The cellular coding of temperature in the mammalian cortex.

Temperature is a fundamental sensory modality separate from touch, with dedicated receptor channels and primary afferent neurons for cool and warm1-3. Unlike for other modalities, however, the cortical encoding of temperature remains unknown, with very few cortical neurons reported that respond to non-painful temperature, and the presence of a 'thermal cortex' is debated4-8. Here, using widefield and two-photon calcium imaging in the mouse forepaw system, we identify cortical neurons that respond to cooling and/or warming with distinct spatial and temporal response properties. We observed a representation of cool, but not warm, in the primary somatosensory cortex, but cool and warm in the posterior insular cortex (pIC). The representation of thermal information in pIC is robust and somatotopically arranged, and reversible manipulations show a profound impact on thermal perception. Despite being positioned along the same one-dimensional sensory axis, the encoding of cool and that of warm are distinct, both in highly and broadly tuned neurons. Together, our results show that pIC contains the primary cortical representation of skin temperature and may help explain how the thermal system generates sensations of cool and warm.

An AI-based approach driven by genotypes and phenotypes to uplift the diagnostic yield of genetic diseases.

Identifying disease-causing variants in Rare Disease patients' genome is a challenging problem. To accomplish this task, we describe a machine learning framework, that we called "Suggested Diagnosis", whose aim is to prioritize genetic variants in an exome/genome based on the probability of being disease-causing. To do so, our method leverages standard guidelines for germline variant interpretation as defined by the American College of Human Genomics (ACMG) and the Association for Molecular Pathology (AMP), inheritance information, phenotypic similarity, and variant quality. Starting from (1) the VCF file containing proband's variants, (2) the list of proband's phenotypes encoded in Human Phenotype Ontology terms, and optionally (3) the information about family members (if available), the "Suggested Diagnosis" ranks all the variants according to their machine learning prediction. This method significantly reduces the number of variants that need to be evaluated by geneticists by pinpointing causative variants in the very first positions of the prioritized list. Most importantly, our approach proved to be among the top performers within the CAGI6 Rare Genome Project Challenge, where it was able to rank the true causative variant among the first positions and, uniquely among all the challenge participants, increased the diagnostic yield of 12.5% by solving 2 undiagnosed cases.

Efficacy and safety of 5-hydroxytryptophan on depression and apathy in Parkinson's disease: a preliminary finding.

BACKGROUND AND PURPOSE: Several studies have indicated that altered serotonergic neurotransmission may contribute to non-motor features commonly associated with Parkinson's disease (PD) such as apathy and depression. 5-hydroxytryptophan (5-HTP) is the intermediate metabolite of L-tryptophan in the production of serotonin. To date, there has been inconsistent research on the use of 5-HTP in PD. The purpose of this study was to compare the effects of 5-HTP with those of placebo on apathy and depressive symptoms in patients with PD. METHODS: A single-center, randomized, double-blind placebo-controlled cross-over trial was employed; 25 individuals were subsequently enrolled into the study. Patients received placebo and 50 mg of 5-HTP daily over a period of 4 weeks. For the assessment of efficacy on depressive and apathy symptoms the Beck Depression Inventory-II (BDI-II), Hamilton Depression Rating Scale (HDRS) and Apathy Scale (AS) were respectively administered at screening, baseline and weeks 4, 8, 12 and 16. Primary efficacy outcomes were the comparison of 5-HTP to placebo in mean change from baseline to weeks 4, 8, 12 and 16 in total score on the AS, BDI-II and HDRS. RESULTS: Repeated-measures analysis revealed a significant improvement of depressive symptoms during the 50-mg 5-HTP treatment compared with placebo as assessed by the HDRS. No effect of 5-HTP was seen on apathy symptoms assessed by the AS. CONCLUSIONS: This study provides preliminary evidence of clinical benefit of 5-HTP for treating depressive symptoms in PD. Larger studies with a longer treatment duration are needed to corroborate these early findings.

