A novel p.Gly417Valfs*12 mutation in the MTTP gene causing abetalipoproteinemia: Presentation of the first patient in Mexico and analysis of the previously reported cases

BackgroundOur aims were to describe the first Mexican patient with abetalipoproteinemia and to perform a comparative analysis of biochemical, clinical, and genetic characteristics of 100 cases reported in the literature.MethodsWe performed biochemical and molecular screenings in a Mexican girl with extremely low lipid levels and in her family. Further, we integrated and evaluated the characteristics of the cases with abetalipoproteinemia described in the literature.ResultsOur patient is a six‐year‐old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels. MTTP gene sequencing revealed homozygosity for a novel mutation p.Gly417Valfs*12 (G deletion c.1250). With the analysis of the reported cases, 60 clinical features (14 classical and 46 non‐classical) were observed, being the most common acanthocytosis (57.5%), malabsorption (43.7%), and diarrhea (42.5%); 48.8% of the patients presented only classic clinical features, while the remaining 51.2% developed secondary effects due to a fat‐soluble vitamin deficiency. An odds ratio analysis disclosed that patients diagnosed after 10 years of age have an increased risk for presenting clinical complications (OR = 18.0; 95% CI 6.0‐54.1, p < 0.0001). A great diversity of mutations in MTTP has been observed (n = 76, being the most common p.G865X and p.N139_E140) and some of them with possible residual activity.ConclusionThe first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12. Three factors that could modulate the phenotype in abetalipoproteinemia were identified: age at diagnosis, treatment, and the causal mutation.     

Efficacy of using NRT thresholds in cochlear implants fitting,in prelingual pediatric patients

ObjectiveTo evaluate the efficacy of using neural response telemetry (NRT) thresholds in predicting behavioural thresholds during programming of cochlear implant in prelingual children.MethodProspective study of 28 cochlear implants implanted with Nucleus 24 cochlear implant. We recorded NRT-thresholds on electrode numbers 1, 6, 11, 16 and 22 of the electrode array in each patient, the neural response thresholds were correlated with the behavioural map after six months of programming the device.ResultsThe mean neural response telemetry level was significantly higher than the mean threshold level (T-level) but lower than the comfortable level (C-level) in all the electrodes tested. NRT levels could statistically significantly predict T behavioural levels and comfortable behavioural levels, p < 0.01. There was a strong positive correlation between comfortable thresholds and neural response telemetry level measurements and behavioural threshold level and neural response telemetry threshold measurements.ConclusionThere is a useful role for neural response telemetry values in predicting the behavioural threshold and comfortable values in prelingual children. Combining the NRT values with behavioural observations can improve the programming of cochlear implants.     

卵巢上皮癌术后激素补充治疗对肿瘤预后的影响

目的探讨上皮性卵巢癌患者术后行激素补充治疗(HRT)对肿瘤预后的影响。方法连续收集北京协和医院妇产科2000年1月至2010年12月收治的59岁的卵巢上皮癌患者756例,术后接受HRT者79例,为病例组。随机选取同期术后未行HRT者79例为对照组。详细记录该158例患者的临床资料,对相关因素进行回顾性分析。结果 (1)病例组术后总生存时间的中位时间45个月(术后6~264月),对照组42个月(术后6~189月),两组间差异无统计学意义(Z=-0.259,P=0.796)。(2)病例组术后19例复发(24.1%),对照组24例复发(30.3%),两组间差异无统计学意义(P=0.48)。(3)病例组术后2例死亡(3%),对照组术后2例死亡(3%),两组间无差异。(4)病例组术后无进展生存时间的中位时间34个月(术后3~181月),对照组28个月(术后2~189月),log-rank分析显示:两组间的差异无统计学意义(P=0.230)。(5)多因素Cox回归分析显示,HRT不是患者术后复发的独立预后因素(P=0.129),使用HRT复发的风险率(odds ratio,OR)为0.609(95%CI=0.321~1.155),病例组死亡的OR值为0.430(95%CI=0.040~4.682)。结论卵巢上皮癌患者术后的HRT不影响疾病的总体预后。     

Rhodamine B increases hypothalamic cell apoptosis and disrupts hormonal balance in rats

