Assessment of sow herd frequency of PCV-2 using placental umbilical cord serum and serology in 18 breeding farms in Brazil.

Porcine circovirus type 2 (PCV-2) is the agent of one of the most important diseases in the swine industry. Although it has been controlled through vaccination, viremic piglets at birth may represent a risk by reducing vaccination efficacy. Since there are few reports on the viremic status of pre-suckling piglets regarding PCV-2 infection, we assessed the PCV-2 frequency in sows housed in 18 breeding farms with no history of clinical PCVAD in Brazil, using placental umbilical cord serum (PUCS). The selection criteria were: breeding farms with more than 1,000 sows; sows not vaccinated for PCV-2 at least for 2 years prior to the study; farms with no history of PCV-2 clinical disease in the last 12 months; and production systems with a maximum of two sites. Blood from the umbilical cords in sow placenta or directly from piglet's immediately after birth was collected from 30 litters on each farm for PCR. In addition, blood from 538 sows was collected for PCV-2 antibody detection. A total of 17.29% of the PUCS tested positive. The PCV-2 DNA was detected in PUCS from 94.4% of all farms. A total of 94.8% of the sows was positive for PCV-2 antibodies. However, seronegative sows were detected in 44.4% of farms. All 18 farms had at least 46.9% seropositive dams. A higher percentage of seronegative sows was observed for farms with more than 10% of PCV-2-positive litters compared to those with ≤10% of PCV-2 positive litters (8.9 +/-1.7% vs. 1.5 +/- 0.7%, p < 0.01, respectively).

Glibenclamide-Loaded Engineered Nanovectors (GNVs) Modulate Autophagy and NLRP3-Inflammasome Activation.

Activation of the NLRP3 inflammasome in response to either exogenous (PAMPs) or endogenous (DAMPs) stimuli results in the production of IL-18, caspase-1 and IL-1ß. These cytokines have a beneficial role in promoting inflammation, but an excessive activation of the inflammasome and the consequent constitutive inflammatory status plays a role in human pathologies, including Alzheimer's disease (AD). Autophagic removal of NLRP3 inflammasome activators can reduce inflammasome activation and inflammation. Likewise, inflammasome signaling pathways regulate autophagy, allowing the development of inflammatory responses but preventing excessive and detrimental inflammation. Nanotechnology led to the development of liposome engineered nanovectors (NVs) that can load and carry drugs. We verified in an in vitro model of AD-associated inflammation the ability of Glibenclamide-loaded NVs (GNVs) to modulate the balance between inflammasome activation and autophagy. Human THP1dM cells were LPS-primed and oligomeric Aß-stimulated in the presence/absence of GNVs. IL-1ß, IL-18 and activated caspase-1 production was evaluated by the Automated Immunoassay System (ELLA); ASC speck formation (a marker of NLRP3 activation) was analyzed by FlowSight Imaging flow-cytometer (AMNIS); the expression of autophagy targets was investigated by RT-PCR and Western blot (WB); and the modulation of autophagy-related up-stream signaling pathways and Tau phosphorylation were WB-quantified. Results showed that GNVs reduce activation of the NLRP3 inflammasome and prevent the Aß-induced phosphorylation of ERK, AKT, and p70S6 kinases, potentiating autophagic flux and counteracting Tau phosphorylation. These preliminary results support the investigation of GNVs as a possible novel strategy in disease and rehabilitation to reduce inflammasome-associated inflammation.

TSPO Modulates Oligomeric Amyloid-ß-Induced Monocyte Chemotaxis: Relevance for Neuroinflammation in Alzheimer's Disease.

BACKGROUND: Neuroinflammation is one of the cardinal mechanisms of Alzheimer's disease (AD). with amyloid-ß (Aß) playing a critical role by activating microglia to produce soluble inflammatory mediators, including several chemokines. Peripheral monocytes are, therefore, attracted into the central nervous system (CNS), where they change into blood-born microglia and participate in the attempt of removing toxic Aß species. The translocator protein-18 kDa (TSPO) is a transmembrane protein overexpressed in response to neuroinflammation and known to regulate human monocyte chemotaxis. OBJECTIVE: We aimed to evaluate the role of the oligomeric Aß1-42 isoform at inducing peripheral monocyte chemotaxis, and the possible involvement of TSPO in this process. METHODS: In vitro cell lines, and ex vivo monocytes from consecutive AD patients (n = 60), and comparable cognitively intact controls (n = 30) were used. Chemotaxis analyses were carried out through both µ-slide chambers and Boyden assays, using 125 pM oligomeric Aß1-42 as chemoattractant. TSPO agonists and antagonists were tested (Ro5-4864, Emapunil, PK11195). RESULTS: Oligomeric Aß directly promoted chemotaxis in all our models. Interestingly, AD monocytes displayed a stronger response (about twofold) with respect to controls. Aß-induced chemotaxis was prevented by the TSPO antagonist PK11195; the expression of the TSPO and of the C-C chemokine receptor type 2 (CCR2) was unchanged by drug exposure. CONCLUSION: Oligomeric Aß1-42 is able to recruit peripheral monocytes, and we provide initial evidence sustaining a role for TSPO in modulating this process. This data may be of value for future therapeutic interventions aimed at modulating monocytes motility toward the CNS.

Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer's disease.

OBJECTIVE: The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients. METHODS: The study enrolled 70 AD patients and 74 cognitively normal controls comparable for age and sex. Lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF. RESULTS: AD patients have normal plasma lipids but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in the plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls but the content of small discoidal preß-HDL particles was significantly reduced. In agreement with the reduced preß-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients' plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aß1-42 CSF content. CONCLUSION: Taken together our data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aß1-42).

Value of Including the Children's Experience for Improving Their Rights During Hospitalization: Protocol for the VoiCEs Project.

BACKGROUND: Users' feedback is a key asset for organizations that want to improve their services. Studying how organizations are enabling their users to participate in evaluation activities is particularly important, especially when there are vulnerable or disadvantaged people, and the services to be evaluated can be life-changing. This is the case in the coassessment by pediatric patients experiencing hospital stay. The international literature reports a few attempts and several challenges in systematically collecting and using the pediatric patient experience with respect to hospitalization, to undertake quality improvement actions. OBJECTIVE: This paper describes the research protocol of a European project intended to develop and implement a systematic pediatric patient-reported experience measures (PREMs) observatory that will be shared by 4 European children's hospitals in Finland, Italy, Latvia, and the Netherlands. METHODS: The VoiCEs (Value of including the Children's Experience for improving their rightS during hospitalization) project uses a participatory action research approach, based on a mixture of qualitative and quantitative methods. It consists of 6 different phases, including a literature review, an analysis of the previous experiences of pediatric PREMs reported by project partners, a Delphi process, a cycle of focus groups or in-depth interviews with children and their caregivers, a series of workshops with interactive working groups, and a cross-sectional observational survey. The project guarantees the direct participation of children and adolescents in the development and implementation phases of the project. RESULTS: The expected results are (1) a deeper knowledge of published methodologies and tools on collecting and reporting pediatric patients' voice; (2) lessons learnt from the analysis of previous experiences of pediatric PREMs; a consensus reached through a participatory process (3) among experts, (4) pediatric patients and caregivers about a standard set of measures for the evaluation of hospitalization by patients; (5) the implementation of a European observatory on pediatric PREMs; and (6) the collection and comparative reporting of the pediatric patients' voice. In addition, the project is aimed at studying and proposing innovative methodologies and tools for capturing the pediatric patients' feedback directly, avoiding the intermediation of parents/guardians. CONCLUSIONS: Over the last decade, the collection and use of PREMs have gained importance as a research field. Children and adolescents' perspectives have also been increasingly taken into consideration. However, to date, there are limited experiences regarding the continuous and systematic collection and use of pediatric PREMs data for implementing timely improvement actions. In this perspective, the VoiCEs project provides room for innovation, by contributing to the creation of an international, continuous, and systematic pediatric PREMs observatory that can be joined by other children's hospitals or hospitals with pediatric patients, and foresees the return of usable and actionable data in benchmarking. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42804.

Relationship between dexamethasone treatment around parturition of primiparous sows and farrowing performance and newborn piglet traits.

This study evaluated the relationship between the steroidal anti-inflammatory action of dexamethasone treatment in primiparous sows and farrowing and piglet performance in the first 5 d of life. For this purpose, 234 gilts were selected on the day of farrowing and distributed among three treatments: CON - control, without dexamethasone treatment; DexaPF - treatment with dexamethasone (20 mg im) per female at the moment of copious colostrum secretion (pre-farrowing); and DexaFO - treatment with dexamethasone (20 mg im), per female when the first piglet was born (farrowing onset). All females and their litters were evaluated regarding farrowing duration, obstetric interventions, colostrum yield and intake, newborn piglet traits, and piglet performance until 5 d of age. A subsample of 79 females (∼26 per treatment) had their blood glucose concentration evaluated hourly shortly after the first piglet was born until the end of farrowing. Additionally, blood samples from 11 litters per treatment were collected for immunocrit evaluation. As a result, faster farrowing was observed in the DexaPF treatment (188.14 min; P = 0.002) compared with CON (229.99 min) and DexaFO (221.79 min). Additionally, lower obstetric intervention rates were observed in sows treated with dexamethasone (DexaPF = 7.69%; DexaFO = 5.13%) compared with CON (19.23%; P = 0.02). The sow's blood glucose concentration during farrowing was higher in DexaPF (90.55 mg/dL) than in CON (73.15 mg/dL) and DexaFO (80.06 mg/dL) treatments (P < 0.01). Besides the effect on farrowing duration, no differences among treatments were observed regarding piglets born alive and stillbirths, newborn piglet vitality, colostrum consumption, immunocrit, and colostrum yield (P ≥ 0.17). Regarding piglet traits, higher percentages of piglets born without meconium staining and lower percentages of piglets with meconium scores 2 and 3 were observed in the groups treated with dexamethasone (DexaPF and DexaFO; P < 0.01) compared with CON. However, piglet weight gain and survival rate until 5 d of age were not affected by the treatment (P ≥ 0.61). In summary, dexamethasone treatment before farrowing onset, in primiparous sows, had the potential to reduce the farrowing duration and the necessity of obstetric intervention, but it did not affect the main productive parameters such as the occurrence of stillbirths, piglet weight gain, and survival rates until 5 d of age.

