Analysis of cytotoxic effects of silver nanoclusters on human peripheral blood mononuclear cells ‘in vitro’

The antimicrobial properties of silver nanoparticles (AgNPs) have made these particles one of the most used nanomaterials in consumer products. Therefore, an understanding of the interactions (unwanted toxicity) between nanoparticles and human cells is of significant interest. The aim of this study was to assess the in vitro cytotoxicity effects of silver nanoclusters (AgNC, < 2 nm diameter) on peripheral blood mononuclear cells (PBMC). Using flow cytometry and comet assay methods, we demonstrate that exposure of PBMC to AgNC induced intracellular reactive oxygen species (ROS) generation, DNA damage and apoptosis at 3, 6 and 12 h, with a dose‐dependent response (0.1, 1, 3, 5 and 30 µg ml^–1). Advanced electron microscopy imaging of complete and ultrathin‐sections of PBMC confirmed the cytotoxic effects and cell damage caused by AgNC. The present study showed that AgNC produced without coating agents induced significant cytotoxic effects on PBMC owing to their high aspect ratio and active surface area, even at much lower concentrations (<1 µg ml^–1) than those applied in previous studies, resembling what would occur under real exposure conditions to nanosilver‐functionalized consumer products. Copyright © 2015 John Wiley & Sons, Ltd.     

Vida PURA: A Cultural Adaptation of Screening and Brief Intervention to Reduce Unhealthy Drinking Among Latino Day Laborers

Background: Brief intervention is known to reduce drinking in primary care; however, because health care access is limited for Latino immigrants, traditional brief interventions are unlikely to reach this population. Methods: Using Barrera and Castro's framework, our study aims to culturally adapt a screening and brief intervention program to reduce unhealthy alcohol use among Latino day laborers, a particularly vulnerable group of Latino immigrant men. We conducted 18 interviews with Latino day laborers and 13 interviews with mental health and substance use providers that serve Latino immigrant men. Interviews were conducted until saturation of themes was reached. Themes from interviews were used to identify sources of mismatch between traditional screening and brief intervention in our target population. Results: Unhealthy alcohol use was common, culturally accepted, and helped relieve immigration-related stressors. Men had limited knowledge about how to change their behavior. Men preferred to receive information from trusted providers in Spanish. Men faced significant barriers to accessing health and social services but were open to receiving brief interventions in community settings. Findings were used to design Vida PURA, a preliminary adaptation design of brief intervention for Latino day laborers. Key adaptations include brief intervention at a day labor worker center provided by promotores trained to incorporate the social and cultural context of drinking for Latino immigrant men. Conclusions: Culturally adapted brief intervention may help reduce unhealthy drinking in this underserved population.     

Preventive effect of zaprinast and 3-isobutyl, 1-methylxanthine (phosphodiesterase inhibitors) on gastric injury induced by nonsteroidal antiinflammatory drugs in rats

Cyclic GMP plays an important role in maintaining homeostasis in the gastric mucosa. NSAIDs damage the mucosa by mechanisms that may be mediated by alterations in the intragastric concentration of cyclic GMP. To test this hypothesis we studied the effects of the oral administration of acetylsalicylic acid (100, 300, and 500 mg/kg), piroxicam (5, 10, and 20 mg/kg) and sodium diclofenac (10, 25, 50, and 100 mg/kg), and of their interaction with zaprinast (5 mg/kg) and IBMX (10 mg/kg), on intragastric concentrations of cyclic GMP and the gastric erosive index in rats. All determinations were done 3 hr after the NSAID was given. All NSAIDs induced dose-dependent decreases in mucosal concentrations of cyclic GMP, which correlated inversely with the surface area showing mucosal injury. In contrast, cyclic GMP concentrations remained normal, and no intragastric damage was seen in rats given zaprinast (cyclic GMP-specific phosphodiesterase inhibitor) or IBMX (non-specific phosphodiesterase inhibitor) or in combination with NSAIDs. These findings are in line with the hypothesis that cyclic GMP is involved in the biochemical mechanisms of NSAID-induced gastric injury.     

The inhibition of gastric ghrelin production by food intake in rats is dependent on the type of macronutrient

Ghrelin is a peptide mainly produced by the stomach that increases food intake and body weight. Ghrelin expression increases with fasting and is diminished by re-feeding, but although the expression of this hormone is regulated by the feeding state, the relation with diet composition is not yet well established. We have studied the inhibitory effect of the intake of two different macronutrients (fat and carbohydrates) on ghrelin production by the stomach in fasted rats, as well as the relation with another important signal in the regulation of energy balance, leptin. Ghrelin mRNA expression in the gastric mucosa was determined by Northern blotting, and leptin mRNA expression was determined by Northern blotting in the adipose tissue and by RT-PCR in the stomach; circulating and gastric concentrations of ghrelin and leptin were measured by enzyme immunosorbent assay and ELISA, respectively. Our results showed an increase in ghrelin mRNA levels in response to 14 h of fasting. Food intake for 20 min after the fast produced a decrease in ghrelin mRNA expression that was recovered in 45 min in rats that ate the fat diet, whereas levels remained low when rats ate the carbohydrate diet. Serum ghrelin followed a similar tendency. The decrease in ghrelin expression by feeding was associated with an increased expression of gastric leptin only when animals ate carbohydrates. We conclude that the inhibition of ghrelin production by the stomach after re-feeding of fasted rats is dependent on diet composition and can be related to the different satiating capacity of the ingested macronutrients, which is higher for carbohydrates than fat.     