[An evolutionist approach of mood disorders from a transcultural perspective]. / Une approche évolutionniste de la manie dans une perspective transculturelle.

INTRODUCTION: The objective of this paper is to verify if traits and symptoms defined as pathological and maladjusted in certain contexts may produce adaptive effects in other contexts, especially if they occur in sub-threshold forms. METHODS: A historical examination of how the symptoms of depression have changed in front of great social changes and an analysis of Sardinian migrants' thymic profiles toward several metropolises. RESULTS AND CONCLUSIONS: Mood disorders have been increasing since the "English malady" in the 17th century, and we suppose that some forms of mood disorders might have an adaptive advantage. Otherwise, the increase of such an epidemic would have been self-limited. From a sociobiological point of view, it is highly probable that the environment of a rapidly evolving society can select people who are explorers and able to support accelerated biorhythms and that the condition of social change stimulates psychological and psychopathologic changes. It is also possible that hyperthymic persons modulate and create the new environment. If this model can explain the epidemic of mood disorders, its verification should guide future research.

Coping with the New Era: Noise and Light Pollution, Hperactivity and Steroid Hormones. Towards an Evolutionary View of Bipolar Disorders.

Human population is increasing in immense cities with millions of inhabitants, in which life is expected to run 24 hours a day for seven days a week (24/7). Noise and light pollution are the most reported consequences, with a profound impact on sleep patterns and circadian biorhythms. Disruption of sleep and biorhythms has severe consequences on many metabolic pathways. Suppression of melatonin incretion at night and the subsequent effect on DNA methylation may increase the risk of prostate and breast cancer. A negative impact of light pollution on neurosteroids may also affect mood. People who carry the genetic risk of bipolar disorder may be at greater risk of full-blown bipolar disorder because of the impact of noise and light pollution on sleep patterns and circadian biorhythms. However, living in cities may also offers opportunities and might be selective for people with hyperthymic temperament, who may find themselves advantaged by increased energy prompted by increased stimulation produced by life in big cities. This might result in the spreading of the genetic risk of bipolar disorder in the coming decades. In this perspective the burden of poor quality of life, increased disability adjusted life years and premature mortality due to the increases of mood disorders is the negative side of a phenomenon that in its globality also shows adaptive aspects. The new lifestyle also influences those who adapt and show behaviors, reactions and responses that might resemble the disorder, but are on the adaptive side.

Active Aging and Elderly's Quality of Life: Comparing the Impact on Literature of Projects Funded by the European Union and USA.

BACKGROUND: The objective of this research is to verify whether European projects on Active Aging (AA) and Elderly Quality of Life (Qol) funded by the Seventh Framework Programme (FP7) produce an impact on literature similar to projects funded by the National Health Institute (NHI) of the United States on international literature using well-known bibliometric indicators. This effort may be useful in developing standardized and replicable procedures. METHODS: Fifteen randomly selected projects on AA and Elderly Qol concluded in August 2017 and funded by FP7 were compared to similar projects funded by the US NHI with reference to papers published (Scopus and Scholar), papers published in Q1 journals, and the number of citations of the papers linked to the projects. RESULTS: In all the indicators considered, the European projects showed no difference with the US NHI projects. CONCLUSIONS: The EU-funded AA and Qol Elderly projects have an impact on scientific literature comparable to projects funded in the United States by the NHI Agency.Our results are consistent with the data on general medical research, which indicates that, European research remains at a high level of competitiveness.In this experimental study, our methodology appeared to be convincing and reliable and it could be applied to the extent of the impact of more extensive research areas.Our research did not evaluate the relationship between funding required by research and scientific productivity.

Risk for Depression, Burnout and Low Quality of Life Among Personnel of a University Hospital in Italy is a Consequence of the Impact One Economic Crisis in the Welfare System?