ObjectiveTo investigate whether orally exposure to rhodamine B could be changes the expression of Bax, Bcl-2 of the hypothalamic, and also levels of Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) in female rats.MethodsTwenty eight virgin female Wistar rats were divided into four groups, including control group, group exposed to dose of 4.5, 9 and 18 milligram/200 gram body weight (mg/200 g BW) of rhodamine B daily for 36 days. The hypothalamic expressions of Bax and Bcl-2 were examined immunohistochemically. The levels of serum FSH and LH were determined by the enzyme-linked immunosorbent assay (ELISA) technique.ResultsThe level of Bax was significantly higher in the rhodamine B treatment group compred to control group (P<0.05). Out of the 4.5, 9, and 18 mg/200 g BW doses of rhodamine B treatment, only the two highest doses significantly decreased the Bcl-2 levels compared to the control group (P<0.05). The serum FSH and LH levels were significantly lower in all dose's rhodamine B treatment groups compared with the control (P<0.05).ConclusionIn conclusion, rhodamine B increases hypothalamic cell apoptosis and disrupts hormonal balance in rats.     

激素与自杀行为关系的研究进展

自杀是一个世界范围内严重的公共卫生问题和社会问题。WHO估计世界自杀死亡率为14.5/10 万, 相当于每40 s就有1人自杀^[1]。Phillips 等^[2]曾估计中国的自杀率为23/10万, 自杀是15～34 岁人群的首位死亡原因。     

The next era of treatment for hormone receptor-positive,HER2-negative advanced breast cancer: Triplet combination-based endocrine therapies

Until recently, the standard of care for hormone receptor-positive (HR+) breast cancer was single-agent endocrine therapy, which aims to prevent estrogen receptor signaling. This therapeutic strategy has extended survival without the toxicity associated with chemotherapy, but primary endocrine therapy resistance is common, and secondary resistance develops over time. Adjunct downstream inhibition of the cyclin-dependent kinase (CDK)4/6 pathway, intended to delay and prevent endocrine therapy resistance, has further extended progression-free survival in patients receiving endocrine therapy; however, resistance still eventually develops in these patients. Addition of phosphatidylinositol-3 kinase (PI3K) or mammalian target of rapamycin (mTOR) inhibitors to combined CDK4/6 and endocrine inhibitor regimens may help prolong CDK4/6 inhibitor sensitivity. Early trials combining CDK4/6 inhibitors, PI3K or mTOR inhibitors, and endocrine therapy have shown encouraging signs of clinical activity. However, further research is needed to help understand the extent of treatment benefit from triplet therapy and where this strategy will fit in the treatment sequence for patients with HR+ breast cancer.     

Transferring psychiatric specialist services to local authorities—Characteristics of the patients involved

Background: To obtain more co-ordinated services, better co-operation between the services and more efficient use of resources, a pilot project for transferring some district psychiatric centres (DPCs) to large municipalities is planned by the Norwegian government. Systematic knowledge about the patients involved is needed when clinical needs and standards, funding, and political agendas are discussed. This study identifies the clinical, socio-demographic, and behavioural characteristics of patients who need services from both the municipality and the DPC.

Method: A national mapping of patients in specialist mental health services was conducted in 2012/2013, including 65% of all inpatients (n?=?2358) and 60% of all outpatients (n?=?23?124). The need for services was assessed by each patient’s clinician.

Results: It was found that 74% of inpatients and 43% of outpatients needed one or more services from the municipality, usually involving housing, mental health treatment/therapy, or economic support according to their clinicians. These were typically patients with severe mental illness, young inpatients, older outpatients and persons with low education and weak social networks. Only small differences in the need for municipal services were found between patients in hospitals and DPCs.

Conclusions: Many of the patients in specialist mental health services, especially the inpatients, needed services from municipal social and health services. Because these patients had the most severe mental illnesses and were the most socially deprived, a stronger integration of service levels would potentially benefit these patients most. The pilot project should be evaluated to identify the consequences for patients, staff, quality of services, and costs of transferring services to a lower system level.     

Alteration of serum thymus and activation‐regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti‐interleukin‐17A agents

Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side‐effects of biologics, dose‐reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation‐regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI‐clear with biologics than in the group which did not achieve PASI‐clear. Among biologics, the group treated with secukinumab, an anti‐interleukin (IL)‐17A agent, showed significantly higher TARC level compared with the group treated with anti‐tumor necrosis factor agents. In certain populations achieving PASI‐clear, serum TARC level may be a potent marker reflecting better response to IL‐17A inhibitors, and in this case step down of treatment for psoriasis is possible.