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BACKGROUND: Recent advances in multivariate pattern recognition have fostered the search for reliable neuroimaging-based biomarkers in psychiatric conditions, including schizophrenia. These approaches consider the complex pattern of alterations in brain function and structure, overcoming the limitations of traditional univariate methods. To assess the reliability of neuroimaging-based biomarkers and the contribution of study characteristics in distinguishing individuals with schizophrenia spectrum disorder (SSD) from healthy controls (HCs), we conducted a systematic review of the studies that used multivariate pattern recognition for this objective. METHODS: We systematically searched PubMed, Scopus, and Web of Science for studies on SSD classification using multivariate pattern analysis on magnetic resonance imaging data. We employed a bivariate random-effects meta-analytic model to explore the classification of sensitivity (SE) and specificity (SP) across studies while also evaluating the moderator effects of clinical and non-clinical variables. RESULTS: A total of 119 studies (with 12,723 patients with SSD and 13,196 HCs) were identified. The meta-analysis estimated a SE of 79.1% (95% confidence interval [CI], 77.1%-81.0%) and a SP of 80.0% (95% CI, 77.8%-82.0%). In particular, the Positive and Negative Syndrome Scale and the Global Assessment of Functioning scores, age, age of onset, duration of untreated psychosis, deep learning, algorithm type, features selection, and validation methods had significant effects on classification performance. CONCLUSIONS: Multivariate pattern analysis reliably identifies neuroimaging-based biomarkers of SSD, achieving â¼80% SE and SP. Despite clinical heterogeneity, discernible brain modifications effectively differentiate SSD from HCs. Classification performance depends on patient-related and methodological factors crucial for the development, validation, and application of prospective models in clinical settings.
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Escherichia coli causes a significant number of clinical mastitis cases in dairy cattle worldwide. The antimicrobial susceptibility of E. coli is important for both human and animal health. Surveillance reports recorded that the efficacy of most antibiotics is substantially preserved but detection of E. coli from clinical mastitis cases producing extended-spectrum beta-lactamases and plasmid-encoded AmpC beta-lactamases has been reported. These resistance determinants have frequently been associated with multidrug resistance. The aim of this study was to determine if a MacConkey agar medium supplemented with 8 mg/L of ceftiofur (MC-CEF) could be a useful tool to identify cephalosporin-resistant and multidrug-resistant (MDR) E. coli among bovine mastitis isolates. During the period 2010-2011, 773 E. coli were isolated from bovine clinical mastitis milk samples collected in 80 dairy farms in Northern Italy. A total of 105 E. coli were selected and assigned either to group randomly selected E. coli (RSEC; n = 53), based on a random selection among the whole collection of 773 E. coli, or to group ceftiofur-resistant E. coli (CEFREC; n = 52). CEFREC isolates were identified by spreading the 773 E. coli isolates on MC-CEF. Minimum inhibitory concentration (MIC) was used to test the phenotypic antimicrobial susceptibility to 16 antibiotics. The MIC results confirmed the ceftiofur resistance in 73.1% (38/52) of CEFREC isolates, whereas all RSEC isolates were susceptible to ceftiofur. The comparison of MIC values for each antibiotic tested between the two groups revealed significantly higher frequencies of resistance to antimicrobials other than ceftiofur in the CEFREC group. Resistance profiles highlighted a significantly higher frequency of MDR isolates among CEFREC (73.1%) than RSEC (17%) E. coli. The results showed that MC-CEF may be a useful selective medium to identify cephalosporin-resistant and MDR E. coli on dairy farms, without performing MIC on all the isolates.