BACKGROUND: Research literature suggests that burnout, depression, and a low mental quality of life (QOL) are common among health care workers. Economic crisis might have increased the burden of burnout, depression and low QOL in health care workers. OBJECTIVES: To identify depression risk, burnout levels, and quality of life in a sample of workers of an Italian university hospital. METHOD: Cross sectional study with comparison with two community surveys database results (n = 2000 and 1500, respectively). Overall, 522 workers accepted to take part in the study, representing a 78% response rate (out of 669 individuals). RESULTS: The frequency of positivity at the screener for Major Depressive Disorder among health care workers was more than double than that in the standardized community sample (33.3% vs 14.1%, p<0.0001). All professionals, except the administrative staff and technicians (i.e. those who do not have contact with patients), showed a statistically higher frequency of positivity for depressive episodes compared to the controls. Among the medical staff, the highest risk was found in the surgeon units, while the lowest one was in the laboratories. Surgeons also were those most exposed to high risk of burnout, as measured by the Maslach Burnout Inventory. CONCLUSION: Since burnout is linked to patient safety and quality of patient care, and contribute to medical errors, dedicated interventions aimed at reducing poor mental health and low quality of life in medical staff are indicated.

Traces of medieval migrations in a socially stratified population from Northern Italy. Evidence from uniparental markers and deep-rooted pedigrees.

Social and cultural factors had a critical role in determining the genetic structure of Europe. Therefore, socially stratified populations may help to focus on specific episodes of European demographic history. In this study, we use uniparental markers to analyse the genetic structure of Partecipanza in San Giovanni in Persiceto (Northern Italy), a peculiar institution whose origins date back to the Middle Ages and whose members form the patrilineal descent of a group of founder families. From a maternal point of view (mtDNA), Partecipanza is genetically homogeneous with the rest of the population. However, we observed a significant differentiation for Y-chromosomes. In addition, by comparing 17 Y-STR profiles with deep-rooted paternal pedigrees, we estimated a Y-STR mutation rate equal to 3.90 * 10(-3) mutations per STR per generation and an average generation duration time of 33.38 years. When we used these values for tentative dating, we estimated 1300-600 years ago for the origins of the Partecipanza. These results, together with a peculiar Y-chromosomal composition and historical evidence, suggest that Germanic populations (Lombards in particular) settled in the area during the Migration Period (400-800 AD, approximately) and may have had an important role in the foundation of this community.

Progressive multiple sclerosis and mood disorders.

Mood disorders are very common among multiple sclerosis (MS) patients, but their frequency in patients with progressive course (PMS) has not been adequately researched. Our study aimed to determine the frequency of mood disorders among patients with PMS compared with those with relapsing-remitting MS (RMS) and to explore the associations with disability and disease duration. The study included consecutive outpatients affected by MS according the 2010 revised Mc Donald diagnostic criteria. Psychiatric diagnoses were determined according to DSM-IV by psychiatrists using structured interview tools (ANTAS-SCID). Demographic and clinical data of patients were also collected. Disease courses were defined according to the re-examined phenotype descriptions by the Committee and MS Phenotype Group. Intergroup comparisons were performed by Chi-square test, while logistic regression analysis was performed to assess possible factors associated with mood disorders. In total, 240 MS patients (167 women) were enrolled; of these, 18 % (45/240) had PMS. The lifetime DSM-IV major depression diagnosis (MDD) was established in 40 and 23 % of the PMS and RMS patients, respectively. Using logistic regression analysis, the presence of MDD was independent from disease duration and disability and dependent on PMS course (P = 0.02; OR 2.2). Patients with PMS presented with MDD more frequently than those with RMS, independently from disease duration and physical disability. These findings highlight the importance of considering mood disorders, especially MDD, in the management of PMS patients.

Oxytocin nasal spray in fibromyalgic patients.

