Virtual Reality Cognitive Remediation in Older Adults with Bipolar Disorder: The Effects on Cognitive Performance and Depression in a Feasibility Randomized Controlled Trial.

INTRODUCTION: Dementia, depression, and cardiovascular disease are major public health concerns for older adults, requiring early intervention. This study investigates whether a virtual reality cognitive remediation program (VR-CR) can improve cognitive function and depressive symptoms in older adults, and determines the necessary sample size for future studies. Integrated VR and CR interventions have shown promising outcomes in older adults with neurodegenerative and mental health disorders. METHODS: This secondary analysis of a randomized controlled trial involves adults aged 58-75 years with bipolar disorder, excluding those with acute episodes, epilepsy, or severe eye diseases. The experimental group received standard treatment plus VR-CR, while the control group received only standard treatment. RESULTS: No baseline differences were found between the experimental and control groups. No significant improvement was observed in the overall cognitive function test (p = 0.897) or in depressive symptoms (p = 0.322). A phase III efficacy study requires a sample size of 28 participants (alpha = 0.05, beta = 0.20). CONCLUSIONS: VR-CR can potentially treat depressive symptoms in adults and older adults, but the results support conducting phase III studies to further investigate these outcomes. However, the improvement in cognitive performance in the elderly is less pronounced than in younger individuals.

Hyperactivity and Risk for Dysregulation of Mood, Energy, and Social Rhythms Syndrome (DYMERS): Standardization of a Simple One-Item Screener versus the Mood Disorder Questionnaire (MDQ).

Background: This study aims to verify the accuracy of item 10 on the energy level of the Short-Form Health Survey (SF-12) in an item screening according to Mood Disorder Questionnaire (MDQ) results, providing a measure of hyper-energy. Methods: Regression techniques were employed in a dataset comprising 4093 records of respondents to test both linear and nonlinear relationships between predictor and outcome variables (energy level and symptoms considered in the MDQ). We examined the relationship of energy level with cases identified using MDQ with a cut-off of 7. Results: Levels of energy, as rated on item 10 of the SF-12, were related to the MDQ score with sensitivity = 0.72 and specificity = 0.70. In linear regression, the associations were stronger with MDQ items on excessive energy or activity, showing a medium effect size and an explained variance of 10% or higher. A greater association was observed for items on excessive energy and activity, as expected, as well as for items concerning self-confidence, sociability, and talkativeness. Conclusions: This result may have implications for the research on risk factors and the pathogenesis of the dysregulation of mood, energy, and social rhythms syndrome (DYMERS), a syndrome that is hypothesized to occur in stressful conditions like those shown under the COVID-19 pandemic.

Prior Engagement in Physical Activity Correlates with Enhanced Quality of Life Perceptions among Older Adults during COVID-19 Lockdown.

BACKGROUND: This longitudinal study aimed to evaluate whether prior engagement in a physical exercise program correlated with enhanced perceptions of quality-of-life components among older adults during the COVID-19 lockdown period. METHODS: The cohort comprised elderly individuals (aged ≥ 65 years) who had previously partaken in a 12-week randomized controlled trial investigating the effects of a mixed aerobic-anaerobic, moderate-intensity exercise program. Participants' health-related quality of life was assessed using the Short Form Health Survey-12 item (SF-12) at the beginning of the initial trial and, again, one year later during the COVID-19 lockdown. In the exercise group, 44 participants were included, while the control group consisted of 49 participants, with computer-based, double-blind randomization conducted in Cagliari, Italy. The differences in scores for each SF-12 item between the two groups from T0 to T1 were compared using one-way ANOVA with Bonferroni corrections. Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 27. RESULTS: No statistically significant differences were observed on average by age (exercise group vs. control group 72.20 ± 4.78 vs. 72.91 ± 4.77; F = 0.513, p = 0.476). A decrease from T0 to T1 towards a better score on the SF-12 was observed in the exercise group compared to the control group in item 1 (F = 67.463, p < 0.0001); in item 5 (F = 4.319, p = 0.041); item 8 (F = 4.269, p = 0.041); item 9 (F = 10.761, p = 0.001); item 10 (F = 170.433, p < 0.001); and item 11 (F = 4.075, p = 0.046). CONCLUSIONS: The results suggest that participation in a moderate physical exercise program one year prior may have equipped older adults with better coping mechanisms to navigate the stress and isolation imposed by the COVID-19 lockdown, as reflected by their enhanced scores on quality-of-life components pertaining to mental well-being. Exercise may confer a protective effect against the adverse psychological impacts of stressful events like the pandemic, even among older adults with chronic conditions. This study underscores the potential benefits of exercise interventions for promoting quality of life and preventing mood disorders in the elderly population.