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Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Indústria de Laticínios , Escherichia coli/isolamento & purificação , Mastite Bovina/microbiologia , Animais , Bovinos , Meios de Cultura , Farmacorresistência Bacteriana Múltipla , Escherichia coli/efeitos dos fármacos , Feminino , Itália/epidemiologia , Mastite Bovina/epidemiologia , Testes de Sensibilidade MicrobianaRESUMO
Decreased availability of serotonin in the central nervous system has been suggested to be a central factor in the pathogenesis of depression. Activation of indoleamine 2-3 dioxygenase following a pro-inflammatory state could reduce the amount of tryptophan converted to serotonin and increase the production of tryptophan catabolites such as kynurenic acid, an antagonist of ionotropic excitatory aminoacid receptors, whose levels are reduced in bipolar disorder. Abnormalities in white matter (WM) integrity have been widely reported in BD. We then hypothesized that metabolites involved in serotoninergic turnover in BD could influence DTI measures of WM microstructure. Peripheral levels of tryptophan, kynurenine, kynurenic acid, 3-hydroxy-kynurenine, and 5-HIAA were analysed in 22 patients affected by BD and 15 healthy controls. WM microstructure was evaluated using diffusion tensor imaging and tract-based spatial statistics with threshold-free cluster enhancement only in bipolar patients. We observed that kynurenic acid and 5-HIAA were reduced in BD and associated with DTI measures of WM integrity in several association fibres: inferior and superior longitudinal fasciculus, cingulum bundle, corpus callosum, uncus, anterior thalamic radiation and corona radiata. Our results seem to suggest that higher levels of 5-HIAA, a measure of serotonin levels, and higher levels of kynurenic acid, which protects from glutamate excitotoxicity, could exert a protective effect on WM microstructure. Reduced levels of these metabolites in BD thus seem to confirm a crucial role of serotonin turnover in BD pathophysiology.
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Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/metabolismo , Cinurenina/metabolismo , Transdução de Sinais/fisiologia , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismo , Adulto , Imagem de Tensor de Difusão , Feminino , Humanos , Ácido Hidroxi-Indolacético/metabolismo , Ácido Cinurênico/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Serotonina/metabolismo , Triptofano/metabolismo , Adulto JovemRESUMO
Abnormalities of T cell-mediated immune activation, in the absence of active somatic immune diseases, have consistently been reported in mood disorders. Apart from being important players in the regulation of cells of the immune system, T cells are essential for normal brain development. We here report studies on the relationship between circulating levels of T helper cells and structural and functional brain imaging in depressed bipolar patients. Since the CCL20-CCR6 axis is an important entry to the brain we differentiated the various T helper cell subpopulations on the basis of their chemokine receptor expression. METHODS: FACS staining was performed for Th1, Th2, Th17, Th22 and T regulatory cells on frozen leukocytes of 25 consecutively admitted inpatients affected by a major depressive episode, without psychotic features, in the course of Bipolar Disorder I and 21 healthy controls. The frequency of the T helper populations was associated with DTI and fMRI data acquired on a Philips 3.0 Tesla scanner. Tract based spatial statistic was used to obtain measures of white matter integrity (fractional anisotropy, axial, radial and mean diffusivity) from a standard DTI sequence with 35 directions. Patients were also studied for fMRI through a moral valence decision task were subjects had to decide whether morally tuned stimuli were positive or negative. RESULTS: The percentage of circulating Th17 (CCR6+CXCR3negCCR4+CCR10neg) cells correlated positively with higher fractional anisotropy in fiber tracts contributing to the functional integrity of the brain both in patients and healthy controls, while the frequency of circulating T regulatory (CD4+CD25+FOXP3+) cells correlated positively with higher radial and mean diffusivity in patients. The frequency of circulating T regulatory cells also correlated to lower neuronal responses to negative versus positive morally tuned stimuli in the right dorsolateral prefrontal cortex of patients. Th1 cells correlated negatively with white matter integrity in several tracts (healthy controls), while the cells showed a positive correlation to the levels of pro-inflammatory cytokines (patients). CONCLUSION: This study shows a new putative role for Th17 cells. Th17 cells are not only playing a role in inducing autoimmunity and auto-inflammation, but might also play a counter intuitive anabolic role in the maintenance of the functional and structural integrity of the brain.
