Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause

Nager syndrome belongs to the group of acrofacial dysostosis, which are characterized by the association of craniofacial and limb malformations. Recently, exome sequencing studies identified the SF3B4 gene as the cause of this condition in most patients. SF3B4 encodes a highly conserved protein implicated in mRNA splicing and bone morphogenic protein (BMP) signaling. We performed SF3B4 sequencing in 14 families (18 patients) whose features were suggestive of Nager syndrome and found nine mutations predicted to result in loss‐of‐function. SF3B4 is the major gene responsible for autosomal dominant Nager syndrome. All mutations reported predict null alleles, therefore precluding genotype–phenotype correlations. Most mutation‐negative patients were phenotypically indistinguishable from patients with mutations, suggesting genetic heterogeneity.     

小儿健脾开胃合剂联合赖氨酸维B12颗粒治疗小儿厌食症的临床研究

目的研究小儿健脾开胃合剂联合赖氨酸维B_(12)颗粒治疗小儿厌食症的临床疗效。方法选取2017年12月—2018年12月青海省妇女儿童医院收治的80例厌食症患儿为研究对象,将所有患儿随机分为对照组和治疗组,每组各40例。对照组患儿口服赖氨酸维B_(12)颗粒,1～5岁,0.5袋/次,2次/d,6～12岁,1袋/次,2次/d;治疗组患儿在对照组治疗的基础上口服小儿健脾开胃合剂,10 mL/次,2次/d。两组患儿持续治疗30 d。观察两组的临床疗效,比较两组的微量元素、生化指标水平。结果治疗后,对照组和治疗组的总有效率分别为82.50%、95.00%,两组比较差异有统计学意义(P0.05)。治疗后,两组患儿铁、钙和锌水平均显著升高,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患儿铁、钙和锌水平均明显高于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患儿血红蛋白(Hb)、血清淀粉酶(AMS)、血清铁蛋白(SF)水平均显著升高,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患儿Hb、AMS、SF水平明显高于对照组,两组比较差异有统计学意义(P0.05)。结论小儿健脾开胃合剂联合赖氨酸维B_(12)颗粒治疗小儿厌食症具有较好的临床疗效,能改善患儿贫血症状,调节血清微量元素水平,具有一定的临床推广应用价值。     

Increased activation of blood coagulation in pregnant women with the Factor V Leiden mutation

Background

The risk of venous thromboembolism is enhanced in pregnant carriers of the Factor V Leiden mutation. The primary aim of the study was to compare prothrombin fragments 1 + 2, soluble fibrin and D-dimer levels in pregnant Factor V Leiden mutation carriers with those in non-carriers. Secondary aims were to evaluate whether these biomarkers could predict placenta-mediated complications or venous thromboembolism, and to study blood coagulation after caesarean section with thromboprophylaxis and after vaginal delivery without thromboprophylaxis.

Material/Methods

Prothrombin fragments 1 + 2, soluble fibrin and D-dimer levels were studied longitudinally in 476 carriers with singleton pregnancies from gestational weeks 23–25 until 8–10 weeks postpartum.

Results

Prothrombin fragments 1 + 2 and D-dimer levels gradually increased during pregnancy. D-dimer levels were higher in carriers, both during pregnancy and puerperium, compared to non-carriers. D-dimer levels above 0.5 mg/l were found in about 30% and 20% of the heterozygous carriers at 4–5 and 8–10 weeks postpartum, respectively. Soluble fibrin levels were mainly unchanged during pregnancy, with no difference between carriers and non-carriers. Biomarker levels were similar in carriers with uncomplicated and complicated pregnancies.

Conclusion

Higher D-dimer levels indicate increased blood coagulation and fibrinolysis activity in carriers. The high proportion of carriers with D-dimer levels exceeding 0.5 mg/l postpartum must be considered when assessing the probability of venous thromboembolism. Large overlaps in biomarker levels in normal and complicated pregnancies suggest that these biomarkers cannot be used as predictors. Thromboprophylaxis following caesarean section may prevent increased activation of blood coagulation.     

The role of hypothalamic estrogen receptors in metabolic regulation

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ‘classical’ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1^−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism.     

