The effects of low frequency electrical stimulation on satellite cell activity in rat skeletal muscle during hindlimb suspension

<p>Abstract</p> <p>Background</p> <p>The ability of skeletal muscle to grow and regenerate is dependent on resident stem cells called satellite cells. It has been shown that chronic hindlimb unloading downregulates the satellite cell activity. This study investigated the role of low-frequency electrical stimulation on satellite cell activity during a 28 d hindlimb suspension in rats.</p> <p>Results</p> <p>Mechanical unloading resulted in a 44% reduction in the myofiber cross-sectional area as well as a 29% and 34% reduction in the number of myonuclei and myonuclear domains, respectively, in the soleus muscles (<it>P </it>< 0.001 <it>vs </it>the weight-bearing control). The number of quiescent (M-cadherin⁺), proliferating (BrdU⁺and myoD⁺), and differentiated (myogenin⁺) satellite cells was also reduced by 48-57% compared to the weight-bearing animals (<it>P </it>< 0.01 for all). Daily application of electrical stimulation (2 × 3 h at a 20 Hz frequency) partially attenuated the reduction of the fiber cross-sectional area, satellite cell activity, and myonuclear domain (<it>P </it>< 0.05 for all). Extensor digitorum longus muscles were not significantly altered by hindlimb unloading.</p> <p>Conclusion</p> <p>This study shows that electrical stimulation partially attenuated the decrease in muscle size and satellite cells during hindlimb unloading. The causal relationship between satellite cell activation and electrical stimulation remain to be established.</p

Fluctuation of BCR-ABL1 qPCRIS level beyond 0.1%IS after stopping tyrosine kinase inhibitor in chronic myeloid leukaemia patients with deep molecular response for at least two years

Fluctuation of BCR-ABL1 real-time quantitative polymerase chain reaction in International Scale (qPCRIS ) level below major molecular response (MMR) (0.1%IS ) is a known phenomenon after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukaemia (CML) patients who are attempting treatment free remission (TFR). We report here four cases of fluctuation beyond MMR during conduct of a Malaysia Stop TKI Trial (MSIT) to examine the validity of the commonly used relapse criterion – loss of MMR for one reading – aiming to provide evidence in setting relapse criteria for future CML patients who want to attempt TFR

Emerged HA and NA Mutants of the Pandemic Influenza H1N1 Viruses with Increasing Epidemiological Significance in Taipei and Kaohsiung, Taiwan, 2009–10

The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA) and neuraminidase (NA) of pH1N1 strains that spread in two metropolitan areas -Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post–peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K) was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p<0.0001). E374K persisted until ten months post-nationwide vaccination without further antigenic changes (e.g. prior to the highest selective pressure). In public health measures, the epidemic peaked at seven weeks after oseltamivir treatment was initiated. The emerging E374K mutants spread before the first peak of school class suspension, extended their survival in high-density population areas before vaccination, dominated in the second wave of class suspension, and were fixed as herd immunity developed. The tempo-spatial spreading of E374K mutants was more concentrated during the post–peak (p = 0.000004) in seven districts with higher spatial clusters (p<0.001). This is the first study examining viral changes during the naïve phase of a pandemic of influenza through integrated virological/serological/clinical surveillance, tempo-spatial analysis, and intervention policies. The vaccination increased the percentage of E374K mutants (22.86% vs 72.34%, p<0.001) and significantly elevated the frequency of mutations in Sa antigenic site (2.36% vs 23.40%, p<0.001). Future pre-vaccination public health efforts should monitor amino acids of HA and NA of pandemic influenza viruses isolated at exponential and peak phases in areas with high cluster cases

A randomized control trial comparing peginterferon-α-2a versus observation after stopping tyrosine kinase inhibitor in chronic myeloid leukemia with deep molecular response for at least two years