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Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Células Th17/imunologia , Adulto , Anisotropia , Transtorno Bipolar/imunologia , Encéfalo/imunologia , Imagem de Tensor de Difusão , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
OBJECTIVES: Obesity has been reported in over 60% of bipolar disorder (BD) patients. It worsens the severity of illness, and influences cognition and functional outcomes. White matter (WM) abnormalities are one of the most consistently reported findings in neuroimaging studies of BD. We hypothesized that body mass index (BMI) could correlate with WM integrity in bipolar patients. METHODS: We evaluated BMI in a sample of 164 depressed patients affected by BD. We performed whole-brain tract-based spatial statistics with threshold-free cluster enhancement for the diffusion tensor imaging (DTI) measures of WM integrity: fractional anisotropy; axial, radial, and mean diffusivity. RESULTS: We observed that BMI was associated with DTI measures of WM integrity in several fiber tracts: anterior corona radiata, anterior thalamic radiation, inferior fronto-occipital fasciculus and corpus callosum. CONCLUSIONS: The association of BMI in key WM tracts that are crucial to mood regulation and neurocognitive functioning suggests that BMI might contribute to the pathophysiology of BD through a detrimental action on structural connectivity in critical cortico-limbic networks.
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Transtorno Bipolar , Índice de Massa Corporal , Córtex Cerebral , Sistema Límbico , Substância Branca , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Análise por Conglomerados , Conectoma/métodos , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Regressão Espacial , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaAssuntos
Envelhecimento , Infecções por Coronavirus , Transtornos Mentais , Pandemias , Pneumonia Viral , Fatores Etários , Idoso , Envelhecimento/fisiologia , Envelhecimento/psicologia , Betacoronavirus , COVID-19 , Gestão de Mudança , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/psicologia , Serviços de Saúde para Idosos/organização & administração , Serviços de Saúde para Idosos/tendências , Humanos , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Itália/epidemiologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/fisiopatologia , Transtornos Mentais/terapia , Serviços de Saúde Mental/organização & administração , Serviços de Saúde Mental/tendências , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/psicologia , Medição de Risco , Fatores de Risco , SARS-CoV-2 , Populações Vulneráveis/psicologiaRESUMO
OBJECTIVE: Bipolar disorder (BD) is associated with a higher risk of suicide and with worse early life stress. A serotonin (5-hydroxytryptamine; 5-HT) transporter-linked polymorphic region (5-HTTLPR) has been shown to influence the relationship between stress and the risk of attempting suicide in the general population, but has not been investigated in BD. METHODS: We studied 136 inpatients (93 females, 43 males) with a major depressive episode in the course of BD. Early and recent stressful life events were scored on the Social Readjustment Rating Scale (SRRS). Regional gray matter (GM) volumes were analyzed, acquiring T1-weighted images on a 3.0 Tesla scanner. RESULTS: Homozygote l/l patients attempted suicide in a higher proportion than *s carriers. A separate-slopes logistic regression showed a significant effect of 5-HTTLPR on the relationship between stress, depression, and suicide among *s carriers, but not among l/l homozygotes, early stress associated with worse probability of attempting suicide and with earlier age at onset of BD. Exposure to early stress correlated with GM volumes in the right prefrontal cortex (Brodmann area 46) - again, in *s carriers only. CONCLUSIONS: 5-HTTLPR modulated the relationship between early life stress and the core features of bipolar illness. 5-HTTLPR*s carriers showed a higher sensitivity to the effects of stress; when exposed to low levels of early stress, they were protected against suicide in respect to l/l, but higher levels of stress progressively increased their risk of suicide and reduced the age at onset of illness.
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Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Predisposição Genética para Doença , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Estresse Psicológico/complicações , Suicídio/psicologia , Adulto , Transtorno Bipolar/patologia , Encéfalo/patologia , Feminino , Frequência do Gene , Genótipo , Humanos , Processamento de Imagem Assistida por Computador , Acontecimentos que Mudam a Vida , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Valor Preditivo dos Testes , Escalas de Graduação Psiquiátrica , Estresse Psicológico/psicologiaRESUMO
Non-aureus staphylococci and mammaliicocci (NASM) are associated with bovine mastitis and increased milk somatic cell count (SCC) but their relationships with mammary gland health at the species level are not clearly defined. Regional differences have also been reported in their specific prevalence. The implementation of MALDI-TOF MS in milk microbiology is generating large and dependable datasets with the potential of providing useful epidemiological information. We present the retrospective analysis of 17,213 milk samples sent to our laboratory in 2021-2022, including 13,146 quarter samples from cows with subclinical (SCM) or clinical mastitis (CM) from 104 farms, and 4,067 composite herd survey (HS) samples from 21 farms. NASM were isolated from 21.12% of SCM, 11.49% of CM, and 15.59% of HS milk samples. The three most frequently identified NASM in SCM milk were Staphylococcus chromogenes (33.33%), S. haemolyticus (26.07%), and S. epidermidis (10.65%); together with S. microti and S. hyicus, these species were significantly more prevalent in quarters with SCM (p < 0.05). The three most frequently identified NASM in CM milk were S. chromogenes (31.69%), S. haemolyticus (21.42%), and Mammaliicoccus sciuri (18.38%), although no significant associations were found between these NASM species and CM. The three most frequently identified NASM in HS milk were S. chromogenes (44.49%), S. epidermidis (17.84%), and S. haemolyticus (17.23%), with S. chromogenes being isolated in all the farms sending HS milk (100%). In conclusion, this retrospective study provides the first information on the NASM species isolated from cow milk in Italy, expanding our knowledge on the epidemiology of NASM at the species level and providing further insights into their relationships with mammary gland health in modern dairy farms.
