Investigating G-quadruplex structures in RPGR gene: Implications for understanding X-linked retinal degeneration.

Aims: This pilot study investigates the potential pathogenic role of G-quadruplex (G4) structures in RPGR-associated retinal degeneration, starting from a case of suspected X-linked form affected family. We hypothesize that the stabilization of these structures might alter DNA replication and transcription, inducing genetic instability and influencing gene expression. Main methods: We conducted whole genome amplification experiments and next-generation sequencing to detect the blockade of polymerase activity by G4 structures. Our specific focus was the RPGR gene, which hosts a high concentration of predicted G4-forming motifs and is implicated in most X-linked retinal degeneration cases. To understand the potential interference of G4 structures, we applied computational and 3D molecular modeling to visualize interferences in DNA replication and transcription regulation. Key findings: Our data confirmed the obstruction of DNA polymerase enzymes by G4 structures, particularly when stabilized by the compound pyridostatin. This obstruction was evident in the reduced amplification of RPGR gene regions and a shift in the start/end sites of putative G4 motifs. Moreover, the modeling indicated a potential disruption of critical promoter elements and RNA polymerase binding, which could drastically alter gene expression. Significance: Our findings suggest that G4 formation in the RPGR gene could lead to genetic instability and affect the expression of RPGR, contributing to retinal dystrophy. Moreover, this study underscores the broader implications of G4 structures in other genetic disorders. Improved understanding of G4 structures could reveal novel therapeutic targets to combat genetic disorders, promoting the advancement of personalized medicine and precision health.

Effectiveness of a combined lifestyle intervention for older people in long-term care: A randomized controlled trial.

PURPOSE: Lifestyle medicine interventions combining physical, nutritional, and psychological components have been found effective in general older population. However, evidence from the long-term care (LTC) is scarce. METHODS: We conducted a pragmatic, two-arm, parallel group, superiority randomized controlled trial. Residents living in a LTC facility for one or more years, able to discern and to express informed consent, and requiring nursing care were considered eligible. The three-months intervention combined bi-weekly physical exercise groups, a healthy diet, and weekly psychological wellbeing sessions. Patients of the control group were subjected to routine care. At the end of the study participants were assessed using Barthel Index, Katz Activities of Daily Living, and Tinetti scales. RESULTS: A total of 54 patients with a mean age of 84 years took part to the study. Physical exercise and psychological wellbeing sessions were mostly attended by all the subjects of the intervention group. Both groups took less calories than planned in the diets; in addition, the intervention group showed a lower energy and carbohydrates intake than the control group. At the end of the study, the intervention group showed a significant improvement in the total scores of all the scales. CONCLUSIONS: This intervention was effective in improving functionality in older people living in the LTC setting. Results were achieved in a short timeframe, likely due to synergistic interactions between components. However, a further exploration of underlying factors is needed, to better understand the barriers that hampered a complete intervention delivery in this context.

The practice of defensive medicine among Jordanian physicians: A cross sectional study.

BACKGROUND: Defensive medicine (DM) is a deviation from medical practice that is induced primarily by a threat of liability. While the DM behavior is well studied in the developed countries, little is known in developing countries and never been evaluated in Jordan. OBJECTIVE: To evaluate the prevalence of DM practice in Jordan among physicians and to investigate reasons behind its practice and potential strategies to alleviate this practice. METHODS: In this Cross-sectional study, self-administered questionnaire was distributed to a sample of physicians in both public and private sectors in Jordan. The collection period was from Jan 2021 to June 2021. The prevalence of DM practice was estimated among the study sample. Frequency scores of different DM behaviors, reasons of DM behaviors, and effectiveness of strategies in changing DM behaviors were summarized as average frequency scores with standard deviations. Multivariable linear regression models were conducted to evaluate potential predictors of total assurance and avoidance behavior scores. RESULTS: A total of 175 Jordanian physicians completed the survey. The prevalence of adopting (or witnessing) DM behaviors among the study sample was 68% (n = 119). Diagnostic laboratory exams followed by prescribed medications were the most practiced behaviors in excessive rate during a typical working week. Unfavorable legislation for the physician was reported as the headmost reason for practicing DM, followed by pressure from the public and mass media opinion. Continuous update of knowledge, abilities, and performance and following specific protocols and/or appropriate clinical evidence and appropriate multidisciplinary and multi-professional communication were the most effective strategies that can mitigate DM behaviors. CONCLUSIONS: Defensive medicine practice is common among Jordanian physicians with concerns about increasing pattern in the future.

