Silver-nanoparticles increase bactericidal activity and radical oxygen responses against bacterial pathogens in human osteoclasts

Bone infections are difficult to treat and can lead to severe tissue destruction. Acute bone infections are usually caused by Staphylococcus aureus. Osteoclasts, which belong to the monocyte/macrophage lineage, are the key cells in bone infections. They are not well equipped for killing bacteria and may serve as a reservoir for bacterial pathogens. Silver has been known for centuries for its bactericidal activity. Here, we investigated the bactericidal effects of nano-silver particles in bacteria infected human osteoclasts. We found that nano-silver in per se non-toxic concentration enhanced the bactericidal activity in osteoclasts against intracellular Methicillin-resistant, virulent Staphylococcus aureus. The reduced bacterial survival in nano-silver pretreated cells correlated with increased reactive oxygen responses towards the invading pathogens. Overall, these results indicate that nano-silver compounds should be considered as an effective treatment and prevention option for bacterial bone and orthopedic implant infections.     

Prolonged Versus Short-Duration Use of Nasogastric Tubes in Patients with Head and Neck Cancer During Radiotherapy Alone or Combined Chemoradiotherapy

To compare safety and effectiveness of prolonged (>28 days) versus short duration (≤28 days) use of nasogastric tube for enteral nutrition and weight loss prevention during curative radiotherapy with or without concurrent chemotherapy or cetuximab for head and neck cancer patients. We performed a retrospective study and database review of all patients at our center, treated with radiotherapy for head and neck cancer receiving enteral nutrition by nasogastric tube. Type of treatment, weight and body mass index changes, and related complications (gastroesophageal reflux, pneumonia, ulcer, feeding tube obstruction, or dislocation) were documented. Comparison between patients with prolonged (>28 days, group A) and short duration (≤28 days, group B) of EN through nasogastric tube was performed. Data expressed as mean?±?SD or median (min; max) values as appropriate, and analyzed by ANOVA repeated measures and Kaplan-Meier estimates. We identified 114 patients who fulfilled the inclusion criteria. Among them, 10% were treated with radiotherapy alone, while 90% received concurrent chemotherapy or cetuximab. Ninety-four patients (82%, group A) had a nasogastric tube in place for a period >28 days and 20 (18%, group B) for ≤28 days during treatment. Patients were mainly men (86 patients, 75%), with a median age of 61 years (range 49–73) and advanced stage IV disease in most cases (87 patients, 76%) without differences between both groups (p = 0.53, 0.47, and 0.30, respectively). Treatment discontinuation did not occur within both groups. Fifty-six patients (49%) developed complications, without a significant difference between both groups (P = 0.23). Body weight and BMI changes did not differ during EN (–0.8?±?4.5 and –0.3?±?1.6), the oncological treatment (–5.3?±?4.0 and –1.8?±?1.4), or 6 months after the end of treatment (–0.6?±?4.4 and –0.2?±?1.5). Our findings suggest that prolonged enteral nutrition by nasogastric tube is safe and effective in preventing weight loss during curative radiotherapy or radio-chemotherapy for head and neck cancer.     

Improving disease incidence estimates in primary care surveillance systems

Background

In primary care surveillance systems based on voluntary participation, biased results may arise from the lack of representativeness of the monitored population and uncertainty regarding the population denominator, especially in health systems where patient registration is not required.

Methods

Based on the observation of a positive association between number of cases reported and number of consultations by the participating general practitioners (GPs), we define several weighted incidence estimators using external information on consultation volume in GPs. These estimators are applied to data reported in a French primary care surveillance system based on voluntary GPs (the Sentinelles network) for comparison.

Results

Depending on hypotheses for weight computations, relative changes in weekly national-level incidence estimates up to 3% for influenza, 6% for diarrhea, and 11% for varicella were observed. The use of consultation-weighted estimates led to bias reduction in the estimates. At the regional level (NUTS2 level - Nomenclature of Statistical Territorial Units Level 2), relative changes were even larger between incidence estimates, with changes between -40% and +55%. Using bias-reduced weights decreased variation in incidence between regions and increased spatial autocorrelation.

Conclusions

Post-stratification using external administrative data may improve incidence estimates in surveillance systems based on voluntary participation.