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Doenças dos Bovinos , Mastite Bovina , Infecções Estafilocócicas , Feminino , Bovinos , Animais , Estudos Retrospectivos , Leite/microbiologia , Infecções Estafilocócicas/veterinária , Fazendas , Mastite Bovina/epidemiologia , Mastite Bovina/microbiologia , Doenças dos Bovinos/microbiologiaRESUMO
Non-aureus staphylococci and mammaliicocci (NASM) are the microorganisms most frequently isolated from milk. Given their numerosity and complexity, MALDI-TOF MS is one of the preferred species identification approaches. Nevertheless, reference mass spectra for the novel species Staphylococcus borealis were included only recently in the Bruker Biotyper System (MBT) library, and other species of veterinary interest such as S. rostri are still absent. This work provides an updated picture of the NASM species found in milk, gained by retrospectively analyzing the data relating to 21,864 milk samples, of which 6,278 from clinical mastitis (CM), 4,039 from subclinical mastitis (SCM), and 11,547 from herd survey (HS), with a spectrum library including both species. As a result, S. borealis was the second most frequently isolated NASM (17.07%) after S. chromogenes (39.38%) in all sample types, with a slightly higher percentage in CM (21.84%), followed by SCM (17.65%), and HS (14.38%). S. rostri was also present in all sample types (3.34%), reaching 8.43% of all NASM in SCM and showing a significant association (p < 0.01) with this condition. Based on our findings, the presence of S. borealis and S. rostri in milk and their potential association with mastitis might have been overlooked, possibly due to the difficulties in differentiating these species from other closely related NASM. Our results indicate that S. borealis could be a more frequent contributor to bovine udder infections than previously thought and that S. rostri should also not be underestimated considering its significant association with SCM.
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Mastite Bovina , Leite , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Staphylococcus , Animais , Leite/microbiologia , Bovinos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/veterinária , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Staphylococcus/isolamento & purificação , Staphylococcus/classificação , Feminino , Mastite Bovina/microbiologia , Estudos Retrospectivos , Infecções Estafilocócicas/veterinária , Infecções Estafilocócicas/microbiologiaRESUMO
A cross-sectional study was conducted to estimate the prevalence of intramammary infection (IMI) associated bacteria and to identify risk factors for pathogen group-specific IMI in water buffalo in Bangladesh. A California Mastitis Test (CMT) and bacteriological cultures were performed on 1,374 quarter milk samples collected from 763 water buffalo from 244 buffalo farms in nine districts in Bangladesh. Quarter, buffalo, and farm-related data were obtained through questionnaires and visual observations. A total of 618 quarter samples were found to be culture positive. Non-aureus staphylococci were the predominant IMI-associated bacterial species, and Staphylococcus (S.) chromogenes, S. hyicus, and S. epidermidis were the most common bacteria found. The proportion of non-aureus staphylococci or Mammaliicoccus sciuri (NASM), S. aureus, and other bacterial species identified in the buffalo quarter samples varied between buffalo farms. Therefore, different management practices, buffalo breeding factors, and nutrition were considered and further analyzed when estimating the IMI odds ratio (OR). The odds of IMI by any pathogen (OR: 1.8) or by NASM (OR: 2.2) was high in buffalo herds with poor milking hygiene. Poor cleanliness of the hind quarters had a high odds of IMI caused by any pathogen (OR: 2.0) or NASM (OR: 1.9). Twice daily milking (OR: 3.1) and farms with buffalo purchased from another herd (OR: 2.0) were associated with IMI by any pathogen. Asymmetrical udders were associated with IMI-caused by any bacteria (OR: 1.7). A poor body condition score showed higher odds of IMI by any pathogen (OR: 1.4) or by NASM (OR: 1.7). This study shows that the prevalence of IMI in water buffalo was high and varied between farms. In accordance with the literature, our data highlight that IMI can be partly controlled through better farm management, primarily by improving hygiene, milking management, breeding, and nutrition.
