Genetic variants involved in bipolar disorder, a rough road ahead

Background: Bipolar Disorder (BD), along with depression and schizophrenia, is one of the most serious mental illnesses, and one of the top 20 causes of severe impairment in everyday life. Recent molecular studies, using both traditional approaches and new procedures such as Whole-Genome Sequencing (WGS), have suggested that genetic factors could significantly contribute to the development of BD, with heritability estimates of up to 85%. However, it is assumed that BD is a multigenic and multifactorial illness with environmental factors that strongly contribute to disease development/progression, which means that progress in genetic knowledge of BD might be difficult to interpret in clinical practice. Objective: The aim of this study is to provide a synthetic description of the main SNPs variants identified/confirmed by recent extensive WGS analysis as well as by reconstruction in an in vitro mechanism or by amygdala activation protocol in vivo. Method: Bibliographic data, genomic and protein Data Banks were consulted so as to carry out a cross genomic study for mutations, SNPs and chromosomal alterations described in these studies in BD patients. Results: Fifty-five different mutations have been described in 30 research papers by different genetic analyses including recent WGS analysis. Many of these studies have led to the discovery of the most probable susceptibility genes for BD, including ANK3, CACNA1C, NCAN, ODZ4, SYNE1, and TRANK1. Exploration has started the role of several of these mutations in BD pathophysiology using in vitro and animal models. Conclusion: Although new genomic research technology in BD opens up new possibilities, the current results for common variants are still controversial because of four broad conditions: analytical validity, clinical validity, clinical utility and a reasonable cost for genetic analysis are not yet accessible

Does Living in Previously Exposed Malaria or Warm Areas is Associated with a Lower Risk of Severe COVID-19 Infection in Italy?

Incidence of Covid-19 positivity (21/2/2020-28/3/2020) in provinces of 4 Italian regions whose territory was described as previously exposed to Malaria was compared with those of other provinces of the same regions. The climate of such provinces was compared with the climate of the other provinces in some regions. Previously malarial areas show a lower risk than other provinces of the same regions: Mantua (Lombardy) RR=0.94 (CI95%0.89-0.99); Venice-Rovigo (Veneto) RR=0.61 (CI95%0.58-0.65); Ferrara-Ravenna (Emilia-Romagna) RR=0.37 (CI95%0.35-0.41); Cagliari Oristano-South Sardinia (Sardinia) RR=0.25 (0.17-0.31). The maximum temperature in March 2020 in those provinces was higher in mean 1.5° for other provinces. The lower frequency of COVID-19 in the provinces previously exposed to Malaria of four Italian regions does not reveal a causal link. The phenomenon has emerged independently in all the regions investigated. People born between the 1920s and 1950s were those most exposed to malaria years ago and today are the most exposed to the severest forms of COVID-19. A warmer climate seems to be associated with a lower risk of COVID, in line with the evidence highlighted in equatorial states where a lower lethality of the virus has emerged, however this regardless of the presence of Malaria. This may suggest that climate and not Malaria is the real risk factor, though further studies need to determine the role of the association climate / COVID

A Novel Technique for Region and Linguistic Specific nTMS-based DTI Fiber Tracking of Language Pathways in Brain Tumor Patients

Navigated transcranial magnetic stimulation (nTMS) has recently been introduced as a non-invasive tool for functional mapping of cortical language areas prior to surgery. It correlates well with intraoperative neurophysiological monitoring (IONM) findings, allowing defining the best surgical strategy to preserve cortical language areas during surgery for language-eloquent tumors. Nevertheless, nTMS allows only for cortical mapping and postoperative language deficits are often caused by injury to subcortical language pathways. Nowadays, the only way to preoperatively visualize language subcortical white matter tracts consists in DTI fiber tracking (DTI-FT). However, standard DTI-FT is based on anatomical landmarks that vary interindividually and can be obscured by the presence of the tumor itself. It has been demonstrated that combining nTMS with DTI-FT allows for a more reliable visualization of the motor pathway in brain tumor patients. Nevertheless, no description about such a combination has been reported for the language network. The aim of the present study is to describe and assess the feasibility and reliability of using cortical seeding areas defined by error type-specific nTMS language mapping (nTMS-positive spots) to perform DTI-FT in patients affected by language-eloquent brain tumors. We describe a novel technique for a nTMS-based DTI-FT to visualize the complex cortico- subcortical connections of the language network. We analyzed quantitative findings, such as fractional anisotropy values and ratios, and the number of visualized connections of nTMS-positive spots with subcortical pathways, and we compared them with results obtained by using the standard DTI-FT technique. We also analyzed the functional concordance between connected cortical nTMS- positive spots and subcortical pathways, and the likelihood of connection for nTMS-positive vs. nTMS-negative cortical spots. We demonstrated, that the nTMS-based approach, especially what we call the “single-spot” strategy, is able to provide a reliable and more detailed reconstruction of the complex cortico-subcortical language network as compared to the standard DTI-FT. We believe this technique represents a beneficial new strategy for customized preoperative planning in patients affected by tumors in presumed language eloquent location, providing anatomo-functional information to plan language- preserving surgery

Co-infection of Streptococcus pneumoniae in Respiratory Infections Caused by SARS-CoV-2

Abstract: Viral respiratory infections are often associated with bacterial co-infections that often lead to increased severity and mortality of the disease. During the recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hospitalized patients reported developing secondary bacterial infections ranging from 0 to 40% of the cases. In the previous influenza pandemics, Streptococcus pneumoniae was the most isolated bacterial pathogen causing increased mortality in patients affected by viral pneumonia. Due to the difficulty to detect pneumococcal infection in SARSCoV-2 patients by a rapid clinical test, the real prevalence of S. pneumoniae might be underestimated, and only a few cases have been documented so far. It has been estimated that 90% of patients admitted to the Intensive Care Unit are empirically treated with antimicrobial. The application of more rapid and sensitive diagnostic methods could help with targeted antibiotic therapy. Additionally, pneumococcal vaccination of high-risk individuals could reduce bacterial pneumonia, hospital admissions, and comorbidities associated with serious illness

The patient with rhinitis in the pharmacy. A cross-sectional study in real life

In the practical management of allergic rhinitis (AR), pharmacists are usually the first-line contact, also because some medications are available as over the counter. Therefore, pharmacists may represent an important resource, in mediating the interaction between patients and physicians. We evaluated the clinical/demographic characteristics of patients with respiratory allergies who consulted their pharmacists as first-line contact. A patient-oriented questionnaire was developed by a scientific committee including pharmacists, GPs, allergists, pulmonologists and ENT specialists

Antenatal Thymosin β4: a New Tool for Accelerating Fetal Development in Preterms? Thymosin Beta-4: a Breakthrough in the "Physiological" Regenerative Medicine in Preterm Newborns

To prevent the health risks related to prematurity, multiple drugs have been introduced in clinical practice in recent years. This paper focuses on a new "physiological" regenerative approach to be started in the perinatal period, particularly on very low birth weight preterm infants. This new preventive approach underlined the necessity to start regenerative medicine very early after birth, a period in which kidney, brain, pancreas, and lung stem cells maintain their proliferative and differentiating abilities. Among the multiple factors proposed in the literature as potential growth promoters for preterm neonates, thymosin beta-4 (Tβ4) has been indicated as one of the most important candidates for regenerative medicine