Highly Specific Memory B Cells Generation after the 2nd Dose of BNT162b2 Vaccine Compensate for the Decline of Serum Antibodies and Absence of Mucosal IgA.

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA.

Oxidative Status of Goats with Different CSN1S1 Genotypes Fed ad Libitum with Fresh and Dry Forages.

Forty late-lactation Girgentana goats were used to study the effect of diets fed ad libitum and αS1-casein (CSN1S1) genotype on redox balance. The goats genotyped at CSN1S1 locus (A/A, A/F) were subjected to four feeding treatments different for percentage inclusion of dry and fresh forage: DAF100 (98% of Dry Alfalfa Forage), DAF65 (65% of Dry Alfalfa Forage), FSF100 (100% of Fresh Sulla Forage) and FSF65 (65% of Fresh Sulla Forage). Blood samples were analyzed for superoxide dismutase (SOD) and glutathione peroxidase (GPX) activity, reactive oxygen metabolites (ROMs), biological antioxidant potential (BAP) and non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), albumin, glucose and cholesterol contents. The oxidative stress index (OSI) was calculated as percentage ratio of ROMs to BAP. Redox balance was improved by Sulla inclusion, as reflected in the lower OSI values found in FSF100 and FSF65 groups. DAF100 group displayed the highest GPX activity, while other groups exhibited the highest SOD activity. Fresh forage diets increased albumin concentration while no effect of tested factors was noted on glucose, NEFA, BHBA and cholesterol contents. The interaction diet × genotype was significant only for GPX activity. GPX and albumin were negatively correlated and were correlated positively and negatively with ROMs, respectively. Diet rather than genotype affects redox balance in dairy goats and a possible role of forage polyphenol compounds on oxidative status needs to be tested in future studies.

Improvement of Oxidative Status, Milk and Cheese Production, and Food Sustainability Indexes by Addition of Durum Wheat Bran to Dairy Cows' Diet.

Durum wheat bran (DWB) is a by-product mostly used in feeding ruminants, contributing to decrease in the utilization of feeds suitable as foods for human consumption, thus improving the sustainability of livestock production. However, the potential benefits of DWB, due to its content in phenolic acids, mainly consisting of ferulic acid with antioxidant properties, have not been well clarified yet. Accordingly, in this experiment, 36 lactating cows divided into three groups received, over a period of 100 days, one of three concentrates including DWB at 0% (DWB0), 10% (DWB10), or 20% (DWB20). The concentrates were formulated to be isoproteic and isoenergetic and, to balance the higher fiber content of the concentrates with DWB, the hay in the diets was slightly reduced. During the trial, the group feed intake and the individual milk production were monitored, and cheese was made with bulk milk from each group. Milk yield and microbiological characteristics of milk and cheese were similar among groups, indicating no DWB effect on cows performance and fermentation process. Milk from DWB20 group resulted slightly higher in casein and curd firmness (a2r). In cows fed DWB, the higher polyphenol intake was responsible for higher blood contents of these bioactive compounds, that seemed to have contributed in reducing the level of reactive oxygen metabolites (ROMs), which were higher in DWB0 cows. DWB20 cheeses showed a higher polyphenol content, lower number of peroxides, and higher antioxidant capacity than DWB0 cheeses. DWB20 and DWB10 diets resulted less expensive. In addition, the DWB20 group showed the best indexes heFCE (human edible feed conversion efficiency = milk/human edible feed) and NFP (net food production = milk - human edible food), expressed as crude protein or gross energy. In conclusion, the DWB fed to dairy cows at 12% of diet dry matter (DM) can lead to benefits, such as the improvement of oxidative status of cows, milk quality, shelf-life, and functional properties of cheese, and might contribute to reduce the feeding cost and limit the human-animal competition for feeding sources.

Leptin Gene Polymorphism in Goats Fed with Diet at Different Energy Level: Effects on Feed Intake, Milk Traits, Milk Fatty Acids Composition, and Metabolic State.

The study investigated the effects of a polymorphism at the LEP gene intron 1 microsatellite region and its interaction with diet energy level on feed intake, milk traits, milk fatty acid composition, and metabolic state in goats. Sixteen Girgentana lactating goats at mid-lactation, selected on the basis of their genotype (8 goats homozygous 266 bp/266 bp, L genotype; 8 goats heterozygous 266 bp/264 bp, H genotype), were fed ad libitum according to a change-over design, with two diets at different energy levels reached with different hay inclusion: low energy diet (LE)-100% of hay; and high energy diet (HE)-65% of hay. No differences in milk yield and composition or in dry matter intake were found between leptin genotypes or between diets. Leptin genotype had no effect on plasma metabolite concentrations. The differences between diets were recorded for plasma ß-hydroxybutyric acid (BHBA) concentrations with higher (p = 0.01) values for the HE compared to the LE diet (0.44 vs. 0.24 mmol/L, respectively). Nonesterified fatty acid (NEFA) values seem to indicate a positive energy balance in goats. No interaction genotype per diet was evident for most of the studied parameters. Fatty acid composition was strongly influenced by LEP genotype: L goats, compared to H goats, showed higher levels of monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and 14:1/14:0 desaturation index; lower levels of saturated fatty acids (SFA); and a more favorable atherogenic index. These results seem to suggest an improvement of health characteristics of milk with the L genotype.