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Mastite Bovina , Infecções Estafilocócicas , Staphylococcus , Animais , Feminino , Bovinos , Staphylococcus aureus , Infecções Estafilocócicas/microbiologia , Búfalos , Estudos Transversais , Mastite Bovina/microbiologia , Leite/microbiologia , Staphylococcus epidermidis , Fatores de Risco , Glândulas Mamárias Animais/microbiologiaRESUMO
Accurate and precise differentiation of staphylococci isolated from milk is of importance for udder health management. In particular, the rapid and specific identification of Staphylococcus aureus plays an essential role in the prevention and treatment programs for bovine mastitis. Plasma gelatinization in coagulase assays is routinely used to discriminate S. aureus from other species by detecting the presence of extracellular free staphylocoagulase. However, rarely occurring coagulase-deficient S. aureus strains can be responsible for clinical and subclinical mastitis cases. By investigating S. aureus isolates from a single herd over a 10-year period we identified the persistence of a phenotypically coagulase-negative S. aureus strain and pinpointed the possible cause to a single base pair deletion in the coa gene sequence. Our results support the need to integrate primary biochemical tests with molecular/sequence analysis approaches for correctly identifying and discriminating atypical S. aureus in bovine herds, as the coagulase test alone may fail to detect persistent mastitis-causing strains.
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BACKGROUND: Since COVID-19 outbreak, clinical experience on its management during the acute phase has rapidly grown, including potential effects on the psychopathological dimension. However, still few data are available regarding the impact on survivors' mental health over the long-term. METHODS: A sample of 1457 COVID-19 patients underwent a multidisciplinary follow-up protocol, approximately 3 months after hospital discharge, including a psychological evaluation. The primary outcomes were anxiety, depression, resilience, post-traumatic symptoms, and health-related quality of life. Furthermore, we examined the potential role of hospitalization and delay in the follow-up assessment on the increased burden of illness. RESULTS: Although a general high level of resilience emerged, suggesting most patients relied on their individual and interpersonal resources to face difficulties related to the pandemic, almost one third of the sample reported signs of psychological distress over time, especially post-traumatic symptoms, with anxiety being more represented than depression. Furthermore, hospitalization - regardless of the setting of care - and promptness in follow-up evaluation were found to play a protective role on patients' recovery and mental wellbeing. LIMITATIONS: Selection bias of patients exclusively admitted to the hospital; absence of a control group; psychological assessment relying on self-reported instruments. CONCLUSIONS: The current crisis demands resilience and adjustment resources, either in the acute and post-acute phase. Thus, the clinical effort should aim at relieving the traumatic impact of such condition through timely interventions. Further investigation may address potential predictors of developing a traumatic stress response, in order to identify and promptly treat at-risk subpopulations.
