fibreoptic bronchoscopy revealed an endoluminal growth in the right lower lobe bronchus. Histopathological examination of bronchoscopic biopsy specimen confirmed adenoid cystic carcinoma.

Molecular and biochemical mining of heat-shock and 14-3-3 proteins in drug-induced protoscolices of Echinococcus granulosus and the detection of a candidate gene for anthelmintic resistance.

Cystic echinococcosis (CE) caused by the larval stage of Echinococcus granulosus is a disease that affects both humans and animals. In humans the disease is treated by surgery with a supplementary option of chemotherapy with a benzimidazole compound. During the present study heat-shock protein 60 (HSP 60) was identified as one of the most frequently expressed biomolecules by E. granulosus after albendazole treatment. Data were correlated with 14-3-3 protein signature, and overexpression of this molecule after albendazole induction was an indicator of cell survival and signal transduction during in vitro maintenance of E. granulosus for up to 72 h. This observation was further correlated with a uniform expression pattern of a housekeeping gene (actin II). Out of three ß-tubulin gene isoforms of E. granulosus, ß-tubulin gene isoform 2 showed a conserved point mutation indicative of benzimidazole resistance.

Kinetic mechanism of streptomycin adenylyltransferase from a recombinant Escherichia coli.

Bacterial resistance to the aminoglycoside antibiotics is manifested primarily by enzymic modification of these drugs. One important mechanism of streptomycin modification is through ATP-dependent O-adenylation, catalyzed by streptomycin adenylyltransferase. Initial velocity patterns deduced from steady state kinetics indicate a sequential mechanism. Dead-end inhibition by tobramycin and neomycin is non-competitive versus streptomycin and uncompetitive versus ATP, indicative of ordered substrate binding where ATP binds first and then streptomycin. These results surmise that streptomycin adenylyltransferase follows an ordered, sequential kinetic mechanism in which one substrate (ATP) binds prior to the antibiotic and pyrophosphate is released prior to formation of AMP-streptomycin.

RNA interference: potential therapeutic targets.

One of the most exciting findings in recent years has been the discovery of RNA interference (RNAi). RNAi methodologies hold the promise to selectively inhibit gene expression in mammals. RNAi is an innate cellular process activated when a double-stranded RNA (dsRNA) molecule of greater than 19 duplex nucleotides enters the cell, causing the degradation of not only the invading dsRNA molecule, but also single-stranded (ssRNAs) RNAs of identical sequences, including endogenous mRNAs. The use of RNAi for genetic-based therapies has been widely studied, especially in viral infections, cancers, and inherited genetic disorders. As such, RNAi technology is a potentially useful method to develop highly specific dsRNA-based gene-silencing therapeutics.

Five-year follow up of the ATS mechanical heart valve.

BACKGROUND AND AIM OF THE STUDY: Between January 1, 1997 and December 31, 2001, a total of 342 patients underwent aortic valve replacement (AVR) or mitral valve replacement (MVR) with the ATS Medical prosthesis. The initial three-year phase of this study took place under a United States Food and Drug Administration-approved investigational device exemption study. The study aim was to determine the incidence of valve-related events in up to five years of follow up after valve implantation, and to assess patient disturbance from valve noise. METHODS: Patients were consecutively enrolled to undergo AVR or MVR with the ATS prosthesis. Follow up studies were conducted by patient questionnaire and/or telephone call. Follow up was 96% complete. AVR was conducted in 246 patients (80 with coronary bypass), and MVR in 96 patients (29 with coronary bypass). RESULTS: The overall operative mortality was 2.6% (n = 9; AVR 3.2%, n = 8; MVR 1.0%, n = 1), with two deaths being valve-related (0.6%). In 878 patient-years (pt-yr) of follow up (613 pt-yr for AVR; 265 pt-yr for MVR) there were an additional 22 deaths. Five deaths (0.6%/pt-yr) were valve-related: two were neuroembolic (both MVR), one from endocarditis (AVR), and two from bleeding events (both AVR). Late valve-related complications (>30 days) included 17 episodes of major bleeding (11 AVR, 1.8%/pt-yr; six MVR, 2.3%/pt-yr), five permanent neuroembolic events (four AVR, 0.7%/pt-yr; one MVR, 0.4%/pt-yr); 16 transient neuroembolic events (10 AVR, 1.6%/pt-yr; six MVR, 2.3%/pt-yr); three transient peripheral emboli (two AVR, 0.3%/pt-yr; one MVR, 0.4%/pt-yr); four paravalvular leaks (two AVR, 0.3%/pt-yr; two MVR, 0.8%/pt-yr); and one episode of valve thrombosis (MVR, 0.4%/pt-yr; AVR, 0%/pt-yr). Reoperation was required in two patients: one AVR (paravalvular leak, 0.2%/pt-yr) and one MVR (replacement due to thrombosis, 0.4%/pt-yr). CONCLUSION: These results indicate that intermediate-term results with the ATS mechanical prosthesis continue to be excellent, though further long-term follow up is warranted.

Purification of p53/55 kinase from nuclear ribonucleoproteins of Namalwa cells.

A nuclear p53/55 protein kinase has been isolated from nuclear ribonucleoprotein particles from human tumor cells. The enzyme was purified approximately 2200-fold cell nuclei by sequential ribonuclease digestion of the RNP particles, DEAE cellulose and phosphocellulose chromatography. The kinase which was cAMP independent, catalyzed the phosphorylation of rabbit muscle glycogen synthase in the amino terminal domain, and conversion of the I to D form. The D synthase had a phosphorylation stoichiometry of 8 moles 32P per mole of synthase subunit with maximal specificity for ATP as phosphate donor; its Km was 30 microM. An antinucleolar antibody inhibited enzyme activity by 80%. Substrates for most other kinases were inactive. The kinase was essentially unaffected by the Walsh inhibitor, EGTA, regulatory subunits of protein kinase, calmodulin, trifluoperazine or heparin. Its activity was lost at 1 mM polyamine, but was enhanced 3-fold by MnCl2 and 4- to 9-fold by deoxymononucleotides. The nuclei of HeLa cells contained 64% of the total kinase of which 64% of the total kinase of which 11% were in nucleoli; the specific activity of the nucleolar kinase was twice that of the nuclear supernatant and four times that of the cytoplasmic kinase. These results indicate that nucleolar ribonucleoprotein particles of human tumor cells contain a cAMP-independent protein kinase which is similar to glycogen synthase kinase.

A 38,000-dalton antigen found in Namalwa cells induced by Newcastle disease virus.

An antigen has been isolated from Namalwa cells, a Burkitt lymphoma line, that was induced by Newcastle disease virus (NDV) for interferon production. The antigen was extracted by 3 M NaCl from ribonucleoprotein particles (RNP), obtained from the nuclear 0.01 M Tris extract, and was purified by hydroxylapatite chromatography, phosphocellulose chromatography, and preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Its molecular weight was 38 kilodalton (kDa) as determined by SDS-PAGE. The tryptic peptide map of 125I-labeled antigen contained seven major peptides. The antigen was not found in HeLa cells, normal human liver or in Namalwa cells that had not been induced by the virus. This result suggests that this antigen was produced in Namalwa cells as a result of induction by the NDV virus.