Correlation between fall risk increasing drugs (FRIDs) and fall events at a rehabilitation hospital.

Background and aim Falls and fall-related injuries are a major public health issue which needs global attention due to its clinical and socioeconomic impact. Important risk factors for falls are polypharmacy and the assumption of so-called Fall Risk Increasing Drugs (FRIDs). Aims of our study were to investigate the associations between falls and the use of medications among inpatients by conducting a retrospective case-control study in a rehabilitation hospital in Northern Italy in 2018. Methods A Conditional Logistic Regression was performed to analyze the impact that 13 types of FRIDs individually and the number of administrated FRIDs had on the risk of falling. A second regression model was obtained adjusting the case-control matching for CIRS, Morse and Barthel scores. Results We identified 148 cases and 444 controls. 3 types of FRIDs were significantly correlated (p < 0,05) with an increased risk of falling: Antipsychotics, Antidepressants, Diuretics. Antidepressants were the only type of FRID significantly correlated (p=0,008) even in the model adjusted for CIRS, Morse and Barthel scores. The unadjusted model showed that the addition of one type of FRID to therapy was significantly associated with the fall event (p<0.05). Conclusion Assumption of drugs, in particular antidepressant and polypharmacy, can play a role in hospital falling. The fall risk assessment tools available, suffer from low specificity and sensitivity and do not assess these risk factors. A holistic approach with a multidimensional evaluation of the patient through screening tools, functional assessment tools and a full medical evaluation should be pursued to improve prediction.

DNA Methylation Changes in Fibromyalgia Suggest the Role of the Immune-Inflammatory Response and Central Sensitization.

Fibromyalgia (FM) has been explained as a result of gene-environment interactions. The present study aims to verify DNA methylation differences in eleven candidate genome regions previously associated to FM, evaluating DNA methylation patterns as potential disease biomarkers. DNA methylation was analyzed through bisulfite sequencing, comparing 42 FM women and their 42 healthy sisters. The associations between the level of methylation in these regions were further explored through a network analysis. Lastly, a logistic regression model investigated the regions potentially associated with FM, when controlling for sociodemographic variables and depressive symptoms. The analysis highlighted significant differences in the GCSAML region methylation between patients and controls. Moreover, seventeen single CpGs, belonging to other genes, were significantly different, however, only one cytosine related to GCSAML survived the correction for multiple comparisons. The network structure of methylation sites was different for each group; GRM2 methylation represented a central node only for FM patients. Logistic regression revealed that depressive symptoms and DNA methylation in the GRM2 region were significantly associated with FM risk. Our study encourages better exploration of GCSAML and GRM2 functions and their possible role in FM affecting immune, inflammatory response, and central sensitization of pain.

[Women's perception, preconceptions, and information preferences for the limitations of breast cancer screening and overdiagnosis: a think-aloud study on the new information materials of the Agency for Health Protection of the Metropolitan Area of Milan]. / Percezione, pregiudizi e preferenze informative delle donne milanesi sui limiti dello screening mammografico e sulla sovradiagnosi: indagine think-aloud sul nuovo materiale comunicativo dell'Agenzia di tutela della salute della Città Metropolitana di Milano.

BACKGROUND: communicating breast cancer screening (BCS) limits and overdiagnosis implies providing complete and balanced information to allow informed decision-making. OBJECTIVES: to describe women's perceptions, preconceptions, and information preferences regarding the breast cancer screening (BCS) programme paper and web information materials of the Agency for Health Protection of the Metropolitan Area of Milan (Lombardy Region, Northern Italy). DESIGN: qualitative, descriptive study. SETTING AND PARTICIPANTS: participants' voluntary recruitment took place in the registration departments of three hospitals. Participants were purposively recruited based on sociodemographic characteristics of the target population of the programme (44 women aged 40-74 years, living in the Metropolitan Area of Milan). In each material type subgroup, different health literacy levels and age classes were included, until thematic saturation was reached. MAIN OUTCOME MEASURES: thematic analysis of qualitative data collected during think-aloud interviews. RESULTS: the thematic analysis identified 5 main themes: 1. validation of the information reported in the materials, according to the interviewees' personal experiences;2. information preferences of particular subgroups of women, which led to a tailored approach for the web materials;3. negative emotions elicited while receiving information regarding BCS limits, which guided the rewriting of certain definitions; 4. disproportioned risk perception, with greater weight attributed to the risk of false negative results than the risk of overdiagnosis; 5. organizational preferences regarding the type and frequency of the provided tests and the age limits of the programme. CONCLUSIONS: in the present sample of women living in the Metropolitan Area of Milan, knowledge and comprehension of overdiagnosis are scarce. The main reasons for distrust in the BCS programme rely on the preexisting beliefs regarding the most appropriate tests and age limits. These beliefs were established from previously received information, inconsistent with that officially provided by the programme.