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COVID-19 , Transtornos de Estresse Pós-Traumáticos , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Depressão/diagnóstico , Depressão/epidemiologia , Seguimentos , Hospitais , Humanos , Alta do Paciente , Qualidade de Vida , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/terapiaRESUMO
Streptococcus uberis, an environmental pathogen responsible also for contagious transmission, has been increasingly implicated in clinical mastitis (CM) cases in Europe. We described a 4-month epidemiological investigation of Strep. uberis CM cases in an Italian dairy farm. We determined molecular characteristics and phenotypic antimicrobial resistance of 71 Strep. uberis isolates from dairy cows with CM. Genotypic variability was investigated via multiplex PCR of housekeeping and virulence genes, and by RAPD-PCR typing. Antimicrobial susceptibility was assessed for 14 antimicrobials by MIC assay. All the isolates carried the 11 genes investigated. At 90% similarity, two distinct clusters, grouping 69 of the 71 isolates, were detected in the dendrogram derived from the primer ERIC1. The predominant cluster I could be separated into two subclusters, containing 38 and 14 isolates, respectively. Strep. uberis strains belonging to the same RAPD pattern differed in their resistance profiles. Most (97.2%) of them were resistant to at least one of the drugs tested, but only 25.4% showed a multidrug resistance phenotype. The highest resistance rate was observed for lincomycin (93%), followed by tetracycline (85.9%). This study confirmed a low prevalence of ß-lactam resistance in Strep. uberis, with only one isolate showing resistance to six antimicrobial classes, including cephalosporins.
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Aims: The aim was to analyse the psychiatric consultations in nine Italian hospital emergency departments, by comparing the lockdown and post-lockdown periods of 2020 with the equivalent periods of 2019. Methods: Characteristics of psychiatric consultations, patients, and drug prescriptions were analyzed. Joinpoint models were used to identify changes in the weekly trend of consultations. Results: A 37.5% decrease in the number of consultations was seen during the lockdown period and 17.9% after the lockdown. The number of individual patients seen decreased by 34.9% during the lockdown and 11.2% after the lockdown. A significant change in the number of consultations from week 11 to week 18 occurred, followed by a gradual increase. There was a higher percentage of patients with previous psychiatric hospitalizations during the lockdown period (61.1 vs. 56.3%) and a lower percentage after the lockdown (59.7 vs. 64.7%). During the lockdown there was a large increase in psychiatric consultations for substance use disorders, whereas more consultations for manic episodes occurred after the lockdown. A 3.4% decrease was observed in consultations for suicidal ideation and planning during the lockdown, followed by an upward rebound after the lockdown, along with an increase in consultations for suicide attempts. During lockdown antipsychotic and benzodiazepine prescriptions increased by 5.2 and 4.1%, respectively. After the lockdown, the number of compulsory hospitalizations was higher than in 2019. Conclusions: We observed a decrease of psychiatric consultations during and after the lockdown. There was an increase in consultations for manic episodes and suicidality after the lockdown. The focus of psychiatric services must remain high particularly in this latter period.
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Lactating cows are routinely treated at dry-off with antibiotic infusions in each quarter for the cure and prevention of pathogenic intramammary infection, which remains the most common disease in dairy herds. This approach is known as blanket dry-cow therapy, usually effective for the prevention and cure of infections, but has been shown to potentially contribute to the emergence and spreading of antibiotic resistant bacterial strains. Exploring the use of non-antibiotic treatments coupled with selective dry-cow therapy is necessary to reduce the risk of antibiotic resistance and potential interference with milk microbiome balance. The impact of selective dry-cow therapy on the physiological milk microbiome needs to be carefully evaluated. In this small-scale trial, five healthy (no mastits, SCC <200,000 cells mL-1) second-parity cows from dry-off to 5 days after calving were sampled. For every cow, each quarter received a different treatment: (i) bismuth salnitrate (internal teat sealant, OrbSeal®, Zoetis, Italy), front right quarter; (ii) cephalonium dihydrate (Cepravin®, MSD, Italy), rear right quarter; (iii) benzathine cloxacillin (Cloxalene dry, Ati, Italy), rear left quarter. No treatment was applied to the remaining quarter (front left) which served as experimental control. For 16S rRNA gene sequencing, bacterial DNA was extracted from 5 ml of milk samples, amplified using the primers for the V3-V4 hypervariable regions and sequenced in one MiSeq (Illumina) run with 2 × 250-base paired-end reads. Bacteriological results confirmed that the quarters were all healthy. The phyla Proteobacteria, Firmicutes, and Actinobacteria were the most abundant for all treatments and controls at all three timepoints, accounting for over 80% of the entire milk microbiota composition. No significant differences were found between treatments and controls in terms of the major alpha and beta diversity indexes, revealing that antibiotic, and non-antibiotic treatments for selective dry-cow therapy did not alter significantly the milk microbiome of dairy cows. The milk microbiota composition showed a clear evolution over the lactation cycle, and the overall changes in the milk microbiota diversity over the lactation cycle were mainly independent of treatments.