Longitudinal monitoring of SARS-CoV-2 viral load in self-collected saliva from health care workers during breakthrough infections to spare working days.

IMPORTANCE: Real-time quantitative PCR (RT-qPCR) on nasopharyngeal swabs (NPS) has been used as the standard method for detecting and monitoring SARS-CoV-2 infection during the pandemic. However, NPS collection often causes discomfort and poses a higher risk of transmission to health care workers (HCW). Furthermore, RT-qPCR only provides relative quantification and does not allow distinguishing those samples with residual, no longer active infection, whereas droplet digital PCR (ddPCR) allows for precise quantification of viral load, offering greater sensitivity and reproducibility. This study highlights the effectiveness of using self-collected saliva as a convenient and reliable sampling method. By utilizing ddPCR to measure the SARS-CoV-2 viral load in saliva samples, individuals with low or undetectable viral loads can be quickly identified. This approach is particularly advantageous for surveillance programs targeting HCW, as it enables the early identification and release of uninfected personnel, minimizing lost workdays. Additionally, analyzing viral load in saliva samples by ddPCR is valuable in determining virus shedding duration across different SARS-CoV-2 variants, informing transmission and disease control. Finally, testing saliva could overcome the detection of historic cases due to prolonged RNA swabbing past-infection and the unnecessary exclusion of those individuals from the workplace.

Human retinal secretome: A cross-link between mesenchymal and retinal cells.

In recent years, mesenchymal stem cells (MSC) have been considered the most effective source for regenerative medicine, especially due to released soluble paracrine bioactive components and extracellular vesicles. These factors, collectively called the secretome, play crucial roles in immunomodulation and in improving survival and regeneration capabilities of injured tissue. Recently, there has been a growing interest in the secretome released by retinal cytotypes, especially retinal pigment epithelium and Müller glia cells. The latter trophic factors represent the key to preserving morphofunctional integrity of the retina, regulating biological pathways involved in survival, function and responding to injury. Furthermore, these factors can play a pivotal role in onset and progression of retinal diseases after damage of cell secretory function. In this review, we delineated the importance of cross-talk between MSCs and retinal cells, focusing on common/induced secreted factors, during experimental therapy for retinal diseases. The cross-link between the MSC and retinal cell secretomes suggests that the MSC secretome can modulate the retinal cell secretome and vice versa. For example, the MSC secretome can protect retinal cells from degeneration by reducing oxidative stress, autophagy and programmed cell death. Conversely, the retinal cell secretome can influence the MSC secretome by inducing changes in MSC gene expression and phenotype.

UPO Biobank: The Challenge of Integrating Biobanking into the Academic Environment to Support Translational Research.

Biobanks are driving motors of precision and personalized medicine by providing high-quality biological material/data through the standardization and harmonization of their collection, preservation, and distribution. UPO Biobank was established in 2020 as an institutional, disease, and population biobank within the University of Piemonte Orientale (UPO) for the promotion and support of high-quality, multidisciplinary studies. UPO Biobank collaborates with UPO researchers, sustaining academic translational research, and supports the Novara Cohort Study, a longitudinal cohort study involving the population in the Novara area that will collect data and biological specimens that will be available for epidemiological, public health, and biological studies on aging. UPO Biobank has been developed by implementing the quality standards for the field and the ethical and legal issues and normative about privacy protection, data collection, and sharing. As a member of the "Biobanking and Biomolecular Resources Research Infrastructure" (BBMRI) network, UPO Biobank aims to expand its activity worldwide and launch cooperation with new national and international partners and researchers. The objective of this manuscript is to report an institutional and operational experience through the description of the technical and procedural solutions and ethical and scientific implications associated with the establishment of this university research biobank.