Effects of Grazing on the Behaviour, Oxidative and Immune Status, and Production of Organic Dairy Cows.

This study compared the effects of a short daily grazing time with those of permanent free-stall housing on the behaviour, oxidative status, immune response, and milk production of organically reared cows. During a 63-day period, two homogeneous groups of eight lactating Brown cows were allocated to either housing (H) in a free-stall building for 24 h/day. Feeding was based on a total mixed ration or grazing (G) on barley grass for 5 h/day, and housing in a free-stall structure with feeding was based on the same total mixed ration offered to the H group. With regard to behaviour, H cows spent more time idling, walking, drinking, and self-grooming, whereas G cows showed a greater intent to eat and interact socially. Moreover, G cows exhibited slightly higher reactive oxygen metabolites and similar biological antioxidant potential concentrations than the H group, which indicates that short grazing resulted in an almost negligible increase in oxidative stress and an unchanged antioxidant capacity. Skin tests, performed by injecting phytohemoagglutinin intradermally, indicated that G cows had thicker skin than H cows at the end of the trial, an index of a better cell-mediated immune response. Grazing did not affect milk yield but improved milk quality in terms of an increase in fat and a reduction in urea content, somatic cell count, and total microbial count. Milk from G cows was richer in saturated fatty acids, likely because of the contribution of palmitic acid present in the grazed barley grass, and also showed higher contents of some healthy fatty acids, such as rumenic acid and α-linolenic acid, and a lower omega-6/omega-3 ratio. These results show that including a short grazing time in the diets of organic dairy cows does not have negative consequences for milk production and contributes to improved milk quality as well as to a more efficient immune response in the cows.

Prevalence and outcome of malnutrition in pediatric patients with chronic diseases: Focus on the settings of care.

BACKGROUND: Information on disease-related malnutrition and related outcomes in pediatric patients with chronic diseases in different settings of care is not available. METHODS: Consecutive eligible patients attending the out-patient clinic (n = 177) or admitted to the day-hospital clinic (n = 163) or to hospital (n = 201) were screened for the presence of malnutrition (BMI and/or height/length for age z-scores < -2). We recorded data on emergency care admissions to hospital that occurred during the 3 years before screening and related total days of stay, as well as data on emergency care admissions to hospital occurring within 6 months after screening. RESULTS: Prevalence of malnutrition was 2-fold higher (P < 0.001) in in-patients (56.7% [95% CI, 49.6-63.7]) than in patients assessed at the out-patient (33.3% [95% CI, 26.4-40.8]) and day-hospital (28.3% [95% CI, 21.5-35.8]) clinics. Estimates were heterogeneous across diagnostic groups with higher rates in patients with neurologic (61%) and cardiac (56%) diseases. Stunting was more frequent among in-patients, who also had more evident nutritional derangements. Multivariate logistic regression (covariates: age, gender, healthcare setting and disease group), showed that malnutrition (OR = 1.86 [95% CI, 1.21-2.88]; P = 0.005) was significantly associated with prolonged hospitalization (≥15 days) in the 3 years before screening. In-patients were also more likely to have been hospitalized ≥15 days (using out-patients as reference category, OR = 2.24 [95% CI, 1.39-3.63], P = 0.001), but we did not find any modifying effect (interaction) of the setting of care on the association between malnutrition and prolonged hospitalization. DISCUSSION: The rates of malnutrition in children with chronic diseases are very high and increase hospital care needs, especially when they are admitted to hospital. Nutritional care in this patient population is recommended.

Prognostic implications of high-sensitivity cardiac troponin T assay in a real-world population with non-ST-elevation acute coronary syndrome.