     

Discovery and optimization of new benzimidazole- and benzoxazole-pyrimidone selective PI3Kβ inhibitors for the treatment of phosphatase and TENsin homologue (PTEN)-deficient cancers

Most of the phosphoinositide-3 kinase (PI3K) kinase inhibitors currently in clinical trials for cancer treatment exhibit pan PI3K isoform profiles. Single PI3K isoforms differentially control tumorigenesis, and PI3Kβ has emerged as the isoform involved in the tumorigenicity of PTEN-deficient tumors. Herein we describe the discovery and optimization of a new series of benzimidazole- and benzoxazole-pyrimidones as small molecular mass PI3Kβ-selective inhibitors. Starting with compound 5 obtained from a one-pot reaction via a novel intermediate 1, medicinal chemistry optimization led to the discovery of compound 8, which showed a significant activity and selectivity for PI3Kβ and adequate in vitro pharmacokinetic properties. The X-ray costructure of compound 8 in PI3Kδ showed key interactions and structural features supporting the observed PI3Kβ isoform selectivity. Compound 8 achieved sustained target modulation and tumor growth delay at well tolerated doses when administered orally to SCID mice implanted with PTEN-deficient human tumor xenografts.     

Influence of Spirituality and Religiousness on Substance Misuse in Patients with Schizophrenia or Schizo-Affective Disorder

Substance misuse represents a major issue in the treatment of schizophrenia patients. Spirituality and religiousness have been shown to reduce substance misuse and to foster recovery among substance misusers in the general population. One hundred and fifteen stabilized outpatients with schizophrenia (mean age 39; 70% male) were selected in 2004 for an interview about religious coping. Religious involvement was significantly inversely correlated to substance use and abuse. A content analysis showed that religion may play a protective role toward substance misuse in 14% of the total sample, especially for patients who had stopped substance misuse (42%). It played a negative role in 3% of cases. Religion may play a role in the recovery of schizophrenia patients with substance misuse comorbidity.     

Smoking during pregnancy according to obstetric complications and parity: results of the EUROPOP study

This study aimed to analyse the relationship between smoking and preterm birth (22-36 weeks) according to the main obstetric complications leading to the preterm birth, both overall and by parity. The EUROPOP study is a case-control study carried out between 1994 and 1997; 3,787 preterm and 5,602 full-term births were included, from maternity units in 10 countries, using the same protocol. Social, demographic and medical information was collected after delivery, from obstetric records and interviews with the mothers. Cases were classified according to the main obstetric complication (hypertension, haemorrhage, preterm premature rupture of membranes (PPROM), idiopathic spontaneous preterm labour, intrauterine growth retardation, all other causes). Multiple logistic regression analysis was used to control for confounders. Twenty four percent of cases and 20% of controls were smokers. Smoking during pregnancy, heavy smoking (>or=10 cigarettes per day) in particular, was a risk factor for preterm birth (aOR = 1.39, 95% CI:1.20-1.60). Smoking increased the risk of preterm delivery due to all obstetric complications other than hypertension. For these complications, the risk of preterm delivery associated with smoking was higher for multiparae (aOR = 1.46, 95% CI:1.24-1.71) than for primiparae (aOR = 1.18, 95% CI:1.00-1.38). In conclusion, smoking during pregnancy increases the risk of preterm birth among women with all obstetric complications except hypertension. This association is stronger in multiparae than in primiparae and the risk is higher for heavy smokers.     

Characteristics of the patients seen in 1999 by referral centres for sexually transmitted diseases in Ceará (Northeast Brazil)

Since 1995, in the State of Ceará, in Northeast Brazil, there is a public health project focusing on training and continuing education of health reference teams taking care of patients with sexually transmitted diseases (STD). An information system including a patient's form was worked out and established. The characteristics of the patients seen at consultation in 1999 are described. Ten units provided 1,478 filled forms. Women are more present than men (72% vs 28%). Multipartnership during the last three months is more frequent among males (52%) than among females (5%). Taking antibiotics prior to the first medical advice was frequent in the male population (17%). The main syndromes presented by women were vaginal discharge (81%) and genital warts (19%), whereas with men genital warts (47%) and urethral discharge (43%) were more frequent. The frequency of positive serology for syphilis and HIV among patients presenting an STD syndrome was 7.9% and 1.3%, respectively. It was higher among males (12% and 3%) than among females (7% and 1%). The way the referral facilities are used is different according to sex, the women corning more often spontaneously. The need for accurate etiologic data for each STD syndrome was identified. The analysis of the data resulting from these STD referral units allowed to produce relevant information whose follow-up will be of great interest for both health professionals and decision-makers.