Amplification of protease-activated receptors signaling in sporadic cerebral cavernous malformation endothelial cells.

In the central nervous system, thrombin-mediated activation of protease-activated receptors (PARs) results in neuroinflammation and increased vascular permeability. These events have been linked to cancer and neurodegeneration. Endothelial cells (ECs) isolated from sporadic cerebral cavernous malformation (CCM) specimens showed dysregulation of genes involved in "thrombin-mediated PAR-1 activation" signaling. CCM is a vascular disease involving brain capillaries. In CCM, ECs show defective cell junctions. Oxidative stress and neuroinflammation play a key role in disease onset and progression. In order to confirm the possible role of thrombin pathway in sporadic CCM pathogenesis, we evaluated PARs expression in CCM-ECs. We found that sporadic CCM-ECs overexpress PAR1, PAR3 and PAR4, together with other coagulation factor encoding genes. Moreover, we investigated about expression of the three familial CCM genes (KRIT1, CCM2 and PDCD10) in human cerebral microvascular ECs, following thrombin exposure, as well as protein level. Thrombin exposure affects EC viability and results in dysregulation of CCM gene expression and, then, in decreased protein level. Our results confirm amplification of PAR pathway in CCM suggesting, for the first time, the possible role of PAR1-mediated thrombin signaling in sporadic CCM. Thrombin-mediated PARs over activation results in increased blood-brain barrier permeability due to loss of cell junction integrity and, in this context, also the three familial CCM genes may be involved.

The impact of modifier genes on cone-rod dystrophy heterogeneity: An explorative familial pilot study and a hypothesis on neurotransmission impairment.

Cone-rod dystrophies (CORDs) are a heterogeneous group of inherited retinopathies (IRDs) with more than 30 already known disease-causing genes. Uncertain phenotypes and extended range of intra- and interfamilial heterogenicity make still difficult to determine a precise genotype-phenotype correlation. Here, we used a next-generation sequencing approach to study a Sicilian family with a suspected form of CORD. Affected family members underwent ophthalmological examinations and a proband, blind from 50 years, underwent whole genome and exome sequencing. Variant analysis was enriched by pathway analysis and relevant variants were, then, investigated in other family members and in 100 healthy controls from Messina. CORD diagnosis with an intricate pattern of symptoms was confirmed by ophthalmological examinations. A total of about 50,000 variants were identified in both proband's genome and exome. All affected family members presented specific genotypes mainly determined by mutated GUCY2D gene, and different phenotypical traits, mainly related to focus and color perception. Thus, we looked for possible modifier genes. According to relationship with GUCY2D, predicted functional effects, eye localization, and ocular disease affinity, only 9 variants, carried by 6 genes (CACNG8, PAX2, RXRG, CCDC175, PDE4DIP and LTF), survived the filtering. These genes encode key proteins involved in cone development and survival, and retina neurotransmission. Among analyzed variants, CACNG8c.*6819A>T and the new CCDC175 c.76C>T showed extremely low frequency in the control group, suggesting a key role on disease phenotypes. Such discovery could enforce the role of modifier genes into CORD onset/progression, contributing to improve diagnostic test towards a better personalized medicine.

Healthcare Students and Medical Residents as Second Victims: A Cross-Sectional Study.