BACKGROUND: High-sensitivity cardiac troponin T (hsTnT) was recently approved for clinical use by the Food and Drug Administration. The transition from contemporary to hsTnT assays requires a thorough understanding of the clinical differences between these assays. HYPOTHESIS: HsTnT may provide a more accurate prognostic stratification than contemporary cardiac troponin I (cTnI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS: HsTnT and cTnI were measured in 644 patients with CK-MB negative NSTE-ACS who were enrolled in the prospective multicenter SPAI (Stratificazione Prognostica dell'Angina Instabile) study. Patients were stratified at the 99th percentile reference limit for each assay. The primary endpoint was cardiovascular death (CVD) or non-fatal myocardial infarction (MI); the secondary endpoint was the occurrence of unstable angina (UA). Follow-up lasted 180 days. RESULTS: Patients with hsTnT ≥99th percentile were at higher risk of CVD/MI (30-day: 5.9% vs 0.8%, p = 0.001; 180-day: 11.1% vs 4.7%, p = 0.004), also after adjusting for TIMI Risk Score. No significant difference in CVD/MI at 180-day was found between hsTnT-positive/cTnI-negative and hsTnT-negative/cTnI-negative patients (adjHR 1.61, 95% CI 0.74-3.49, p = 0.232). Occurrence of UA was not differently distributed between hsTnT groups dichotomized at the 99th percentile (12.4% vs 12.5% p = 0.54). CONCLUSIONS: Our investigation on a real-world NSTE-ACS population showed good prognostic performance of hsTnT in the risk stratification of the hard endpoint, but did not demonstrate the improved prognostic ability of hsTnT over contemporary cTn. Neither troponin assay predicted the recurrence of UA, suggesting the acute rise of cardiac troponin as a marker of severity, but not the occurrence of future coronary instability.

Pediatric Short Bowel Syndrome: Predicting Four-Year Outcome after Massive Neonatal Resection.

OBJECTIVES: The aim of this study was to ascertain predictors of survival, liver disease (LD), and enteral autonomy 48 months after resection in neonatal short bowel syndrome (SBS) patients with residual small bowel length (SBL) ≤40 cm. PATIENTS AND METHODS: Medical records of all SBS patients followed up between 1996 and 2016 were retrospectively reviewed. Survival rate, prevalence of LD, and of enteral autonomy were evaluated. RESULTS: Forty-seven patients were included, and 43 were still alive at the end of the study period, with cumulative 48-month survival of 91.5%. Twenty-one (45%) patients developed LD, all within the first 6 months. On the final follow-up visit, three (6%) patients were still jaundiced and progressed toward end-stage LD. LD prevalence was higher in patients with recurrent bloodstream infections (odds ratio [OR] 5.4, 95% confidence interval [CI] 1.5-19.3). Of the 43 surviving patients, 22 (51%) had enteral autonomy 48 months after resection. The probability of weaning off parenteral nutrition (PN) was strongly correlated with the remaining SBL. CONCLUSION: Survival of patients who have undergone neonatal massive small bowel resection has improved in recent years. Multidisciplinary strategies can improve the course of LD, but not the probability of weaning off PN, which seems to be strongly dependent on the anatomical profile of residual bowel. Therefore, the primary surgical approach should be as conservative as possible to gain even small amounts of intestinal length, which may be crucial in promoting intestinal adaptation.

Understanding Growth Failure in Costello Syndrome: Increased Resting Energy Expenditure.

Costello syndrome is a rare multisystem disorder caused by mutations in the proto-oncogene HRAS. Failure to thrive is one of its cardinal clinical features. This study documents that individuals with Costello syndrome have increased resting energy expenditure. We speculate this could be one of the potential mechanisms causing failure to thrive.

The Effect of Yerba Mate (Ilex Paraguariensis) Supplementation on Nutrient Degradability in Dairy Cows: An In sacco and In vitro Study.

This study was carried out to investigate the effects of Yerba Mate (YM) supplementation on nutrients' degradation, in vitro dry matter disappearance, gas production and rumen ammonia concentration. Three rumen-fistulated Holstein Friesian cows were used for the in situ incubations and provided rumen liquor for in vitro incubations. The inclusion of YM in a control diet (pasture+pellets) affected some in sacco degradation parameters. YM supplementation decreased the effective degradability and degradation rate of pasture crude protein (CP), and it seems to slow down the degradation of pasture neutral detergent fiber. A significant increase of degradation of pasture acid detergent fiber (ADF) was detected after YM inclusion in the control diet. YM supplementation reduced in vitro gas production of pasture and ammonia concentration of pellets. The addition of YM in ruminant diet could decrease ammonia production and increase protein availability for productive purposes. The moderate presence of tannins in YM could have affected the degradation kinetics of pasture CP and ADF and the ammonia production of pellets.

Three novel alleles at the HLA-DRB1 locus identified by sequence-based typing.

We describe here the sequences of 3 new HLA-DRB1 variants officially named DRB1*03:05:03, DRB1*11:10:02, and DRB1*14:86. These novel alleles have been detected in 3 Caucasoid individuals by sequence-based typing. The first and second alleles are the result of a silent mutation, which does not imply any amino acid change. The sequence of DRB1*14:86 exhibits a single nucleotide difference with the allele DRB1*14:01:01 at position 239.