Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy

The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy.     

BEAUTY and the breast: is adjuvant chemotherapy the right time for a beauty boost? Lessons learned from a large randomized controlled trial

Quality of Life Research - Beauty care (BTC) is offered at many cancer hospitals having a great uptake among patients. Nevertheless, its benefits in the Quality of life (QoL) of cancer survivors...     

Impact of 970 nm photobiomodulation therapy on wound healing in cellular models of hidradenitis suppurativa

Lasers in Medical Science -     

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??Respiratory infections??especially respiratory viral infections??are common diseases in children. Although most respiratory viral infection diseases are self-limiting??some children may be hospitalized or even life-threatened due to severe viral lower respiratory tract infection. With the progress of virology research??new and effective antiviral drugs have been developed. Thus??the study focuses on the therapeutic progress of respiratory viral infections so as to improve the treatment for common respiratory viral infections in children.     

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??Objective??To analyze the clinical and gene mutation characteristics of Duchenne progressive muscular dystrophy ??DMD????summarize the gene mutation hotspots in 97 cases and to explore the correlation between clinical manifestations and genotype. Methods??Totally 97 patients with DMD diagnosed by genetic examination from January 2014 to 2018 were collected and analyzed. The clinical manifestations??serum analyses and gene mutation results were analyzed. Results??The main clinical manifestations of 97 patients??96 boys?? were feeding difficulties?? increased muscle enzyme and limb weakness. Creatine kinase??CK???? lactate dehydrogenase??LDH?? and aspartate aminotransferase??AST?? muscle enzymes were significantly increased. By combining deep-sequencing technologies??the large deletions of DMD gene mutation was in 62 cases??63.92%????there were 11 cases??11.34%?? of large duplication mutation??and 24 cases??24.74%?? of point mutation. All of the mutations could occur in any position in the DMD gene??but there were two hot spots??45 cases were located in the central region gene exon 45??55??72.58% ????12 cases of deletion mutation were located in 5’exon end exon 2??19 area??19.35%??. Conclusion??The main clinical manifestations of the DMD children are feeding difficulty??increased muscle enzyme and limb weakness. The patients with significantly increased muscle enzyme should receive a timely defection of DMD gene.     

Circulating tumor DNA predicts efficacy of a dual AKT/p70S6K inhibitor (LY2780301) plus paclitaxel in metastatic breast cancer: plasma analysis of the TAKTIC phase IB/II study

The phosphatidylinositol‐3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently activated in HER2‐negative breast cancer and may play a role in taxane resistance. The phase IB/II TAKTIC trial ({"type":"clinical-trial","attrs":{"text":"NCT01980277","term_id":"NCT01980277"}}NCT01980277) has shown that combining a dual AKT and p70 ribosomal protein S6 kinase (p70S6K) inhibitor (LY2780301) taken orally with weekly paclitaxel in HER2‐negative advanced breast cancer is feasible, with preliminary evidence of efficacy. We wanted to explore whether circulating tumor DNA (ctDNA) may be a surrogate marker of treatment efficacy in this setting. Serial plasma samples were collected and cell‐free DNA was sequenced using low‐coverage whole‐genome sequencing, and analysis was completed with droplet digital polymerase chain reaction (PCR) for some patients with driver mutations. Baseline tumor fraction (TF) and TF after 7 weeks on treatment were compared to progression‐free survival (PFS) and the overall response rate. We also explored circulating copy number alterations associated with treatment failure. Of the 51 patients enrolled in the TAKTIC trial, at least one plasma sample was available for 44 cases (96 timepoints). All patients with tumor TP53, PI3KCA, or AKT1 mutations harbored at least one of these alterations in plasma. TF at inclusion was correlated with PFS (6m‐PFS was 92% for ctDNAneg patients vs 68% for ctDNApos cases; hazard ratio [HR] = 3.45, 95% confidence interval [CI] [1.34–8.90], P = 0.007). ctDNA status at week 7 was not correlated with prognosis. Even though most circulating copy number alterations were conserved at disease progression, some genomic regions of interest were altered in post‐progression samples. In conclusion, ctDNA detection at baseline was associated with shorter PFS in patients included in the TAKTIC trial. Plasma‐based copy number analysis may help to identify alterations involved in resistance to treatment.     

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??Objective To investigate the relationship between CCL2-2518A/G gene polymorphism and severity of enterovirus 71??EV71?? infection. Methods CCL2 gene polymorphism in 188 EV71-infected patients and 235 healthy controls were detected by the improved multiplex ligation detection reaction technique??iMLDR??. The level of CCL2 in two groups was determined by enzyme-linked immunosorbent assay??ELISA??. Results No significant differences were found in the distribution of genotype CCL2-2518A/G between EV71-infected patients and the healthy control group??P??0.05??. The G allele??genotypes AG or GG?? in the CCL2-2518A/G??P??0.001?? was more frequent in patients with severe EV71 infection. The level of CCL2 in infected patients was higher than that of the heathy controls ??P??0.05???? the severe cases had higher level of CCL2 than that of the slight cases and healthy controls??P??0.05??. The level of CCL2 in GG gene group was significantly higher than that in AG gene group and the level of CCL2 in AG gene group was significantly higher than that in AA gene group.The people with CCL2-2518G allele??GG+AG?? had higher level of CCL2 than those only with CCL2-2518A allele??AA????P??0.05??. Conclusion The G carrier of the CCL2-2518A/G is found to be associated with severity of EV71 infection??and could be susceptibility factors in the development of EV71 infection.     

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??Toward New Classification Criteria for Juvenile Idiopathic Arthritis??First Steps??Pediatric Rheumatology International Trials Organization International Consensus was published onJournal of Rheumatologyin October??2018??and then at the2018Annual Meeting of AmericanColleage of Rheumatology??ACR????the relevant experts introduced the samecontent. Although the new JIA classification criteria in the process of improvement in western countries is still??PRINTO has designed a two-step’sprospective study??which will form a mature new JIA classification criteria after itscompletion. The new trend and progress of this subject is of great significance to the diagnosis??treatment and research of JIAin the world. CCIHA has organized a group of relevant Chinese experts to interpret the international consensus??aiming at putting forward suggestions and opinions of Chinese experts on the new classification of JIA??providing a basis for future research on the real world researchof JIA in China??and putting forward the opinions of Chinese experts to be in line with the new international criteria. This paper only interprets faithfully the original English text. The formation and application of JIA’s new classification criteria in China still need further study and discussion.