Fibromyalgia is a pain disorder associated with frequent comorbid mood, anxiety, and sleep disorders. Despite the frequent use of a complex, poly-drug pharmacotherapy, treatment for fibromyalgia is of limited efficacy. Oxytocin has been reported to reduce the severity of pain, anxiety, and depression, and improve the quality of sleep, suggesting that it may be useful to treat fibromyalgia. To evaluate this hypothesis, 14 women affected by fibromyalgia and comorbid disorders, assuming a complex pharmacotherapy, were enrolled in a double-blind, crossover, randomized trial to receive oxytocin and placebo nasal spray daily for 3 weeks for each treatment. Order of treatment (placebo-oxytocin or oxytocin-placebo) was randomly assigned. Patients were visited once a week. At each visit, the following instruments were administered: an adverse drug reaction record card, Visual Analog Scale of Pain Intensity, Spielberger State Anxiety Inventory, Zung Self-rating Depression Scale, and SF-12. Women self-registered painkiller assumption, pain severity, and quality of sleep in a diary. Unlikely, oxytocin nasal spray (80 IU a day) did not induce positive therapeutic effects but resulted to be safe, devoid of toxicity, and easy to handle.

Trauma- and stressor related disorders in the tuareg refugees of a cAMP in burkina faso.

BACKGROUND: Post-traumatic stress disorder (PTSD) is reported to be common among refugees. We set out to explore risk of Trauma- and Stress-or-Related Disorders and the associated burden of psychological distress in a refugee camp of Malian Refugees in Burkina Faso. METHODS: One out of five persons living in the camp was selected randomly and interviewed using the French version of the Short Screening Scale for PTSD and the validated K6 scale to measure psychiatric morbidity. RESULTS: Around 60% of the interviewed sample (N=408) met the criteria for Trauma- and Stress-or-Related Disorders and also reported severe mental distress on K6 scores. Women aged 40 and over were found to be at higher risk of Trauma- and Stress-or-Related Disorders whereas young people (39 or younger) scored higher on K6 ratings. Around 83% of the surveyed subjects had a family member killed in the war, 91% a relative in the war, more than 80% had a family member suffering from physical injuries, and 90% reported problems with food and housing. The frequency of these life events was not surprisingly higher in persons with Trauma- and Stress-or-Related Disorders, with the death of a family member and severe problems with food being specifically related to them. CONCLUSION: These results point to important psychological suffering in a population that is often ignored by the media and international political authorities. Immediate steps are required to provide urgent legal and humanitarian protection to those who are forced to flee their homes and cross international borders because of disasters.

Comparing the responses of countries and National Health Systems to the COVID-19 pandemic: a critical analysis with a case-report series.

This review aimed to compare the different responses of countries to the pandemic, their National Health Systems, and their impact on citizens' health. This work aimed to create a narrative plot that connects different discussion points and suggests organizational solutions and strategic choices in the face of the pandemic. In particular, this work focused on public health organizations, specifically the European Union and vaccination politics. It is also based on a case report series (about the United States, Germany, Vietnam, New Zealand, Cuba, and Italy), where each country has responded differently to the pandemic in terms of political decisions such as vaccination type, information to citizens, dealings with independent experts, and other specific country factors. In comparing the various models of care systems response to the pandemic, it emerges that: we have found some (few) good practices, but without global coordination, and this is obviously not enough. It is now quite clear that there cannot be a "good answer" in a single nation. Uncoordinated local responses cannot counter a global phenomenon. The second point is that the general context must be considered from a strategic point of view. With the threat of new pandemics (but also of health disasters linked to climate change, pollution, and wars), humanity finds itself at the crossroads between investing in a "democratic" management of international bodies but without power (and at the mercy of the need for funds with consequent conflicts) or in some new leadership proposals that advocate efficiency and problem-solving (and that would probably be able to implement it) but that would place processes totally outside of the public's control.

Evolution of public attitudes about mental illness: a systematic review and meta-analysis.

