DhhP,a Cyclic di-AMP Phosphodiesterase of Borrelia burgdorferi,Is Essential for Cell Growth and Virulence

Cyclic di-AMP (c-di-AMP) is a recently discovered second messenger in bacteria. Most of work on c-di-AMP signaling has been done in Gram-positive bacteria, firmicutes, and actinobacteria, where c-di-AMP signaling pathways affect potassium transport, cell wall structure, and antibiotic resistance. Little is known about c-di-AMP signaling in other bacteria. Borrelia burgdorferi, the causative agent of Lyme disease, is a spirochete that has a Gram-negative dual membrane. In this study, we demonstrated that B. burgdorferi BB0619, a DHH-DHHA1 domain protein (herein designated DhhP), functions as c-di-AMP phosphodiesterase. Recombinant DhhP hydrolyzed c-di-AMP to pApA in a Mn²⁺- or Mg²⁺-dependent manner. In contrast to c-di-AMP phosphodiesterases reported thus far, DhhP appears to be essential for B. burgdorferi growth both in vitro and in the mammalian host. Inactivation of the chromosomal dhhP gene could be achieved only in the presence of a plasmid-encoded inducible dhhP gene. The conditional dhhP mutant had a dramatic increase in intracellular c-di-AMP level in comparison to the isogenic wild-type strain. Unlike what has been observed in Gram-positive bacteria, elevated cellular c-di-AMP in B. burgdorferi did not result in an increased resistance to β-lactamase antibiotics, suggesting that c-di-AMP''s functions in spirochetes differ from those in Gram-positive bacteria. In addition, the dhhP mutant was defective in induction of the σ^S factor, RpoS, and the RpoS-dependent outer membrane virulence factor OspC, which uncovers an important role of c-di-AMP in B. burgdorferi virulence.     

Virtual reality surgical anatomy of the sphenoid sinus and adjacent structures by the transnasal approach

ObjectiveTo examine the three-dimensional virtual anatomical features of the sphenoid sinus and adjacent structures during virtual surgery and explore their relevance to actual transsphenoidal surgery.MethodsCT images of the sphenoid sinus and surrounding structures from 28 Chinese adult patients were measured using a 16-slice helical CT scanner. Image analysis was performed using the volume-rendering method. Two experienced neurosurgeons wearing stereoscopic glasses performed virtual transsphenoidal surgery by the transnasal approach.ResultsThe virtual anatomical features of the sphenoid sinus and the adjacent structures during virtual surgery were described. The distance from the sphenopalatine foramen to the left and right sphenoid ostium was 10.1 ± 2.7 mm and 10.5 ± 3.2 mm, respectively, to the left and right sphenoidal crest 12.9 ± 2.0 mm and 12.8 ± 2.2 mm, respectively, and to the left and right uncinate process 24.0 ± 1.9 mm and 23.9 ± 2.0 mm, respectively. The distance from the uncinate process to the medial and lateral edge of the most prominent part of the anterior bend of the cavernous internal carotid artery (ICA) was 33.7 ± 3.7 mm and 34.8 ± 3.7 mm, respectively, and the angle between the two lines was 9.7 ± 1.9°.ConclusionThe study provides virtual anatomical information about the sphenoid sinus and important surrounding structures that is essential for successful real life transsphenoidal surgery.     

Epidemiologic investigation of burns in the elderly in Sichuan Province

Objective

This study analysed the epidemiology of burns in the elderly in Sichuan Province, China, with the objective of formulating a prevention programme.

Methods

A retrospective review of elderly patients admitted to the Burn Centre of West China Hospital during 2003–2009 was performed, including patient demographics, education and burn aetiology.

Results

A total of 103 patients, mean age 69.5 years (range 60–95 years; 58 male, 45 female) were admitted. The most common causes of burn were flames (51.5%), scalding (37.9%), electrical (4.9%) and chemical (2.9%), respectively. The majority occurred at home (68.9%), principally in the kitchen (35.9%), while 19.4% occurred in the workplace. Burns with total body surface area (TBSA) of 0–10% accounted for 52.5% of those admitted for treatment; 10–30% TBSA burns accounted for 20.3%; 30–50% TBSA burns accounted for 15.5%; and burns with a TBSA >50% accounted for 11.7%. Only 6% of patients received appropriate first aid, and 32% did not receive treatment until more than 24 h after injury. The education level was lower in the rural group. Both urban and rural groups had little knowledge of first aid for burns.

Conclusions

Burn-prevention programmes should promote improved living conditions and medical insurance, with prevention education for the elderly, especially in rural areas.     

Cutaneous applied nano-ZnO reduce the ability of hair follicle stem cells to differentiate

The ability of metal oxide nanoparticles to penetrate the skin has aroused a great deal of interest during the past decade due to concerns over the safety of topically applied sunscreens that contain physical UV-resistant metal particles, such as nano-Zinc oxide (nZnO). Previous studies demonstrate that metal oxide nanoparticles accumulate in skin furrows and hair follicles following topical application while little is known about the consequence of these nanoparticles on skin homeostasis. The current investigation tested the effects of nZnO (0.5?mg/day mouse) on hair follicle physiology. Topical application of Vaseline containing nZnO, bulk ZnO (bZnO), or ionized Zn to newborn mice vibrissa pad over a period of 7 consecutive days revealed that nZnO accumulated within hair follicles, and this induced the apoptosis of hair follicle stem cells (HFSCs). In vitro studies also indicated that nZnO exposure caused obvious DNA damage and induced apoptosis in HFSCs. Furthermore, it was found that nZnO exposure perturbed genes associated with HFSC apoptosis, cell communication, and differentiation. HFSCs transplantation assay demonstrated that the potential of HFSCs to differentiate was reduced. This investigation indicates a potential risk of topically applied ZnO nanoparticles on skin homeostasis.     

Risk Factors Associated With Sphincter-Preserving Resection in Patients With Low Rectal Cancer

Abdominoperineal resection (APR) and sphincter-preserving resection (SPR) are the two primary surgical options for rectal cancer. Retrospectively we collected rectal cancer patients for SPR and APR observation between 2005 and 2007. The patient-related, tumor-related, and surgery-related variables of the SPR and APR groups were analyzed by using logistic regression techniques. The mean distance from the anal verge (DAV) of cancer is significantly higher in SPR than that in APR (P < 0.001). In cancers with DAV <40 mm (SPR, 40 versus APR, 110), multivariate analysis shows that surgeon procedure volume (odds ratio [OR] = 0.244; 95% confidence interval [CI]: 0.077–0.772; P = 0.016) and neoadjuvant radiotherapy (OR = 0.031; 95% CI: 0.002–0.396; P = 0.008) are factors influencing SPR. In cancers with DAV ranging from 40 mm to 59 mm (SPR 190 versus APR 50), analysis shows that patient age (OR = 2.139; 95% CI: 1.124–4.069; P = 0.021), diabetes (OR = 2.657; 95% CI: 0.872–8.095; P = 0.086), and colorectal surgeon (OR = 0.122, 95% CI: 0.020–0.758; P = 0.024), are influencing factors for SPR. The local recurrence and disease-free survival reveal no significant difference. A significant difference exists in DAV, surgeon specialization, procedure volume, age, diabetes, and neoadjuvant radiotherapy between SPR and APR.Key words: Abdominoperineal resection, Sphincter-preserving resection, Anterior resection, Rectal cancer, TreatmentAbdominoperineal resection (APR) with permanent colostomy and sphincter-preserving resection (SPR) of the rectum are the two primary surgical options for the curative treatment of rectal cancer. With the introduction of the concept of total mesorectal excision (TME), combined with the significant effects of adjuvant radiochemotherapy and surgical staplers, SPR indication has been significantly expanded compared with APR in low or ultra-lower rectal cancer.For patients with rectal cancer, sphincter preservation (SP) is often as important as curing cancer. Surgeons need to determine whether a patient with lower rectal cancer is suitable for SP. However, a standard method of determining patient suitability is unavailable because this judgment depends on the different individual experiences of surgeons.In addition to the distance of the tumor from the anal verge (DAV), other important factors such as the patient''s individual condition, oncologic consideration, technical feasibility, and the surgeon''s personal experience, are reported as risk factors that may influence the SP rate.^1–3 This study aims to determine the significance of these factors on achieving SPR in a single large-volume institution.     

Rapid determination of benzophenone derivatives in cereals using FaPEx coupled with ultra–high-performance liquid chromatography–tandem mass spectrometry

A robust and sensitive analytical method was developed and validated for the simultaneous analysis of the levels of 10 benzophenone derivatives (BPs; BP, BP-1, BP-2, BP-3, BP-8, 2-hydroxybenzophenone [2-OHBP], 4-hydroxybenzophenone [4-OHBP], 4-methylbenzophenone [4-MBP], methyl-2-benzoylbenzoate [M2BB], and 4-benzoylbiphenyl [PBZ]) in 54 breakfast cereal samples. A fast pesticide extraction (FaPEx) technique coupled with isotope-labeled internal standards ultra–high-performance liquid chromatography–tandem mass spectrometry was employed. The developed method exhibited satisfactory linearity (R² > 0.998), high precision (intraday and interday relative standard deviations in the ranges of 1.4%–20.8% and 3.2%–23.9%, respectively), and a limit of detection ranging from 0.001 to 0.122 ng/g. BP and 4-MBP were detected in all samples, BP-3 was detected in >59% of the samples, M2BB was detected in 14% of the samples, and 4-OHBP was detected in 7% of the samples. The mean level (range) of BP was significantly higher in corn flakes [146.9 (25.3–1083.8) ng/g] than in oatmeal [22.8 (14.2–67.5) ng/g], and it contributed the most to the overall levels of the BPs, followed by 4-MBP. When the samples were stratified according to their packaging material, the mean level of BP was significantly higher in corn flake samples with plastic packaging (251.9 ng/g) than in corn flake and oatmeal samples with laminated aluminum foil packaging. Two samples of six-grain muesli contained remarkably high levels of BP (1084 and 1055 ng/g); both were nonorganic samples packaged in a polylactide bag. Future studies must examine the possible risks that these contaminants pose to human health.     