Improving Social and Personal Rhythm Dysregulation in Young and Old Adults with Bipolar Disorder: Post-Hoc Analysis of a Feasibility Randomized Controlled Trial Using Virtual Reality-Based Intervention.

Introduction: Rehabilitative interventions employing technology play a crucial role in bipolar disorder (BD) treatment. The study aims to appraise the virtual reality (VR)-based cognitive remediation (CR) and the interpersonal rhythm approaches to treatment outcomes of BD across different age groups. Methods: Post-hoc analysis of a 12-week randomizedcontrolled cross-over feasibility trial involving people with mood disorders (BD, DSM-IV) aged 18-75 years old: thirty-nine exposed to the experimental VR-based CR vs 25 waiting list controls. People with BD relapse, epilepsy or severe eye diseases (due to the potential VR risks exposure) were excluded. Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) was used to measure the outcome. Results: Cases and controls did not statistically significantly differ in age and sex distributions. Personal rhythm scores improved over the study follow-up in the experimental vs the control group (APC = 8.7%; F = 111.9; p < 0.0001), both in young (18-45 years) (APC = 5.5%; F = 70.46; p < 0.0001) and, to a lesser extent, older (>46 years) adults (APC = 10.5%; F = 12.110; p = 0.002). Conclusions: This study observed improved synchronization of personal and social rhythms in individuals with BD after a virtual reality cognitive remediation intervention, particularly in social activity, daily activities, and chronotype, with greater benefits in the younger population.

An e-Health Psychoeducation Program for Managing the Mental Health of People with Bipolar Disorder during the COVID-19 Pandemic: A Randomized Controlled Study.

Background: Social rhythm dysregulation has been identified as a determining factor in bipolar disorder (BD) relapses. It directly impacts individuals' quality of life (QoL). This study aims to present preliminary data on the efficacy of an e-health psychoeducational intervention for BD for improving clinical outcomes. Methods: This study used an open-label, crossover, randomized controlled trial design. The inclusion criteria consisted of a BD diagnosis, affiliation with the Consultation Psychiatry and Psychosomatic Center at the University Hospital in Cagliari, Italy, age over 18, and the obtaining of informed consent. Anxiety and depressive symptoms, QoL, and social and biological rhythms were measured using standardized instruments validated in Italian. Results: A total of 36 individuals were included in the experimental group (EG) and 18 in the control group (CG). The final sample consisted of 25 in the EG and 14 in the CG. A statistically significant improvement in QoL was found in the EG post-treatment (p = 0.011). Significant correlations were found between QoL and the dysregulation of biorhythms in the EG at T0 (p = 0.0048) and T1 (p = 0.0014). Conclusions: This study shows that, during extreme distress, an e-health group psychoeducation intervention for people with BD could significantly improve the perception of QoL. The results must be confirmed by studies conducted with larger-sized samples.

The long-term adherence following the end of Community Treatment Order: A systematic review.