Sortilin receptor 1 predicts longitudinal cognitive change

The gene encoding sortilin receptor 1 (SORL1) has been associated with Alzheimer's disease risk. We examined 15 SORL1 variants and single nucleotide polymorphism (SNP) set risk scores in relation to longitudinal verbal, spatial, memory, and perceptual speed performance, testing for age trends and sex-specific effects. Altogether, 1609 individuals from 3 population-based Swedish twin studies were assessed up to 5 times across 16 years. Controlling for apolipoprotein E genotype (APOE), multiple simple and sex-moderated associations were observed for spatial, episodic memory, and verbal trajectories (p = 1.25E-03 to p = 4.83E-02). Five variants (rs11600875, rs753780, rs7105365, rs11820794, rs2070045) were associated across domains. Notably, in those homozygous for the rs2070045 risk allele, men demonstrated initially favorable performance but accelerating declines, and women showed overall lower performance. SNP set risk scores predicted spatial (Card Rotations, p = 5.92E-03) and episodic memory trajectories (Thurstone Picture Memory, p = 3.34E-02), where higher risk scores benefited men's versus women's performance up to age 75 but with accelerating declines. SORL1 is associated with cognitive aging, and might contribute differentially to change in men and women.     

Thalamic atrophy in patients with pure hereditary spastic paraplegia type 4

Journal of Neurology - SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder...     

Early imaging signs of the use of antiresorptive medication and MRONJ: a systematic review

Objective

The main aim is to identify, by means of different imaging modalities, the early bone changes in patients “at risk” and in stage 0 MRONJ.

Materials and methods

A search of the literature was performed on PubMed, Embase, Web of Science, and Cochrane Library databases, until June 9, 2020. No language or year restrictions were applied. Screening of the articles, data collection, and qualitative analysis was done. The Newcastle-Ottawa Scale (NOS) was used for observational studies, and the Systematic Review Centre for Laboratory Animal Experimentation’s (SYRCLE) risk of bias tool for the animal studies.

Results

A total of 1188 articles were found, from which 47 were considered eligible, whereas 42 were suitable for the qualitative analysis. They correspond to 39 human studies and 8 animal studies. Radiographic findings such as bone sclerosis, osteolytic areas, thickening of lamina dura, persisting alveolar socket, periapical radiolucency, thicker mandibular cortex, widening of the periodontal ligament space, periodontal bone loss, and enhancement of the mandibular canal were identified as early bone changes due to antiresorptive therapy. All those findings were also reported later in Stage 0 patients.

Conclusion

The main limitations of these results are the lack of prospective data and comparisons groups; therefore, careful interpretation should be made. It is a fact that radiographic findings are present in antiresorptive-treated patients, but the precise timepoint of occurrence, their relation to the posology, and potential risk to develop MRONJ are not clear.

Clinical relevance

The importance of a baseline radiographic diagnosis for antiresorptive-treated patients.

     

Outcomes of a Peritoneal Dialysis Program in Remote Communities Within Colombia

♦ Background and Objective: Colombia is a country of diverse geographic regions, some with mountainous terrain that can make access to urban areas difficult for individuals who live in remote areas. In 2005, a program was initiated to establish remote peritoneal dialysis (PD) centers in Colombia to improve access to PD for patients with end-stage renal disease who face geographic or financial access barriers.♦ Patients and Methods: The present study was a multi-center cohort observational study of prevalent home PD patients who were at least 18 years of age and were being managed by one of nine established remote PD centers in Colombia over a 2-year period. Data were collected from clinical records, databases, and patient interviews. Patient survival, incidence of peritonitis, and rate of withdrawal from PD therapy were assessed.♦ Results: A total of 345 patients were eligible for the study. The majority (87.8%) of patients lived on one to two times a minimum monthly salary (equivalent to US$243 – US$486). On average, patients traveled 1.2 hours and 4.3 hours from their home to their remote PD center or an urban reference renal clinic, respectively. The incidence rate of peritonitis was 2.54 episodes per 100 patient-months of therapy. A bivariate analysis showed a significantly higher risk of peritonitis in patients who were living on less than one times a monthly minimum salary (p < 0.05) or who had a dirt, cement, or unfinished wood floor (p < 0.05). The 1-year and 2-year patient survival rates were 92.44% and 81.55%, respectively. The 1-year and 2-year technique survival rates were 97.27% and 89.78%, respectively.♦ Conclusions: With the support of remote PD centers that mitigate geographic and financial barriers to healthcare, home PD therapy is a safe and appropriate treatment option for patients who live in remote areas in Colombia.