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Infants born preterm miss out on the peak period of in utero DHA accretion to the brain during the last trimester of pregnancy which is hypothesised to contribute to the increased prevalence of neurodevelopmental deficits in this population. This study aimed to determine whether DHA supplementation in infants born preterm improves attention at 18 months’ corrected age. This is a follow-up of a subset of infants who participated in the N3RO randomised controlled trial. Infants were randomised to receive an enteral emulsion of high-dose DHA (60 mg/kg per d) or no DHA (soya oil – control) from within the first days of birth until 36 weeks’ post-menstrual age. The assessment of attention involved three tasks requiring the child to maintain attention on toy/s in either the presence or absence of competition or a distractor. The primary outcome was the child’s latency of distractibility when attention was focused on a toy. The primary outcome was available for seventy-three of the 120 infants that were eligible to participate. There was no evidence of a difference between groups in the latency of distractibility (adjusted mean difference: 0·08 s, 95 % CI –0·81, 0·97; P = 0·86). Enteral DHA supplementation did not result in improved attention in infants born preterm at 18 months’ corrected age.
The paper describes the rigorous implementation of a validated methodological experimental protocol to divergent and convergent thinking tasks occurring in Design by neurophysiological means (EEG and eye-tracking). EEG evidence confirms the findings coherently to the literature. Interesting is the confirmation of such results through eye-tracking ones, and further evidence emerged. In particular, neurophysiological results in idea generation differ between designers and engineers. This study was supported by a multidisciplinary team, both for the neuropsychological and data analysis aspects.
In this research paper we describe the technological properties of beneficial lactic acid bacteria (LAB) obtained from a dairy production chain and the development of a fermented milk produced with Lactobacillus casei MRUV6. Fifteen LAB isolates (Lactobacillus sp., Pediococcus sp. and Weissela sp.) presented acidifying abilities (pH ranges from 0.73 to 2.11), were able to produce diacetyl (except by 5 isolates) and exopolysaccharides, and two were proteolytic. L. casei MRUV6 was selected for producing a fermented milk, stored up to 35 d at 4 and 10°C. Counts on MRS agar with added vancomycin (10 mg/l) and MRS agar with added bile salts (1.5% w/v) ranged from 9.7 to 9.9 log CFU/g, independently of the tested conditions, indicating stability and intestinal resistance of L. casei MRUV6, despite some significant differences (P < 0.05). The study demonstrated the technological potential of a potential probiotic candidate strain, L. casei MRUV6, to be used as a starter culture in the dairy industry.
Postpartum depression can mark the onset of bipolar disorder. The coding region of Per3 gene contains a variable-number tandem-repeat polymorphism, which has been shown to influence bipolar disorder onset and to affect breast cancer risk. We showed a relationship between Per3 polymorphism and postpartum depressive onset in bipolar disorder.
The catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (rs4680) influences the enzyme activity. Recent clinical studies found a significant effect of rs4680 on antidepressant response to fluoxetine and paroxetine, but several other studies were negative. No study considered drug plasma levels as possible nuisance covariate.
We studied the effect of rs4680 on response to fluvoxamine antidepressant monotherapy.
Patients and methods
Forty-one consecutively admitted inpatients affected by a major depressive episode in course of major depressive disorder were administered fluvoxamine for 6 weeks. Changes in severity of depression were assessed with weekly Hamilton Depression ratings and analyzed with repeated measures ANOVA in the context of General Linear Model, with rs4680 and fluvoxamine plasma levels as factors.
rs4680 significantly interacted with time in affecting antidepressant response to fluvoxamine, with outcome being inversely proportional to the enzyme activity: better effects in Met-carriers, worse effects in Val/Val homozygotes. The effect became significant at the fourth week of treatment, and influence final response rates. Fluvoxamine plasma levels had marginal effects on outcome.
This is the first study that reports a positive effect of rs4680 on response to fluvoxamine, and the third independent report of its influence on response to selective 5-HT reuptake inhibitors (SSRIs). Our findings support the hypothesis that factors affecting catecholaminergic neurotransmission might contribute to shape the individual response to antidepressants irrespective of their primary molecular target.
Bipolar disorder (BD) is a severe, disabling and life-threatening illness. Disturbances in emotion and affective processing are core features of the disorder with affective instability being paralleled by mood-congruent biases in information processing that influence evaluative processes and social judgment. Several lines of evidence, coming from neuropsychological and imaging studies, suggest that disrupted neural connectivity could play a role in the mechanistic explanation of these cognitive and emotional symptoms. The aim of the present study is to investigate the effective connectivity in a sample of bipolar patients.