Quality of life in haemophilia A: Hemophilia Utilization Group Study Va (HUGS-Va)

Summary. This study describes health‐related quality of life (HRQoL) of persons with haemophilia A in the United States (US) and determines associations between self‐reported joint pain, motion limitation and clinically evaluated joint range of motion (ROM), and between HRQoL and ROM. As part of a 2‐year cohort study, we collected baseline HRQoL using the SF‐12 (adults) and PedsQL (children), along with self‐ratings of joint pain and motion limitation, in persons with factor VIII deficiency recruited from six Haemophilia Treatment Centres (HTCs) in geographically diverse regions of the US. Clinically measured joint ROM measurements were collected from medical charts of a subset of participants. Adults (N = 156, mean age: 33.5 ± 12.6 years) had mean physical and mental component scores of 43.4 ± 10.7 and 50.9 ± 10.1, respectively. Children (N = 164, mean age: 9.7 ± 4.5 years) had mean total PedsQL, physical functioning, and psychosocial health scores of 85.9 ± 13.8, 89.5 ± 15.2, and 84.1 ± 15.3, respectively. Persons with more severe haemophilia and higher self‐reported joint pain and motion limitation had poorer scores, particularly in the physical aspects of HRQoL. In adults, significant correlations (P < 0.01) were found between ROM measures and both self‐reported measures. Except among those with severe disease, children and adults with haemophilia have HRQoL scores comparable with those of the healthy US population. The physical aspects of HRQoL in both adults and children with haemophilia A in the US decrease with increasing severity of illness. However, scores for mental aspects of HRQoL do not differ between severity groups. These findings are comparable with those from studies in European and Canadian haemophilia populations.     

Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.     

The patient-reported outcome of age-related cataract using Catquest-8SF questionnaire

AIM: To assess the patient-reported outcome of phacoemulsification with posterior chamber single focus foldable intraocular lens (SIOL) using the Chinese version of Catquest-8SF questionnaire (Catquest-8SF-CN), evaluate the applicability of Catquest-8SF scale in northern Chinese and its sensitivity to cataract surgery. METHODS: Prospective clinical case follow-up study. The patients were recruited from the Central Hospital of Tai’an and completed the Catquest-8SF questionnaire by face-to-face interviews before and 3mo after surgery at the hospital. RESULTS: A total of 120 cataract patients with median age 67.6y and 52.5% female completed the Catquest-8SF. The Cronbach’s α coefficient of the total scale, daily-activity sub-table and comprehensive-evaluation sub-table were 0.861, 0.853 and 0.748 respectively. There was a high level of consistency between two investigators. The cumulative contribution rate was 66.64% by using the principal component analysis and the maximum variance orthogonal rotation method. The preoperative score of the Catquest-8SF-CN had a significant negative correlation with preoperative binocular mean weighted visual acuity and age (P<0.05), while a significant positive correlation with education level (F=6.094, P<0.001). The patients without systemic comorbidities got higher score than those who with (P<0.05). Three months after surgery, 102 (85%) patients came for follow-up and completed the questionnaire. Significant improvement of visual acuity was observed in both binocular and monocular surgery groups (t=10.404, P<0.001). There was higher improvement in binocular weighted visual acuity of binocular surgery group than in monocular surgery group (t=-20.77, P<0.001). The postoperative score was significantly higher in both groups than before (P<0.001). There was a significant improvement in the total score after cataract surgery. The 94 patients (92.2%) were very satisfied or satisfied with the operation; 92 patients (90.2%) thought the surgery achieved their expectations, and they all felt satisfactory. The degree of satisfaction was significantly correlated with the improvement score of the scale and it was also correlated with their expectation of the surgery. CONCLUSION: The Chinese version of Catquest-8SF questionnaire is suitable for the age-related cataract population in northern China. It is highly responsive to cataract surgery and brief, so it may have the potential to become part of a routine clinical assessment for cataract surgery in China. The patient’s overall satisfaction is high, which illustrates that the medical service we provide matches the patient’s needs. The degree of satisfaction was significantly correlated with the improvement score of the scale and it was also correlated with their expectation of the surgery.