Indagine molecolare sulla diffusione di Bartonella spp. in equidi della provincia di Pisa.

Le Bartonellosi sono una serie di infezioni sostenute da numerose specie di batteri appartenenti al genere Bartonella. Mentre gli animali, che svolgono spesso un ruolo di reservoir generalmente sono asintomatici, l'uomo può sviluppare diverse patologie in relazione alla specie batterica infettante. Le Bartonellosi sono considerate “vector-borne infections”, dal momento che la loro trasmissione è principalmente dovuta all'intervento di artropodi ematofagi quali pulci, pidocchi, flebotomi e zecche. Tra gli animali domestici, il gatto viene riconosciuto come l'animale più rilevante per quanto riguarda l'infezione nei confronti dell'uomo, in quanto ospite reservoir di B. henseale e non solo. Diverse bartonelle sono state segnalate in altri animali domestici e selvatici, ma in letteratura sono particolarmente scarse le informazioni sulla diffusione di questi batteri negli equidi e sul loro eventuale potere patogeno in questi animali. Alla luce di tali considerazioni, obiettivo della presente tesi è stato quello di determinare la diffusione di Bartonella spp. in equidi della provincia di Pisa. A tale scopo, i campioni di sangue prelevati da 77 cavalli e 15 asini asintomatici, sono stati sottoposti ad estrazione del DNA per l’esecuzione successiva di prove di PCR specifiche per la ricerca di questo patogeno. Dodici soggetti (9 cavalli e 3 asini) sono risultati positivi, dimostrando che anche gli equidi possono essere infettati da batteri del genere Bartonella, anche se non necessariamente sviluppano uno specifico quadro clinico. Sulla base dei dati presenti in letteratura, questo è il primo studio che ha rilevato l’infezione da Bartonella spp. negli asini (Equus asinus)

Bartonella infection in asymptomatic horses and donkeys from Tuscany, Central Italy.

Objective To investigate the occurrence of Bartonella sp. infection in asymptomatic horses and donkeys living in Tuscany, Central Italy. Methods Blood samples were collected from 77 horses and 15 donkeys and tested by indirect immunofluorescent test to detect antibodies against Bartonella sp. and by PCR to detect the pathogen. Results Fifty-four (58.69%; 95% CI: 47.95%–68.87%) animals, 9 donkeys and 45 horses, were seropositive with antibody titers ranging from 1:64 to 1:512. PCR assays detected 9 horses positive for Bartonella sp. and 3 donkeys for Bartonella henselae genotype I. Conclusions The detected sero-prevalence suggests a common and frequent exposure of equids living in Central Italy to bartonellae and PCR results show that Bartonella sp. infection is possible both in horses and donkeys. At the best of our knowledge, this is the first report of Bartonella henselae infection in donkeys

Exploring potential risk factors of antimicrobial use in beef cattle.

Livestock species are major contributors to the increase of antimicrobial (AM) resistance which is a worldwide concern for both human and animal health. The over-use of AM is widely acknowledged, however, unlike pigs, poultry and dairy cattle, knowledge on potential risk factors affecting AM usage (AMU) in beef industry is limited. Hence, this study aimed to investigate the impact of farm, breed, sex and season of arrival of purchased beef cattle on AMU in Italian beef cattle. Data on 1063 batches were collected from January 2016 to April 2019 from specialised beef fattening farms located in the north of Italy. Information on breed, sex, date of arrival, performance traits and AM agents used on farm was collected, and the treatment incidence 100 (TI100) indexes per batch were calculated using the defined daily dose animal estimated according to Italian summaries of product characteristics. Factors affecting TI100 indexes were investigated using a cross-classified multilevel model. Farms largely differed in terms of AMU. Males had greater AMU than females (P < 0.001), likely due to their higher susceptibility to disease. Statistically significant differences were observed between seasons of arrival with summer and spring having lower TI100 indexes than winter and autumn (P < 0.001). Indeed, winter is commonly linked to an increase in respiratory diseases in beef cattle. Finally, the TI100it indexes tended to be different among breeds with Blonde d'Aquitaine and Limousine having greater AMU compared to the other breeds. Results of this study provided valuable information on potential risk factors of AMU in beef production which may be useful to address its reduction. For instance, the development of tailored management strategies for specific breeds, targeted approaches to improve the health of males as well as greater care towards batches purchased in winter are possible advice to implement on-farm for a more responsible AM stewardship

Changes in upper airways microbiota in ventilator-associated pneumonia

Background: The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. Methods: Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72&nbsp;h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). Results: Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value &lt; 0.012). Furthermore, an overall decrease in microbial diversity was observed in both groups at T3 as compared to T0. At T3, a loss of some genera (Prevotella 7, Fusobacterium, Neisseria, Escherichia-Shigella and Haemophilus) was found in VAP patients. In contrast, eight genera belonging to the Bacteroidetes, Firmicutes and Fusobacteria phyla was predominant in this group. However, it is unclear whether VAP caused dysbiosis or dysbiosis caused VAP. Conclusions: In a small sample size of intubated patients, microbial diversity at intubation was less in patients with VAP compared to patients without VAP

COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy)

Objective To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the frst pandemic wave, Lombardia. Methods Adult patients admitted to 20 Neurological Units between 1/3–30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). Results Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. Conclusions We detected an increased incidence of GBS in COVID-19 patients which can refect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS &lt; 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders

An Assessment of Selected Sensorimotor Parameters and Muscle Performance in Hand Osteoarthritis for the Development of Treatment