Dynamic causal modeling (DCM) technique was used to study 52 inpatients affected by bipolar disorders consecutively admitted to San Raffaele hospital in Milano and forty healthy subjects. A face-matching task was used as activation paradigm.
Patients with BD showed a significantly reduced endogenous connectivity in the DLPFC to Amy connection. There was no significant group effect upon the endogenous connection from Amy to ACC, from ACC to Amy and from DLPFC to ACC.
Both DLPFC and ACC are part of a network implicated in emotion regulation and share strong reciprocal connections with the amygdale. The pattern of abnormal or reduced connectivity between DLPFC and amygdala may reflect abnormal modulation of mood and emotion typical of bipolar patients.
The presence of panic disorder (PD) [1,2,3] is associated with numerous of cardiovascular, respiratory, gastroenterologic and neuro-otologic symptoms. PD is an anxiety disorder with a good outcome and prognosis, but if it isn't recognized cause a worse quality of life and a reduction of global functioning. The aim of our study is to put the attention on this delayed form of PD that are very good treated with duloxetine.
GV, a 29-year-old caucasian woman affected by PD with agoraphobia referred for recurrent gastroenteric symptoms (heartburn, chest tightness). PA, a 64-year-old caucasian woman affected by PD without agoraphobia referred for recurrent gastroenteric symptoms (heartburn). TB, a 45-year-old caucasian man affected by PD without agoraphobia referred for recurrent gastroenteric symptoms (heartburn, tightness, eructation). All patients are evaluated by gastroenterologist to excluded fisical gastroenterological problems. After 6 months all patients treated with duloxetine 60 mg/day, showed a complete remission of gastric and panic related symptoms.
Three case report positive treated with duloxetine, without particular adverse effects and litterature review.
Discussion and conclusion
Others authors hypothesized the duloxetine, a serotonin-norepinephrine inhibitor that has greater initial noradrenergic effects than venlafaxine, would have broad efficacy for individuals with PD. Descending serotonin and norepinephrine pathways are modulators of pain perception, and duloxetine have an analgesic effect on painful physical symptoms. Further research is warranted to replicate our clinical observations.
Asenapine is an atypical antipsychotic indicated for the treatment of schizophrenia and of the manic or mixed episodes in bipolar I disorder . The different therapeutics option like mood stabilizers and atypical antipsychotics are used to better treat the single episode but also to stabilize manic/depressive cyclicity . The aim of this case report is to underline a possible augmentation of asenapine to clozapine.
'Mrs. T.P.', is a caucasian woman aged 45 suffering from bipolar disorder type I followed by mixed depressive phases with subsequent short free period. The patient was treated with different typical and atypical antipsychotics, combined with mood stabilizers, with a partial response. With lithium 900 mg/day, valproate 1500 mg/day and clozapine 250 mg/day showed a partial improvement and remission of the symptoms. To that point we introduced asenapine 20 mg/day with rapid clinical improvement without major side effects. After 1 year the patient is still showing a good affective stability, with an improvemnt of metabolic and without cognitive side effects.
Discussion and conclusions
Our case report underlines the possibility of asenapine augmentation of clozapine in bipolar I disorder therapy resistant manic patients . Asenapine can increase the plasmatic levels of clozapine, exhibits a unique effect and his pharmacodynamic characteristics may mediate its symptom relief in positive, negative and mood symptoms. Further research is warranted to replicate our clinical observation.
Few questionnaires on the psychopathological onset and latency to treatment in psychiatric patients are currently available.
In this perspective we developed a brief questionnaire: the Psychopathological Onset Latency and Treatment Questionnaire (POLQ).
The questionnaire was administered to 265 patients with any psychiatric diagnosis. Statistical analyses were performed using SPSS.
The sample showed the following demographic variables in terms of age (48 ± 15 years), occupation (17% unemployed) and familiarity (54%). Clinical variables included: age at onset (30.66 ± 15 years), age at first diagnosis (36 ± 19 years) and age at first drug treatment (35 ± 14 years). the most common symptoms at onset were related to the anxiety spectrum (41.2%), mood spectrum (24.5%) or both (25.3%). Stressful life-events in relation to onset occurred in 63% of patients (12.1% familiar issues, 11.3% work problems, bereavement or end of a relationship in 16.6%). Most frequent first diagnoses were major depressive episode (26.8%), manic/hypomanic/mixed episode (13.6%) and anxiety disorders (11.7%). Average latency to the first visit was 34 months. in the 76.2% of the sample, the first contact was with a psychiatrist, a psychologist in 15.8%; 78.1% were treated with drugs as a first treatment, 11.7% with psychotherapy, 7.2% with both. the average duration of first treatment was 23 months (4 weeks - 360 months) and reasons for discontinuation were: lack of efficacy (23.8%) or complete remission (21.9%).
