Učinak primjene melatonina prije teljenja na izlučivanje mlijeka tijekom laktacije u mliječnih krava

This study evaluated the effects of melatonin administration 60 days prior to expect calving (drying-off period) on milk yield during the next lactation. Sixty dairy cows were treated with subcutaneous melatonin implants during summer (n=30) or winter (n=30) period. Another 60 animals were not treated and served as the control. There were no differences in the average milk yield between treated and untreated animals (44.5±3.7 and 44.8±5.0 kg/day for melatonin and control cows, respectively). There was an effect of season with a higher winter milk yield than in summer (43.8±5.0 and 47.1±3.0 kg/day for melatonin and control groups, respectively). The interaction between melatonin and season showed no significant effect; however, during winter, milk yield tended to be higher (P=0.06) in control cows than in melatonin treated cows (45.3±3.7 and 49.2±3.0, respectively). This study indicates that treatment with melatonin prior to calving did not modify milk yield during the following lactation. Only a tendency for a reduction in milk yield during winter was observed in melatonin treated cows.U ovom istraživanju procjenjivan je učinak primjene melatonina 60 dana prije očekivanog teljenja (razdoblje isušivanja) na proizvodnju mlijeka tijekom kasnije laktacije. Šezdeset mliječnih krava tretirano je potkožnim implantatima melatonina tijekom ljetnog (n=30), odnosno zimskog (n=30) razdoblja. Drugih 60 životinja nije tretirano i one su poslužile kao kontrola. Nije bilo razlika u prosječnoj proizvodnji mlijeka između tretiranih i netretiranih životinja (44,5±3,7 kg/ dan u krava tretiranih melatoninom, odnosno 44,8±5,0 kg/dan u kontrolnih krava). Postojao je učinak sezone, pri čemu je proizvodnja mlijeka bila veća zimi u odnosu na ljeto (43,8±5,0 kg/ dan u krava tretiranih melatoninom, odnosno 47,1±3,0 kg/dan u kontrolnoj skupini). Interakcija između melatonina i sezone nije pokazala značajniji učinak, ali tijekom zimske sezone proizvodnja mlijeka u kontrolnih krava bila je veća (P=0,06) u odnosu na krave tretirane melatoninom (45,3±3,7 u kontrolnoj skupini, odnosno 49,2±3,0 u krava tretiranih melatoninom). Ova studija ukazuje da tretman melatoninom prije teljenja ne mijenja proizvodnju mlijeka tijekom kasnije laktacije. Primijećena je samo tendencija smanjenja proizvodnje mlijeka u zimskoj sezoni u krava tretiranih melatoninom

Effect of melatonin administration prior to calving on milk secretion in the next lactation in dairy cows

This study evaluated the effects of melatonin administration 60 days prior to expect calving (drying-off period) on milk yield during the next lactation. Sixty dairy cows were treated with subcutaneous melatonin implants during summer (n=30) or winter (n=30) period. Another 60 animals were not treated and served as the control. There were no differences in the average milk yield between treated and untreated animals (44.5±3.7 and 44.8±5.0 kg/day for melatonin and control cows, respectively). There was an effect of season with a higher winter milk yield than in summer (43.8±5.0 and 47.1±3.0 kg/day for melatonin and control groups, respectively). The interaction between melatonin and season showed no significant effect; however, during winter, milk yield tended to be higher (P=0.06) in control cows than in melatonin treated cows (45.3±3.7 and 49.2±3.0, respectively). This study indicates that treatment with melatonin prior to calving did not modify milk yield during the following lactation. Only a tendency for a reduction in milk yield during winter was observed in melatonin treated cows

Unmet needs for treatment in 102 individuals with brief and limited intermittent psychotic symptoms (BLIPS): implications for current clinical recommendations

