How Does SARS-CoV-2 Affect the Central Nervous System? A Working Hypothesis

Interstitial pneumonia was the first manifestation to be recognized as caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, in just a few weeks, it became clear that the coronavirus disease-2019 (COVID-19) overrun tissues and more body organs than just the lungs, so much so that it could be considered a systemic pathology. Several studies reported the involvement of the conjunctiva, the gut, the heart and its pace, and vascular injuries such as thromboembolic complications and Kawasaki disease in children and toddlers were also described. More recently, it was reported that in a sample of 214 SARS-CoV-2 positive patients, 36.4% complained of neurological symptoms ranging from non-specific manifestations (dizziness, headache, and seizures), to more specific symptoms such hyposmia or hypogeusia, and stroke. Older individuals, especially males with comorbidities, appear to be at the highest risk of developing such severe complications related to the Central Nervous System (CNS) involvement. Neuropsychiatric manifestations in COVID-19 appear to develop in patients with and without pre-existing neurological disorders. Growing evidence suggests that SARS-CoV-2 binds to the human Angiotensin-Converting Enzyme 2 (ACE2) for the attachment and entrance inside host cells. By describing ACE2 and the whole Renin Angiotensin Aldosterone System (RAAS) we may better understand whether specific cell types may be affected by SARS-CoV-2 and whether their functioning can be disrupted in case of an infection. Since clear evidences of neurological interest have already been shown, by clarifying the topographical distribution and density of ACE2, we will be able to speculate how SARS-CoV-2 may affect the CNS and what is the pathogenetic mechanism by which it contributes to the specific clinical manifestations of the disease. Based on such evidences, we finally hypothesize the process of SARS-CoV-2 invasion of the CNS and provide a possible explanation for the onset or the exacerbation of some common neuropsychiatric disorders in the elderly including cognitive impairment and Alzheimer disease

Compulsory treatments in eating disorders: a systematic review and meta-analysis

Introduction: The aims of this systematic review and meta-analysis are to provide a summary of the current literature concerning compulsory treatments in patients with eating disorders (ED) and to understand whether compulsorily and involuntarily treated patients differ in terms of baseline characteristics and treatment outcomes. Methods: Relevant articles were identified following the PRISMA guidelines by searching the following terms: “treatment refusal”, “forced feeding”, “compulsory/coercive/involuntary/forced treatment/admission”, “eating disorders”, “feeding and eating disorders”, “anorexia nervosa”, “bulimia nervosa”. Research was restricted to articles concerning humans and published between 1975 and 2020 in English. Results: Out of 905 articles retrieved, nine were included for the analyses allowing the comparisons between 242 compulsorily and 738 voluntarily treated patients. Mean body mass index (BMI) was slightly lower in patients compelled to treatments. Mean illness duration, BMI at discharge and BMI variation showed no significant differences between the two groups. Average length of hospitalization was 3 weeks longer among compulsory-treated patients, but this did not result in a higher increase in BMI. No significant risk difference on mortality was estimated (three studies). Conclusions: Compulsory treatments are usually intended for patients having worse baseline conditions than voluntary ones. Those patients are unlikely to engage in treatments without being compelled but, after the treatments, albeit with longer hospitalisations, they do achieve similar outcomes. Therefore, we can conclude that forcing patients to treatment is a conceivable option. Level of evidence: Level I, systematic review and meta-analysis

Socio-demographic and clinical characterization of patients with obsessive-compulsive tic-related disorder (OCTD) : An Italian multicenter study

