Effects of Mindfulness-Based Interventions (MBIs) in Patients with Early-Stage Alzheimer's Disease: A Pilot Study.

Bachground In this study, we hypothesize that mindfulness-based interventions (MBIs) may improve well-being and the related outcomes in Alzheimer's dementia patients (AD-P) at an early stage. MBIs consist of the practice of consciously observing the psychic contents in the present moment (thoughts, sensations, feelings, and other events). This attention allows one to become aware of the psychic contents and integrate them, thus favoring the quality of life and an increase in the mood of practitioners. Methods The randomized controlled study enrolled 22 AD-P at an early stage (age ≥ 60 years) treated with MBIs and 22 patients without treatment (six months of MBI training). Tests (T0-T1 six months): Mini-Mental State Examination (MMPI); Spiritual Well-Being (SWB); Beck Depression Inventory (BDI); SF36. Test-Caregiver: Everyday Cognition scales (ECOG). Results AD-P with mindfulness: Improvement of ECOG (p = 0.026), quality of life (p < 0.001), spiritual well-being (p < 0.001); decrease in depression BDI (p < 0.001). The MMSE remains unchanged. The control group of untreated patients showed a significant worsening in all these dimensions. Conclusions MBI training is effective in increasing quality of life and preventing worsening in patients with early-stage Alzheimer's dementia.

To accelerate the Zika beat: Candidate design for RNA interference-based therapy.

Zika virus infection is associated with the development of severe neurological disorders in adults and newborns. Although at the moment Zika virus outbreak is not threatening to become again an emergency, infection cases are still being sporadically reported and there is still no effective therapy available. A possible treatment to suppress Zika replication is represented by short interfering RNAs (siRNAs), since they have been successfully used even against Ebola, H5N1 and SARS viruses and clinical trials of siRNA-based drugs are ongoing. In order to speed up the time consuming experimental validation of effective siRNAs, we have performed a comprehensive bioinformatic analysis to design only a few promising siRNAs against Zika virus. Besides siRNA efficacy, we paid attention to broad-spectrum antiviral activity, obtained by analysing all known Zika genomes, and siRNA safety, by excluding siRNAs that could potentially provoke an immune response or interfere with host mRNAs, lncRNAs, circRNAs and RNA binding proteins. In Zika genome we identified several highly conserved regions targetable by only 20 siRNAs. In particular, only a few siRNAs survived highly stringent criteria for siRNA safety. Notably, two of our candidate siRNAs have been successfully used against other flaviviruses like Zika, both in in vitro and in vivo models. Since they were effective against two different flaviviruses, by targeting a highly conserved region, it is reasonable to hypothesize that they could be active also against Zika. Therefore, we encourage researchers to experimentally validate these promising siRNAs.

Identification of candidate miRNA biomarkers for pancreatic ductal adenocarcinoma by weighted gene co-expression network analysis.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal prognosis which is, among others, due to a lack of suitable biomarkers and therapeutic targets. Previously, basic gene expression analysis methods have been used for their identification, but recently new algorithms have been developed allowing more comprehensive data analyses. Among them, weighted gene co-expression network analysis (WGCNA) has already been applied to several cancer types with promising results. METHODS: We applied WGCNA to miRNA expression data from PDAC patients. Specifically, we processed microarray-based expression data of 2555 miRNAs in serum from 100 PDAC patients and 150 healthy subjects. We identified network modules of co-expressed miRNAs in the healthy subject dataset and verified their preservation in the PDAC dataset. In the non-preserved modules, we selected key miRNAs and carried out functional enrichment analyses of their experimentally known target genes. Finally, we tested their prognostic significance using overall survival analyses. RESULTS: Through WGCNA we identified several miRNAs that discriminate healthy subjects from PDAC patients and that, therefore, may play critical roles in PDAC development. At a functional level, we found that they regulate p53, FoxO and ErbB associated cellular signalling pathways, as well as cell cycle progression and various genes known to be involved in PDAC development. Some miRNAs were also found to serve as novel prognostic biomarkers, whereas others have previously already been proposed as such, thereby validating the WGCNA approach. In addition, we found that these novel data may explain at least some of our previous PDAC gene expression analysis results. CONCLUSIONS: We identified several miRNAs critical for PDAC development using WGCNA. These miRNAs may serve as biomarkers for PDAC diagnosis/prognosis and patient stratification, and as putative novel therapeutic targets.

The choice of endogenous controls in exosomal microRNA assessments from biofluids.

The assessment of differentially expressed microRNAs in patients and healthy controls is important to identify potential tumor biomarkers. Recently, it has been shown that the microRNA levels in exosomes are more correlated with the clinical-pathological variables than vesicle-free microRNAs (miRNAs) in biofluids; therefore, there is an increasing interest in these specific evaluations. However, these measurements can be affected by experimental problems that not always are evaluated and/or by inadequate procedural choices. In particular, exosome isolation and miRNA extraction procedures are crucial to avoid contaminations, and even the choice of the most suitable purity controls is important. Moreover, a stable endogenous RNA should be used for normalization of miRNA expression obtained by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) in order to make these measures comparable among different samples. A rushed choice of the endogenous control can bias study conclusions without revealing inconsistencies. Unfortunately, a few studies systematically identified the best normalizer for their specific experimental context. Instead, sometimes, the normalization procedures were performed in a disputable way or the normalizer choices simply based on the previous literature. Here, we reviewed the studies where the exosomal miRNA profiling was assessed in human biofluids to point out the adopted procedures and the specific endogenous controls chosen for normalization.

Role of delivery on serum iron-related parameters in Macaca fascicularis females.

Few data exist on the iron status and metabolism in macaques, which are considered optimal models for the study of reproductive biology and anemia. The delivery influence on the hematological parameters of iron metabolism was investigated in adult Macaca fascicularis females during late pregnancy and at 6 weeks postpartum follow-up. No significant differences were detected for each parameter by one-way analysis of variance. A decrease of all parameters was observed at delivery. During the following weeks, however, the hematological values progressively came back to normal. In conclusion, notwithstanding the increased need of iron faced during pregnancy, a balanced diet, including iron, does not allow the development of either iron deficiency or sideropenic anemia.

Reference blood values of iron metabolism in cynomolgus macaques.

Iron deficiency anemia is a human health problem of global significance, particularly as it affects pregnant women and infants. While the study of nonhuman primates has resulted in valuable knowledge about iron metabolism, hematologic and biochemical reference ranges for the parameters of iron metabolism are difficult to document in healthy monkeys. At our institution, we maintain a large breeding colony of healthy cynomolgus monkeys (Macaca fascicularis). Data compiled after sampling nonpregnant females and male members of this colony are presented as reference ranges for red cell number, hemoglobin, hematocrit, mean cellular volume, mean cellular hemoglobin, mean cellular hemoglobin concentration, serum iron, total iron-binding capacity, serum transferrin, and serum ferritin.

[Handicapped patients. General anesthesia or sedation?]. / Pazienti handicappati. Anestesia generale o sedazione?

The Authors consider the problems involved in dental treatment of the handicapped patients. Accuracy in diagnosis of the handicap factor, knowledge about its consequences on pathophysiological status and about chronically assumed drugs are the first step: in fact these patients may be affected by a wide variety of physiopathologic and mental diseases. Failure of cooperation requires general anesthesia or sedation techniques. General anesthesia can be dangerous (malignant hyperthermia in myopathies, difficult intubation in facial anomalies, pharmacological interactions); furthermore, its frequent application even in order to perform minimal treatment is often unsuitable. Sedation techniques offer a more convenient possibility, but must be practised by trained operators. Nitrous oxide alone rarely produces in fact a sufficient degree of sedation and is suitable only in patients affected by very slight mental insufficiency. In the other cases, association with various drugs (as benzodiazepines, barbiturates etc) is needed. In such a situation, the active and continuous presence of the anesthesiologist becomes mandatory.

[Dental care for the handicapped patient]. / L'assistenza odontoiatrica al paziente handicappato.

The aim of the present paper is to find out the most suitable object to take into consideration in order to improve the dental assistance for handicapped people.