BACKGROUND: The term second victim (SV) describes healthcare professionals who remain traumatized after being involved in a patient safety incident (PSI). They can experience various emotional, psychological, and physical symptoms. The phenomenon is quite common; it has been estimated that half of hospital workers will be an SV at least once in their career. Because recent literature has reported high prevalence (>30%) among nursing students, we studied the phenomenon among the whole population of healthcare students. METHODS: We conducted a cross-sectional study with an online questionnaire among nursing students, medical students, and resident physicians at the teaching hospital of the University of the Piemonte Orientale located in Novara, Italy. The study included 387 individuals: 128 nursing students, 174 medical students, and 85 residents. RESULTS: We observed an overall PSI prevalence rate of 25.58% (lowest in medical students, 14.37%; highest in residents, 43.53%). Of these, 62.63% experienced symptoms typical of an SV. The most common temporary symptom was the feeling of working badly (51.52%), whereas the most common lasting symptom was hypervigilance (51.52%). Notably, none of the resident physicians involved in a PSI spoke to the patient or the patient's relatives. CONCLUSION: Our findings highlighted the risk incurred by healthcare students of becoming an SV, with a possible significant impact on their future professional and personal lives. Therefore, we suggest that academic institutions should play a more proactive role in providing support to those involved in a PSI.

Epitranscriptome Analysis of Oxidative Stressed Retinal Epithelial Cells Depicted a Possible RNA Editing Landscape of Retinal Degeneration.

Oxidative stress represents one of the principal causes of inherited retinal dystrophies, with many related molecular mechanisms still unknown. We investigated the posttranscriptional RNA editing landscape of human retinal pigment epithelium cells (RPE) exposed to the oxidant agent N-retinylidene-N-retinyl ethanolamine (A2E) for 1 h, 2 h, 3 h and 6 h. Using a transcriptomic approach, refined with a specific multialgorithm pipeline, 62,880 already annotated and de novo RNA editing sites within about 3000 genes were identified among all samples. Approximately 19% of these RNA editing sites were found within 3' UTR, including sites common to all time points that were predicted to change the binding capacity of 359 miRNAs towards 9654 target genes. A2E exposure also determined significant gene expression differences in deaminase family ADAR, APOBEC and ADAT members, involved in canonical and tRNA editing events. On GO and KEGG enrichment analyses, genes that showed different RNA editing levels are mainly involved in pathways strongly linked to a possible neovascularization of retinal tissue, with induced apoptosis mediated by the ECM and surface protein altered signaling. Collectively, this work demonstrated dynamic RNA editome profiles in RPE cells for the first time and shed more light on new mechanisms at the basis of retinal degeneration.

Public Attitude towards Biobanking: An Italian University Survey.

Biobanks have established a critical role in biomedical research by collecting, preserving, organizing, and disseminating biospecimens and related health data, contributing to precision medicine development. Participation in biobanks is influenced by several factors, such as trust in institutions and scientists, knowledge about biobanking, and the consideration of benefit sharing. Understanding public attitudes, fears, and concerns toward biobanking is fundamental to designing targeted interventions to increase trust towards biobanks. The aim of our study was to investigate the level of knowledge and perception of biobanks in students and personnel of the University of Piemonte Orientale. An online questionnaire was designed and administered via e-mail. A total of 17,758 UPO personnel and students were invited to participate in the survey, and 1521 (9.3%) subjects completed the survey. The results showed that 65.0% of the participants were aware of the term "biobank" and knew what the activity of a biobank was, and 76.3% of subjects were willing to provide biospecimens to a research biobank, whereas 67.3% of the respondents were willing to contribute, in addition to biospecimens, their health and lifestyle data. Concerns were raised about the confidentiality of the information (25.6%) and the commercial use of the samples (25.0%). In conclusion, participants were aware of the role that biobanks play in research and were eager to participate for the sake of furthering scientific research. Still, several concerns need to be addressed regarding the confidentiality of the data along with the commercial use of the samples and associated data.

Health-related lifestyles among Italian university students: A cross-sectional study.