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We tested if peripheral levels of cytokines and chemokines associate to grey matter volumes, cortical thickness and fMRI neural responses to a moral valence decision task in bipolar patients. ICAM1 and CCL4 negatively correlated with cortical thickness in Inferior Temporal Gyrus, and sCD25 in Parahippocampal Gyrus. TNF-α, Interleukine-8, and CCL2 correlated positively with cortical thickness in the Anterior Cingulate Cortex, and with lower BOLD responses to negative stimuli. Markers of immune activation are associated with measures of brain structural and functional integrity in bipolar depression.
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Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/metabolismo , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Mediadores da Inflamação/metabolismo , Adulto , Biomarcadores/metabolismo , Transtorno Bipolar/psicologia , Tomada de Decisões/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/fisiologia , Adulto JovemRESUMO
BACKGROUND: The combination of three cycles of sleep deprivation (SD), light therapy (LT), and lithium has recently been proposed as a possible first-line treatment for bipolar depression. However, it is unclear whether early improvement predicts final response/remission in bipolar depression treated with this regimen. METHOD: We studied 220 consecutively admitted inpatients with a major depressive episode in the course of bipolar disorder. The relation between response to first SD and response/remission at the end of the treatment (day 6) was analyzed using logistic regression analysis. Severity of depression was rated using the Hamilton Depression Rating Scale (HDRS). Clinical response was defined as a ≥50% reduction in HDRS scores, and remission was defined as an HDRS score of ≤7. RESULTS: Among the 217 completers, 67.7% showed response and 54.4% reached remission at the end of the treatment. Multiple logistic regression analysis revealed that response after first recovery sleep (day 2) predicted final response and remission at the end of the treatment with high odds ratios (10.9 for response and 8.2 for remission); however, response immediately after the first SD (day 1) did not predict final response or remission. LIMITATIONS: Whether our results can be generalized to unipolar depression remains uncertain. CONCLUSION: Clinical status after first recovery sleep is a strong predictor of successful final outcome in patients with bipolar depression treated with the combination of repeated SD, LT, and lithium. Recovery sleep may play a role in inducing the antidepressant effect associated with the success of treatment.
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Transtorno Bipolar/terapia , Lítio/uso terapêutico , Fototerapia/métodos , Privação do Sono , Adulto , Antidepressivos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Indução de Remissão/métodos , Resultado do TratamentoRESUMO
Bipolar disorder (BD) is a severe illness characterized by recurrent depressive and manic episodes and by emotional dysregulation. Altered cortico-limbic connectivity could account for typical symptoms of the disorder such as mood instability, emotional dysregulation, and cognitive deficits. Functional connectivity positively associated with glutamatergic neurotransmission. The inactivation of glutamate is handled by a series of glutamate transporters, among them, the excitatory amino acid transporter 1 (EAAT1) which is modulated by a SNP rs2731880 (C/T) where the C allele leads to increased EAAT1 expression and glutamate uptake. We hypothesized that rs2731880 would affect cortico-limbic functional connectivity during an implicit affective processing task. Sixty-eight BD patients underwent fMRI scanning during implicit processing of fearful and angry faces. We explored the effect of rs2731880 on the strength of functional connectivity from the amygdalae to the whole brain. A significant activation in response to emotional processing was observed in two main clusters encompassing the right and left amygdala. Amygdalae to whole-brain functional connectivity analyses revealed a significant interaction between rs2731880 and the task (emotional stimuli vs geometric shapes) for the functional connections between the right amygdala and right subgenual anterior cingulate cortex. Post-hoc analyses revealed that T/T patients showed a significant negative connectivity between the amygdala and anterior cingulate cortex compared to C carriers. T/T subjects also performed significantly better in the face-matching task than rs2731880*C carriers. Our findings reveal an EAAT1 genotype-associated difference in cortico-limbic connectivity during affective regulation, possibly identifying a neurobiological underpinning of emotional dysfunction in BD.
