Susceptibility of Primary HTLV-1 Isolates from Patients with HTLV-1-Associated Myelopathy to Reverse Transcriptase Inhibitors

Since human T-lymphotropic virus type 1 (HTLV-1)-associated diseases are associated with a high HTLV-1 load, reducing this load may treat or prevent disease. However, despite in vitro evidence that certain nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs) are active against HTLV-1, in vivo results have been disappointing. We therefore assayed the sensitivity of HTLV-1 primary isolates to a panel of RT inhibitors. HTLV-1 primary isolates were obtained, pre- and post- NRTI treatment, from patients with HTLV-1-associated myelopathy. Sensitivity to azidothymidine (AZT), lamivudine (3TC), tenofovir (TDF) and three phosphonated carbocyclic 2’-oxa-3’aza nucleosides (PCOANs) was assessed in a RT inhibitor assay. With the exception of 3TC, HTLV RT from primary isolates was less sensitive to all tested inhibitors than HTLV-1 RT from MT-2 cells. HTLV-1 RT from primary isolates and from chronically infected, transformed MT-2 cells was insensitive to 3TC. Sensitivity of primary isolates to RT inhibitors was not reduced following up to 12 months of patient treatment with AZT plus 3TC. The sensitivity of HTLV-1 primary isolates to NRTIs differs from that of cell lines and may vary among patients. Failure of NRTIs to reduce HTLV-1 viral load in vivo was not due to the development of phenotypic NRTI resistance. AZT and the three PCOANs assayed all consistently inhibited primary isolate HTLV-1 RT

In Vitro Application of Exogenous Fibrolytic Enzymes from Trichoderma spp. to Improve Feed Utilization by Ruminants

Treating ruminant feeds with exogenous fibrolytic enzymes may potentially increase forage cell wall degradability and thus feed efficiency. In nature, fungi biosynthesize lignocellulolytic enzymes that can break down lignocellulosic material into its sugar components, thereby providing ready fermentable substrates. This work showed the in vitro fibrolytic activity of three Trichoderma strains (T. atroviride strain P1, T. afroharzianum strain T22, T. reesei strain T67). Total protein concentration and enzymatic (e.g., glucanase, cellulase, and xylanase) activities were determined in fungal culture filtrates after 7 and 14 days of growth on different fiber-based media. The enzymatic mixtures produced by Trichoderma spp. showed the highest concentration of fibrolytic enzymes and were added to industrial feed to test their ability to hydrolyze insoluble fibers. The supplementation of industrial feeds containing medium-fiber or low-fiber concentrates with T22 enzymes produced in the presence of lyophilized mushrooms and durum wheat fiber reduced hemicellulose concentration up to 33% and 24%, respectively. These results may offer novel opportunities to develop livestock feeds with improved fiber digestibility

Breed and Feeding System Impact the Bioactive Anti-Inflammatory Properties of Bovine Milk

In the present study, we aimed at assessing the influence of breed and feeding system on the bovine milk profile of betaines and carnitines and milk capacity in counteracting the inflammatory endothelial cell (EC) damage induced by interleukin (IL)-6. In the first experimental design, two breeds were chosen (Holstein vs. Modicana) to investigate the biomolecule content and antioxidant capacity in milk and dairy products. In the second experimental design, two feeding systems (pasture vs. total mixed ratio) were tested only in Holstein to evaluate the possible effect on the functional profile of milk and dairy products. Finally, the bulk milk from the two experimental designs was used to evaluate the efficacy of preventing IL-6-induced endothelial inflammatory damage. Results showed that Modicana milk and whey had higher biomolecule content and antioxidant activity compared to Holstein milk (p < 0.01). Milk from Holstein fed TMR showed higher concentration of γ-butyrobetaine, δ-valerobetaine (p < 0.01), and l-carnitine (p < 0.05). Similarly, whey from Holstein fed TMR also showed higher content of δ-valerobetaine, glycine betaine, l-carnitine, and acetyl-l-carnitine (p < 0.01) compared to the Holstein fed pasture. Conversely, the antioxidant activity of milk and dairy products was not affected by the feeding system. In ECs, all milk samples reduced the IL-6-induced cytokine release, as well as the accumulation of reactive oxygen species (ROS) and the induction of cell death, with the most robust effect elicited by Modicana milk (p < 0.01). Overall, Modicana milk showed a higher content of biomolecules and antioxidant activity compared to Holstein, suggesting that the breed, more than the feeding system, can positively affect the health-promoting profile of dairy cattle milk

Increased gyrification in schizophrenia and non affective first episode of psychosis

Prefrontal cortex gyrification has been suggested to be altered in patients with schizophrenia and first episode psychosis. Therefore, it may represent a possible trait marker for these illnesses and an indirect evidence of a disrupted underlying connectivity. The aim of this study was to add further evidence to the existing literature on the role of prefrontal gyrification in psychosis by carrying out a study on a sizeable sample of chronic patients with schizophrenia and non-affective first-episode psychosis (FEP-NA) patients. Methods: Seventy-two patients with schizophrenia, 51 FEP-NA patients (12 who later develop schizophrenia) and 95 healthy controls (HC) underwent magnetic resonance imaging (MRI). Cortical folding was quantified using the automated gyrification index (GI). GI values were compared among groups and related to clinical variables. Results: Both FEP-NA and patients with schizophrenia showed a higher mean prefrontal GI compared to HC (all p. <. 0.05). Interestingly, no differences have been observed between the two patients groups as well as between FEP-NA patients who did and did not develop schizophrenia. Conclusions: Our results suggest the presence of a shared aberrant prefrontal GI in subjects with both schizophrenia and first-episode psychosis. These findings support the hypothesis that altered GI represents a neurodevelopmental trait marker for psychosis, which may be involved in the associated neurocognitive deficits

The prevalence of specific phobia by age in an Italian nationwide survey: How much does it affect the quality of life?