OBJECTIVES: to investigate lifestyle, health-related behaviours, and nutritional knowledge among a sample of Italian university students and to identify social determinants of - and barriers to - healthier lifestyles. DESIGN: cross-sectional observational study. SETTING AND PARTICIPANTS: students attending degree courses in health professions in a single university in Northern Italy (No. 1,495) were invited to participate in a structured web survey. MAIN OUTCOME MEASURES: a comprehensive, validated questionnaire was used. Questions regarded nutritional knowledge and habits, smoking habit, physical activity, self-efficacy, and barriers to change. Anthropometric and sociodemographic information was collected. Descriptive statistics were used to summarize results. With single and multiple regression models, differences between subgroups and ranked predictors of students' attitudes towards healthy behaviours were analysed. Statistical significance was set at p<0.05. RESULTS: a total of 554 subjects completed the survey (participation rate: 42%; completion rate: 88%). Students showed good nutritional knowledge (73%), but some deficiencies related to low fruit/high sweets consumption, and a lack of basic macronutrients information. Only 30% of the students led a very active lifestyle and physical inactivity was greatest among overweight/obese students. Sedentary lifestyle and unhealthy diet were mainly associated with modifiable risk factors, e.g., being overweight and smoking. CONCLUSIONS: this study provides evidence that health profession students have good knowledge, but their health-related lifestyle is a concern, especially given the role of prescribers that they will play. Structured programmes need to be developed to address the modifiable risk factors associated with detrimental behaviours manifest already during the university years.

Adaptive Modelling of Mutated FMO3 Enzyme Could Unveil Unexplored Scenarios Linking Variant Haplotypes to TMAU Phenotypes.

BACKGROUND: Trimethylaminuria (TMAU) is a rare genetic disease characterized by the accumulation of trimethylamine (TMA) and its subsequent excretion trough main body fluids, determining the characteristic fish odour in affected patients. We realized an experimental study to investigate the role of several coding variants in the causative gene FMO3, that were only considered as polymorphic or benign, even if the available literature on them did not functionally explain their ineffectiveness on the encoded enzyme. METHODS: Mutational analysis of 26 TMAU patients was realized by Sanger sequencing. Detected variants were, subsequently, deeply statistically and in silico characterized to determine their possible effects on the enzyme activity. To achieve this goal, a docking prediction for TMA/FMO3 and an unbinding pathway study were performed. Finally, a TMAO/TMA urine quantification by 1H-NMR spectroscopy was performed to support modelling results. RESULTS: The FMO3 screening of all patients highlighted the presence of 17 variants distributed in 26 different haplotypes. Both non-sense and missense considered variants might impair the enzymatic kinetics of FMO3, probably reducing the interaction time between the protein catalytic site and TMA, or losing the wild-type binding site. CONCLUSIONS: Even if further functional assays will confirm our predictive results, considering the possible role of FMO3 variants with still uncertain effects, might be a relevant step towards the detection of novel scenarios in TMAU etiopathogenesis.

[The relationship between physical exercise and gut microbiota in the human being: a systematic review]. / Relazione tra esercizio fisico e microbiota intestinale nell'essere umano: revisione sistematica.

BACKGROUND: the relationship between physical exercise and gut microbiota has opened new therapeutic frontiers for many inflammatory diseases. However, there is still a lot of uncertainty about how to administer exercise. OBJECTIVES: to review the literature to bridge this gap and examine the relationship between cardiorespiratory fitness (CRF) and microbiota. DESIGN: systematic review. SETTING AND PARTICIPANTS: studies involving humans who undergoing exercise programmes of any lengths, intensities, and types were included. The research was carried out through PubMed, Scopus, and Web of Science. MAIN OUTCOME MEASURES: the primary outcome was change in gut microbiota composition (α and ß-diversity), while the secondary outcome was the CRF level. RESULTS: the 15 studies included (all with PEDro scale <=5) used aerobic training alone or combined with resistance exercises. In general, exercise has shown positive effects on the microbiota, influencing the faecal count of some bacterial phyla (in particular Bacteroidetes, Firmicutes, and Proteobacteria), with a weak tendency towards proportionality in relation to training duration and intensity. However, the evidence supporting the exercise effects on the gut microbiota and the relationship with CRF are of low quality. CONCLUSIONS: despite the weak evidence in favour of the effects of the practice of physical exercise on the intestinal microbiota, there are still many aspects that need to be explored. In particular, future studies shall have higher quality and methodological rigour, standardize the methods for outcome assessment, and determine type and thresholds of interventions intensity and duration.