BACKGROUND: The community treatment order (CTO) is designed to deliver mental healthcare in the community and has been introduced in around 75 jurisdictions worldwide. It constitutes a legal obligation in which individuals with severe mental illness must adhere to out-of-hospital treatment plans. Despite intense criticism and the debated nature of published evidence, it has emerged as a clinical and policy response to frequent hospital readmissions and to enhance adherence in cases where there is refusal of pharmacological treatments. This systematic review outlines findings on CTO long-term adherence, after mandatory outpatient treatment has ended, in studies that include people with psychiatric disorders. METHOD: Following PRISMA guidelines, we performed a review of published articles from PubMed, PsycINFO, EMBASE, and CINAHL up to January 15, 2023. We included studies that assessed adherence after CTO ends. The study is registered with PROSPERO number CRD42022360879. RESULTS: Six independent studies analyzing the main indicators of long adherence: engagement with services and medication adherence, were included. The average methodological quality of the studies included is fair. Long-term adherence was assessed over a period ranging from 11 to 28 months. Only two studies reported a statistically significant improvement. Regarding the remaining studies, no positive correlation was observed, except for certain subgroup samples, while in one study, medication adherence decreased. CONCLUSION: Scientific evidence supporting the hypothesis that CTO has a positive role on long-term adherence post-obligation is currently not sufficient. Given the importance of modern recovery-oriented approaches and the coercive nature of compulsory outpatient treatment, it is necessary that future studies ensure the role of CTO in effectively promoting adherence.

Development and Validation of the Questionnaire for Adaptive Hyperactivity and Goal Achievement (AHGA).

Objective: This paper illustrates the preliminary psychometric properties of the Questionnaire for Adaptive Hyperactivity and Goal Achievement (AHGA), aimed at measuring adaptive characteristics of hyperactivity and goal pursuit in older adults. Methods: The 12-item scale was administered to a sample of 120 subjects (older adults) between February 2022 and June 2022. The reliability of AHGA was measured using Cronbach's alpha, and factor structure was established using parallel analysis (PA) and principal component analysis (PCA). Convergent validity was tested against the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). Results: All included subjects have an average age of 74.1±5.1 years. AHGA reliability was good (Cronbach's alpha: 0.713 [95%CI: 0.630 to 0.783]). Factor analysis suggested two main components: goal achievement and hyperactivity, which explained 41% of the variance in the data. The results support the convergent validity of the scale: AHGA measures adaptive characteristics of hyperactivity and goal pursuit, in contrast to BRIAN, which measures pathological characteristics. Conclusion: The reported findings represent an innovative approach to hyperthymic features by embracing a broader spectrum concept that conceptualizes the potential transition between pathological and adaptive aspects as a continuum.

Is a Genetic Variant associated with Bipolar Disorder Frequent in People without Bipolar Disorder but with Characteristics of Hyperactivity and Novelty Seeking?

Objective: The objective is to verify whether a genetic condition associated with bipolar disorder (BD) is frequent in old adults adapted to their environment, without BD, but with aptitudes for hyperactivity and novelty seeking (H/NS). Methods: In this cross-sectional study, the study sample included healthy elderly people (40 participants, aged 60 or older) living in an urban area and recruited from a previous study on physical exercise and active aging, who were compared with 21 old adults with BD from the same area. The genetic methodology consisted of blood sampling, DNA extraction, real-time PCR jointly with FRET probes, and the SANGER sequencing method. The genetic variant RS1006737 of CACNA1C, found to be associated with bipolar disorder diagnosis, was investigated. Results: The frequency of the RS1006737 genetic variant in the study group (H/NS) is not higher than in the BD group and is statistically significantly higher than in all the control groups found in the literature. However, the familiarity for BD is higher in old adults with BD than in the H/NS sample without BD. The risk of BD in the family (also considering those without BD but with family members with BD) is not associated with the presence of the genetic variant examined. Conclusion: The study suggests that the gene examined is associated with characteristics of hyperactivity rather than just BD. Nevertheless, choosing to participate in an exercise program is an excessively general way to identify H/NS. The next step would be to identify the old adults with well-defined H/NS features with an adequate tool.

The impact of MDQ positivity on quality of life impairment: Does it support the hypothesis of "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS)?