POLQ resulted to be a useful and reliable instrument in the collection of information on the psychopatological onset and latency to treatment.
Evidence has suggested that immune imbalance is involved with bipolar disorder (BD); however, its precise mechanism is poorly understood.
This study investigated whether biochemical changes in the serum from BD patients could modulate the phenotype of macrophages.
Eighteen subjects with BD and healthy individuals (n = 5) were included in this study. The human monocyte cell line U-937 was activated with PMA (phorbol 12-myristate 13-acetate) and polarization was induced with RPMI-1640 media supplemented with 10% serum from each patient for 24 h. Gene expression of selected M1 and M2 markers was assessed by qPCR.
Macrophages exposed to serum of manic and depressive BD patients displayed an increase of IL-1β (6.40 ± 3.47 and 9.04 ± 5.84 versus 0.23 ± 0.11; P < 0.05) and TNF-α (2.23 ± 0.91 and 2.03 ± 0.45 versus 0.62 ± 0.24; P = 0.002 and P = 0.004, respectively) compared to remitted group. In parallel, U-937 macrophages treated with serum of patients in acute episode displayed a down-regulation of CXCL9 (0.29 ± 0.20 versus 1.86 ± 1.61; P = 0.006) and CXCL10 expression (0.36 ± 0.15 and 0.86 ± 0.24 versus 1.83 ± 0.88; P < 0.000 and P = 0.04) compared to remitters.
Our results are consistent with previous studies showing that changes in peripheral blood markers could modulate M1/M2 polarization in BD. The evidence of macrophages as source of inflammatory cytokines might be helpful to unravel how the mononuclear phagocyte system can be involved in the etiology of BD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Suicides that occur during psychiatric hospitalization are tragic events causing immense distress to relatives, peers, and physicians. Suicide risk is particularly high in patients with mood disorders.
To identify a clinical risk profile which can be predictive of suicide in patients undergoing a major depressive episode, hospitalized and within three months after discharge.
We are going to include consecutively admitted depressed patients in San Raffaele Turro hospital (Milan), with a diagnosis of major depressive disorder or bipolar disorder, for a longitudinal prospective study. Demographical and clinical characteristics will be assessed. Barratt impulsiveness scale, aggression questionnaire, Hamilton psychiatric rating scale for depression, scale for suicide ideation, Columbia suicide severity rating scale will be administered to evaluate, respectively, traits of impulsiveness and aggression, severity of psychopathology and suicidal ideation. A follow-up program has been established to evaluate suicidal ideation one month and three months after discharge.
Considering suicide rates in other psychiatric wards, we retrospectively analyzed in our mood disorder unit the inpatient suicide rate of the last 3 years. In this period, we admitted 1794 patients. The suicide rate has been cumulatively of 0.17% (4 patients): 0.16% in 2014, 0.16% in 2015, and 0.19% in 2016. In the same period, outpatient suicide rate has been of 0.39%; 57.14% of outpatient suicides happened within three months after discharge.
Hospitalization and discharge are critical circumstances for psychiatric patients. Evaluation of risk factors will contribute to explain our ward suicide rate and hopefully to reduce it in the future.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
In this paper, a rectangular aerostatic bearing with multiple supply holes is optimised with a multiobjective optimisation approach. The design variables taken into account are the supply holes position, their number and diameter, the supply pressure, while the objective functions are the load capacity, the air consumption and the stiffness and damping coefficients. A genetic algorithm is applied in order to find the Pareto set of solutions. The novelty with respect to other optimisations which can be found in literature is that number and location of the supply holes is completely free and not associated to a pre-defined scheme. A vector x associated with the supply holes location is introduced in the design parameters and given in input to the optimizer.