Abstract Aims To investigate clinical outcomes and unmet needs in individuals at Clinical High Risk for Psychosis presenting with Brief and Limited Intermittent Psychotic Symptoms (BLIPS). Methods Prospective naturalistic long-term (up to 9 years) cohort study in individuals meeting BLIPS criteria at the Outreach And Support In South-London (OASIS) up to April 2016. Baseline sociodemographic and clinical characteristics, specific BLIPS features, preventive treatments received and clinical outcomes (psychotic and non-psychotic) were measured. Analyses included Kaplan Meier survival estimates and Cox regression methods. Results One hundred and two BLIPS individuals were followed up to 9 years. Across BLIPS cases, 35% had an abrupt onset; 32% were associated with acute stress, 45% with lifetime trauma and 20% with concurrent illicit substance use. The vast majority (80%) of BLIPS individuals, despite being systematically offered cognitive behavioural therapy for psychosis, did not fully engage with it and did not receive the minimum effective dose. Only 3% of BLIPS individuals received the appropriate dose of cognitive behavioural therapy. At 4-year follow-up, 52% of the BLIPS individuals developed a psychotic disorder, 34% were admitted to hospital and 16% received a compulsory admission. At 3-year follow-up, 52% of them received an antipsychotic treatment; at 4-year follow-up, 26% of them received an antidepressant treatment. The presence of seriously disorganising and dangerous features was a strong poor prognostic factor. Conclusions BLIPS individuals display severe clinical outcomes beyond their very high risk of developing psychosis and show poor compliance with preventive cognitive behavioural therapy. BLIPS individuals have severe needs for treatment that are not met by current preventive strategies

Outreach and support in South-London (OASIS) 2001-2020:Twenty years of early detection, prognosis and preventive care for young people at risk of psychosis

This study aims to describe twenty years of early detection, prognosis and preventive care in the Outreach and Support In South-London (OASIS) mental health service for individuals at Clinical High risk of psychosis (CHR-P). The study presents a comprehensive analysis of the 2001– 2020 activity of the OASIS team encompassing core domains: (i) service characteristics, (ii) detection, (iii) prognosis, (iv) treatment and (v) clinical research. The analyses employed descriptive statistics, population-level data, the epidemiological incidence of psychosis, Kaplan Meier failure functions and Greenwood 95% CIs and Electronic Health Records. OASIS is part of the South London and Maudsley (SLaM) NHS trust, the largest European mental health provider, serving a total urban population of 1,358,646 individuals (population aged 16-35: 454,525). Incidence of psychosis in OASIS's catchment area ranges from 58.3 to 71.9 cases per 100,000 person-years, and it is higher than the national average of 41.5 cases per 100,000 person-year. OASIS is a standalone, NHS-funded, multidisciplinary (team leader, consultant and junior psychiatrists, clinical psychologists, mental health professionals), transitional (for those aged 14-35 years) community mental health service with a yearly caseload of 140 CHR-P individuals. OASIS regularly delivers a comprehensive service promotion outreach to several local community organisations. Referrals to OASIS (2366) are made by numerous agencies; about one-third of the referrals eventually met CHR-P criteria. Overall, 600 CHR-P individuals (55.33% males, mean age 22.63 years, white ethnicity 46.44%) have been under the care of the OASIS service: 80.43% met attenuated psychotic symptoms, 18.06% brief and limited intermittent psychotic symptoms and 1.51% genetic risk and deterioration CHR-P criteria. All CHR-P individuals were offered cognitive behavioural therapy and psychosocial support; medications were used depending on individual needs. The cumulative risk of psychosis at ten years was 0.365 (95%CI 0.302-0.437). At six years follow-up, across two-third of individuals non-transitioning to psychosis, 79.24% still displayed some mental health problem, and only 20.75% achieved a complete clinical remission. Research conducted at OASIS encompassed clinical, prognostic, neurobiological and interventional studies and leveraged local, national and international infrastructures; over the past ten years, OASIS-related research attracted about £ 50 million of grant income, with 5,922 citations in the international databases. Future developments may include broadening OASIS to prevent other serious mental disorders beyond psychosis and fostering translational risk prediction and interventional research. With a twenty-years activity, OASIS’ cutting-edge quality of preventive care, combined with translational research innovations, consolidated the service as a leading reference model for evidence-based prevention of psychosis worldwide

Učinak primjene melatonina prije teljenja na izlučivanje mlijeka tijekom laktacije u mliječnih krava