DNA methylation changes in genes involved in inflammation and depression in fibromyalgia: a pilot study.

OBJECTIVES: The present pilot study aims to investigate DNA methylation changes of genes related to fibromyalgia (FM) development and its main comorbid symptoms, including sleep impairment, inflammation, depression and other psychiatric disorders. Epigenetic modifications might trigger or perpetuate complex interplay between pain transduction/transmission, central pain processing and experienced stressors in vulnerable individuals. METHODS: We conducted DNA methylation analysis by targeted bisulfite NGS sequencing testing differential methylation in 112 genomic regions from leukocytes of eight women with FM and their eight healthy sisters as controls. RESULTS: Tests for differentially methylated regions and cytosines brought focus on the GRM2 gene, encoding the metabotropic glutamate receptor2. The slightly increased DNA methylation observed in the GRM2 region of FM patients may confirm the involvement of the glutamate pathway in this pathological condition. Logistic regression highlighted the simultaneous association of methylation levels of depression and inflammation-related genes with FM. CONCLUSIONS: Altogether, the results evidence the glutamate pathway involvement in FM and support the idea that a combination of methylated and unmethylated genes could represent a risk factor to FM or its consequence, more than single genes. Further studies on the identified biomarkers could contribute to unravel the causative underlying FM mechanisms, giving reliable directions to research, improving the diagnosis and effective therapies.

The Master Regulator Protein BAZ2B Can Reprogram Human Hematopoietic Lineage-Committed Progenitors into a Multipotent State.

Bi-species, fusion-mediated, somatic cell reprogramming allows precise, organism-specific tracking of unknown lineage drivers. The fusion of Tcf7l1-/- murine embryonic stem cells with EBV-transformed human B cell lymphocytes, leads to the generation of bi-species heterokaryons. Human mRNA transcript profiling at multiple time points permits the tracking of the reprogramming of B cell nuclei to a multipotent state. Interrogation of a human B cell regulatory network with gene expression signatures identifies 8 candidate master regulator proteins. Of these 8 candidates, ectopic expression of BAZ2B, from the bromodomain family, efficiently reprograms hematopoietic committed progenitors into a multipotent state and significantly enhances their long-term clonogenicity, stemness, and engraftment in immunocompromised mice. Unbiased systems biology approaches let us identify the early driving events of human B cell reprogramming.

Alu RNA Modulates the Expression of Cell Cycle Genes in Human Fibroblasts.

Alu retroelements, whose retrotransposition requires prior transcription by RNA polymerase III to generate Alu RNAs, represent the most numerous non-coding RNA (ncRNA) gene family in the human genome. Alu transcription is generally kept to extremely low levels by tight epigenetic silencing, but it has been reported to increase under different types of cell perturbation, such as viral infection and cancer. Alu RNAs, being able to act as gene expression modulators, may be directly involved in the mechanisms determining cellular behavior in such perturbed states. To directly address the regulatory potential of Alu RNAs, we generated IMR90 fibroblasts and HeLa cell lines stably overexpressing two slightly different Alu RNAs, and analyzed genome-wide the expression changes of protein-coding genes through RNA-sequencing. Among the genes that were upregulated or downregulated in response to Alu overexpression in IMR90, but not in HeLa cells, we found a highly significant enrichment of pathways involved in cell cycle progression and mitotic entry. Accordingly, Alu overexpression was found to promote transition from G1 to S phase, as revealed by flow cytometry. Therefore, increased Alu RNA may contribute to sustained cell proliferation, which is an important factor of cancer development and progression.

Interpreting and integrating big data in non-coding RNA research.

In the last two decades, we have witnessed an impressive crescendo of non-coding RNA studies, due to both the development of high-throughput RNA-sequencing strategies and an ever-increasing awareness of the involvement of newly discovered ncRNA classes in complex regulatory networks. Together with excitement for the possibility to explore previously unknown layers of gene regulation, these advancements led to the realization of the need for shared criteria of data collection and analysis and for novel integrative perspectives and tools aimed at making biological sense of very large bodies of molecular information. In the last few years, efforts to respond to this need have been devoted mainly to the regulatory interactions involving ncRNAs as direct or indirect regulators of protein-coding mRNAs. Such efforts resulted in the development of new computational tools, allowing the exploitation of the information spread in numerous different ncRNA data sets to interpret transcriptome changes under physiological and pathological cell responses. While experimental validation remains essential to identify key RNA regulatory interactions, the integration of ncRNA big data, in combination with systematic literature mining, is proving to be invaluable in identifying potential new players, biomarkers and therapeutic targets in cancer and other diseases.