Excitable temperament disrupts physiological events required for reproductive development in cattle, but no research has investigated the impacts of temperament on growth and puberty attainment in Bos indicus females. Hence, this experiment evaluated the effects of temperament on growth, plasma cortisol concentrations and puberty attainment in B. indicus heifers. A total of 170 Nelore heifers, weaned 4 months before the beginning of this experiment (days 0 to 91), were managed in two groups of 82 and 88 heifers each (mean ± SE; initial BW=238±2 kg, initial age=369±1 days across groups). Heifer temperament was evaluated via exit velocity on day 0. Individual exit score was calculated within each group by dividing exit velocity into quintiles and assigning heifers with a score from 1 to 5 (1=slowest; 5=fastest heifer). Heifers were classified according to exit score as adequate (ADQ, n=96; exit score⩽3) or excitable temperament (EXC, n=74; exit score>3). Heifer BW, body condition score (BCS) and blood samples were obtained on days 0, 31, 60 and 91. Heifer exit velocity and score were recorded again on days 31, 60 and 91. Ovarian transrectal ultrasonography was performed on days 0 and 10, 31 and 41, 60 and 70, 81 and 91 for puberty evaluation. Heifer was declared pubertal at the first 10-day interval in which a corpus luteum was detected. Exit velocity and exit score obtained on day 0 were correlated (r⩾0.64, P<0.01) with evaluations on days 31, 60 and 91. During the experiment, ADQ had greater (P<0.01) mean BCS and BW gain, and less (P<0.01) mean plasma cortisol concentration compared with EXC heifers. Temperament × time interactions were detected (P<0.01) for exit velocity and exit score, which were always greater (P<0.01) in EXC v. ADQ heifers. A temperament × time interaction was also detected (P=0.03) for puberty attainment, which was delayed in EXC v. ADQ heifers. At the end of the experiment, a greater (P<0.01) proportion of ADQ were pubertal compared with EXC heifers. In summary, B. indicus heifers classified as EXC had reduced growth, increased plasma cortisol concentrations and hindered puberty attainment compared to ADQ heifers. Moreover, exit velocity may serve as temperament selection criteria to optimize development of B. indicus replacement heifers.
As apex predators, sharks are known to play an important role in marine food webs. Detailed information on their diet and trophic level is however needed to make clear inferences about their role in the ecosystem. A total of 335 stomachs of smooth hammerhead sharks, Sphyrna zygaena, were obtained from commercial fishing vessels operating in the Ecuadorian Pacific between January and December 2004. A total of 53 prey items were found in the stomachs. According to the Index of Relative Importance (%IRI), cephalopods were the main prey (Dosidicus gigas, Sthenoteuthis oualaniensis, Ancistrocheirus lesueurii and Lolliguncula [Loliolopsis] diomedeae). Sphyrna zygaena was thus confirmed to be a teutophagous species. The estimated trophic level of S. zygaena was between 4.6 and 5.1 (mean ± SD: 4.7 ± 0.16; males: 4.7; females: 4.8). Levin's index (BA) was low (overall: 0.07; males: 0.08; females: 0.09), indicating a narrow trophic niche. We found that sharks <150 cm in total length consumed prey of coastal origin, whereas sharks ≥150 cm foraged in oceanic waters and near the continental shelf. The analyses indicate that S. zygaena is a specialized predator consuming mainly squids.
Posthodiplostomum minimum utilizes a three-host life cycle with multiple developmental stages. The metacercarial stage, commonly known as ‘white grub’, infects the visceral organs of many freshwater fishes and was historically considered a host generalist due to its limited morphological variation among a wide range of hosts. In this study, infection data and molecular techniques were used to evaluate the host and tissue specificity of Posthodiplostomum metacercariae in centrarchid fishes. Eleven centrarchid species from three genera were collected from the Illinois portion of the Ohio River drainage and necropsied. Posthodiplostomum infection levels differed significantly by host age, host genera and infection locality. Three Posthodiplostomum spp. were identified by DNA sequencing, two of which were relatively common within centrarchid hosts. Both common species were host specialists at the genus level, with one species restricted to Micropterus hosts and the other preferentially infecting Lepomis. Host specificity is likely dictated by physiological compatibility and deviations from Lepomis host specificity may be related to host hybridization. Posthodiplostomum species also differed in their utilization of host tissues. Neither common species displayed strong genetic structure over the scale of this study, likely due to their utilization of bird definitive hosts.
Pottery-manufacturing sequences can act as proxies for human migration and interaction. A good example is provided by the ‘spiralled patchwork technology’ (SPT) identified at two key early farming sites in the Ligurian-Provencal Arc in the north-west of the Italian peninsula. SPT is distinct from the ceramic technology used by early farmer communities in south-east Italy that shows technical continuity with the southern Balkans. Macroscopic analysis and micro-computed tomography suggests the presence of two communities of practice, and thus two distinct social groups in the northern Mediterranean: one of southern Balkan tradition, the other (associated with SPT) of as yet unknown origin. The identification of SPT opens up the exciting possibility of tracing the origins and migrations of a second distinct group of early farmers into Southern Europe.