Non-pharmacological Approaches to Depressed Elderly With No or Mild Cognitive Impairment in Long-Term Care Facilities. A Systematic Review of the Literature.

Introduction: Compared to old people who live at home, depressive symptoms are more prevalent in those who live in long-term care facilities (LTCFs). Different kinds of non-pharmacological treatment approaches in LTCFs have been studied, including behavioral and cognitive-behavioral therapy, cognitive bibliotherapy, problem-solving therapy, brief psychodynamic therapy and life review/reminiscence. The aim of the current review was to systematically review non-pharmacological treatments used to treat depressed older adults with no or mild cognitive impairment (as described by a Mini Mental State Examination score > 20) living in LTCFs. Methods: A research was performed on PubMed and Scopus databases. Following the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) flowchart, studies selection was made. The quality of each Randomized Controlled Trial was scored using the Jadad scale, Quasi-Experimental Design studies and Non-Experimental studies were scored based on the Newcastle-Ottawa Scale (NOS) Results: The review included 56 full text articles; according to the type of intervention, studies were grouped in the following areas: horticulture/gardening (n = 3), pet therapy (n = 4), physical exercise (n = 9), psychoeducation/rehabilitation (n = 15), psychotherapy (n = 3), reminiscence and story sharing (n = 14), miscellaneous (n = 8). Discussion and Conclusion: Despite mixed or negative findings in some cases, most studies included in this systematic review reported that the non-pharmacological interventions assessed were effective in the management of depressed elderly in the LTCFs context. Regrettably, the limitations and heterogeneity of the studies described above hinder the possibility to generalize and replicate results.

Oxidative Stress and the Neurovascular Unit.

The neurovascular unit (NVU) is a relatively recent concept that clearly describes the relationship between brain cells and their blood vessels. The components of the NVU, comprising different types of cells, are so interrelated and associated with each other that they are considered as a single functioning unit. For this reason, even slight disturbances in the NVU could severely affect brain homeostasis and health. In this review, we aim to describe the current state of knowledge concerning the role of oxidative stress on the neurovascular unit and the role of a single cell type in the NVU crosstalk.

New evaluation methods of read mapping by 17 aligners on simulated and empirical NGS data: an updated comparison of DNA- and RNA-Seq data from Illumina and Ion Torrent technologies.

During the last (15) years, improved omics sequencing technologies have expanded the scale and resolution of various biological applications, generating high-throughput datasets that require carefully chosen software tools to be processed. Therefore, following the sequencing development, bioinformatics researchers have been challenged to implement alignment algorithms for next-generation sequencing reads. However, nowadays selection of aligners based on genome characteristics is poorly studied, so our benchmarking study extended the "state of art" comparing 17 different aligners. The chosen tools were assessed on empirical human DNA- and RNA-Seq data, as well as on simulated datasets in human and mouse, evaluating a set of parameters previously not considered in such kind of benchmarks. As expected, we found that each tool was the best in specific conditions. For Ion Torrent single-end RNA-Seq samples, the most suitable aligners were CLC and BWA-MEM, which reached the best results in terms of efficiency, accuracy, duplication rate, saturation profile and running time. About Illumina paired-end osteomyelitis transcriptomics data, instead, the best performer algorithm, together with the already cited CLC, resulted Novoalign, which excelled in accuracy and saturation analyses. Segemehl and DNASTAR performed the best on both DNA-Seq data, with Segemehl particularly suitable for exome data. In conclusion, our study could guide users in the selection of a suitable aligner based on genome and transcriptome characteristics. However, several other aspects, emerged from our work, should be considered in the evolution of alignment research area, such as the involvement of artificial intelligence to support cloud computing and mapping to multiple genomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00521-021-06188-z.