Intravaginal devices impregnated with medroxyprogesterone acetate avoid early parturition and synchronize farrowing in sows.

Two experiments were performed to evaluate the use of an intravaginal device (IVD) impregnated with medroxyprogesterone acetate (MPA) to avoid early parturition and synchronize farrowing in sows. In both experiments with IVDs, the gestation length, stillbirth rate, birth weight, colostrum yield, lactational litter performance, and subsequent reproductive performance of sows were assessed. In Experiment 1 (Exp. 1; n = 91), sows were assigned to four treatments to evaluate the minimum required MPA dose: without IVD (CONT; control), 400 mg (MPA400), 600 mg (MPA600), and 800 mg (MPA800) of MPA in the IVD. The IVD was inserted on day 110 of gestation and removed on day 115. No sows farrowed during IVD treatment. Gestation length was increased in treatments with MPA (116.4 days) compared to the control (CONT; 114.9 days; P < 0.01), without effects on piglet birth weight (P = 0.98). A lower percentage of deaths around the farrow (P = 0.02) was observed in the CONT (1.8%) compared to MPA treatments (6.8%). The dose of 400 mg of MPA, validated in Exp. 1, was used in Experiment 2 (Exp. 2; n = 84) to evaluate the performance of sows and piglets in a sow farrowing synchronization protocol. Sows were treated with MPA from days 110-114 of gestation with or without 0.168 mg of cloprostenol sodium (PGF2α), for luteolysis induction, at IVD removal. Thus, four treatments were considered: CONT - without MPA or luteolysis induction (no interventions); PGF2α - luteolysis induction on day 114 of gestation without MPA; MPA114 - MPA treatment till 114 days of gestation without luteolysis induction; MPA114 + PGF2α - MPA treatment and luteolysis induction on day 114 of gestation. The gestation length in treatments with IVDs was longer (P < 0.01) than CONT without a difference for PGF2α treatment (P = 0.46). No impact of IVD use on piglet birth weight (P = 0.67) and deaths around the farrow (P = 0.50) were observed. The colostrum yield (P = 0.65), immunocrit (P = 0.72), piglet performance during lactation (P = 0.81), and weaning-to-estrus interval (P = 0.21) were similar among treatments. In conclusion, the use of IVDs impregnated with 400 mg of MPA between days 110 and 114 of gestation prevented early parturition with no implications for piglet survival at birth, colostrum yield, or litter performance.

Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review.

Background: The mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such treatment. A huge body of literature exists on possible predictors of response, but a comprehensive review is lacking. Therefore, our aim is to perform a systematic review of the predictors of response to AChEI in neurodegenerative dementias, providing a categorization and interpretation of the results. Methods: We conducted a systematic review of the literature up to December 31st, 2021, searching five different databases and registers, including studies on rivastigmine, donepezil, and galantamine, with clearly defined criteria for the diagnosis of dementia and the response to AChEI therapy. Records were identified through the string: predict * AND respon * AND (acetylcholinesterase inhibitors OR donepezil OR rivastigmine OR galantamine). The results were presented narratively. Results: We identified 1,994 records in five different databases; after exclusion of duplicates, title and abstract screening, and full-text retrieval, 122 studies were finally included. Discussion: The studies show high heterogeneity in duration, response definition, drug dosage, and diagnostic criteria. Response to AChEI seems associated with correlates of cholinergic deficit (hallucinations, fluctuating cognition, substantia innominate atrophy) and preserved cholinergic neurons (faster alpha on REM sleep EEG, increased anterior frontal and parietal lobe perfusion after donepezil); white matter hyperintensities in the cholinergic pathways have shown inconsistent results. The K-variant of butyrylcholinesterase may correlate with better response in late stages of disease, while the role of polymorphisms in other genes involved in the cholinergic system is controversial. Factors related to drug availability may influence response; in particular, low serum albumin (for donepezil), CYP2D6 variants associated with reduced enzymatic activity and higher drug doses are the most consistent predictors, while AChEI concentration influence on clinical outcomes is debatable. Other predictors of response include faster disease progression, lower serum cholesterol, preserved medial temporal lobes, apathy, absence of concomitant diseases, and absence of antipsychotics. Short-term response may predict subsequent cognitive response, while higher education might correlate with short-term good response (months), and long-term poor response (years). Age, gender, baseline cognitive and functional levels, and APOE relationship with treatment outcome is controversial.

