Ceftriaxone Blocks the Polymerization of α-Synuclein and Exerts Neuroprotective Effects in Vitro

相似文献   

Information and communication technology in chronic diseases: a patient’s opportunity

The increasing aging population, the prevalence of chronic diseases and rising costs have brought about some unique health care challenge to our global society. In response to the unmet health care needs, researchers are actively seeking for innovative solutions that target for (1) prevention of diseases and (2) personalized diagnosis and treatment. It is envisaged that by taking preventive measures for health monitoring, diagnosing and treating patients with a personalized approach at an early stage of disease development, health care will be more cost effective and sustainable. The authors provide an overview of the advancements in Information and Communication Technology (ICT), and explain how some innovative health solutions, through the use of Telemedicine, can now be an opportunity for patients and their family.     

Mast Cells Kill Candida albicans in the Extracellular Environment but Spare Ingested Fungi from Death

Mast cells (MCs) reside in tissues that are common targets of Candida spp. infections, and can exert bactericidal activity, but little is known about their fungicidal activity. MCs purified from rat peritoneum (RPMC) and a clinical isolate of C. albicans, were employed. Ingestion was evaluated by flow cytometry (FACS) and optical microscopy. The killing activity was assayed by FACS analysis and by colony forming unit method. RPMC degranulation was evaluated by β-hexosaminidase assay and phosphatidylserine externalization by FACS. Phagocytosing RPMC were also analyzed by transmission electron microscopy. Herein, we show that the killing of C. albicans by RPMC takes place in the extracellular environment, very likely through secreted granular components. Ultrastructural analysis of the ingestion process revealed an unusual RPMC–C. albicans interaction that could allow fungal survival. Our findings indicate that MCs have a positive role in the defense mechanism against Candida infections and should be included among the cell types involved in host-defense against this pathogen.     

A comparative in vivo ultrasonometric evaluation of normal and delayed fracture healing in sheep tibiae

OBJECTIVE:

To compare normal and delayed bone healing by measuring ultrasound conduction velocity across the bone callus.

METHODS:

A model of transverse linear and 5 mm resection osteotomies of sheep tibiae was used. Fourteen sheep were operated on and were divided into two groups of seven according to osteotomy type. The procedure was performed on the right tibiae and the intact left tibiae were used as controls. The transverse and axial ultrasound velocities were measured at 30-day intervals for 90 days, after which the animals were killed and both the right and left tibiae were resected for in vitro biomechanical analysis.

RESULTS:

Both the transverse and axial ultrasound velocities progressively increased, but the increase was smaller for the delayed union that resulted from the resection osteotomy. The mechanical resistance was higher for the normally healed tibiae that resulted from a linear osteotomy; this result closely correlated with the ultrasound velocity results. Significant differences were found for the comparisons between the intact and operated tibiae in both groups and between the groups for both the transverse and axial ultrasound velocities, but the differences were greater for the latter.

CONCLUSION:

We conclude that in vivo transverse and axial ultrasound velocities provide highly precise information about the healing state of both linear and resection diaphyseal osteotomies, but the axial ultrasound velocity most likely has greater discriminatory power. This method has the potential for clinical application in humans.     

Skeletal versus conventional intraoral anchorage for the treatment of class II malocclusion: dentoalveolar and skeletal effects

Background

The purpose of this retrospective study is to investigate the dentoalveolar and skeletal effects of two distalizing protocols featuring different anchorage systems used in patients with class II malocclusion: the MGBM system (skeletal anchorage) and Pendulum (intraoral anchorage).

Methods

The sample comprised 57 patients who were assigned to one of the two treatments: the MGBM group (30 patients, mean age 13.3 ± 2.3 years) or the Pendulum group (27 patients, mean age 12.8 ± 1.7 years). Three serial cephalograms were obtained at baseline (T0), after molar distalization (T1), and after fixed appliance treatment (T2). Esthetic, skeletal, and dental parameters were considered. Pancherz''s superimposition method was used to assess sagittal dental changes. The initial and final measurements and treatment changes were compared by means of a paired t test or a paired Wilcoxon test. Statistical significance was tested at p < 0.05, p < 0.01, and p < 0.001.

Results

In the MGBM group, the upper molar distalization was achieved in 7 months and showed a mean value of 4.9 mm (ms-PLO); the amount of molar relationship correction was 5.9 mm. In the Pendulum group, the upper molar distalization was obtained in 9 months and showed a mean value of 2.5 mm (ms-PLO), while the molar relationship correction amounted to 4.9 mm. Anterior anchorage loss occurred in both groups, although in the MGBM group, there was less mesial movement of the premolars.

Conclusions

The MGBM system and the Pendulum appliance are both effective in the correction of class II malocclusions. The MGBM system was found to be more efficient than the Pendulum appliance, producing greater molar distalization in a shorter treatment time.     