This study evaluated the effects of melatonin administration 60 days prior to expect calving (drying-off period) on milk yield during the next lactation. Sixty dairy cows were treated with subcutaneous melatonin implants during summer (n=30) or winter (n=30) period. Another 60 animals were not treated and served as the control. There were no differences in the average milk yield between treated and untreated animals (44.5±3.7 and 44.8±5.0 kg/day for melatonin and control cows, respectively). There was an effect of season with a higher winter milk yield than in summer (43.8±5.0 and 47.1±3.0 kg/day for melatonin and control groups, respectively). The interaction between melatonin and season showed no significant effect; however, during winter, milk yield tended to be higher (P=0.06) in control cows than in melatonin treated cows (45.3±3.7 and 49.2±3.0, respectively). This study indicates that treatment with melatonin prior to calving did not modify milk yield during the following lactation. Only a tendency for a reduction in milk yield during winter was observed in melatonin treated cows.U ovom istraživanju procjenjivan je učinak primjene melatonina 60 dana prije očekivanog teljenja (razdoblje isušivanja) na proizvodnju mlijeka tijekom kasnije laktacije. Šezdeset mliječnih krava tretirano je potkožnim implantatima melatonina tijekom ljetnog (n=30), odnosno zimskog (n=30) razdoblja. Drugih 60 životinja nije tretirano i one su poslužile kao kontrola. Nije bilo razlika u prosječnoj proizvodnji mlijeka između tretiranih i netretiranih životinja (44,5±3,7 kg/ dan u krava tretiranih melatoninom, odnosno 44,8±5,0 kg/dan u kontrolnih krava). Postojao je učinak sezone, pri čemu je proizvodnja mlijeka bila veća zimi u odnosu na ljeto (43,8±5,0 kg/ dan u krava tretiranih melatoninom, odnosno 47,1±3,0 kg/dan u kontrolnoj skupini). Interakcija između melatonina i sezone nije pokazala značajniji učinak, ali tijekom zimske sezone proizvodnja mlijeka u kontrolnih krava bila je veća (P=0,06) u odnosu na krave tretirane melatoninom (45,3±3,7 u kontrolnoj skupini, odnosno 49,2±3,0 u krava tretiranih melatoninom). Ova studija ukazuje da tretman melatoninom prije teljenja ne mijenja proizvodnju mlijeka tijekom kasnije laktacije. Primijećena je samo tendencija smanjenja proizvodnje mlijeka u zimskoj sezoni u krava tretiranih melatoninom

Intranasal oxytocin increases heart-rate variability in men at clinical high risk for psychosis: a proof-of-concept study

Autonomic nervous system (ANS) dysfunction (i.e., increased sympathetic and/or decreased parasympathetic activity) has been proposed to contribute to psychosis vulnerability. Yet, we still lack directed therapeutic strategies that improve ANS regulation in psychosis or at-risk states. The oxytocin system constitutes a potential therapeutic target, given its role in ANS regulation. However, whether intranasal oxytocin ameliorates autonomic regulation during emerging psychosis is currently unknown. We pooled together two datasets, one of 30 men at clinical high risk for psychosis (CHR-P), and another of 17 healthy men, who had participated in two double-blinded, placebo-controlled, randomised, crossover MRI studies with similar protocols. All participants self-administered 40 IU of intranasal oxytocin or placebo using a nasal spray. We recorded pulse plethysmography during a period of 8 min at about 1 h post dosing and estimated heart rate (HR) and high-frequency HR variability (HF-HRV), an index of cardio-parasympathetic activity. CHR-P and healthy men did not differ at resting HR or HF-HRV under placebo. We found a significant condition × treatment effect for HF-HRV, showing that intranasal oxytocin, compared with placebo, increased HF-HRV in CHR-P but not in healthy men. The main effects of treatment and condition were not significant. In this proof-of-concept study, we show that intranasal oxytocin increases cardio-parasympathetic activity in CHR-P men, highlighting its therapeutic potential to improve autonomic regulation in this clinical group. Our findings support the need for further research on the preventive and therapeutic potential of intranasal oxytocin during emerging psychosis, where we lack effective treatments

Long term outcomes of acute and transient psychotic disorders:The missed opportunity of preventive interventions

