Benzimidazole-2-Phenyl-Carboxamides as Dual-Target Inhibitors of BVDV Entry and Replication

Bovine viral diarrhea virus (BVDV), also known as Pestivirus A, causes severe infection mostly in cattle, but also in pigs, sheep and goats, causing huge economical losses on agricultural farms every year. The infections are actually controlled by isolation of persistently infected animals and vaccination, but no antivirals are currently available to control the spread of BVDV on farms. BVDV binds the host cell using envelope protein E2, which has only recently been targeted in the research of a potent and efficient antiviral. In contrast, RdRp has been successfully inhibited by several classes of compounds in the last few decades. As a part of an enduring antiviral research agenda, we designed a new series of derivatives that emerged from an isosteric substitution of the main scaffold in previously reported anti-BVDV compounds. Here, the new compounds were characterized and tested, where several turned out to be potent and selectively active against BVDV. The mechanism of action was thoroughly studied using a time-of-drug-addition assay and the results were validated using docking simulations

Compass Fundus-Guided Perimetry in Geographic Atrophy

To evaluate compass (CMP), a recently introduced device that combines scanning ophthalmoscopy, automated perimetry, and eye tracking, for fundus-guided perimetry (microperimetry) with the purpose of correlating perimetric retinal sensitivity (PRS) and retinal geographic atrophy (GA) features

Sintesi e valutazione biologica di nuovi "lead compounds" per la terapia antitubercolare. Derivati del 2-(benzotriazol-1(2)-il)-3- acrilonitrile e delle chinossaline 1,4-diossido

L'insorgenza sempre più elevata di ceppi di M. tuberculosis chemioresistenti ai farmaci abitualmente impiegati in terapia (MDR) ha spronato la ricerca di nuovi "lead compounds" per lo sviluppo di molecole che, agendo con meccanismo diverso da quello dei farmaci attualmente impiegati in terapia, possano contribuire a superare il problema della farmacoresistenza. In quest'ambito le nostre ricerche si sono orientate verso due differenti direzioni. La prima prende lo spunto dai risultati ottenuti in passato da vari gruppi di ricerca con alcuni derivati di sintesi di sistemi eterociclici aromatici quali benzimidazolo, benzotiazolo, benzoisotiazolo e benzofurano, che avevano dimostrato attività  antimicobatterica in vitro soprattutto nei confronti di ceppi MDR. La seconda linea di ricerca si è basata sulla nota attività  antibatterica e soprattutto antimicotica della chinossalina 1,4-diossido, con la consapevolezza che spesso l'attività  antimicobatterica è associata a quella antifungina

Alexithymia for cardiologists: a clinical approach to the patient

Alexithymia literally meaning ‘no words for emotions’ is a term used in mental health settings to describe people who have difficulties in identifying and verbalizing their emotional states. There is evidence in the literature that this personality trait may influence negatively the illness behavior when an acute coronary event occurs. In fact, people with high alexithymia are more likely to experience wrong appraisal and interpretation of symptoms, and because of their difficulty in describing feelings to others, they can be poor in reporting symptoms at the first consultation with a physician. This behavioral pattern (alexithymic) may put patients with acute myocardial infarction at higher risk for delayed medical care. Here, we aim to present an overview of alexithymia from the perspective of the clinical cardiologist, with a focus on the definition, clinical recognition, and potential impact on cardiovascular health

An Overview of the Main Genetic, Epigenetic and Environmental Factors Involved in Autism Spectrum Disorder Focusing on Synaptic Activity

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that aects social interaction and communication, with restricted interests, activity and behaviors. ASD is highly familial, indicating that genetic background strongly contributes to the development of this condition. However, only a fraction of the total number of genes thought to be associated with the condition have been discovered. Moreover, other factors may play an important role in ASD onset. In fact, it has been shown that parental conditions and in utero and perinatal factors may contribute to ASD etiology. More recently, epigenetic changes, including DNA methylation and micro RNA alterations, have been associated with ASD and proposed as potential biomarkers. This review aims to provide a summary of the literature regarding ASD candidate genes, mainly focusing on synapse formation and functionality and relevant epigenetic and environmental aspects acting in concert to determine ASD onset