Introduction: The study aimed to see if a community survey conducted by clinical interviewers with semi-structured psychiatric interviews shows lifetime prevalence rates of Specific Phobia (SP) similar to those found by surveys carried out by lay interviewers and if the high level of impairment found in SP may be confirmed. Methods: This is a community survey on an Italian nationwide sample randomly selected from registers of municipalities. Tools: semi-structured ANTAS psychiatric interview derived from the SCID-DSM-IV, carried out by clinicians (psychologists or physicians); Short Form Health Survey (SF-12) as a measure of Quality of Life (QoL). Analyses: means of the χ2 test odds ratios were adopted to test several associations regarding SP prevalence. One-way ANOVA was used to compare different groups on attributable burden due to SP and/or other disorders in worsening QoL. Results: The lifetime prevalence of SP was 2.3%. No difference was found by age class. Females showed more than twice the frequency of males (p&lt;0.0001). The disorders showing the closest association with SP were: social phobia (OR=17.53); general anxiety disorder (OR=11.57); anorexia (OR=11.13) and agoraphobia (OR=10.03), but also obsessive compulsive disorders (OR=8.8), eating disorders (OR=7.2), panic disorder (OR=5.9), post-traumatic stress disorder (OR=5.8), and major depressive disorder (OR=4.8) presented an association that achieved statistical significance. The QoL of people with SP and at least one disorder of anxiety, mood or eating in comorbidity, measured as a score at SF12, was worse than controls without SP (p &lt;0.001) but that of people with SP without co-morbidity was not (p = 0.809). Conclusion: An epidemiological study conducted by clinical interviewers through semi-structured interviews appears to re-dimension the impact of SP, at least from the public health perspective. Future prospective studies will better clarify the role of SP in the context of anxiety disorders

The Burden of Comorbidity Between Bipolar Spectrum and Obsessive-Compulsive Disorder in an Italian Community Survey

© 2020 Carta, Fineberg, Moro, Preti, Romano, Balestrieri, Caraci, Dell’Osso, Disciascio, Drago, Hardoy, Roncone, Minerba, Faravelli and Angst. 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 use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Background: The impact of the comorbidity between Obsessive-Compulsive Disorder (OCD) and Bipolar Disorder Spectrum (BDS) remains to be clarified. The objective of this study was to examine the lifetime prevalence of OCD, the strength of the association of OCD with comorbid BDS and the role of comorbidity of OCD with BDS in the impairment of health-related quality of life (HRQoL) in an Italian community survey. Methods: The study is a community survey. The sample (N = 2,267; women: 55.3%) was randomly selected after stratification by sex and four age groups from the municipal records of the adult population of one urban, one suburban, and at least one rural area in six Italian regions. Physicians using a semi-structured interview (Advanced Tools and Neuropsychiatric Assessment Schedule, ANTAS-SCID) made Diagnostic and Statistical Manual of Mental Disorders – 4th revision (DSM-IV) diagnoses of OCD, Major Depressive Disorder (MDD) and Bipolar Disorder (BD). HR-QoL was measured by the Health Survey Short Form (SF-12). Lifetime Hypomania and subthreshold hypomania were screened by the Mood Disorder Questionnaire (MDQ). BDS was defined as the sum of people shown to be positive for hypomania by the MDQ—with or without a mood disorder diagnosis—plus people with a BD-DSMIV diagnosis even if negative for hypomania at the MDQ. Results: Overall, 44 subjects were diagnosed with OCD, 6 with MDD and 1 with BD. The lifetime prevalence of OCD was 1.8% in men (n = 18) and 2.0% in women (n = 26). MDD with lifetime subthreshold hypomania (i.e., people screened positive at the MDQ, even without diagnosed mania or hypomania at the interview) was associated with OCD (OR = 18.15, CI 95% 2.45–103.67); MDD without subthreshold hypomania (and screened negative at the MDQ) was not (OR = 2.33, CI 95% 0.69–7.01). People with BDS were strongly associated with OCD (OR = 10.5, CI 95% 4.90–12.16,). People with OCD and BDS showed significantly poorer HR-QoL than people with OCD without BDS (F = 9.492; P < 0.003). Discussion: The study found a strong association between BDS and OCD. BDS comorbid with OCD was associated with more severe impairment of HR-QoL than OCD without comorbid BDS. Identification of symptoms of hypomania, including subthreshold symptoms, may therefore be important in people with OCD as they might predict a course with poorer HR-QoL.Peer reviewedFinal Published versio

Angiotensin receptor/Neprilysin inhibitor effects in CRTd non-responders: From epigenetic to clinical beside

We evaluated whether Angiotensin receptor/Neprilysin inhibitors (ARNI) reduce heart failure (HF) hospitalizations and deaths in cardiac resynchronization therapy with defibrillator (CRTd) non-responders patients at 12 months of follow-up, modulating microRNAs (miRs) implied in adverse cardiac remodeling