Background: There is much advancement in treatment of chronic myeloid leukemia (CML) since the approval of first tyrosine kinase inhibitor (TKI), imatinib, by US FDA in 2001. One of them is definitely the concept of stopping TKI, starting at the CML patients who have achieved deep molecular response (MR) of MR4.5 for a reasonable long period of at least two years, pioneered by the researchers from French and Australia. Meanwhile, interferon, the standard treatment of CML before the era of TKI, showed that interferon-responded patients may indeed retain the response once interferon was withdrawn via interferon-induced immunity towards the leukemic clone. This is further supported by stop trial in Japan, in which after stopping TKI, interferon was given for 2 years and it showed a higher drug-free rate compared to stop trial from French and Australia. Hence, it is logical to postulate the use of interferon after TKI was stopped when patients have attained deep MR for more than two years will increase the percentage of patients remain TKI-free on follow-up. Materials and Methods: This is a multi-center randomized controlled trial. Adult CML patients, diagnosed in chronic phase, treated with ongoing TKI for at least 3 years without previous history of TKI failure and have achieved stable deep MR on International Scale for ≥2 years with at least 2 readings of MR4.5 (including the latest before study entry), were randomized into 2 arms: (1) peginterferon-α-2a, subcutaneous weekly, starting at 180 mcg, or (2) observation. Disease is monitored by PCR (centralized in Ampang Hospital) at monthly for the first year, 2 monthly for the second year and 3 monthly for the third year. Relapse is defined as either (i) one reading of loss of major MR, i.e. reading of >0.1% IS and confirmed by second analysis taken 1 month later if the first analysis point reading is ≤1% IS, or (ii) positivity of BCR-ABL1 transcripts, as confirmed by a second analysis point, indicating the increase (at least 1 log) in relation to the first analysis point at two successive assessments. Quality of Life is assessed using EORTC QLO-C30. Results: At the time of writing, total of 8 patients were randomized, 5 into peginterferon arm, 3 into observation arm, all were on imatinib, M:F = 4:4, Malay: Chinese:Indian = 3:4:1, median age 49.5 (range 25-58), median follow-up 4 months (range 1-6) and none of them relapse. Two patients developed imatinib withdrawal syndrome, both female on observation arm, one was mild and resolved after 2 months but one was severe and needed termination after 2 months and restarted on imatinib. Two patients in peginterferon arm developed mild hepatitis with liver enzymes <2x of ULN. Four patients were able to tolerate peginterferon-α-2a at the dose of 180 mcg weekly, while one patient needed dose reduction to 90 mcg weekly. Quality of life score comparing two months after stopping TKI and baseline will be presented in the conference later. Conclusion: No conclusive date can be drawn so far because sample size is small and follow-up is short. Nonetheless, this trial provides Malaysian CML a platform to stop TKI safely

Diversity of the association of serum levels and genetic variants of MHC class I polypeptide-related chain A with liver fibrosis in chronic hepatitis C

Background/Aims Genetic variants of MHC class I polypeptide-related chain A (MICA) at rs2596542 have been associated with hepatocellular carcinoma. The linkage between serum MICA (sMICA) and liver fibrosis in chronic hepatitis C is elusive. Results: Linear regression analysis revealed that sMICA were independently correlated to α-fetoprotein (β: 0.149; 95% confidence interval [CI]: 0.001, 0.003; P = 0.007)and MICA rs2596542 GG genotype (β: 0.209; 95% CI: 0.153, 0.483; P 50 pg/mL provided a positive predictive value of 72 % in predicting advanced liver fibrosis (F3-4) and of 90% in significant fibrosis (> F2) in MICA rs2596542 A allele carriers. Materials and Methods Serum level and single nucleotide polymorphism at rs2596542 of MICA were tested for the association with liver fibrosis in 319 biopsy proven chronic hepatitis C patients. Conclusions: Levels of sMICA were highly correlated to liver disease severity in chronic hepatitis C patients who carried the MICA rs738409 A allele. Patients possessing the genetic predisposition had a higher likelihood of progressed liver fibrosis if they expressed higher sMICA levels

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma