IgG Against Dengue Virus in Healthy Blood Donors,Zanzibar, Tanzania

We conducted a seroprevalence survey among 500 healthy adult donors at Zanzibar National Blood Transfusion Services. Dengue virus IgG seroprevalence was 50.6% and independently associated with age and urban residence. These data will aid in building a surveillance, preparedness, and response plan for dengue virus infections in the Zanzibar Archipelago.Key words: dengue, seroprevalence, Zanzibar, viruses, vector-borne infections     

Tumor mutational load predicts time to first treatment in chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis beyond the CLL international prognostic index

Next-generation sequencing identified about 60 genes recurrently mutated in chronic lymphocytic leukemia (CLL). We examined the additive prognostic value of the total number of recurrently mutated CLL genes (i.e., tumor mutational load [TML]) or the individually mutated genes beyond the CLL international prognostic index (CLL-IPI) in newly diagnosed CLL and high-count monoclonal B-cell lymphocytosis (HC MBL). We sequenced 59 genes among 557 individuals (112 HC MBL/445 CLL) in a multi-stage design, to estimate hazard ratios (HR) and 95% confidence intervals (CI) for time-to-first treatment (TTT), adjusted for CLL-IPI and sex. TML was associated with shorter TTT in the discovery and validation cohorts, with a combined estimate of continuous HR = 1.27 (CI:1.17-1.39, P = 2.6 × 10⁻⁸; c-statistic = 0.76). When stratified by CLL-IPI, the association of TML with TTT was stronger and validated within low/intermediate risk (combined HR = 1.54, CI:1.37-1.72, P = 7.0 × 10⁻¹⁴). Overall, 80% of low/intermediate CLL-IPI cases with two or more mutated genes progressed to require therapy within 5 years, compared to 24% among those without mutations. TML was also associated with shorter TTT in the HC MBL cohort (HR = 1.53, CI:1.12-2.07, P = .007; c-statistic = 0.71). TML is a strong prognostic factor for TTT independent of CLL-IPI, especially among low/intermediate CLL-IPI risk, and a better predictor than any single gene. Mutational screening at early stages may improve risk stratification and better predict TTT.     

Parkinsonism as a late presentation of lymphomatosis cerebri following high-dose chemotherapy with autologous stem cell transplantation for primary central nervous system lymphoma

Journal of Neurology - Primary central nervous system lymphoma is an aggressive form of non-Hodgkin lymphoma arising in the eyes, meninges, spinal cord, or brain. Treatment of primary CNS lymphoma...     

Pulp revascularization for immature replanted teeth: a case report

Immature avulsed teeth are not usually treated with pulp revascularization because of the possibility of complications. However, this therapy has shown success in the treatment of immature teeth with periapical lesions. This report describes the case of an immature replanted tooth that was successfully treated by pulp revascularization. An 8‐year‐old boy suffered avulsion on his maxillary left lateral incisor. The tooth showed incomplete root development and was replanted after 30 minutes. After diagnosis, revascularization therapy was performed by irrigating the root canal and applying a calcium hydroxide paste and 2% chlorhexidine gel for 21 days. In the second session, the intracanal dressing was removed and a blood clot was stimulated up to the cervical third of the root canal. Mineral trioxide aggregate was placed as a cervical barrier at the entrance of the root canal and the crown was restored. During the follow‐up period, periapical repair, apical closure and calcification in the apical 4 mm of the root canal was observed. An avulsed immature tooth replanted after a brief extra‐alveolar period and maintained in a viable storage medium may be treated with revascularization.     

Human Cytomegalovirus Infection Leads to Elevated Levels of Transplant Arteriosclerosis in a Humanized Mouse Aortic Xenograft Model