Impairments of Photoreceptor Outer Segments Renewal and Phototransduction Due to a Peripherin Rare Haplotype Variant: Insights from Molecular Modeling.

BACKGROUND: Retinitis pigmentosa punctata albescens (RPA) is a particular form of retinitis pigmentosa characterized by childhood onset night blindness and areas of peripheral retinal atrophy. We investigated the genetic cause of RPA in a family consisting of two affected Egyptian brothers with healthy consanguineous parents. METHODS: Mutational analysis of four RPA causative genes was realized by Sanger sequencing on both probands, and detected variants were subsequently genotyped in their parents. Afterwards, found variants were deeply, statistically, and in silico characterized to determine their possible effects and association with RPA. RESULTS: Both brothers carry three missense PRPH2 variants in a homozygous condition (c.910C > A, c.929G > A, and c.1013A > C) and two promoter variants in RHO (c.-26A > G) and RLBP1 (c.-70G > A) genes, respectively. Haplotype analyses highlighted a PRPH2 rare haplotype variant (GAG), determining a possible alteration of PRPH2 binding with melanoregulin and other outer segment proteins, followed by photoreceptor outer segment instability. Furthermore, an altered balance of transcription factor binding sites, due to the presence of RHO and RLBP1 promoter variants, might determine a comprehensive downregulation of both genes, possibly altering the PRPH2 shared visual-related pathway. CONCLUSIONS: Despite several limitations, the study might be a relevant step towards detection of novel scenarios in RPA etiopathogenesis.

The Early Detection of Osteoporosis in a Cohort of Healthcare Workers: Is There Room for a Screening Program?

Workforce aging is becoming a significant public health problem due to the resulting emergence of age-related diseases, such as osteoporosis. The prevention and early detection of osteoporosis is important to avoid bone fractures and their socio-economic burden. The aim of this study is to evaluate the sustainability of a screening workplace program able to detect workers with osteoporosis. The screening process included a questionnaire-based risk assessment of 1050 healthcare workers followed by measurement of the bone mass density (BMD) with a pulse-echo ultrasound (PEUS) at the proximal tibia in the at-risk subjects. Workers with a BMD value ≤ 0.783 g/cm² were referred to a specialist visit ensuring a diagnosis and the consequent prescriptions. Any possible association between the outcome variable BMD ≤ 0.783 g/cm² and the risk factors was evaluated. The costs were calculated with a full costing method. We identified 60 pathological subjects. We observed increased risks for women, older ages, and menopause (p < 0.01). The yearly cost of our screening program estimated for this study was 8242 euros, and, considering the fragility bone fracture costs, we hypothesize a considerable economic savings, with a possible positive benefits/cost ratio of 2.07. We can say that the margin between the investment and results leads to a preference for this type of screening program. Osteoporosis is an occupational health problem, and a workplace screening program could be a cost-effective intervention.

The biological pathways of Alzheimer disease: a review.

Alzheimer disease is a progressive neurodegenerative disorder, mainly affecting older people, which severely impairs patients' quality of life. In the recent years, the number of affected individuals has seen a rapid increase. It is estimated that up to 107 million subjects will be affected by 2050 worldwide. Research in this area has revealed a lot about the biological and environmental underpinnings of Alzheimer, especially its correlation with ß-Amyloid and Tau related mechanics; however, the precise molecular events and biological pathways behind the disease are yet to be discovered. In this review, we focus our attention on the biological mechanics that may lie behind Alzheimer development. In particular, we briefly describe the genetic elements and discuss about specific biological processes potentially associated with the disease.