Update on acute disseminated encephalomyelitis in children and adolescents

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated, inflammatory demyelinating disease of the central nervous system (CNS) that usually affects children and young adults after an infection or vaccination. The presence of several conditions mimicking ADEM, added to the lack of specific biomarkers, makes diagnosis potentially hard. Prompt diagnosis is necessary to start adequate treatment to improve the clinical course and long-term outcome. Because of its heterogeneity in both clinical presentation and course, challenges remain in establishing the most appropriate therapeutic approach in each patient. The aim of this review is to provide an update on management of this disease with a focus on acute treatment and to give suggestions for future research. We showed that there are currently no guidelines that help clinicians manage ADEM and therapeutic decisions are often made on a case-by-case basis. Further studies are necessary to identify clinical, laboratory, and instrumental criteria that could be correlated with outcomes and guide clinicians in choosing when and what treatment should be given in each case

The role of micronutrients in support of the immune response against viral infections

Viral infections are a leading cause of morbidity and mortality worldwide, and the importance of public health practices including handwashing and vaccinations in reducing their spread is well established. Furthermore, it is well known that proper nutrition can help support optimal immune function, reducing the impact of infections. Several vitamins and trace elements play an important role in supporting the cells of the immune system, thus increasing the resistance to infections. Other nutrients, such as omega-3 fatty acids, help sustain optimal function of the immune system. The main aim of this manuscript is to discuss of the potential role of micronutrients supplementation in supporting immunity, particularly against respiratory virus infections. Literature analysis showed that in vitro and observational studies, and clinical trials, highlight the important role of vitamins A, C, and D, omega-3 fatty acids, and zinc in modulating the immune response. Supplementation with vitamins, omega 3 fatty acids and zinc appears to be a safe and low-cost way to support optimal function of the immune system, with the potential to reduce the risk and consequences of infection, including viral respiratory infections. Supplementation should be in addition to a healthy diet and fall within recommended upper safety limits set by scientific expert bodies. Therefore, implementing an optimal nutrition, with micronutrients and omega-3 fatty acids supplementation, might be a cost-effective, underestimated strategy to help reduce the burden of infectious diseases worldwide, including coronavirus disease 2019 (COVID-19)

New antibiotics for the treatment of acute bacterial skin and soft tissue infections in pediatrics

Acute bacterial skin and soft tissue infections (aSSTIs) are a large group of diseases that can involve exclusively the skin or also the underlying subcutaneous tissues, fascia, or muscles. Despite differences in the localization and severity, all these diseases are due mainly to Gram-positive bacteria, especially Staphylococcus aureus and Streptococcus pyogenes. aSSTI incidence increased considerably in the early years of this century due to the emergence and diffusion of community-acquired methicillin-resistant S. aureus (CA-MRSA). Despite the availability of antibiotics effective against CA-MRSA, problems of resistance to these drugs and risks of significant adverse events have emerged. In this paper, the present knowledge on the potential role new antibiotics for the treatment of pediatric aSSTIs is discussed. The most recent molecules that have been licensed for the treatment of aSSTIs include ozenoxacin (OZ), ceftaroline fosamil (CF), dalbavancin (DA), oritavancin (OR), tedizolid (TD), delafloxacin (DL), and omadacycline (OM). However, only OZ and CF have been licensed for use in children with aSSTIs, although the superiority of these antibiotics to those routinely used for the treatment of aSSTIs should be further demonstrated. Waiting for additional studies, OZ and CF should be prescribed for aSSTI treatment in the presence of the potential failure of old molecules

Therapeutic perspectives in food allergy

Background: In the last twenty years, several studies have been conducted in the search for new therapeutic strategies in patients with food allergy; in particular, after the failure of injection immunotherapy, three different routes of administration, oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT), have been tested. The aim of this manuscript is to review OIT, SLIT, and EPIT clinical trials on food allergies and to suggest advantages and limits of the different routes of immunotherapy administration. Main body: Of the three different routes of immunotherapy used in the treatment of food allergy, OIT is, at present, the only one actually able to induce an increase in tolerance in the majority of patients. However, its use is affected by serious secondary effects, such as major abdominal symptoms and anaphylaxis. The combination with omalizumab reduces the percentage of serious side effects. There are not many studies with SLIT for food allergy, but they have nevertheless shown that it is possible to obtain an increase in tolerance; however, this increase is modest in comparison with that obtained by OIT. EPIT, performed through the diffusion of allergens on intact skin, is the most recent form of immunotherapy. Although there are many works on EPIT carried out in laboratory animals, only few clinical studies have been published in humans. EPIT, unlike OIT and SLIT, is not responsible for systemic secondary effects such as anaphylaxis and eosinophilic oesophagitis but only for local and mild effects in areas where the devices are applied. Moreover, EPIT is characterized by high patient adherence. Conclusion: OIT seems to have a prevalent application in patients who do not report previous symptoms of systemic or gastroenteric anaphylaxis, while SLIT and EPIT, in particular, could be more preferentially used in patients with a risk of anaphylaxis