OBJECTIVE: To explore whether the increase in knowledge about the biological correlates of mental disorders over the last decades has translated into improved public understanding of mental illness, increased readiness to seek mental health care and more tolerant attitudes towards mentally ill persons. METHOD: A systematic review of all studies on mental illness-related beliefs and attitudes in the general population published before 31 March 2011, examining the time trends of attitudes with a follow-up interval of at least 2 years and using national representative population samples. A subsample of methodologically homogeneous studies was further included in a meta-regression analysis of time trends. RESULTS: Thirty-three reports on 16 studies on national time trends met our inclusion criteria, six of which were eligible for a meta-regression analysis. Two major trends emerged: there was a coherent trend to greater mental health literacy, in particular towards a biological model of mental illness, and greater acceptance of professional help for mental health problems. In contrast, however, no changes or even changes to the worse were observed regarding the attitudes towards people with mental illness. CONCLUSION: Increasing public understanding of the biological correlates of mental illness seems not to result in better social acceptance of persons with mental illness.

Controlling Nonlinear Dynamics of Milling Bodies in Mechanochemical Devices Driven by Pendular Forcing.

Understanding the dynamics of milling bodies is key to optimize the mixing and the transfer of mechanical energy in mechanochemical processing. In this work, we present a comparative study of mechanochemical reactors driven by harmonic pendular forcing and characterized by different geometries of the lateral borders. We show that the shape of the reactor bases, either flat or curved, along with the size of the milling body and the elasticity of the collisions, represents relevant parameters that govern the dynamical regimes within the system and can control the transition from periodic to chaotic behaviors. We single out possible criteria to preserve target dynamical scenarios when the size of the milling body is changed, by adapting the relative extent of the spatial domain. This allows us to modulate the average energy of the collisions while maintaining the same dynamics and paves the way for a unifying framework to control the dynamical response in different experimental conditions. We finally explore the dynamical and energetic impact of an increasingly asymmetric mechanical force.

The loss of sadness: the public's view.

OBJECTIVE: With the exception of bereavement, the diagnosis of major depressive disorder in the DSM-IV does not take into account the context in which the symptoms occur. Recent criticism has maintained that common sense suggests making a distinction between depression as mental disorder and sorrow as 'normal' reaction to social stress. This study sets out to investigate whether the public does in fact make this distinction. METHOD: In spring 2009, a population-based survey was conducted by phone in the city of Vienna (n = 1205). A fully structured interview was carried out which began with the presentation of a vignette describing a diagnostically unlabeled case of depression, with or without provision of information about preceding stressful life events. RESULTS: Respondents presented with vignettes containing information on loss events were less likely to define depressive symptoms as indication of mental illness. They were also not as willing to recommend professional help. And if they were, they tended to less frequently recommend seeking help from someone with a medical background. CONCLUSION: In contrast to the conceptualization in the DSM-IV, the public tends to perceive depressive symptoms differently depending on the context in which they occur.

Insight into susceptibility genes associated with bipolar disorder: a systematic review.

OBJECTIVE: Bipolar disorder (BD) is a severe disorder, and it is associated with an increased risk of mortality. About 25% of patients with BD have attempted and 11% have died by suicide. All these characteristics suggest that the disorders within the bipolar spectrum are a crucial public health problem. With the development of molecular genetics in recent decades, it was possible to more easily detect risk genes associated with this disorder. This study aimed at summarizing the findings of systematic reviews and meta-analyses on the topic and assessing the quality of the available evidence. MATERIALS AND METHODS: PubMed/Medline and Web of Science were searched to identify systematic reviews and meta-analyses published during 2013-2019. Standard methodology was applied to synthesize and assess the retrieved literature. RESULTS: This systematic review identifies a number of potential risk genes associated with bipolar disorder whose mechanism of action has yet to be confirmed. They are divided into several groups: 1) a list of the most significant susceptibility genetic factors associated with BD; 2) the implication of the ZNF804A gene in BD; 3) the role of genes involved in calcium signaling in BD; 4) DNA methylation in BD; 5) BD and risk suicide genes; 6) susceptibility genes for early-onset BD; 7) candidate genes common to both BD and schizophrenia; 8) genes involved in cognitive status in BD cases; 9) genes involved in structural alteration in BD brain tissue; 10) genes involved in lithium response in BD. CONCLUSIONS: Future research should concentrate on molecular mechanisms by which genetic variants play a major role in BD. Supplemental research is needed to replicate the applicable results.