Symptomatic hand osteoarthritis (OA) affects twenty percent of people over the age of 70. Its socioeconomic burden is increasing and despite severe repercussions on people’s quality of life, it has not received as much scientific attention as OA at other joints such as the knee and hip. The need for effective conservative interventions for hand OA has been suggested by several authors. Moreover, in light of recent research at other joints, it is important to assess sensorimotor and muscle impairments and their relation to function to determine the primary needs of a conservative program of rehabilitation. The first study compared selected measures of sensorimotor and muscle performance between people with hand OA and healthy controls. Furthermore, the relationship between these measures and function was assessed. People with hand OA were slower and less accurate in a hand left/right discrimination task and experienced neglect-like symptoms more frequently, suggesting they had a disrupted working body schema. However, no association was found between left/right discrimination performance and measures of hand function. While grip endurance was not different between groups, a significant loss of grip strength and a moderate relationship with self-reported function was identified in people with hand OA. We therefore hypothesised that improving grip strength may have beneficial effects in people with hand OA. To test this hypothesis, we completed a review and meta-analysis of research papers assessing the effectiveness of resistance training interventions on grip strength, pain and function in people with hand OA (Study two). Five studies with 350 participants were included. The findings showed no improvements in grip strength or function and limited effects on joint pain. However, it was apparent that most studies utilised exercise regimes considered inadequate to induce strength changes. In some studies, fear of pain exacerbations or doing further damage to the affected joints led researchers to limit load during the prescribed exercise regimes. The findings suggested that a low intensity exercise alternative may be beneficial to improve muscle strength and function in people with hand OA, while reducing the risk of pain exacerbations and attenuating joint compressive forces. After a subsequent search of the literature for low load strengthening programs, blood flow restriction training (BFR) appeared to be a viable treatment. This intervention has been shown to improve muscle strength and size in young, healthy people while utilising low exercise intensities. It was unclear however, if it was effective and safe in older people or individuals undergoing a period of disuse, as is common in OA. We therefore completed a systematic review and meta-analysis on this topic (Study three). Twenty-four studies, including a total of 485 individuals, were included. Findings suggested that BFR alone decreases the magnitude of strength loss associated with disuse. Furthermore, BFR training was found to be effective in improving strength and muscle size compared to matched low intensity exercise without BFR or a no intervention control. No difference was shown in treatment effects when comparing BFR to traditional high intensity strength training and there were few side effects associated with BFR. Thus, study four assessed the feasibility of BFR training in people with hand OA and compared training effects to a traditional high intensity strength training program (HIT). A six-week intervention was trialled and feasibility issues regarding recruitment potential were identified. These included regional differences in recruitment as well as potential for greater involvement of surgeons in the recruitment process. In patients who joined the study, compliance with treatment was good in both groups and after six weeks of training, pre-exercise joint pain reduced significantly. Both BFR and HIT rarely led to acute exacerbations in joint pain. Pinch strength improved significantly in both groups, while grip strength improved significantly in the BFR group only. The findings from this thesis suggest that people with hand OA present with both sensorimotor and muscle impairments but only grip strength was moderately associated with self-reported function. Both BFR and HIT appear effective in improving muscle strength and do not result in frequent pain exacerbations, with an overall decrease in pre-exercise joint pain intensity over the six-week training period, despite a progressive increase in training volume. Thus, in the future, an appropriately powered randomised controlled trial appears indicated and feasible, although additional strategies may be required to facilitate recruitment. Finally, although not explored in depth in this thesis, findings from study one suggest it is possible that interventions aiming at improving sensorimotor function may reduce symptoms and/or improve functional performance in people with hand OA. However, further research is required to explore these alternative treatment options

Phenomic Microglia Diversity as a Druggable Target in the Hippocampus in Neurodegenerative Diseases

Phenomics, the complexity of microglia phenotypes and their related functions compels the continuous study of microglia in disease animal models to find druggable targets for neurodegenerative disorders. Activation of microglia was long considered detrimental for neuron survival, but more recently it has become apparent that the real scenario of microglia morphofunctional diversity is far more complex. In this review, we discuss the recent literature on the alterations in microglia phenomics in the hippocampus of animal models of normal brain aging, acute neuroinflammation, ischemia, and neurodegenerative disorders, such as AD. Microglia undergo phenomic changes consisting of transcriptional, functional, and morphological changes that transform them into cells with different properties and functions. The classical subdivision of microglia into M1 and M2, two different, all-or-nothing states is too simplistic, and does not correspond to the variety of phenotypes recently discovered in the brain. We will discuss the phenomic modifications of microglia focusing not only on the differences in microglia reactivity in the diverse models of neurodegenerative disorders, but also among different areas of the brain. For instance, in contiguous and highly interconnected regions of the rat hippocampus, microglia show a differential, finely regulated, and region-specific reactivity, demonstrating that microglia responses are not uniform, but vary significantly from area to area in response to insults. It is of great interest to verify whether the differences in microglia reactivity may explain the differential susceptibility of different brain areas to insults, and particularly the higher sensitivity of CA1 pyramidal neurons to inflammatory stimuli. Understanding the spatiotemporal heterogeneity of microglia phenomics in health and disease is of paramount importance to find new druggable targets for the development of novel microglia-targeted therapies in different CNS disorders. This will allow interventions in three different ways: (i) by suppressing the pro-inflammatory properties of microglia to limit the deleterious effect of their activation; (ii) by modulating microglia phenotypic change to favor anti-inflammatory properties; (iii) by influencing microglia priming early in the disease process