Background: DSM-5 separates bipolar (BD) from depressive disorders, but some experts consider BD as part of a spectrum of mood disorders. The interpretation of numerous false positives of BD screened by the Mood Disorders Questionnaire (MDQ) is part of this debate. Recent study results suggest that the worsening of health-related quality of life (H-Qol) associated with MDQ positivity does not depend solely on mood disorders. This study aims to clarify whether the impairment may be due to other concomitant disorders, unrelated to mood disorders, leading to a worsening of H-Qol. Additionally, the study aims to explore if MDQ positivity itself observe clinical significance. Design and methods: The study involved pairs of cases (MDQ+) and controls (MDQ-) matched for sex, age, and absence of DSM-IV psychiatric comorbidity. The impact of MDQ positivity on the quality of life in a sample of MDQ+ comorbid with MDD was measured and compared to impact of MDD in other chronic disorders. Results: The H-Qol was significantly worse in MDQ+ than in controls (both groups without any psychiatric co-morbidity). The worsening was similar to severe chronic disorders The burden of worsening quality of life due to MDD was mild in another sample of MDQ positives with comorbid MDD. Conclusion: The study hypothesizes that MDQ positivity may be related to hyperactivation and dysregulation of rhythms typical of stress disorders. In fact, MDQ+ was found strongly related to sleep disturbances. Future studies could verify if a "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS), causes worsening the H-Qol in MDQ+.

Does Screening for Bipolar Disorders Identify a "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS)? A Heuristic Working Hypothesis.

The aim of this paper is to verify if people with a positive score on the Mood Disorder Questionnaire (MDQ) without comorbidity of mood disorders showed a worse level of Health-related Quality of life (HRQol) compared to a control-matched sample of MDQ negatives, identifying a specific syndrome. This is a case-control study based on a database from a community survey. Cases: MDQ-positive without mood disorders; Controls: MDQ negatives matched by sex, age, and psychiatric diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria. Tools: MDQ, the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS) semi-structured interview for psychiatric diagnosis, and the Health Survey Short Form (SF-12) for measuring HRQol. People scoring positive on the MDQ without a diagnosis of mood disorders showed significantly lower scores on the SF-12 compared to people of the same age and of the same sex with an equal diagnosis of psychiatric disorders not related to mood disorders (35.21 ± 6.30 vs. 41.48 ± 3.39, p < 0.0001). In the debate whether a positive score on the MDQ selects an area of "malaise" due to the presence of disorders differing from Bipolar Disorders, or if a positive score on the MDQ may be considered a "subthreshold" form of bipolar disorder in people who may later develop bipolar disorder, a third hypothesis can be advanced, i.e., that a positive score on the MDQ identifies a specific "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS), characterized by a considerable amount of suffering and not attributable to other disorders, and which might represent a trigger for the previously mentioned disorders with which a positive score on the MDQ is associated, probably including, in severe conditions, bipolar disorder.

Screening, Genetic Variants, and Bipolar Disorders: Can Useful Hypotheses Arise from the Sum of Partial Failures?

Bipolar disorder (BD) is a relevant public health issue, therefore accurate screening tools could be useful. The objective of this study is to verify the accuracy of the Mood Disorder Questionnaire (MDQ) and genetic risk as screeners, and their comparison in terms of reliability. Older adults (N = 61, ≥60 years) received a clinical psychiatric evaluation, the MDQ, and were evaluated according to the presence of the genetic variant RS1006737 of CACNA1C. MDQ+ versus the diagnosis of BD as a gold standard shows a sensitivity of 0.286 (Cl 95% 0.14-0.39); a specificity of 0.925 (Cl 95% 0.85-0.08); a predictive positive value (PPV) of 0.667 (Cl 95% 0.33-0.91); and a predictive negative value (PNV) of 0.702 (Cl 95% 0.65-0.75). The positivity for the variant RS1006737 of the CACNA1C against the diagnosis of BD as a gold standard shows a sensitivity of 0.750 (Cl 95% 0.55-0.90); a specificity of 0.375 (Cl 95% 0.28-0.45); a PPV of 0.375 (Cl 95% 0.28-0.45); and a PNV of 0.750 (Cl 95% 0.55-0.90). The reliability between the MDQ+ and positivity for the variant RS1006737 of the CACNA1C was very low (K = -0.048, Cl 95% -0.20-0.09). The study found that both the genetic and the paper and pencil test were quite accurate, but were not reliable in case finding. In fact, despite some validity, albeit specular (in the case of a positive genetic test, the probability of having the disorder is very high, whereas in the case of a negative score on the paper and pencil test, the probability of not having the disorder is very high), the unreliability of the two tests (i.e., they certainly do not measure the same underlying dimension) opens the door to the need for an interpretation and the possibility of a synergistic use for screening. From a heuristic perspective, which obviously requires all of the necessary verifications, this study seems to suggest the hypothesis that a condition of hyperactivation common to disorders and stress conditions, and identified by a positive score on the MDQ (which is common to BD, post-traumatic stress disorder (PTSD), and anxiety disorders and whose genetic basis has not yet been clarified) can trigger BD in people with a predisposition to hyperactivity (i.e., in people with the condition identified by the analyzed genetic variant).