Recent findings emphasized an important role of human cytomegalovirus (HCMV) infection in the development of transplant arteriosclerosis. Therefore, the aim of this study was to develop a human peripheral blood lymphocyte (hu‐PBL)/Rag‐2^–/–γc^–/– mouse‐xenograft‐model to investigate both immunological as well as viral effector mechanisms in the progression of transplant arteriosclerosis. For this, sidebranches from the internal mammary artery were recovered during coronary artery bypass graft surgery, tissue‐typed and infected with HCMV. Then, size‐matched sidebranches were implanted into the infrarenal aorta of Rag‐2^–/–γc^–/– mice. The animals were reconstituted with human peripheral blood mononuclear cells (PBMCs) 7 days after transplantation. HCMV‐infection was confirmed by Taqman‐PCR and immunofluorescence analyses. Arterial grafts were analyzed by histology on day 40 after transplantation. PBMC‐reconstituted Rag‐2^–/–γc^–/– animals showed splenic chimerism levels ranging from 1–16% human cells. After reconstitution, Rag‐2^–/–γc^–/– mice developed human leukocyte infiltrates in their grafts and vascular lesions that were significantly elevated after infection. Cellular infiltration revealed significantly increased ICAM‐1 and PDGF‐R‐β expression after HCMV‐infection of the graft. Arterial grafts from unreconstituted Rag‐2^–/–γc^–/– recipients showed no vascular lesions. These data demonstrate a causative relationship between HCMV‐infection as an isolated risk factor and the development of transplant‐arteriosclerosis in a humanized mouse arterial‐transplant‐model possibly by elevated ICAM‐1 and PDGF‐R‐β expression.     

The Role of Smoking in Breast Cancer Development: An Analysis of a Mayo Clinic Cohort

Abstract:  The purpose of this study was to assess the predictive value of smoking history on breast cancer diagnosis in a referral clinic population. We conducted a case–control study using clinical data collected on 8,097 female patients (1,225 breast cancer cases and 6,872 controls) seen in the Mayo Clinic Breast Clinic between August 1, 1993 and November 31, 2003. Breast cancer patients and noncancer patients significantly differed with respect to age at time of the index visit (p < 0.001), number of pregnancies (p = 0.006), number of live births (p = 0.002), vital status at last known follow-up (p < 0.001), current menstruation (p < 0.001), age at menopause (p < 0.001), history of hysterectomy (p < 0.001), use of oral contraception (p = 0.05), duration of oral contraception use (p = 0.001), use of other exogenous hormones (p < 0.001), duration of exogenous hormone use (p = 0.05), breast pain at time of index visit (p = 0.002), smoking status (p < 0.001), and use of five or more alcoholic beverages per week (p = 0.002). After adjustment for these baseline characteristics, having a personal history of smoking was found to be predictive of breast cancer diagnosis (odds ratios [OR] = 1.25, p = 0.004). Other positive predictors for breast cancer diagnosis were: age (OR = 1.02, p < 0.001), history of hysterectomy (OR = 0.66, p < 0.001), prior use of oral contraception for more than 11 years (OR = 2.10, p < 0.001), and prior use of other exogenous hormones/estrogen (OR = 1.81, p < 0.001). In this referral practice having a personal history of smoking is predictive of breast cancer diagnosis. Further studies are needed to further explore this relationship.     

Spontaneous abortion following mid-trimester amniocentesis. Clinical significance of placental perforation and blood-stained amniotic fluid

Summary. The clinical significance of placental perforation and bloodstained amniotic fluid was studied in a group of 7238 Danish women undergoing mid-trimester amniocentesis for prenatal diagnosis under ultrasound guidance. The risk of spontaneous abortion was significantly increased both in pregnancies where the placenta was perforated and in those with blood-stained amniotic fluid. The risk estimate nearly doubled after placental perforation and more than doubled with a bloody tap. It is concluded that for women at relatively low risk of a fetal genetic abnormality, the indication of the amniocentesis should be reconsidered if a placental perforation is unavoidable.     

破坏泛素依赖的蛋白水解通路对p53转录激活的抑制作用

目的 :研究功能性泛素化及蛋白酶体水解过程对p5 3转录激活的影响。方法 :通过瞬时转染报告基因法 ,测定内源、外源性p5 3或p5 3转录活性片断的转录能力 (荧光素酶活性 ) ;Western blot法测定细胞内p5 3及其靶蛋白p2 1waf1 的表达水平。结果 :抑制蛋白酶体水解过程 ,细胞内源、外源性p5 3及p5 3转录活性片断的转录能力均降低 ;泛素化途径缺失时 ,p5 3转录能力被显著抑制 ,虽然细胞内p5 3蛋白堆积 ,但其下游靶蛋白p2 1waf1 的表达却无增加。结论 :p5 3泛素蛋白酶体水解途径与其转录激活过程存在功能性联系