Eyelid movements during blinking in patients with Parkinson's disease.

We examined eyelid movements during spontaneous, voluntary, and trigeminal reflex blinks in 16 patients with mild to moderate Parkinson's disease (PD) off medication and 14 controls. Voluntary and reflex blink amplitudes tended to be smaller than normal for PD patients, whereas eyelid kinematics (amplitude-maximum velocity relationship) for all three blink types were normal. Spontaneous blink rate was less than normal for 10 patients and abnormally high for 6 patients. A significant positive correlation between spontaneous blink amplitude and blink rate was found. These observations suggest that PD modifies the gain of a premotor blink circuit shared by spontaneous, voluntary, and reflex blinks.     

Ivermectin for the chemotherapy of bancroftian filariasis: a meta-analysis of the effect of single treatment

Summary The efficacy and safety of ivermectin in the treatment of filariasis due to Wuchereria bancrofti was assessed by a meta-analysis of the results from 15 published clinical trials. Seven hundred and forty-eight microfilaraemic patients were enrolled in 7 dose-finding and 8 comparative studies. Administered as a single dose, ivermectin induced nearly complete clearance of microfilariae from the blood from the first day to 30 days post-treatment, followed by gradual recurrence of microfilaraemia and increase in its intensity. Higher doses of ivermectin showed greater clearance effects and maintained lower microfilaraemia levels for a longer time. The adverse reactions caused by the drug were flu-like, transient, generally mild and well tolerated by patients. The frequency and intensity of adverse reactions were strongly associated with pretreatment microfilaria counts in the blood, but independent of dose. The findings of the meta-analysis suggest that ivermectin given at a single annual dose of 200 μg/kg body weight or higher, whether or not in combination with DEC, has great potential for therapeutic strategies to control bancroftian filariasis.     

Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: A modeling study

OBJECTIVE: To determine whether population differences can explain the contrasting impacts on HIV observed in the Mwanza trial of sexually transmitted disease (STD) syndromic treatment (ST), the Rakai trial of STD mass treatment (MT), and the Masaka trial of information, education, and communication (IEC) with and without ST as well as to predict the effectiveness of each intervention strategy in each population. METHODS: Stochastic modeling of the transmission of HIV and 6 STDs was used with parameters fitted to demographic, sexual behavior, and epidemiological data from the trials and general review of STD/HIV biology. RESULTS: The baseline trial populations could be simulated by assuming higher risk behavior in Uganda compared with Mwanza in the 1980s, followed by reductions in risk behavior in Uganda preceding the trials. In line with trial observations, the projected HIV impacts were larger for the ST intervention in Mwanza than for the MT intervention in Rakai or the IEC and IEC + ST interventions in Masaka. All 4 simulated intervention strategies were more effective in reducing incidence of HIV infection in Mwanza than in either Rakai or Masaka. CONCLUSIONS: Population differences in sexual behavior, curable STD rates, and HIV epidemic stage can explain most of the contrast in HIV impact observed between the 3 trials. This study supports the hypothesis that STD management is an effective HIV prevention strategy in populations with a high prevalence of curable STDs, particularly in an early HIV epidemic.     

Predictors of occult metastasis in clinical stage I nonseminoma: a systematic review.

PURPOSE: Patients with clinical stage I nonseminomatous testicular germ cell tumor should ideally receive adjuvant therapy only when they are at high risk for occult metastasis. We aimed to quantify the importance of predictors for occult metastasis by performing a systematic review of the relevant literature. In addition, we reviewed published multivariable models and risk-adapted treatment policies. PATIENTS AND METHODS: We identified 23 publications between 1979 and 2001, reporting a total of 2,587 patients. Twenty-nine percent of the patients (759 of 2,587 patients) had occult metastases, which was diagnosed either at retroperitoneal lymph node dissection (n = 193) or during follow-up (n = 566). Odds ratios (OR) were pooled using meta-analysis techniques. RESULTS: The presence of vascular invasion of the primary tumor cells had the strongest effect (OR, 5.2; 95% CI, 4.0 to 6.8). Immunohistochemical staining of the primary tumor cells with the MIB-1 monoclonal antibody showing proliferative activity was a promising predictor (OR, 4.7; 95% CI, 2.0 to 11). Intermediate effects were found for embryonal carcinoma in the primary tumor (OR, 2.9; 95% CI, 2.0 to 4.4) and a high pathologic stage of the tumor (OR, 2.6; 95% CI, 1.8 to 3.8). Size of the primary tumor and age of the patient had weaker though also statistically significant associations with occult metastasis. Until now, multivariable models often included vascular invasion and embryonal carcinoma with one or two weaker predictors. None of the published risk-adapted treatment policies included MIB-1 staining. CONCLUSION: Several strong predictors for occult metastasis were identified. A risk-adapted treatment policy should be developed that incorporates all relevant predictors so that adjuvant therapy is targeted better to those with occult metastases.     

