Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults.

Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial-iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA4977) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope (56Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score ≤ 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores ≥ 11 (high-functioning, HF). The mtDNA4977 relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability.

Effectiveness of Yoga on Quality of Life of Breast Cancer Patients Undergoing Chemotherapy: A Randomized Clinical Controlled Study.

BACKGROUND: Cancer of breast is most common cancer among women in India and vast majority of countries worldwide. While undergoing chemotherapy for carcinoma management, women encounter side effects, which affects their quality of life (QOL). A randomized controlled study with quantitative research approach and time series design was conducted, to study the effectiveness of yoga on QOL of breast cancer patients undergoing chemotherapy. METHODOLOGY: One hundred breast cancer patients scheduled for 3-weekly, day-care adjuvant chemotherapy (CEF regimen) were enrolled with consecutive sampling technique, into control (n = 52) and experiment (n = 48) groups, by concealed randomization following written informed consent. Baseline data on QOL were collected before first-cycle chemotherapy using the European Organization for Research and Treatment of Cancer QLQ C30. Patients in the experimental group were taught diaphragmatic breathing techniques, systematic relaxation, and alternate nostril breathing, and Joints and Glands neck and shoulder exercises were instructed to practice twice daily at home. They were supervised in practicing these techniques while they received second, third, fourth, fifth, and sixth cycles of chemotherapy in the day-care facility. Participants in the control group received only routine care. All participants received standard post chemotherapy prescription. Data on QOL were collected from all patients during the second, third, fourth, fifth, and sixth cycles of chemotherapy. RESULTS: The analysis revealed that at the baseline (first chemotherapy cycle), breast cancer patients in control and experimental groups were homogeneous in terms of their sociodemographic and clinical variables and QOL score. Yoga practices were effective in improving the QOL of breast cancer patients in the experimental group in the areas of global health status, physical function, role function, and emotional function and decreasing the symptoms of fatigue, insomnia, loss of appetite, and constipation, during the period of chemotherapy. CONCLUSION: Yoga practices comprising of relaxation techniques reduce many side effects and improve the QOL of women undergoing chemotherapy for breast cancer.

Associations of Poly (ADP-Ribose) Polymerase1 abundance in calf skeletal muscle with walking performance in peripheral artery disease.

OBJECTIVE: This study investigated associations of markers of oxidative stress and mitochondrial function in calf muscle biopsies with walking performance in people with and without lower extremity peripheral artery disease (PAD). METHODS: Participants with PAD (ankle-brachial index (ABI) <0.90) and without PAD (ABI: 0.90-1.50) underwent calf muscle biopsy and measurement of 6-min walk and four-meter walking velocity. PARP1 (Poly (ADP-Ribose) Polymerase 1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), silent information regulator 1 (SIRT1) and 4-hydroxynonenal (4HNE) expression were measured in calf muscle using western blot. RESULTS: Among 15 participants with PAD mean age: 66.8 years (standard deviation (SD): 6.4) and six without PAD (age: 64.4 years, SD: 5.9), mean PARP1-abundance in calf muscle was 1.16 ± 0.92 AU and 0.96 ± 0.38 AU, respectively (P = 0.61). Among participants with PAD after adjustment with ABI, a greater abundance of PARP1 was associated with poorer 6-min walking distance (r = -0.65, P = 0.01), usual-paced 4-m walking velocity (r = -0.73, P = 0.003) and slower fast-paced four-meter walking velocity (r = -0.51, P = 0.07). Among participants with PAD, ABI was not associated with PARP1 abundance in calf muscle (r = 0.02, P = 0.93). Among participants without PAD, skeletal muscle PARP1 abundance was not significantly associated with 6-min walk distance (r = -0.58; P = 0.22), usual-paced walking velocity (r = -0.26; P = 0.62), or fast-paced walking velocity (r = -0.21; P = 0.69), perhaps due to lack of statistical power. There were no associations of remaining calf muscle measures with walking performance. CONCLUSIONS: These findings are consistent with the hypothesis that calf skeletal muscle characteristics are related to walking performance, independently of severity of lower extremity arterial obstruction in people with PAD.

