Neuroprotective Effect of Physical Exercise in a Mouse Model of Alzheimer’s Disease Induced by β-Amyloid1–40 Peptide

This study was designed to investigate the potential neuroprotective effect of exercise in a mouse model of Alzheimer’s disease (AD) induced by intracerebroventricular (i.c.v.) injection of beta-amyloid_1–40 (Aβ_1–40) peptide. For this aim, male Swiss Albino mice were submitted to swimming training (ST) with progressive increase in intensity and duration for 8 weeks before Aβ_1–40 administration (400 pmol/animal; 3 μl/site, i.c.v. route). The cognitive behavioral, oxidative stress, and neuroinflammatory markers in hippocampus and prefrontal cortex of mice were assessed 7 days after Aβ_1–40 administration. Our results demonstrated that ST was effective in preventing impairment in short- and long-term memories in the object recognition test. ST attenuated the increased levels of reactive species and decreased non-protein thiol levels in hippocampus and prefrontal cortex induced by Aβ_1–40. Also, Aβ_1–40 inhibited superoxide dismutase activity and increased glutathione peroxidase, glutathione reductase, and glutathione S-transferase activities in hippocampus and prefrontal cortex—alterations that were mitigated by ST. In addition, ST was effective against the increase of tumor necrosis factor-alpha and interleukin-1 beta levels and the decrease of interleukin-10 levels in hippocampus and prefrontal cortex. This study confirmed the hypothesis that exercise is able to protect against some mechanisms of Aβ_1–40-induced neurotoxicity. In conclusion, we suggest that exercise can prevent the cognitive decline, oxidative stress, and neuroinflammation induced by Aβ_1–40 in mice supporting the hypothesis that exercise can be used as a non-pharmacological tool to reduce the symptoms of AD.     

Why Do Only a Minority of Men Report Severe Levels of Eating Disorder Symptomatology,When so Many Report Substantial Body Dissatisfaction? Examination of Exacerbating Factors

In recent years research employing female samples has indicated that although body dissatisfaction may be necessary for the onset of an eating disorder, it is not sufficient. This study examined body surveillance and difficulties in interpersonal domains (attachment anxiety and social anxiety) as potential moderators of the body dissatisfaction-eating disorder symptomatology relationship amongst Italian college men (N = 359). As expected, all examined variables were found to intensify this relationship such that body dissatisfaction was strongly related to men’s eating disorder symptomatology when each moderator was at its highest level (i.e., 1 SD above the mean). Practical implications are discussed.     

Disease-Specific Quality of Life in Young Patients With Tourette Syndrome

Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and is often associated with comorbid behavioral problems. Research with generic instruments in child populations showed that comorbid disorders can have a greater impact on health-related quality of life than tic severity. This study investigated the usefulness of a newly developed disease-specific instrument, the Gilles de la Tourette Syndrome–Quality of Life Scale for Children and Adolescents (GTS-QOL-C&A), in assessing health-related quality of life in young patients with Tourette syndrome with and without behavioral comorbidity. We recruited 75 patients with Tourette syndrome (60 males; age 12.4 ± 3.2 years). All participants were evaluated by a neuropsychiatrist and completed a standardized psychometric battery, including the GTS-QOL-C&A, Child Depression Inventory, and Multidimensional Anxiety Scale for Children. Forty-two patients (56%) fulfilled diagnostic criteria for at least one comorbidity: obsessive-compulsive disorder (n = 25 patients [33.3%]); attention deficit/hyperactivity disorder (n = 6 patients [8%]); both (n = 11 patients [14.7%]). The GTS-QOL-C&A demonstrated usefulness in differentiating “pure” Tourette syndrome from Tourette syndrome “plus” behavioral problems with regard to health-related quality of life scores for the obsessive-compulsive subscale. In addition to focusing on core tic symptoms, the GTS-QOL-C&A showed sensitivity to the impact of behavioral comorbidities on health-related quality of life and can usefully complement existing nonspecific instruments.     

Adjunctive azithromycin in the treatment of aggressive periodontitis: microbiological findings of a 12-month randomized clinical trial

Objectives

To compare the subgingival microbiological outcomes of azithromycin or placebo as adjuncts to scaling and root planing (SRP) in the treatment of aggressive periodontitis (AgP), and to secondarily evaluate the microbiological effect of supragingival scaling in AgP patients.

Methods

Twenty-four AgP subjects 13–26 years of age received a 15-day programme of supragingival scaling (SC) and were then randomly assigned to SRP with systemic azithromycin or placebo. Subgingival samples were taken with sterile paper points at baseline, 15 days after SC, and at 3, 6 and 12 months following SRP. Microbiological analysis was performed by the checkerboard DNA–DNA hybridization.

Results

Changes in bacterial levels from baseline to 15 days after SC were similar in the 2 groups. When subjects were analysed as a single group, significant reductions after SC were observed for Actinomyces gerencseriae, Capnocytophaga ochracea, and Treponema denticola. During the 12-month follow-up, levels of most of the bacteria decreased in both groups in a similar pattern. For instance, Actinomyces israelli, Veillonella parvula, Streptococcus gordonii, C. ochracea, Eikenella corrodens, Eubacterium nodatum, Fusobacterium periodonticum and Fusobacterium nucleatum ssp. polymorphum decreased significantly within the groups.

Conclusions

Azithromycin was ineffective in lowering the subgingival levels of important putative periodontal pathogens in young AgP subjects compared to placebo.

Clinical significance

Scaling and root planing with adjunctive systemic azithromycin provides little additional benefit compared to placebo in reductions of major subgingival periodontal pathogens.     

Pharmacokinetic drug evaluation of osimertinib for the treatment of non-small cell lung cancer

Introduction: First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial activity of an average 9–13 months, disease progression has been reported in the majority of patients. In about 50% of cases the progression is due to the onset of the T790M mutation in exon 20 of the EGFR gene. Third-generation EGFR-TKIs targeting this mutation were investigated, with osimertinib the only reaching clinical practice.

Areas covered: A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question addressing osimertinib, was undertaken.

Expert opinion: Osimertinib is the standard-of-care for EGFR-mutated patients progressing to first-line EGFR-TKIs due to the acquired EGFR T790M mutation. Results from the head-to-head first-line trial comparing osimertinib versus gefitinib or erlotinib in activating EGFR mutations might change the front-line approach. Osimertinib in combination regimens, such as immunotherapy, and in adjuvant setting are ongoing. Thus, the strategic approach for the management of EGFR-mutated NSCLC patients will change further in the next few years.     

Effects of resistance training of moderate intensity on heart rate variability,body composition,and muscle strength in healthy elderly women

Purpose

The practice of resistance training is recommended as non-pharmacological strategy during aging. In this study, we propose training composed of exercises, leg 180° press, seated row, leg curl, bench press, abduction machine, push down, adduction machine, and curl biceps. Accordingly, this study aimed to determine the effects of dynamic resistance training on autonomic response, muscle strength, and body composition of elderly women without comorbidities.

Methods

Twenty-six healthy older women (65 ± 3 years) were randomly divided into two groups. The Control Group (CG) consisted of 13 subjects not engaged in any physical exercise, while the Training Group (GT) (n = 13) performed 8 strength training exercises with 3 sets of 8 maximum repetitions. Heart rate variability, body composition, and muscle strength were assessed before and after the 12 weeks in both groups.

Results

No significant difference was found in body composition, muscle strength, and heart rate variability between CG and TG before (baseline) 12 weeks of training. Significant differences between pre- and post-training moments were found only in training group. In this sense, results demonstrated improvement (p < 0.05) in body fat mass (23.0 ± 1.2 vs. 20.0 ± 1.1 kg), fat-free mass (38.0 ± 1.5 vs. 42.0 ± 1.4 kg), strength of upper (17.8 ± 1.0 vs. 22.2 ± 1.1 kgf) and lower limbs (27.1 ± 2.4 vs. 34.1 ± 2.5 kgf), and in time and frequency domain measures of heart rate variability, highlighting the indices LF/HF (1.2 ± 0.4 vs. 0.7 ± 0.1).

Conclusions

The dynamic resistance training protocol presented in this study may be regarded as an effective approach to prevent cardiovascular morbidity and mortality in elderly women.

     

Impact of Temperature on Porcine Liver Machine Perfusion From Donors After Cardiac Death

Normothermic machine perfusion (NMP) has been introduced as a promising technology to preserve and possibly repair marginal liver grafts. The aim of this study was to compare the effect of temperature on the preservation of donation after cardiac death (DCD) liver grafts in an ex vivo perfusion model after NMP (38.5°C) and subnormothermic machine perfusion (SNMP, 21°C) with a control group preserved by cold storage (CS, 4°C). Fifteen porcine livers with 60 min of warm ischemia were preserved for 10 h by NMP, SNMP or CS (n = 5/group). After the preservation phase all livers were reperfused for 24 h in an isolated perfusion system with whole blood at 38.5°C to simulate transplantation. At the end of transplant simulation, the NMP group showed significantly lower hepatocellular enzyme level (AST: 277 ± 69 U/L; ALT: 22 ± 2 U/L; P < 0.03) compared to both SNMP (AST: 3243 ± 1048 U/L; ALT: 127 ± 70 U/L) and CS (AST: 3150 ± 1546 U/L; ALT: 185 ± 97 U/L). There was no significant difference between SNMP and CS. Bile production was significantly higher in the NMP group (219 ± 43 mL; P < 0.01) compared to both SNMP (49 ± 84 mL) and CS (12 ± 16 mL) with no significant difference between the latter two groups. Histologically, the NMP livers showed preserved cellular architecture compared to the SNMP and CS groups. NMP was able to recover DCD livers showing superior hepatocellular integrity, biliary function, and microcirculation compared to SNMP and CS. SNMP showed some significant benefit over CS, yet has not shown any advantage over NMP.