Eosinophilic Granulomatous Myocarditis in Two Pigs.

Eosinophilic myocarditis is a human condition that has been rarely documented in animals. We now report two unrelated porcine cases of idiopathic eosinophilic granulomatous myocarditis that resembled the human disease and which were associated with sudden death. The most relevant gross finding in both cases was marked cardiomegaly, accompanied by raised, multifocal to coalescent small white nodules (1-2 mm) and poorly demarcated multifocal pale areas in the epicardium. Histologically, there were multifocal to coalescent areas of cardiomyocyte loss with replacement by an intense inflammatory infiltrate of eosinophils and epithelioid macrophages, and proliferation of fibrous connective tissue. Immunohistochemistry for porcine circovirus type 2 (PCV2) and Toxoplasma gondii, in-situ hybridization and quantitative polymerase chain reaction tests for PCV2 and porcine circovirus type 3 and aerobic bacterial culture on myocardium samples were negative.

Effect of sow mass vaccination against Mycoplasma hyopneumoniae on the humoral immune response of newborn piglets.

Pneumonia caused by Mycoplasma (M.) hyopneumoniae is one of the major respiratory diseases in swine production. Commercial vaccines for M. hyopneumoniae are widely used in weaned piglets to reduce lung lesions and clinical signs in the downstream flow; however, no information regarding the effect of mass immunization of the breeding herd is available. The aim of this work was to evaluate a mass vaccination protocol for M. hyopneumoniae on the humoral response of sows and their offspring 24 h post-partum (trial registration number 40156). A total of 52 sows from two different farms (13 primiparous and 13 multiparous sows on each farm), one with mass vaccination (MVF) and one without mass vaccination against M. hyopneumoniae (control farm (CF)) were enrolled in this study. Five piglets from each litter were selected, resulting in 260 piglets. Blood was collected from sows and piglets 24 h post-partum for M. hyopneumoniae antibody detection by ELISA. The results showed that primiparous sows from MVF had higher antibody titers compared to multiparous sows of the same farm, and multiparous and primiparous sows from the CF. Similar results were evidenced in their offspring. The findings of this study suggest that mass vaccination results in a more robust serologic response on primiparous sows, which could be the main target of vaccination strategies for the breeding herd.

Modulation of MAPK- and PI3/AKT-Dependent Autophagy Signaling by Stavudine (D4T) in PBMC of Alzheimer's Disease Patients.

BACKGROUND: Aß42 deposition plays a pivotal role in AD pathogenesis by inducing the activation of microglial cells and neuroinflammation. This process is antagonized by microglia-mediated clearance of Aß plaques. Activation of the NLRP3 inflammasome is involved in neuroinflammation and in the impairments of Aß-plaque clearance. On the other hand, stavudine (D4T) downregulates the NLRP3 inflammasome and stimulates autophagy-mediated Aß-clearing in a THP-1-derived macrophages. METHODS: We explored the effect of D4T on Aß autophagy in PBMC from AD patients that were primed with LPS and stimulated with Aß oligomers in the absence/presence of D4T. We analyzed the NLRP3 activity by measuring NLRP3-ASC complex formation by AMNIS FlowSight and pro-inflammatory cytokine (IL-1ß, IL-18 and Caspase-1) production by ELISA. The phosphorylation status of p38, ERK, AKT, p70, and the protein expression of CREB, LAMP2A, beclin-1, Caspase-3 and Bcl2 were analyzed by Western blot. RESULTS: Data showed that D4T: (1) downregulates NLRP3 inflammasome activation and the production of down-stream pro-inflammatory cytokines in PBMC; (2) stimulates the phosphorylation of AKT, ERK and p70 as well as LAMP2A, beclin-1 and Bcl2 expression and reduces Caspase-3 expression, suggesting an effect of this compound on autophagy; (3) increases phospho-CREB, which is a downstream target of p-ERK and p-AKT, inducing anti-inflammatory cytokine production and resulting in a possible decrease of Aß-mediated cytotoxicity; and (4) reduces the phosphorylation of p38, a protein involved in the production of pro-inflammatory cytokines and tau hyperphosphorylation. CONCLUSIONS: D4T reduces the activation of the NLRP3 inflammasome, and it might stimulate autophagy as well as the molecular mechanism that modulates Aß cytotoxicity, and D4T might reduce inflammation in the cells of AD patients. It could be very interesting to check the possible beneficial effects of D4T in the clinical scenario.