Advanced Age Is Associated with Iron Dyshomeostasis and Mitochondrial DNA Damage in Human Skeletal Muscle.

Whether disruption of iron metabolism is implicated in human muscle aging is presently unclear. We explored the relationship among iron metabolism, muscle mitochondrial homeostasis, inflammation, and physical function in older adults and young controls. Eleven young and 23 older men and women were included. Older adults were classified into high-functioning (HF) and low-functioning (LF) groups according to their Short Physical Performance Battery score. Vastus lateralis muscle biopsies were assayed for total iron content, expression of 8-oxoguanine and DNA glycosylase (OGG1), 3-nitrotyrosine (3-NT) levels, and mitochondrial DNA (mtDNA) content and damage. Circulating ferritin and hepcidin levels were also quantified. Muscle iron levels were greater in the old group. Protein expression of transferrin receptor 1, Zrt-Irt-like protein (ZIP) 8, and ZIP14 were lower in old participants. Circulating levels of ferritin, hepcidin, interleukin 6 (IL6), and C-reactive protein were higher in the old group. Old participants showed lower mtDNA content and greater mtDNA damage. OGG1 protein expression declined with age, whereas 3-NT levels were greater in old participants. Finally, a negative correlation was determined between ZIP14 expression and circulating IL6 levels in LF older adults. None of assayed parameters differed between HF and LF participants. Our findings suggest that muscle iron homeostasis is altered in old age, which might contribute to loss of mtDNA stability. Muscle iron metabolism may therefore represent a target for interventions against muscle aging.

Cancer Pain, Anxiety, and Depression in Admitted Patients at a Tertiary Care Hospital: A Prospective Observational Study.

CONTEXT: Pain is the most common symptom in admitted cancer patients. The association between the severity of cancer pain and distress symptoms such as depression and anxiety is a subject of research. AIMS: The aim is to study the prevalence of pain, anxiety, and depression in admitted cancer patients and determine the association between pain and anxiety and depression at a tertiary cancer care institute. SETTINGS AND DESIGN: This was prospective observational study. SUBJECTS AND METHODS: We enrolled 393 cancer inpatients prospectively after written informed consent. Their disease details, presence, severity, and character of pain were recorded. Numerical Pain Scale was used for pain scores, self-reporting Hospital Anxiety and Depression Scale for anxiety and depression. STATISTICAL ANALYSIS USED: Normal data were analyzed with parametric, nonnormal with nonparametric methods, and categorical with the Chi-square test. RESULTS: The prevalence of moderate-to-severe pain was 41.5%, anxiety 20.3%, and depression 24.8%. Proportion of patients with anxiety and depression was 9.2% and 17.7% in patients with no pain; about 32.8% and 36.7% with severe pain, respectively (P < 0.000). In patients with no depression 6% had anxiety; with depression 44.9% had anxiety (P < 0.000). Odd's ratio to have anxiety and depression was 4.44 (95% confidence interval [CI] 2.0318-9.7024) and 2.92 (95% CI 1.5739-5.4186), respectively, in patients with pain as compared to no pain (P < 0.00). There was a positive correlation between pain, anxiety, and depression scores. CONCLUSIONS: There is strong association between the presence and severity of pain and distress symptoms such as anxiety and depression in admitted cancer patients.

Carcinoma buccal mucosa underlying a giant cutaneous horn: a case report and review of the literature.

Cutaneous horn is a conical, dense, and hyperkeratotic protrusion that often appears similar to the horn of an animal. Giant cutaneous horns are rare; no incidence or prevalence has been reported. The significance of cutaneous horns is that they occur in association with, or as a response to, a wide variety of underlying benign, premalignant, and malignant cutaneous diseases. A case of giant cutaneous horn of left oral commissure along with carcinoma left buccal mucosa is reported here as an extremely rare oral/perioral pathology.