Assuntos
Tonsila do Cerebelo/diagnóstico por imagem , Transtorno Bipolar/genética , Conectoma , Transportador 1 de Aminoácido Excitatório/genética , Polimorfismo de Nucleotídeo Único , Adulto , Tonsila do Cerebelo/fisiopatologia , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/fisiopatologia , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The Homer family of postsynaptic scaffolding proteins plays a crucial role in glutamate-mediated synaptic plasticity, a phenotype associated with Bipolar Disorder (BD). Homer is a target for antidepressants and mood stabilizers. The AA risk genotype of the Homer rs7713917 A>G SNP has been associated with mood disorders and suicide, and in healthy humans with brain function. Despite the evidence linking Homer 1 gene and function to mood disorder, as well as its involvement in animal models of depression, no study has yet investigated the role of Homer in bipolar depression and treatment response. METHODS: We studied 199 inpatients, affected by a major depressive episode in course of BD. 147 patients were studied with structural MRI of grey and white matter, and 50 with BOLD functional MRI of emotional processing. 158 patients were treated with combined total sleep deprivation and light therapy. RESULTS: At neuroimaging, patients with the AA genotype showed lower grey matter volumes in medial prefrontal cortex, higher BOLD fMRI neural responses to emotional stimuli in anterior cingulate cortex, and lower fractional anisotropy in bilateral frontal WM tracts. Lithium treatment increased axial diffusivity more in AA patients than in G*carriers. At clinical evaluation, the same AA homozygotes showed a worse antidepressant response to combined SD and LT. CONCLUSIONS: rs7713917 influenced brain grey and white matter structure and function in BD, long term effects of lithium on white matter structure, and antidepressant response to chronotherapeutics, thus suggesting that glutamatergic neuroplasticity and Homer 1 function might play a role in BD psychopathology and response to treatment.
Assuntos
Antidepressivos/uso terapêutico , Transtorno Bipolar/genética , Transtorno Bipolar/terapia , Encéfalo/efeitos dos fármacos , Proteínas de Arcabouço Homer/genética , Compostos de Lítio/uso terapêutico , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/fisiopatologia , Imagem de Tensor de Difusão , Emoções/efeitos dos fármacos , Emoções/fisiologia , Feminino , Variação Genética , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/efeitos dos fármacos , Substância Cinzenta/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Testes Neuropsicológicos , Oxigênio/sangue , Fototerapia , Privação do Sono , Resultado do Tratamento , Substância Branca/diagnóstico por imagem , Substância Branca/efeitos dos fármacos , Substância Branca/patologia , Substância Branca/fisiopatologia , População Branca/genéticaRESUMO
In healthy humans, both childhood trauma and the short form of the serotonin promoter transporter genotype (5-HTTLPR) are associated with lower levels of brain-derived neurotrophic factor (BDNF). In subjects with bipolar disorder (BD), lower levels of BDNF and a higher degree of childhood trauma were observed compared with healthy controls. However, is still unknown if the functional 5-HTTLPR polymorphisms exerts an effect on both abnormalities. In 40 inpatients affected by a major depressive episode in the course of BD, we genotyped 5-HTTLPR, measured serum BDNF with ELISA, and assessed early adversities by the childhood trauma questionnaire (CTQ). Data were analyzed in the context of the general linear model correcting for age, sex, ongoing lithium treatment, severity of current depression, and CTQ minimization/denial scores to investigate the effect of 5-HTTLPR polymorphism and childhood trauma on BDNF levels. Early trauma were negatively associated with BDNF serum levels (higher CTQ scores, lower BDNF; p=0.0019). 5-HTTLPR l/l homozygotes showed significantly higher BDNF levels than 5-HTTLPR*s carriers (30.57±6.13 vs 26.82±6.41; p=0.0309). A separate-slopes analysis showed that 5-HTTLPR significantly influenced the relationship between early trauma and adult BDNF (interaction of 5-HTTLPR with CTQ scores: p=0.0023), due to a significant relationship between trauma and BDNF in 5-HTTLPR*s carriers, but not among l/l homozygotes. Putatively detrimental effects of childhood trauma exposure on adult BDNF serum levels are influenced by 5-HTTLPR genotype in patients affected by BD. Possible mechanisms include epigenetic modulation of BDNF gene expression, due to different reactivity to stressors in 5-HTTLPR genotype groups.