Effect of parity segregation on Mycoplasma hyopneumoniae infection dynamics and pneumonic lesions in pigs / Efeito da ordem de parto segregada sobre a dinâmica de infecção de Mycoplasma hyopneumoniae e lesões pulmonares ao abate

Gilts represent a group risk for Mycoplasma hyopneumoniae vertical transmission in swine herds. Therefore, parity segregation can be an alternative to control M. hyopneumoniae infections. The study evaluated the effect of parity segregation on M. hyopneumoniae infection dynamics and occurrence and severity of lung lesions at slaughter. For that, three multiple site herds were included in the study. Herd A consisted of the farm where gilts would have their first farrowing (parity order (PO) 1). After the first farrowing PO 1 sows were transferred to herd B (PO2-6). Herd C was a conventional herd with gilt replacement (PO1-6). Piglets born in each herd were raised in separated nursery and finishing units. Sows (n = 33 (A), 37 (B), 34 (C)) in all herds were sampled prior to farrowing and piglets (n = 54 (A), 71 (B), 66 (C)) were sampled longitudinally at 21, 63, 100, 140 days of age and at slaughter for M. hyopneumoniae detection by PCR and lung lesions scoring. M. hyopneumoniae prevalence in sows did not differ among herds. Prevalence of positive piglets was higher at weaning in the PO1 herd (A) (P < 0.05). However, prevalence of positive pigs from 100 days of age to slaughter age was higher in the PO2-6 herd (B) (P < 0.05). Lung lesion occurrence and severity were higher in herd B. The authors suggested that the lack of a proper gilt acclimation might have influenced the results, leading to sows being detected positive at farrowing, regardless of the parity.

As leitoas consistem em um grupo de risco na transmissão vertical de Mycoplasma hyopneumoniae dentro do sistema de produção de suínos. Dessa forma, a segregação de partos poderia ser utilizada como alternativa para controlar as infecções por M. hyopneumoniae. O objetivo deste estudo foi avaliar o efeito da segregação de partos sobre a dinâmica de infecção de M. hyopneumoniae e a ocorrência e severidade das lesões pulmonares ao abate. Para isso três sistemas de produção de suínos com três sítios cada foram incluídos no estudo. A granja A consistia da unidade onde as leitoas tem o primeiro parto, ou seja, alojava somente de fêmeas de ordem de parto 1 (Granja OP1). Após o primeiro parto as fêmeas OP1 foram transferidas para a granja B (Granja OP2-6), ou seja, consistia de fêmeas de ordem de parto 2 a 6, e a granja C consistiu em uma granja convencional com reposição de leitoas (Granja OP1-6), com fêmeas de ordem de parto 1 a 6. Os leitões nascidos de cada granja foram transferidos e criados em creches e terminações segregadas. As matrizes (n = 33 (A), 37 (B), 34 (C)) de todas as granjas do estudo foram amostradas previamente ao parto e os leitões (n = 54 (A), 71 (B), 66 (C)) foram amostrados longitudinalmente aos 21, 63, 100 e 140 dias de idade e ao abate. Em todos os momentos de coleta, as amostras foram avaliadas por PCR para detecção de M. hyopneumoniae. As lesões pulmonares foram avaliadas e escores de lesão foram atribuídos ao abate. A prevalência de matrizes positivas para M. hyopneumoniae não diferiu entre as granjas (P > 0,05). A prevalência ao desmame foi maior na granja A (OP1) (P < 0,05). No entanto, dos 100 dias de idade até o abate a prevalência de leitões positivos para M. hyopneumoniae foi maior na granja B (OP2-6) (P < 0,05). A ocorrência e severidade de lesões pulmonares foram maiores na granja B. Os autores sugerem que a falta de uma aclimatação adequada das leitoas pode ter influenciado nos resultados, levando à detecção de matrizes positivas ao parto, independente da ordem de parto.

Correction: De Conti et al. Histological Lesions and Replication Sites of PCV3 in Naturally Infected Pigs. Animals 2021, 11, 1520.

The authors wish to make the following correction to this paper [...].

Blood-Based Biomarkers of Neuroinflammation in Alzheimer's Disease: A Central Role for Periphery?