Systematic review of involuntary hospitalisation and long-term compliance.

INTRODUCTION: Involuntary hospitalisation denies autonomy and freedom of decision-making and is frequent in psychiatric clinical practice. However, there is still a lack of knowledge of long-term compliance after Involuntary commitment. METHODS: We conducted a systematic review of published studies reporting people compliance after involuntary hospitalisation and people compliance after voluntary admission. Two investigators independently searched PubMed, PsycINFO, EMBASE and CINAHL up to December 17th, 2021 to identify eligible studies. The study is registered with PROSPERO number CRD42022299437. RESULTS: Ten independent studies analysing the main indicators of compliance, engagement with services and medication adherence, were included. Three studies show that compliance is worse in people that have been involuntary hospitalised and in the others no association is found. Just two of the ten studies show an association with improved compliance. Outcomes are assessed from the first follow-up appointment after discharge up to 96 months. CONCLUSIONS: Although evidences carried out so far are weak, the data do not show a trend of improvements and do not seem to exclude the possibility of worse compliance after compulsory hospitalisation. More appropriate methodologies and reliable assessment are needed in future research to provide scientific evidence on involuntary admission health effects.

Usefulness of salivary sampling for the molecular detection of a genetic variant associated with bipolar disorders.

Under certain conditions, the hyperthymic temperament traits associated with an increased risk of developing bipolar disorders may in fact produce adaptive responses. The purpose of this study is to see if the type of biological material used for genetic analysis (saliva or blood) affects the detection of mutations in the CACNA1C (RS1006737) gene. The first experimental group consisted of Sardinian migrants ("volunteers") in South American and European megacities. The second experimental group consisted of older healthy subjects with hyperactivity and novelty-seeking characteristics from Cagliari, Italy. The genetic procedure included DNA extraction, real-time PCR, and the Sanger method. Nonetheless, the authors believe that saliva is the most appropriate biological material, given its many advantages. In contrast to blood, saliva can be collected by any type of healthcare provider after following a few simple instructions.

Does the Response to a Stressful Condition in Older Adults with Life Rhythm Dysregulations Provide Evidence of the Existence of the "Dysregulation of Mood, Energy, and Social Rhythms Syndrome"?

OBJECTIVE: The COVID-19 lockdown periods have given rise to the "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS). This syndrome is characterized by a poor regulation of biological, social, and behavioral rhythms, including sleep, nutrition, and social contacts. The purpose of this cohort study was to examine whether older adults with pre-existing DYMERS had a more negative perception of their health-related quality of life (H-QoL) during the COVID-19 pandemic lockdown, regardless of the presence of concurrent mood disorders. METHOD: The entire study population (N = 93; age > 65 year) was categorized based on whether they exhibited dysregulated rhythms at the outset of the study. A comparison was made between DYMERS-positive individuals and DYMERS-negative individuals, and we assessed their H-QoL at the conclusion of the study. We also compared the H-QoL of individuals in the cohort who did not have a positive depression score to understand the impact of the rhythm dysregulation alone. RESULTS: The frequency of individuals with a critical health-related quality of life score (SF12 < 25) was higher in the cohort with pre-existing DYMERS during lockdown (33.33% vs. 6.17%). This difference remained significant even when only individuals without depressive symptomatology were considered (27.27% vs. 2.60%). CONCLUSION: The results of this study indicate that DYMERS can exert a substantial influence on health-related quality of life (H-QoL), even when mood disturbances are not present. Additional research is required to investigate the relationship between DYMERS and other psychiatric conditions as well as its nature as a standalone disorder.

The Effects of Tyrosine Kinase Inhibitors (TKIs) in Monotherapy and with Add-on Treatments on Health-related Quality of Life of People with Chronic Myeloid Leukemia: A Systematic Review of Randomized-Controlled Trials.