Association between the spread of COVID-19 and weather-climatic parameters.

OBJECTIVE: To explore whether the climate has played a role in the COVID-19 outbreak, we compared virus lethality in countries closer to the Equator with others. Lethality in European territories and in territories of some nations with a non-temperate climate was also compared. MATERIALS AND METHODS: Lethality was calculated as the rate of deaths in a determinate moment from the outbreak of the pandemic out of the total of identified positives for COVID-19 in a given area/nation, based on the COVID-John Hopkins University website. Lethality of countries located within the 5th parallels North/South on 6 April and 6 May 2020, was compared with that of all the other countries. Lethality in the European areas of The Netherlands, France and the United Kingdom was also compared to the territories of the same nations in areas with a non-temperate climate. RESULTS: A lower lethality rate of COVID-19 was found in Equatorial countries both on April 6 (OR=0.72 CI 95% 0.66-0.80) and on May 6 (OR=0.48, CI 95% 0.47-0.51), with a strengthening over time of the protective effect. A trend of higher risk in European vs. non-temperate areas was found on April 6, but a clear difference was evident one month later: France (OR=0.13, CI 95% 0.10-0.18), The Netherlands (OR=0.5, CI 95% 0.3-0.9) and the UK (OR=0.2, CI 95% 0.01-0.51). This result does not seem to be totally related to the differences in age distribution of different sites. CONCLUSIONS: The study does not seem to exclude that the lethality of COVID-19 may be climate sensitive. Future studies will have to confirm these clues, due to potential confounding factors, such as pollution, population age, and exposure to malaria.

Bipolar disorders and deep grey matter in multiple sclerosis: A preliminary quantitative MRI study.

BACKGROUND: Bipolar disorder (BD) is frequently observed in patients affected by multiple sclerosis (MS), presenting a lifetime estimate of around 8%. However, uncertainty exists on the brain damage associated with this psychiatric comorbidity. This study aimed to investigate the effect of brain atrophy, particularly that of the subcortical grey matter (scGM) structures that notoriously regulate the affective functioning, on the co-occurrence of BD in patients with MS. METHODS: A group of patients with MS affected by BD and a control group of patients with MS without any mood/psychiatric disorder, as defined using standardised diagnostic tools (Advanced Neuropsychiatric Tools and Assessment Schedule), were recruited. The patients underwent brain MRI, and the volumes of the whole brain (WB), white matter (WM), and grey matter (GM) were estimated using SIENAX. Thus, the scGM volumes of the putamen, caudate, thalamus, hippocampus, amygdala, nucleus accumbens, and pallidus were estimated using the FIRST tool. RESULTS: The sample included 61 patients with MS, amongst whom 15 (24.6%) had BD. No differences in the WB, WM, and cortical GM volumes were observed between the patients with MS with and without BD. Conversely, the multiple regression analysis revealed a significant association of BD with lower volumes of the putamen (p = 0.032), nucleus accumbens (p = 0.029), and pallidus (p = 0.061; with a trend towards significance), independently from the demographic and MS clinical features. CONCLUSIONS: Our preliminary results indicated that the nucleus accumbens and putamen are smaller in MS patients with BD. Further investigations in larger cohorts of MS patients with affective disorders are necessary to confirm these data and understand the structural brain damage underlying this psychiatric comorbidity.