Neuroinflammation represents a central feature in the development of Alzheimer's disease (AD). The resident innate immune cells of the brain are the principal players in neuroinflammation, and their activation leads to a defensive response aimed at promoting ß-amyloid (Aß) clearance. However, it is now widely accepted that the peripheral immune system-by virtue of a dysfunctional blood-brain barrier (BBB)-is involved in the pathogenesis and progression of AD; microglial and astrocytic activation leads to the release of chemokines able to recruit peripheral immune cells into the central nervous system (CNS); at the same time, cytokines released by peripheral cells are able to cross the BBB and act upon glial cells, modifying their phenotype. To successfully fight this neurodegenerative disorder, accurate and sensitive biomarkers are required to be used for implementing an early diagnosis, monitoring the disease progression and treatment effectiveness. Interestingly, as a result of the bidirectional communication between the brain and the periphery, the blood compartment ends up reflecting several pathological changes occurring in the AD brain and can represent an accessible source for such biomarkers. In this review, we provide an overview on some of the most promising peripheral biomarkers of neuroinflammation, discussing their pathogenic role in AD.

Histological Lesions and Replication Sites of PCV3 in Naturally Infected Pigs.

Porcine circovirus type 3 (PCV3) has been recently described as a potential cause of abortions and systemic vasculitis in pigs. Although the virus has been detected by real-time PCR in several porcine tissues from countries worldwide, PCV3-associated diseases have not been satisfactorily clarified. The objective of this study was to investigate the association between the presence of PCV3 mRNA detected by in situ hybridization (ISH) within histological lesions and PCV3 DNA detected by real-time PCR in naturally infected pigs. A total of 25 PCV3 PCR-positive cases were analyzed. Formalin-fixed tissues from these cases were evaluated for histologic lesions and for ISH-RNA positive signals for PCV3. The most frequent tissue type with histopathologic lesions was heart, 76.2%, with lymphoplasmacytic myocarditis and epicarditis as the most frequent lesions observed. Lymphoplasmacytic interstitial pneumonia was also a frequent finding, 47.6%. There were also lesions in kidney, liver, spleen and lymph nodes. PCV3-ISH-RNA positive signals were mostly observed in association with lymphoplasmacytic inflammatory infiltrate in various tissues, including arteries. Based on our results, the minimum set of specimens to be submitted for histopathology and mRNA in situ hybridization to confirm or exclude a diagnosis of PCV3 are heart, lung and lymphoid tissues (i.e., spleen and lymph nodes), especially for differential diagnosis related with PCV2-associated diseases.

Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) patients express significant clinical heterogeneity that often hinders a correct diagnostic definition. Intracellular deposition of TDP-43, a protein involved in RNA metabolism characterizes the pathology. Interestingly, this protein can be detected in serum, wherein cognate naturally-occurring auto-antibodies (anti-TDP-43 NAb) might be also present, albeit they have never been documented before. In this exploratory study, we quantified the levels of both anti-TDP-43 NAb and TDP-43 protein as putative accessible markers for improving the ALS diagnostic process by using ELISA in N = 70 ALS patients (N = 4 carrying TARDBP mutations), N = 40 age-comparable healthy controls (CTRL), N = 20 motor neuron disease mimics (MN-m), N = 20 Alzheimer's disease (AD) and N = 15 frontotemporal lobar degeneration (FTLD) patients. Anti-TDP-43 NAb were found to be significantly increased in ALS patients compared to all the other groups (p < 0.001). On the other hand, the distribution of serum levels of TDP-43 protein was highly variable among the various groups. Levels were increased in ALS patients, albeit the highest values were detected in MN-m patients. NAb and protein serum levels failed to correlate. For the first time, we report that serum anti-TDP-43 NAb are detectable in human serum of both healthy controls and patients affected by a variety of neurodegenerative disorders; furthermore, their levels are increased in ALS patients, representing a potentially interesting trait core marker of this disease. Further studies are needed to clarify the exact role of the NAb. This information might be extremely useful for paving the way toward targeting TDP-43 by immunotherapy in ALS.

Efficacy of the DigniCap System in preventing chemotherapy-induced alopecia in breast cancer patients is not related to patient characteristics or side effects of the device.

BACKGROUND: The DigniCap System is an effective scalp cooling device for the prevention of chemotherapy-induced alopecia in early breast cancer patients. AIM: This prospective study was designed to confirm the efficacy and tolerability of the device, to explore potential factors associated with its efficacy and to collect data on patient perceptions and satisfaction. METHODS: Between January 2016 and June 2018, 163 early breast cancer patients eligible for adjuvant chemotherapy were enrolled. Hair loss was assessed using the Dean scale, where a score of 0-2 (hair loss ≤50%) was defined as successful. RESULTS: Hair preservation was successful in 57% of patients in the overall series. The proportion was even higher (81%) in the patient subgroup treated with a paclitaxel and trastuzumab regimen. Side effects (feeling cold, headache, head heaviness, scalp and cervical pain) were mild to moderate and did not correlate with the rate of hair loss. Lifestyle, anthropometric factors and hair characteristics failed to be associated with device efficacy. CONCLUSIONS: The DigniCap System was well tolerated and found to be effective in preventing alopecia in early breast cancer patients. Our study failed to identify factors other than type of chemotherapy regimen associated with hair preservation.