Oral human papillomavirus prevalence and type distribution by country (Brazil,Mexico and the United States) and age among HPV infection in men study participants

Incidence of human papillomavirus (HPV) attributable oropharyngeal cancers (OPCs) has been increasing globally, especially among men in high-income countries. There is a lack of studies comparing oral HPV prevalence by age and country among healthy men. The purpose of our study was to assess oral HPV prevalence by country and age. Participants of the HPV Infection in Men Study (HIM), a cohort of 3,098 healthy men from São Paulo, Brazil, Cuernavaca, Mexico and Tampa, USA, were studied. Oral HPV prevalence and type distribution were assessed using the SPF₁₀ PCR-DEIA-LiPA₂₅ system. The prevalence of any HPV in Brazil, Mexico and the US was 8.7% (95% CI: 7.1%, 10.4%), 10.0% (95% CI: 8.3%, 12.1%) and 7.6% (95% CI: 5.9%, 9.5%), respectively, while the prevalence of high-risk HPV was 5.3% (95% CI: 4.1%, 6.7%), 7.3% (95% CI: 5.7%, 9.0%) and 5.4% (95% CI: 4.0%, 7.0%), respectively. No significant differences in prevalence of grouped HPV types were observed by country despite significant differences in sexual behaviors. However, the age-specific prevalence of oral HPV differed by country. Brazilian (6.0% [95% CI: 3.4%, 9.7%]) and Mexican (9.2% [95% CI: 5.6%, 14.0%]) participants had peak high-risk HPV prevalence among men aged 41–50 years whereas the US participants had peak prevalence at ages 31–40 years (11.0% [95% CI: 6.4%, 17.3%]). In conclusion, oral HPV prevalence was low with no difference in overall prevalence observed by country. Factors associated with the differences in oral HPV age-patterning by country and sexual orientation require further study.     

Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: Exploratory analysis of the GIM2 trial

Dose-dense adjuvant chemotherapy is standard of care in high-risk early breast cancer patients. However, its role in HER2-positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we investigated the efficacy of dose-dense chemotherapy in HER2-positive breast cancer patients with or without exposure to trastuzumab. In the GIM2 trial, node-positive early breast cancer patients were randomized to receive four cycles of (fluorouracil)epirubicin/cyclophosphamide followed by four cycles of paclitaxel administered every 2 (dose-dense) or 3 (standard-interval) weeks. After approval of adjuvant trastuzumab, protocol was amended in April 2006 to allow use of trastuzumab for 1 year after chemotherapy completion in HER2-positive patients. The efficacy of dose-dense chemotherapy in terms of disease-free survival (DFS) and overall survival (OS) was assessed according to HER2 status and trastuzumab use. Out of 2,003 breast cancer patients, HER2 status was negative/unknown in 1,551 patients; among the 452 patients with HER2-positive breast cancer, chemotherapy alone or followed by trastuzumab was given to 320 and 132 patients, respectively. Median follow-up was 8.1 years. No significant interaction between HER2 status, trastuzumab use and chemotherapy treatment was observed for both DFS (p = 0.698) and OS (p = 0.708). Nevertheless, there was no apparent benefit in the HER2-positive group treated with trastuzumab (DFS: HR, 0.99; 95% CI 0.52–1.89; OS: HR, 0.95; 95% CI 0.37–2.41). Although dose-dense chemotherapy was associated with a significant survival improvement in high-risk breast cancer patients, its benefit appeared to be smaller (if any) in patients with HER2-positive disease who received adjuvant trastuzumab.     

IFITM3 Interacts with the HBV/HDV Receptor NTCP and Modulates Virus Entry and Infection

The Na⁺/taurocholate co-transporting polypeptide (NTCP, gene symbol SLC10A1) is both a physiological bile acid transporter and the high-affinity hepatic receptor for the hepatitis B and D viruses (HBV/HDV). Virus entry via endocytosis of the virus/NTCP complex involves co-factors, but this process is not fully understood. As part of the innate immunity, interferon-induced transmembrane proteins (IFITM) 1–3 have been characterized as virus entry-restricting factors for many viruses. The present study identified IFITM3 as a novel protein–protein interaction (PPI) partner of NTCP based on membrane yeast-two hybrid and co-immunoprecipitation experiments. Surprisingly, IFITM3 knockdown significantly reduced in vitro HBV infection rates of NTCP-expressing HuH7 cells and primary human hepatocytes (PHHs). In addition, HuH7-NTCP cells showed significantly lower HDV infection rates, whereas infection with influenza A virus was increased. HBV-derived myr-preS1 peptide binding to HuH7-NTCP cells was intact even under IFITM3 knockdown, suggesting that IFITM3-mediated HBV/HDV infection enhancement occurs in a step subsequent to the viral attachment to NTCP. In conclusion, IFITM3 was identified as a novel NTCP co-factor that significantly affects in vitro infection with HBV and HDV in NTCP-expressing hepatoma cells and PHHs. While there is clear evidence for a direct PPI between IFITM3 and NTCP, the specific mechanism by which this PPI facilitates the infection process remains to be identified in future studies.