Female epispadias repair: a new 1-stage technique

PURPOSE: Female epispadias is a rare anomaly. According to the literature it is usually treated with staged procedures, including bladder neck reconstruction, to achieve continence. We developed a 1-stage surgical technique that offers the possibility of achieving continence and a cosmetically normal appearance of the vulva. MATERIALS AND METHODS: We treated 4 patients 4 months to 8 years old. The main point of the technique is to free completely the urethral plate and bladder neck from surrounding tissue. After tubularizing the urethral plate into a urethra modified needle suspension brings the bladder neck and proximal urethra into the intra-abdominal position. The pelvic floor is then reconstructed between the anterior vaginal wall and urethra. Thus, continence may be attained by intra-abdominal positioning of the bladder neck and proximal urethra as well as by pelvic floor reconstruction. RESULTS: Of our 4 consecutive cases of primary untreated epispadias the technique proved successful in 3, while followup is too short in 1. One patient is completely dry and voids without a further procedure. Postoperatively 2 patients with 5 years or more of followup required injection of a bulking agent at the bladder neck level to achieve continence, including 1 who is damp during the day without the need to change clothes and 1 on clean intermittent catheterization twice daily because post-void residual urine volume causes recurrent urinary tract infection. CONCLUSIONS: The described technique is promising for treating this disabling anomaly.     

Considerations on the EU definition of a nanomaterial: Science to support policy making

In recent years, an increasing number of applications and products containing or using nanomaterials have become available. This has raised concerns that some of these materials may introduce new risks for humans or the environment. A clear definition to discriminate nanomaterials from other materials is prerequisite to include provisions for nanomaterials in legislation. In October 2011 the European Commission published the ‘Recommendation on the definition of a nanomaterial’, primarily intended to provide unambiguous criteria to identify materials for which special regulatory provisions might apply, but also to promote consistency on the interpretation of the term ‘nanomaterial’. In this paper, the current status of various regulatory frameworks of the European Union with regard to nanomaterials is described, and major issues relevant for regulation of nanomaterials are discussed. This will contribute to better understanding the implications of the choices policy makers have to make in further regulation of nanomaterials. Potential issues that need to be addressed and areas of research in which science can contribute are indicated. These issues include awareness on situations in which nano-related risks may occur for materials that fall outside the definition, guidance and further development of measurement techniques, and dealing with changes during the life cycle.     

Prevalence of Anaplasma phagocytophila and Borrelia burgdorferi in Ixodes persulcatus ticks from northeastern China

A total of 1,345 Ixodes persulcatus ticks collected from northeastern China were investigated for the presence of Anaplasma phagocytophila and Borrelia burgdorferi by a nested polymerase chain reaction (PCR). Sixty-two (4.6%) ticks were positive for A. phagocytophila and 454 (33.8%) were positive for B. burgdorferi. Seven (0.5%) were coinfected with both agents. Sequence analysis of 919-basepair PCR amplicons revealed three types of A. phagocytophila. Type 1 was identical to the published sequences of A. phagocytophilas responsible for human granulocytic ehrlichiosis (HGE). The other two variants differed from the HGE agent sequence at one and four positions, respectively. These findings imply that infection with A. phagocytophila poses a potential health threat to both humans and animals in northeastern China, and that ehrlichiosis should be considered in the differential diagnosis of febrile patients with a history of tick bite, particularly when clinical manifestations are atypical for Lyme disease.     

A newly discovered Anaplasma phagocytophilum variant in rodents from southeastern China

Anaplasma phagocytophilum was detected by polymerase chain reaction in 13 (14.1%) of 92 rodents captured from a mountainous area of Zhejiang Province in southeastern China. The nucleotide sequences of 1442-bp, nearly entire 16S rRNA gene amplified from these rodents, had 100% identity, but varied from all known corresponding sequences of A. phagocytophilum deposited in GenBank. To further identify and classify the variant, fragments of 357-bp partial citrate synthase gene (gltA), 849-bp major surface protein 4 gene (msp4), and 443-bp groESL heat-shock operon gene, were amplified and analyzed. The nucleotide sequences of the partial gltA gene amplified from the rodents were identical to each other, but distinct from previously reported A. phagocytophilum sequences,as were msp4 and groESL. These findings indicate that the newly discovered agent represents a novel A. phagocytophilum variant.     

Combined TCRG and TCRA TREC analysis reveals increased peripheral T-lymphocyte but constant intra-thymic proliferative history upon ageing

T-cell receptor (TCR) repertoire diversity, thymic output, clonal size and peripheral T-lymphocyte numbers largely depend on intra-thymic and post-thymic T-lymphocyte proliferation. However, quantitative insight into thymocyte and T-lymphocyte proliferation is still lacking. We developed a new TCRG-based TCR excision circle (TREC) assay, the Vγ-Jγ TREC assay, which we used together with an adjusted δREC-ψJα TREC assay to quantify the proliferative history of human thymocyte and T-lymphocyte subpopulations from children and adults. This revealed that thymocytes undergo ～6–8 intra-thymic cell divisions from the double negative (DN) 3 developmental stage onwards, which appeared independent of age. Thus thymocyte proliferation after the DN3 developmental stages is stable and therefore not contributing to the reduced thymic output upon ageing. Cord blood naive T lymphocytes had already undergone ～2–3 post-thymic cell divisions, which increased to ～6–7 cell divisions in naive T lymphocytes of middle-aged adults, indicating the importance of homeostatic naive T-lymphocyte proliferation from a young age onwards in the maintenance of peripheral T-lymphocyte numbers. In conclusion, our data provide quantitative insight into the proliferative history of thymocyte and T-lymphocyte subpopulations and alterations herein upon ageing. This novel TREC assay approach could prove valuable in immune status monitoring in a variety of conditions.