Serum DBI and biomarkers of neuroinflammation in Alzheimer's disease and delirium.

BACKGROUND: Alzheimer's disease (AD) patients often express significant behavioral symptoms: for this reason, accessible related biomarkers could be very useful. Neuroinflammation is a key pathogenic process in both AD and delirium (DEL), a clinical condition with behavioral symptoms resembling those of AD. METHODS: A total of n = 30 AD patients were recruited together with n = 30 DEL patients and n = 15 healthy controls (CTRL). Serum diazepam binding inhibitor (DBI), IL-17, IL-6, and TNF-α were assessed by ELISA. RESULTS: DBI serum levels were increased in AD patients with respect to CTRL (+ 81%), while DEL values were 70% higher than AD. IL-17 was increased in DEL with respect to CTRL (+ 146%), while AD showed dispersed values and failed to reach significant differences. On the other hand, IL-6 showed a more robust increase in DEL with respect to the other two groups (+ 185% and + 205% vs. CTRL and AD, respectively), and TNF-α failed to show any change. CONCLUSIONS: DBI may be a very promising candidate for AD, perhaps marking psychomotor DEL-like symptoms, in view of developing future helping tool for practicing physicians. Furthermore, DBI rise in DEL offers novel cues for a better comprehension of the pathogenesis of this potentially fatal condition.

Agents of pneumonia in slaughtered pigs in southern Brazil / Agentes patogênicos de pneumonia em suínos abatidos no sul do Brasil

A high prevalence of pneumonic lesions has been reported to affect slaughtered pigs in southern Brazil. In order to identify which microorganisms have been causing those lesions, 30 pig lungs presenting pneumonic gross lesions were collected from five different slaughterhouses, totaling 150 lungs. Samples for bacterial isolation, molecular, histopathologic and immunohistochemistry (IHC) evaluation were taken from each lung. The pneumonic lesion scoring ranged from 1.53 to 2.83. The most frequent histopathological lesions found was the concomitant Influenza A virus (IAV) and Mycoplasma hyopneumoniae infection, corresponding to 55.3% (83/150), and Pasteurella multocida type A was isolated in 54.2% (45/83) of these cases. In 102 samples (68%), there was histopathologic suggestion of involvement of more than one infectious agent. M. hyopneumoniae was the most frequent agent associated with pneumonic lesions, being present in 92.1% (94/102) of the lungs with coinfections, followed by IAV in 89.2% (91/102). Besides the coinfections, IAV lesions were observed also in six samples without another pathogenic microorganism detected. A total of 46 samples with acute and subacute IAV suspected lesions in histopathological examination were assessed for IHC and real time RT-PCR for IAV. A total of 35% (16/46) of them were positive by IHC and 13% (6/46) by real time RT-PCR. Regarding M. hyopneumoniae, 79.3% (119/150) of samples were positive by qPCR and 84.9% (101/119) of them also presented M. hyopneumoniae suspected lesions in the histopathological examination. The results of this study suggest the importance of IAV in respiratory diseases in finishing pigs, even though this virus is more frequently reported in the nursery phase. In addition, our results emphasize the importance of lung coinfections in finishing pigs.(AU)

Lesões sugestivas de pneumonia são frequentemente encontradas em altas prevalências em suínos abatidos no sul do Brasil. Para identificar quais microrganismos causam essas lesões, foram coletados 30 pulmões de suínos com lesão macroscópica sugestiva de pneumonia em cinco frigoríficos diferentes, totalizando 150 pulmões. Amostras para isolamento bacteriano, avaliação molecular, histopatológica e imuno-histoquímica (IHC) foram coletadas de cada pulmão. O escore de lesão pulmonar variou entre 1,53 a 2,83. O achado histopatológico mais observado foi a lesão sugestiva de infecção concomitante pelo vírus Influenza A (IAV) e Mycoplasma (M.) hyopneumoniae, correspondendo a 55,3% (83/150), e em 54,2% (45/83) desses casos Pasteurella (P.) multocida tipo A foi isolado. Em 102 amostras (68%), houve lesão histopatológica sugestiva do envolvimento de mais de um agente infeccioso. M. hyopneumoniae foi o microrganismo mais frequente associado a lesões de pneumonia, estando presente em 92,1% (94/102) dos pulmões com coinfecções, seguido de IAV, que foi encontrado em 89,2% (91/102). Além das coinfecções, lesões de IAV foram observadas em mais seis amostras que não aparentavam envolvimento de outro agente infeccioso. Um total de 46 amostras com suspeita de lesão aguda e subaguda de IAV no exame histopatológico foram avaliadas para IHC e RT-PCR em tempo real para IAV e 35% (16/46) delas foram positivas por IHC e 13% (6/46) foram positivas por RT-PCR em tempo real. Com relação a M. hyopneumoniae, 79,3% (119/150) das amostras foram positivas por qPCR e 84,9% (101/119) delas também apresentaram lesões suspeitas de M. hyopneumoniae no exame histopatológico. Os resultados deste trabalho sugerem a importância do IAV como agente causador de pneumonias em suínos de terminação, embora esse vírus seja mais frequentemente relatado na fase de creche. Além disso, os achados deste trabalho demonstram a presença frequente de coinfecções pulmonares em suínos de terminação.(AU)