© Copyright by Pacini Editore SrlIn the DSM-5 a new "tic-related" specifier for obsessive compulsive disorder (OCD) has been introduced, highlighting the importance of an accurate characterization of patients suffering from obsessive-compulsive tic-related disorder ("OCTD"). In order to characterize OCTD from a socio-demographic and clinical perspective, the present multicenter study was carried out. The sample consists of 266 patients, divided in two groups with lifetime diagnoses of OCD and OCTD, respectively. OCTD vs OCD patients showed a significant male prevalence (68.5% vs 48.5%; p < .001), a higher rate of psychiatric comorbidities (69.4 vs 50%; p < .001) - mainly with neurodevelopmental disorders (24 vs 0%; p < .001), a lower education level and professional status (middle school diploma: 25 vs 7.6%; full-Time job 44.4 vs 58%; p < .001). Moreover, OCTD vs OCD patients showed significantly earlier age of OCD and psychiatric comorbidity onsets (16.1 ± 10.8 vs 22.1 ± 9.5 years; p < .001, and 18.3 ± 12.8 vs 25.6 ± 9.4: p < .001, respectively). Patients with OCTD patients were treated mainly with antipsychotic and with a low rate of benzodiazepine (74.2 vs 38.2% and 20.2 vs 31.3%, respectively; p < .001). Finally, OCTD vs OCD patients showed higher rates of partial treatment response (58.1 vs 38%; p < .001), lower rates of current remission (35.5 vs 54.8%; p < .001) and higher rates of suicidal ideation (63.2 vs 41.7%; p < .001) and attempts (28.9 vs 8.3%; p < .001). Patients with OCTD report several unfavorable socio-demographic and clinical characteristics compared to OCD patients without a history of tic. Additional studies on larger sample are needed to further characterize OCTD patients from clinical and therapeutic perspectives.Peer reviewedFinal Published versio

No association of a set of candidate genes on haloperidol side effects

We previously investigated a sample of patients during an active phase of psychosis in the search for genetic predictors of haloperidol induced side effects. In the present work we extend the genetic association analysis to a wider panel of genetic variations, including 508 variations located in 96 genes. The original sample included 96 patients. An independent group of 357 patients from the CATIE study served as a replication sample. Outcomes in the investigation sample were the variation through time of: 1) the ESRS and UKU total scores 2) ESRS and UKU subscales (neurologic and psychic were included) related to tremors and 3) ESRS and UKU subscales that do not relate to tremors. Outcome in the replication sample was the presence vs absence of motoric side effects from baseline to visit 1 ( 3c one month of treatment) as assessed by the AIMS scale test. Rs2242480 located in the CYP3A4 was associated with a different distribution of the UKU neurologic scores through time (permutated p\u200a=\u200a0.047) along with a trend for a different haloperidol plasma levels (lower in CC subjects). This finding was not replicated in the CATIE sample. In conclusion, we did not find conclusive evidence for a major association between the investigated variations and haloperidol induced motoric side effect

Fenologia da goiabeira 'Paluma' sob diferentes sistemas de cultivos, épocas e intensidades de poda de frutificação.

O trabalho teve como objetivo avaliar os efeitos de diferentes épocas e intensidades de poda de frutificação sobre a fenologia da goiabeira 'Paluma', em dois sistemas de cultivo, em Pedro Canário (ES). O delineamento experimental foi o de blocos ao acaso, em esquema de parcelas sub-subdivididas. As parcelas foram os sistemas de cultivo irrigado e sequeiro; as subparcelas foram as épocas de poda (10/11/2005, 9/12/2005, 13/1/2006 e 10/2/2006); e as sub-subparcelas foram as intensidades de poda (curta, média e longa). O ciclo da goiabeira 'Paluma', entre a poda até o início da colheita dos frutos, variou de 182 (poda em novembro e dezembro) a 203 dias (poda em fevereiro). A queda fisiológica dos frutos ocorreu até os 56 dias após o final do florescimento. A irrigação e a poda longa proporcionaram maior brotação e estabelecimento dos ramos. As plantas submetidas à poda longa em fevereiro produziram maior número de frutos por ramo. Independentemente da época de poda, as plantas submetidas à poda curta apresentaram menor número de frutos por ramo e menor índice de pegamento de frutos. A irrigação e as podas realizadas em dezembro e janeiro favoreceram a produção de frutos maiores

Social withdrawal as a trans-diagnostic predictor of short-term remission: a meta-analysis of five clinical cohorts

Social withdrawal is an early manifestation of several neuropsychiatric disorders, and it is characterised by a gradual disengagement from social interactions, potentially leading to complete isolation. This study investigated the association between social withdrawal at baseline and short-term symptom remission in five independent cohorts, including patients with major depressive disorder (MDD), bipolar spectrum disorders, and schizophrenia. Measures of social withdrawal were derived in each study, and clinical remission was estimated based on the psychopathological severity assessed after short-term psychopharmacological treatment (12weeks). Logistic regression was performed in each sample, adjusting for age and baseline psychopathological severity residualised for social withdrawal. Results were then meta-analysed across samples within a random-effect framework. A total of 4461 patients were included in the analyses (3195 patients with MDD, 655 with bipolar spectrum disorders and 611 with schizophrenia). The meta-analysis showed that higher baseline levels of social withdrawal were associated with a decreased likelihood of short-term remission (ORadj=0.67, 95% CI, 0.58-0.79, P=5.28×10−7), with the strongest effect in patients with schizophrenia. Overall, our study highlighted the need to address social withdrawal in the early phases of the disease to promote symptom remission in patients with major psychiatric disorders. Understanding the neurobiology underlying social withdrawal may aid the development of medications that can specifically reverse social impairment, thereby fostering clinical remission. Int Clin Psychopharmacol 37: 38-45 Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc

A Formalization of the Theorem of Existence of First-Order Most General Unifiers

This work presents a formalization of the theorem of existence of most general unifiers in first-order signatures in the higher-order proof assistant PVS. The distinguishing feature of this formalization is that it remains close to the textbook proofs that are based on proving the correctness of the well-known Robinson's first-order unification algorithm. The formalization was applied inside a PVS development for term rewriting systems that provides a complete formalization of the Knuth-Bendix Critical Pair theorem, among other relevant theorems of the theory of rewriting. In addition, the formalization methodology has been proved of practical use in order to verify the correctness of unification algorithms in the style of the original Robinson's unification algorithm.Comment: In Proceedings LSFA 2011, arXiv:1203.542

Long-period Radio Pulsars: Population Study in the Neutron Star and White Dwarf Rotating Dipole Scenarios

© 2024 The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/The nature of two recently discovered radio emitters with unusually long periods of 18min (GLEAM-X J1627-52) and 21min (GPM J1839-10) is highly debated. Their bright radio emission resembles that of radio magnetars, but their long periodicities and lack of detection at other wavelengths challenge the neutron-star interpretation. In contrast, long rotational periods are common in white dwarfs but, although predicted, dipolar radio emission from isolated magnetic white dwarfs has never been unambiguously observed. In this work, we investigate these long-period objects as potential isolated neutron-star or white-dwarf dipolar radio emitters and find that both scenarios pose significant challenges to our understanding of radio emission via pair production in dipolar magnetospheres. We also perform population-synthesis simulations based on dipolar spin-down in both pictures, assuming different initial-period distributions, masses, radii, beaming fractions, and magnetic-field prescriptions, to assess their impact on the ultra-long pulsar population. In the neutron-star scenario, we do not expect a large number of ultra-long period pulsars under any physically motivated (or even extreme) assumptions for the period evolution. On the other hand, in the white-dwarf scenario, we can easily accommodate a large population of long-period radio emitters. However, no mechanism can easily explain the production of such bright coherent radio emission in either scenarios.Peer reviewe

A long-period radio transient active for three decades: population study in the neutron star and white dwarf rotating dipole scenarios

The nature of two recently discovered radio emitters with unusually long periods of 18min (GLEAM-X J1627-52) and 21min (GPM J1839-10) is highly debated. Their bright radio emission resembles that of radio magnetars, but their long periodicities and lack of detection at other wavelengths challenge the neutron-star interpretation. In contrast, long rotational periods are common in white dwarfs but, although predicted, dipolar radio emission from isolated magnetic white dwarfs has never been unambiguously observed. In this work, we investigate these long-period objects as potential isolated neutron-star or white-dwarf dipolar radio emitters and find that both scenarios pose significant challenges to our understanding of radio emission via pair production in dipolar magnetospheres. We also perform population-synthesis simulations based on dipolar spin-down in both pictures, assuming different initial-period distributions, masses, radii, beaming fractions, and magnetic-field prescriptions, to assess their impact on the ultra-long pulsar population. In the neutron-star scenario, we cannot reproduce the large number of expected ultra-long period pulsars under any physically motivated (or even extreme) assumptions. Thus, if GLEAM-X J1627-52 and GPM J1839-10 are confirmed as neutron-star pulsars (even if they are magnetars), this would necessarily call for a significant revision of our understanding of birth parameters at the population level. On the other hand, in the white-dwarf scenario, no mechanism can explain the production of such a bright coherent radio emission in isolated magnetic white dwarf systems (binaries with low mass companions are still viable), although we can easily accommodate a large population of long-period radio emitters.Comment: 8 pages, 4 figures; ApJ Letters submitte