补肾祛寒化湿方联合甲氨蝶呤对强直性脊柱炎患者疾病活动度及 血清核心结合因子a1水平的影响

探究补肾祛寒化湿方（由骨碎补、杜仲、川续断、羌活、干姜、薏苡仁、怀牛膝等组成）联合甲氨蝶呤对强直 性脊柱炎（ankylosing spondylitis,AS）肾虚督寒证患者疾病活动度及血清核心结合因子a1（Cbfa1）水平的影响。【方法】将90例 AS肾虚督寒证患者随机分为试验组和对照组,每组各45例。对照组给予甲氨蝶呤治疗,试验组在对照组的基础上加用补肾 祛寒化湿方治疗,疗程为3个月。观察2组患者治疗前后巴氏强直性脊柱炎疾病活动指数（BASDAI）评分、巴氏强直性脊柱炎 功能指数（BASFI）评分和血清Cbfa1、Ⅰ型胶原蛋白C末端肽（CTX-Ⅰ）、Dickkopf1蛋白（DKK1）水平的变化情况,并比较2组 患者的临床疗效和不良反应发生率。【结果】（1）疗效方面,治疗3个月后,试验组的总有效率为97.78%（44/45）,对照组为 82.22%（37/45）,组间比较（χ2检验）,试验组的疗效明显优于对照组,差异有统计学意义（P＜0.05）。（2）疾病活动度方面,治 疗后,2组患者的BASDAI评分和BASFI评分均较治疗前明显降低（P＜0.05）,且试验组对BASDAI评分和BASFI评分的降低 幅度均明显优于对照组,差异均有统计学意义（P＜0.01）。（3）血清学指标方面,治疗后,2组患者的血清Cbfa1、CTX-Ⅰ、DKK1 水平均较治疗前降低（P＜0.05）,且试验组对血清Cbfa1、CTX-Ⅰ、DKK1水平的降低幅度均明显优于对照组,差异均有统计 学意义（P＜0.01）。（4）不良反应方面,治疗过程中,试验组的不良反应发生率为6.66%（3/45）,对照组为11.11%（5/45）,2组患 者的不良反应发生率比较,差异无统计学意义（P＞0.05）。【结论】补肾祛寒化湿方联合甲氨蝶呤治疗AS肾虚督寒证患者疗效 确切,能够有效控制患者的疾病活动度,降低血清Cbfa1表达水平。     

The efficacy and safety of treatments for infantile hemangiomas: a Bayesian network meta-analysis

Whether infantile hemangiomas (IHs) need to be treated and which treatment should be preferred are still controversial. We aimed to compare and rank the treatments and identify the optimal treatment for IHs. We searched PubMed, EMBASE, the Cochrane Library, Web of Science, and other sources for randomized controlled trials up to August 2019. We included trials comparingdifferent treatments and reported response or adverse events rate in IH patients. Two reviewers independently evaluated studies by specific criteria and extracted data. We assessed the risk of bias with the Cochrane risk of bias tool. Random-effects were performed for pair-to-pair and Bayesian framework network meta-analyses. The primary outcomes were efficacy and safety. We deemed 20 studies eligible, including 1149 participants and eight interventions. For efficacy, oral propranolol and topical propranolol/timolol were better than observation/placebo (OR, 95% CrI: 17.05, 4.02–94.94; 9.72, 1.91–59.08). For safety, topical propranolol/timolol was significantly better tolerated than oral propranolol (0.05, 0.001–0.66). Cluster analysis demonstrated oral propranolol was the most effective treatment for IHs, while topical propranolol/timolol showed high efficacy and the highest safety. Laser, intralesional propranolol or glucocorticoid, oral glucocorticoid, or captopril had significantly lower priority than oral propranolol or topical propranolol/timolol considering both efficacy and safety. The quality of evidence was rated as moderate or low in most comparisons. This network meta-analysis found topical beta-blockers had the potential to be the most preferable and beneficial option for IHs in consideration of both efficacy and safety.