Agents of pneumonia in slaughtered pigs in southern Brazil

ABSTRACT: A high prevalence of pneumonic lesions has been reported to affect slaughtered pigs in southern Brazil. In order to identify which microorganisms have been causing those lesions, 30 pig lungs presenting pneumonic gross lesions were collected from five different slaughterhouses, totaling 150 lungs. Samples for bacterial isolation, molecular, histopathologic and immunohistochemistry (IHC) evaluation were taken from each lung. The pneumonic lesion scoring ranged from 1.53 to 2.83. The most frequent histopathological lesions found was the concomitant Influenza A virus (IAV) and Mycoplasma hyopneumoniae infection, corresponding to 55.3% (83/150), and Pasteurella multocida type A was isolated in 54.2% (45/83) of these cases. In 102 samples (68%), there was histopathologic suggestion of involvement of more than one infectious agent. M. hyopneumoniae was the most frequent agent associated with pneumonic lesions, being present in 92.1% (94/102) of the lungs with coinfections, followed by IAV in 89.2% (91/102). Besides the coinfections, IAV lesions were observed also in six samples without another pathogenic microorganism detected. A total of 46 samples with acute and subacute IAV suspected lesions in histopathological examination were assessed for IHC and real time RT-PCR for IAV. A total of 35% (16/46) of them were positive by IHC and 13% (6/46) by real time RT-PCR. Regarding M. hyopneumoniae, 79.3% (119/150) of samples were positive by qPCR and 84.9% (101/119) of them also presented M. hyopneumoniae suspected lesions in the histopathological examination. The results of this study suggest the importance of IAV in respiratory diseases in finishing pigs, even though this virus is more frequently reported in the nursery phase. In addition, our results emphasize the importance of lung coinfections in finishing pigs.

RESUMO: Lesões sugestivas de pneumonia são frequentemente encontradas em altas prevalências em suínos abatidos no sul do Brasil. Para identificar quais microrganismos causam essas lesões, foram coletados 30 pulmões de suínos com lesão macroscópica sugestiva de pneumonia em cinco frigoríficos diferentes, totalizando 150 pulmões. Amostras para isolamento bacteriano, avaliação molecular, histopatológica e imuno-histoquímica (IHC) foram coletadas de cada pulmão. O escore de lesão pulmonar variou entre 1,53 a 2,83. O achado histopatológico mais observado foi a lesão sugestiva de infecção concomitante pelo vírus Influenza A (IAV) e Mycoplasma (M.) hyopneumoniae, correspondendo a 55,3% (83/150), e em 54,2% (45/83) desses casos Pasteurella (P.) multocida tipo A foi isolado. Em 102 amostras (68%), houve lesão histopatológica sugestiva do envolvimento de mais de um agente infeccioso. M. hyopneumoniae foi o microrganismo mais frequente associado a lesões de pneumonia, estando presente em 92,1% (94/102) dos pulmões com coinfecções, seguido de IAV, que foi encontrado em 89,2% (91/102). Além das coinfecções, lesões de IAV foram observadas em mais seis amostras que não aparentavam envolvimento de outro agente infeccioso. Um total de 46 amostras com suspeita de lesão aguda e subaguda de IAV no exame histopatológico foram avaliadas para IHC e RT-PCR em tempo real para IAV e 35% (16/46) delas foram positivas por IHC e 13% (6/46) foram positivas por RT-PCR em tempo real. Com relação a M. hyopneumoniae, 79,3% (119/150) das amostras foram positivas por qPCR e 84,9% (101/119) delas também apresentaram lesões suspeitas de M. hyopneumoniae no exame histopatológico. Os resultados deste trabalho sugerem a importância do IAV como agente causador de pneumonias em suínos de terminação, embora esse vírus seja mais frequentemente relatado na fase de creche. Além disso, os achados deste trabalho demonstram a presença frequente de coinfecções pulmonares em suínos de terminação.