AbstractBackground:Acute and transient psychotic disorders (ATPD) are characterized by an acute onset and a remitting course, and overlap with subgroups of the clinical high-risk state for psychosis. The long-term course and outcomes of ATPD are not completely clear.Methods:Electronic health record-based retrospective cohort study, including all patients who received a first index diagnosis of ATPD (F23, ICD-10) within the South London and Maudsley (SLaM) National Health Service Trust, between 1 st April 2006 and 15th June 2017. The primary outcome was risk of developing persistent psychotic disorders, defined as the development of any ICD-10 diagnoses of non-organic psychotic disorders. Cumulative risk of psychosis onset was estimated through Kaplan-Meier failure functions (non-competing risks) and Greenwood confidence intervals.Results:A total of 3074 patients receiving a first index diagnosis of ATPD (F23, ICD-10) within SLaM were included. The mean follow-up was 1495 days. After 8-year, 1883 cases (61.26%) retained the index diagnosis of ATPD; the remaining developed psychosis. The cumulative incidence (Kaplan-Meier failure function) of risk of developing any ICD-10 non-organic psychotic disorder was 16.10% at 1-year (95%CI 14.83–17.47%), 28.41% at 2-year (95%CI 26.80–30.09%), 33.96% at 3-year (95% CI 32.25–35.75%), 36.85% at 4-year (95%CI 35.07–38.69%), 40.99% at 5-year (95% CI 39.12–42.92%), 42.58% at 6-year (95%CI 40.67–44.55%), 44.65% at 7-year (95% CI 42.66–46.69%), and 46.25% at 8-year (95% CI 44.17–48.37%). The cumulative risk of schizophrenia-spectrum disorder at 8-year was 36.14% (95% CI 34.09–38.27%).Conclusions:Individuals with ATPD have a very high risk of developing persistent psychotic disorders and may benefit from early detection and preventive treatments to improve their outcomes.</jats:sec

Myticalins: A novel multigenic family of linear, cationic antimicrobial peptides from marine mussels (Mytilus spp.)

The application of high-throughput sequencing technologies to non-model organisms has brought new opportunities for the identification of bioactive peptides from genomes and transcriptomes. From this point of view, marine invertebrates represent a potentially rich, yet largely unexplored resource for de novo discovery due to their adaptation to diverse challenging habitats. Bioinformatics analyses of available genomic and transcriptomic data allowed us to identify myticalins, a novel family of antimicrobial peptides (AMPs) from the mussel Mytilus galloprovincialis, and a similar family of AMPs from Modiolus spp., named modiocalins. Their coding sequence encompasses two conserved N-terminal (signal peptide) and C-terminal (propeptide) regions and a hypervariable central cationic region corresponding to the mature peptide. Myticalins are taxonomically restricted to Mytiloida and they can be classified into four subfamilies. These AMPs are subject to considerable interindividual sequence variability and possibly to presence/absence variation. Functional assays performed on selected members of this family indicate a remarkable tissue-specific expression (in gills) and broad spectrum of activity against both Gram-positive and Gram-negative bacteria. Overall, we present the first linear AMPs ever described in marine mussels and confirm the great potential of bioinformatics tools for the de novo discovery of bioactive peptides in non-model organisms

Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High-Risk for Psychosis

Background and HypothesisAnimal models indicate GABAergic dysfunction in the development of psychosis, and that benzodiazepine (BDZ) exposure can prevent the emergence of psychosis-relevant phenotypes. However, whether BDZ exposure influences real-world clinical outcomes in individuals at clinical high risk for psychosis (CHR-P) is unknown.Study DesignThis observational cohort study used electronic health record data from CHR-P individuals to investigate whether BDZ exposure (including hypnotics, eg, zopiclone) reduces the risk of developing psychosis and adverse clinical outcomes. Cox proportional-hazards models were employed in both the whole-unmatched sample, and a propensity score matched (PSM) subsample.Study Results567 CHR-P individuals (306 male, mean[±SD] age = 22.3[±4.9] years) were included after data cleaning. The BDZ-exposed (n = 105) and BDZ-unexposed (n = 462) groups differed on several demographic and clinical characteristics, including psychotic symptom severity. In the whole-unmatched sample, BDZ exposure was associated with increased risk of transition to psychosis (HR = 1.61; 95% CI: 1.03–2.52; P = .037), psychiatric hospital admission (HR = 1.93; 95% CI: 1.13–3.29; P = .017), home visit (HR = 1.64; 95% CI: 1.18–2.28; P = .004), and Accident and Emergency department attendance (HR = 1.88; 95% CI: 1.31–2.72; P &lt; .001). However, after controlling for confounding-by-indication through PSM, BDZ exposure did not modulate the risk of any outcomes (all P &gt; .05). In an analysis restricted to antipsychotic-naïve individuals, BDZ exposure reduced the risk of transition to psychosis numerically, although this was not statistically significant (HR = 0.59; 95% CI: 0.32–1.08; P = .089).ConclusionsBDZ exposure in CHR-P individuals was not associated with a reduction in the risk of psychosis transition or adverse clinical outcomes. Results in the whole-unmatched sample suggest BDZ prescription may be more likely in CHR-P individuals with higher symptom severity.</div