Background: The era of establishing tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) changed the outcome and the course of this life-threatening malignancy. People suffering from CML have now a better prognosis and a longer life expectancy due to the development of TKIs, even if it requires long-term, often lifelong, treatments that are nonetheless associated with improved Health-related Quality of life (HRQoL). However, data on the effects of TKIs on HRQoL are not always systematic; sometimes the data have been obtained by studies different from RCTs, or without a clear definition of what HRQoL is. The main purpose of this systematic review is to summarize all randomized-controlled trials (RCTs) including HRQoL as main or secondary outcome in patients with CML treated with TKIs or with TKIs plus an add-on treatment. Methods: A systematic review has been conducted by searching the relevant papers in PubMed/Medline and Web of Science with the following keywords: "quality of life" OR "health-related quality of life" OR "QoL" OR "HRQoL" OR "H-QoL" AND "chronic myeloid leukemia". Interval was set from January 2000 to December 2020. Results: 40 papers were identified through the search. Out of them, 7 RCTs were included. All the studies used standardized measures to assess HRQoL, even not always specific for CML. 5 RCTs randomized subjects to 2 or 3 arms to evaluate the effects of TKIs of the first, second and third generation in monotherapy. 2 RCTs randomized subjects to TKI therapy plus an add-on treatment versus TKI therapy as usual. The results of all these trials were examined and discussed. Conclusion: All the included RCTs pointed out significant findings regarding the positive effects of TKIs on HRQoL of people with CML, both when they were used in monotherapy or, notably, with an add-on treatment to enhance TKIs effects.

Previous functional social and behavioral rhythms affect resilience to COVID-19-related stress among old adults.

BACKGROUND: Functioning of Social Behavioral Rhythms (SBRs) may affect resilience toward stressful events across different age groups. However, the impact of SBRs on the coronavirus disease of 2019 (COVID-19) in elder people is yet to ascertain, representing the aim of the present report. DESIGN AND METHODS: Follow-up of a peer-reviewed randomized controlled trial on exercise on old adults (³65 years), concurrent to the onset of the pandemic-related lockdown. Post-RCT evaluations occurred after further 12 and 36 weeks since the beginning of the lockdown phase. People with Major Depressive Episode (MDE) at week-48 (follow-up endpoint) were deemed as cases, people without such condition were considered controls. MDE was ascertained using the Patient Health Questionnaire-9 (PHQ-9); SBRs functioning at week 12 onward, through the Brief Symptom Rating Scale (BSRS). RESULTS: Seventy-nine individuals (53.2%, females) entered the RCT-follow-up phase. The frequency of MDE did not significantly change before versus during lockdown (OR 2.60, CI95%=0.87-9.13). People with BSRS>1 standard deviation of the whole sample score at week-12 had an inflated risk of DE during lockdown (OR=5.6, 95%CI: 1.5-21.4) compared to those with lower BSRS scores. Such odd hold after excluding individuals with MDD at week-12. The post-hoc analysis could be potentially affected by selection bias. CONCLUSIONS: Overall, older adults were resilient during the first phase of the pandemic when functioning of pre-lockdown was still preserved, in contrast to the subsequent evaluations when the impairment of daily rhythms was associated with impaired reliance.

Covid-19 vaccines work but other factors play a relevant role: a data analysis on spread and mortality in 24 countries.

BACKGROUND: The aim was to outline a methodology to monitor the impact of vaccinations in different countries comparing at two different times within countries and between countries the frequency of new cases and Covid-19 related deaths and the percentage of vaccinations conducted. DESIGN AND METHODS: The 25 countries with the largest increase in SARS-CoV-2 cases on 8 August 2021 were evaluated. In each nation was calculated the proportion of Covid-19 deaths divided per new cases x 100 and the proportion of new cases per 1.000 inhabitants on 10 January 2021 (before vaccinations' distribution) and 8 August 2021 (when large percentage of the population had been vaccinated in many countries). RESULTS: The study shows that in the countries with the highest number of cases as of 8 August 2021, the proportion of vaccinations carried out in the population correlates negatively with both the proportion between Covid-19 dead people x100 infected people and with the rate of new cases. However, the proportion of vaccinations does not correlate with the differences in the two same indicators considered in the weeks observed, thus additional factors seem to play an important role. CONCLUSIONS: This work indicates that mass vaccination is associated with a lower spread of the pandemic and, to greater extent, with a lowering of mortality in infected people.