Prevention of clostridium difficile infection and associated diarrhea: An unsolved problem

For many years, it has been known that Clostridium difficile (CD) is the primary cause of health-care-associated infectious diarrhea, afflicting approximately 1% of hospitalized patients. CD may be simply carried or lead to a mild disease, but in a relevant number of patients, it can cause a very severe, potentially fatal, disease. In this narrative review, the present possibilities of CD infection (CDI) prevention will be discussed. Interventions usually recommended for infection control and prevention can be effective in reducing CDI incidence. However, in order to overcome limitations of these measures and reduce the risk of new CDI episodes, novel strategies have been developed. As most of the cases of CDI follow antibiotic use, attempts to rationalize antibiotic prescriptions have been implemented. Moreover, to reconstitute normal gut microbiota composition and suppress CD colonization in patients given antimicrobial drugs, administration of probiotics has been suggested. Finally, active and passive immunization has been studied. Vaccines containing inactivated CD toxins or components of CD spores have been studied. Passive immunization with monoclonal antibodies against CD toxins or the administration of hyperimmune whey derived from colostrum or breast milk from immunized cows has been tried. However, most advanced methods have significant limitations as they cannot prevent colonization and development of primary CDI. Only the availability of vaccines able to face these problems can allow a resolutive approach to the total burden due to this pathogen

Follicular development, plasma Inhibin-A and Estradiol-17-beta concentrations in Buffalo cows during different treatment schedules for MOET programs

Buffalo cows were submitted to three superovulatory treatments. T1 (n = 7): PRID for 10 days (d0-d9) plus decreasing doses of 500 IU FSH/LH (12 h-intervals d7‑d10); T2 (n = 8): PRID for 11 d (d0-d10) plus 2000 IU PMSG at d7; T3 (n = 9): PRID for 11 d plus 2000 IU PMSG at d7 and decreasing doses of 175 IU FSH/LH (12 h-intervals d10‑ d11). Overall plasma inhibin‑A (In-A) concentrations correlated with large follicles (LF, diameter >6mm, R=0.83, P10 mm at d12- 13 (T1=5.0+/-1.4, T2=1.2+/-0.9, T3=8.3+/-2.3). In-A concentrations significantly rised at d11-13 of T1 and T3. In-A seems a good indicator of the follicular development during superovulation in buffalo cows, while E2 is not. Furthermore T3 was followed by better ovarian follicular responses

GRADES: Gradient descent for similarity caching

A similarity cache can reply to a query for an object with similar objects stored locally. In some applications of similarity caches, queries and objects are naturally represented as points in a continuous space. Examples include 360° videos where user's head orientation - expressed in spherical coordinates - determines what part of the video needs to be retrieved, and recommendation systems where the objects are embedded in a finite-dimensional space with a distance metric to capture content dissimilarity. Existing similarity caching policies are simple modifications of classic policies like LRU, LFU, and qLRU and ignore the continuous nature of the space where objects are embedded. In this paper, we propose Grades, a new similarity caching policy that uses gradient descent to navigate the continuous space and find the optimal objects to store in the cache. We provide theoretical convergence guarantees and show Grades increases the similarity of the objects served by the cache in both applications mentioned above

Exploiting machine learning methods with monthly routine milk recording data and climatic information to predict subclinical mastitis in Italian Mediterranean buffaloes