We analysed the stomach contents of 69 silky sharks Carcharhinus falciformis, 44 blacktip sharks Carcharhinus limbatus and 24 whitenose sharks Nasolamia velox caught in the Ecuadorian Pacific from August 2003 to December 2004. Prey included bony fishes, elasmobranchs, molluscs, crustaceans and turtles, with bony fishes being the most important to the diets of all three sharks, suggesting they are piscivorous predators. Based on the index of relative importance, the C. falciformis diet includes Thunnus albacares, Thunnus sp. and Auxis thazard, as well as some squid, fish and turtles. Similarly, the C. limbatus diet was dominated by T. albacares, Exocoetus monocirrhus, A. thazard, Katsuwonus pelamis, members of the Ophichthidae family and other elasmobranchs. Meanwhile, N. velox consumed mainly Dosidicus gigas, Larimus argenteus, Cynoscion sp. and Lophiodes spilurus. There is little competition for food between these tertiary carnivores: C. limbatus prefers prey from coastal-oceanic habitats; C. falciformis consumes mostly oceanic prey and N. velox focuses on prey from coastal habitats. The lack of information on the biology of sharks in Ecuador hinders the development of appropriate management and conservation plans to protect shark resources. This study increases our knowledge and understanding of sharks in Ecuador, thus contributing to their conservation.
Catechol-O-methyltransferase (COMT) inactivates catecholamines, Val/Val genotype was associated to an increased amygdala (Amy) response to negative stimuli and can influence the symptoms severity and the outcome of bipolar disorder, probably mediated by the COMT polymorphism (rs4680) interaction between cortical and subcortical dopaminergic neurotransmission. The aim of this study is to explore how rs4680 and implicit emotional processing of negative emotional stimuli could interact in affecting the Amy connectivity in bipolar depression. Forty-five BD patients (34 Met carriers vs. 11 Val/Val) underwent fMRI scanning during implicit processing of fearful and angry faces. We explore the effect of rs4680 on the strength of functional connectivity from the amygdalae to whole brain. Val/Val and Met carriers significantly differed for the connectivity between Amy and dorsolateral prefrontal cortex (DLPFC) and supramarginal gyrus. Val/Val patients showed a significant positive connectivity for all of these areas, where Met carriers presented a significant negative one for the connection between DLPFC and Amy. Our findings reveal a COMT genotype-dependent difference in corticolimbic connectivity during affective regulation, possibly identifying a neurobiological underpinning of clinical and prognostic outcome of BD. Specifically, a worse antidepressant recovery and clinical outcome previously detected in Val/Val patients could be associated to a specific increased sensitivity to negative emotional stimuli.
When directly perturbed in healthy subjects, premotor cortical areas generate electrical oscillations in the beta range (20–40 Hz). In schizophrenia, major depressive disorder and bipolar disorder (BD), these oscillations are markedly reduced, in terms of amplitude and frequency. However, it still remains unclear whether these abnormalities can be modulated over time, or if they can be still observed after treatment. Here, we employed transcranial magnetic stimulation (TMS) combined with EEG to assess the frontal oscillatory activity in eighteen BD patients before/after antidepressant treatments (sleep deprivation and light therapy), relative to nine healthy controls. In order to detect dominant frequencies, event related spectral perturbations (ERSP) were computed for each TMS/EEG session in all participants, using wavelet decomposition. The natural frequency at which the cortical circuit oscillates was calculated as the frequency value with the largest power across 300 ms post-stimulus time interval. Severity of depression markedly decreased after treatment with 12 patients achieving response and nine patients achieving remission. TMS/EEG resulted in a significant activation of the beta/gamma band response (21–50 Hz) in healthy controls. In patients, the main frequencies of premotor EEG responses to TMS did not significantly change before/after treatment and were always significantly lower than those of controls (11–27 Hz) and comparable in patients achieving remission and in those not responding to treatment. These results suggest that the reduction of natural frequencies is a trait marker of BD, independent from the clinical status of the patients. The present findings shed light on the neurobiological underpinning of severe psychiatric disorders and demonstrate that TMS/EEG represents a unique tool to develop biomarkers in psychiatry.