Is Bipolar Disorder the Consequence of a Genetic Weakness or Not Having Correctly Used a Potential Adaptive Condition?

It is hypothesized that factors associated with bipolar disorder could, uer defined conditions, produce adaptive behaviors. The aim is to verify whether a genetic feature associated with bipolar disorder can be found in people without bipolar disorder but with hyperactivity/exploration traits. Healthy old adults (N = 40) recruited for a previous study on exercise were subdivided using a previously validated tool into those with and without hyperactivity/exploration traits and compared with a group of old patients with bipolar disorder (N = 21). The genetic variant RS1006737 of CACNA1C was analyzed using blood samples, DNA extraction, real-time PCR, FRET probes, and SANGER method sequencing. People with hyperactivity/exploration traits and without bipolar disorder were like people with bipolar disorder regarding the frequency of the genetic variant (OR = 0.79, CI95%: 0.21-2.95), but were different from people without either hyperactivity/exploration traits and bipolar disorder (OR = 4.75, CI95%: 1.19-18.91). The combined group of people with hyperactivity/exploration traits without bipolar disorder plus people with bipolar disorder had a higher frequency of the variant than people without either hyperactivity/exploration traits or bipolar disorder (OR = 4.25, CI95%: 1.24-14.4). To consider the genetic profile of bipolar disorder not an aberrant condition opens the way to a new approach in which the adaptive potential would be a central point in psychosocial treatment in addition to drug therapy. Future research can confirm the results of our study.

Moderate Exercise Improves Cognitive Function in Healthy Elderly People: Results of a Randomized Controlled Trial.

BACKGROUND: Physical activity in the elderly is recommended by international guidelines to protect against cognitive decline and functional impairment. OBJECTIVE: This Randomized Controlled Trial (RCT) was set up to verify whether medium-intensity physical activity in elderly people living in the community is effective in improving cognitive performance. DESIGN: RCT with parallel and balanced large groups. SETTING: Academic university hospital and Olympic gyms. SUBJECTS: People aged 65 years old and older of both genders living at home holding a medical certificate for suitability in non-competitive physical activity. METHODS: Participants were randomized to a 12-week, 3 sessions per week moderate physical activity program or to a control condition focused on cultural and recreational activities in groups of the same size and timing as the active intervention group. The active phase integrated a mixture of aerobic and anaerobic exercises, including drills of "life movements", strength and balance. The primary outcome was: any change in Addenbrooke's Cognitive Examination Revised (ACE-R) and its subscales. RESULTS: At the end of the trial, 52 people completed the active intervention, and 53 people completed the control condition. People in the active intervention improved on the ACE-R (ANOVA: F(1;102)=4.32, p=0.040), and also showed better performances on the memory (F(1;102)=5.40 p=0.022) and visual-space skills subscales of the ACE-R (F(1;102)=4.09 p=0.046). CONCLUSION: A moderate-intensity exercise administered for a relatively short period of 12 weeks is capable of improving cognitive performance in a sample of elderly people who live independently in their homes.Clinical Trials Registration No: NCT03858114.

Association between Hypomagnesemia, COVID-19, Respiratory Tract and Lung Disease.

The complexity of COVID-19 is also related to the multiple molecular pathways triggered by SARS-CoV-2, which is able to cause type I pneumocyte death, trigger intravascular coagulation, interfere with the renin-angiotensin system, dysregulate iron metabolism, ending with the insurgence of a cytokine storm which may lead to death. Old adults with obesity, hypertension, and diabetes are among the high-risk category groups more prone to SARS-CoV-2 infection. Magnesium has been reported to play a major role both in physiology and in pathology, particularly in elderly people, regulating cytotoxic functions of natural killer (NK) cells and CD8+ T lymphocytes. In spite of the absence of controlled trials, the possibility of magnesium supplementation for supportive treatment in patients with COVID-19 should be encouraged. This could be useful in all phases of the COVID-19 disease.