Atypical presentation of juvenile multiple sclerosis in a patient with COVID-19

Purpose: To report our experience with a case of a very atypical clinical onset of multiple sclerosis in a young boy during a COVID-19 infection. Case report: A 16-year-old boy was referred to our ophthalmology clinic with a complete isolated bilateral horizontal gaze palsy. The condition had onset suddenly 2 weeks prior and he had no associated symptoms, as well as no significant medical history. His corrected visual acuity was 0.0 logMAR in both eyes. While hospitalized, he was found infected with COVID-19. Subsequent brain MRI showed multiple lesions typical of a yet undiagnosed MS, as well as an active pontine plaque which was highly probable the cause of the horizontal gaze palsy. High-dose steroid treatment was initiated 1 week later, after the patient exhibited negative COVID-19 test results. Conclusion: Clinical manifestations of MS are rarely seen in male teenagers and only a few cases of isolated bilateral horizontal gaze palsy have been reported as the initial manifestation, but never during concomitant COVID-19 infection. We presume that the presence of COVID-19 may have been a neuroinflammatory trigger of underlying MS

Takotsubo Syndrome is Associated with Mood Disorders and Antidepressants Use, not with Anxiety and Impairment of Quality of Life Due to the Psychiatric Disorder

Background: The aim was to study the association between mood and anxiety disorders and the Tako-Tsubo Syndrome (TTS) and to determine the role of antidepressants and the impairment of quality of life due the comorbid psychiatric disorder. Methods: Case-control study: 19 consecutive patients (17 female) with TTS compared to 76 controls without TTS, were randomly selected from the database of a Nationwide epidemiological study after matching (gender, age and residence) by controls. Psychiatric diagnoses were carried out according to the ICD-10 using semi-structured interview tools (ANTAS-SCID) administered by clinical staff. Quality of Life (Qol) was assessed by means of SF-12. Results: Only Major Depressive Disorders (MDD) showed higher frequencies in cases with statistical significance difference (p=0.014) as well as at least one Mood Disorder Diagnosis [MDD or BD] (p=0.002). The lifetime prevalence of at least one anxiety disorder with no comorbid mood disorder did not show a higher frequency in cases (p=0.57). The score at SF 12 in the TTS group was similar to those of controls (p=0.71)In the TTS group, the score at SF-12 in people with one mood or anxiety diagnosis (N=7) was similar to those without mood or anxiety diagnosis (p=0.75). The use of antidepressants was higher in TTS group (15.79% vs 1.31%; p=0.030). Conclusion: The study shows an association between TTS with depressive disorders and antidepressants use and does not confirm the association with anxiety syndromes. The study suggests the need to investigate the possible interactions between antidepressants use and mood disorders in studies with appropriate design and sample size

Corrigendum: Child and adolescent behavior inventory (CABI): A new instrument for epidemiological studies and pre-clinical evaluation

Child and Adolescent Behavior Inventory (CABI): A New Instrument for Epidemiological Studies and Pre-Clinical Evaluation Clinical Practice & Epidemiology in Mental Health, 2013, 9: 51-61 Correction: Few corrections have been provided and replaced online in 15th, 20th, 21st and 22nd rows of the Appendix

Intake of palmitic acid and its association with metabolic flexibility in middle-aged individuals: a preliminary study

Objective: This study aimed to assess the relationship between dietary palmitic acid (PA) intake and its association with body fat deposition and metabolic flexibility (MF) in middle-aged healthy individuals. Methods: Fifteen healthy participants (n = 15; 6 males, 9 females) with a mean age of 54 were enlisted. They were subjected to graded exercise tests using a cycle ergometer coupled with a calorimeter. Respiratory gas exchange was evaluated to determine two MF parameters. First, the MF index was derived by multiplying peak fatty acid oxidation (PFO) per kg of fat-free mass (FFM) with the percentage of VO2max at PFO. The second parameter, peak energy substrates’ oxidation (aka PESO), was computed by aggregating the kilocalories from PFO and peak carbohydrate oxidation, normalized per kg FFM. Dietary intake was gauged using a 7-day dietary record. Spearman’s regression was employed to analyze the association between dietary intake of specific fat classes, PA, MF parameters, and body fat percentage. Results: Preliminary results demonstrate that dietary saturated fatty acids (SFA) within physiological limits correlate with enhanced substrate oxidation capacity. This suggests augmented MF in middle-aged subjects. Among dietary SFA, PA was identified as the primary factor in this favorable correlation. Conclusions: Our initial observations, even though preliminary, strongly suggest a beneficial association between PA intake, MF, and body fat percentage. This underscores the potential nutritional importance of PA in promoting MF