: Mastitis has detrimental effects on the world's dairy industry, reducing animal health, milk production and quality, as well as income for farmers. In addition, consumers' growing interest in food safety and rational usage of antibiotics highlights the need to develop novel strategies to improve mastitis detection, prevention, and management. In the present study we applied machine learning (ML) analyses to predict presence or absence of subclinical mastitis in Italian Mediterranean buffaloes, exploiting information collected the previous month during routine milk recording procedures, as well as climatic data. The data set included 3,891 records of 1,038 buffaloes from 6 herds located in Basilicata Region (South Italy). Prediction models were developed using 4 different ML algorithms (Generalized Linear Model, Support Vector Machines, Random Forest, and Neural Network) and 2 data set splitting approaches for the creation of the training and test sets (by record or by animal ID number, always with 80% of the data used for model training and the remaining 20% for model testing). Support Vector Machine was the best method to predict high or low somatic cell count at the subsequent test-day record in the validation set, and therefore it was used to estimate the contribution of each feature to the best model. Independently from the data set splitting approach, the most important features were somatic cell score, differential somatic cell count, electrical conductivity, and milk production. Among climatic data, the most informative were temperature and relative humidity. When the data were split by animal ID, an improvement in models' predictive performance on the test set was observed, suggesting this as the most appropriate data splitting approach in data sets with repeated measures to avoid data leakage. According to different metrics, Neural Network was the best method for making predictions on the test set. Our findings confirmed the promising role of ML methods to improve prevention and surveillance of subclinical mastitis, exploiting the large amount of data currently available to identify animals that would possibly have high somatic cell count the subsequent month

Exploring the sources of variation of electrical conductivity, total and differential somatic cell count in the Italian Mediterranean Buffaloes

: In the buffalo dairy sector, a huge effort is still needed to improve mastitis prevention, detection and management. Electrical conductivity (EC) and total somatic cell count (SCC) are well-known indirect indicators of mastitis. Differential somatic cell count (DSCC), which represents the proportion of neutrophils and lymphocytes on the total SCC, is instead a novel phenotype collected in the dairy cattle sector in the last lustrum. As little is known about this novel trait in dairy buffalo, in the present study we explored the non-genetic factors affecting DSCC, as well as EC and total somatic cell score (SCS), in the Italian Mediterranean Buffalo. The data set used for the analysis included 14,571 test-day (TD) records of 1,501 animals from 6 herds, and climatic information of the sampling locations. The original data were filtered to exclude animals with less than 3 TD/lactation and, for the investigated traits, outliers beyond 4 standard deviations. In the statistical model we included the fixed effects of herd (6 classes), days in milk (10 classes of 30 d, with the last being an open class until 360 d), parity (6 classes, from 1 to 6+), year-season of calving (11 classes, from Summer 2019 to Winter 2021/2022), year-season of sampling (9 classes, from Spring 2020 to Spring 2022), production level (4 classes based on quartiles of average milk yield by herd), and temperature-humidity index (THI; 4 classes based on quartiles, calculated using the average temperature and relative humidity of the 5 d before sampling). Averages EC, SCS and DSCC vary across herds. Considering days in milk, greater EC values were observed at the beginning and the end of lactation; SCS was slightly lower but DSCC was greater around the lactation peak. Increased EC, SCS, and DSCC levels with increasing parity were reported. Year-season calving and year-season sampling only slightly affected the variation of the investigated traits. Milk of highly producing buffaloes was characterized by lower EC and SCS mean values, nevertheless it had slightly greater DSCC percentages. Buffaloes grouped in the highest THI classes (classes 3 and 4) showed, on average, greater EC, SCS and DSCC in comparison to the lower classes, especially to class 2. Results of the present study represent a preliminary as well as necessary step for the possible future inclusion of EC, SCS and/or DSCC in breeding programs aimed to improve mastitis resistance in dairy buffaloes

GRADES: Gradient descent for similarity caching

International audienceA similarity cache can reply to a query for an object with similar objects stored locally. In some applications of similarity caches, queries and objects are naturally represented as points in a continuous space. Examples include 360° videos where user's head orientation-expressed in spherical coordinates determines what part of the video needs to be retrieved, and recommendation systems where the objects are embedded in a finite-dimensional space with a distance metric to capture content dissimilarity. Existing similarity caching policies are simple modifications of classic policies like LRU, LFU, and qLRU and ignore the continuous nature of the space where objects are embedded. In this paper, we propose GRADES, a new similarity caching policy that uses gradient descent to navigate the continuous space and find the optimal objects to store in the cache. We provide theoretical convergence guarantees and show GRADES increases the similarity of the objects served by the cache in both applications mentioned above