Effects of human donor milk on gut barrier function and inflammation: in vitro study of the beneficial properties to the newborn.

Introduction: The gastrointestinal and immune systems of premature infants are not fully developed, rendering them more vulnerable to severe complications like necrotizing enterocolitis. Human milk offers a rich array of bioactive factors that collectively contribute to reducing the incidence of gut infections and inflammatory conditions. When a mother's milk is unavailable, preterm infants are often provided with donor human milk processed in Human Milk Banks. However, it remains uncertain whether pasteurized milk confers the same level of risk reduction as unprocessed milk. This uncertainty may stem from the well-documented adverse effects of heat treatment on milk composition. Yet, our understanding of the comprehensive impact on protective mechanisms is limited. Methods: In this study, we conducted a comparative analysis of the effects of raw versus pasteurized milk and colostrum versus mature milk on cellular functions associated with the gut epithelial barrier and responses to inflammatory stimuli. We utilized THP-1 and HT-29 cell lines, representing monocyte/macrophages and gut epithelial cells, respectively. Results: Our observations revealed that all milk types stimulated epithelial cell proliferation. However, only raw colostrum increased cell migration and interfered with the interaction between E. coli and epithelial cells. Furthermore, the response of epithelial and macrophage cells to lipopolysaccharide (LPS) was enhanced solely by raw colostrum, with a milder effect observed with mature milk. In contrast, both raw and pasteurized milk diminished the LPS induced response in monocytes. Lastly, we examined how milk affected the differentiation of monocytes into macrophages, finding that milk reduced the subsequent inflammatory response of macrophages to LPS. Discussion: Our study sheds light on the impact of human milk on certain mechanisms that potentially account for its protective effects against necrotizing enterocolitis, highlighting the detrimental influence of pasteurization on some of these mechanisms. Our findings emphasize the urgency of developing alternative pasteurization methods to better preserve milk properties. Moreover, identifying the key components critically affected by these protective mechanisms could enable their inclusion in donor milk or formula, thereby enhancing immunological benefits for vulnerable newborns.

Care When It Counts: Establishing Trauma-Sensitive Care as a Preventative Approach for 0-3-Year-Old Children Suffering from Trauma and Chronic Stress.

Adverse childhood experiences are an important societal concern. Children aged 0-3 are particularly vulnerable to unpredictable chronic stress due to the critical period for brain development and attachment. Trauma-sensitive care is a preventative approach to reduce the burden of stressful experiences by committing to positive relationships. Professional caregivers are ideally placed to offer trauma-sensitive care; however, earlier research reveals that the tools they need to consciously apply trauma-sensitive care principles are missing. The current study organized living labs (co-creative research method) to present trauma-sensitive care as a preventative approach aimed at children aged 0-3. Two living labs were organized in Belgium and Hungary, where professional caregivers collaborated to create a protocol that offers guidelines on how to implement trauma-sensitive care. The resulting protocol included a theoretical foundation on trauma as well as a translation of these guidelines into practical recommendations. The protocol was evaluated by incorporating it into a training intervention delivered to 100 professional caregivers from childcare organizations across four European countries. The protocol received positive feedback from participants, with results indicating a self-reported increase in knowledge, attitude and practice of trauma-sensitive care principles. We conclude that this trauma-sensitive care protocol is a promising answer to the needs of professional caregivers working with children aged 0-3.

Lamivudine 24-month-long prophylaxis is a safe and efficient choice for the prevention of hepatitis B virus reactivation in HBsAg-negative/HBcAb-positive patients with advanced DLBCL undergoing upfront R-CHOP-21.

Introduction: Occult hepatitis B infection (OBI) is a condition where replication-competent hepatitis B virus-DNA (HBV-DNA) is present in the liver, with or without HBV-DNA in the blood [<200 international units (IU)/ml or absent] in HB surface antigen (HBsAg)-negative/HB core antibody (HBcAb)-positive individuals. In patients with advanced stage diffuse large B-cell lymphoma (DLBCL) undergoing 6 cycles of R-CHOP-21+2 additional R, OBI reactivation is a frequent and severe complication. There is no consensus among recent guidelines on whether a pre-emptive approach or primary antiviral prophylaxis is the best solution in this setting of patients. In addition, questions still unresolved are the type of prophylactic drug against HBV and adequate prophylaxis duration. Methods: In this case-cohort study, we compared a prospective series of 31 HBsAg-/HBcAb+ patients with newly diagnosed high-risk DLBCL receiving lamivudine (LAM) prophylaxis 1 week before R-CHOP-21+2R until 18 months after (24-month LAM series) versus 96 HBsAg-/HBcAb+ patients (from January 2005 to December 2011) undergoing a pre-emptive approach (pre-emptive cohort) and versus 60 HBsAg-/HBcAb+ patients, from January 2012 to December 2017, receiving LAM prophylaxis [1 week before immunochemotherapy (ICHT) start until 6 months after] (12-month LAM cohort). Efficacy analysis focused primarily on ICHT disruption and secondarily on OBI reactivation and/or acute hepatitis. Results: In the 24-month LAM series and in the 12-month LAM cohort, there were no episodes of ICHT disruption versus 7% in the pre-emptive cohort (P = 0.05). OBI reactivation did not occur in any of the 31 patients in the 24-month LAM series versus 7 out of 60 patients (10%) in the 12-month LAM cohort or 12 out of 96 (12%) patients in the pre-emptive cohort (P = 0.04, by χ 2 test). No patients in the 24-month LAM series developed acute hepatitis compared with three in the 12-month LAM cohort and six in the pre-emptive cohort. Discussion: This is the first study collecting data regarding a consistent and homogeneous large sample of 187 HBsAg-/HBcAb+ patients undergoing standard R-CHOP-21 for aggressive lymphoma. In our study, 24-month-long prophylaxis with LAM appears to be the most effective approach with a null risk of OBI reactivation, hepatitis flare-up, and ICHT disruption.

Efficacy and safety of belantamab-mafodotin in triple-refractory multiple myeloma patients: A multicentric real-life experience.

Belantamab-mafodotin is an innovative and selective treatment for multi-refractory/relapsed multiple myeloma (MM) patients; however, available real-life experiences on efficacy and safety are limited. In this real-world multicentric retrospective study, we enrolled 28 MM patients treated in four Hematology units of Campania region, Italy, who received a median of six treatment lines prior to belantamab-mafodotin. The overall response rate (ORR) was 40% (complete remission, CR, 11%; very good partial remission, VGPR, 11%; and partial remission, PR, 18%), with a median progression-free survival (PFS) and overall survival (OS) of 3 and 8 months, respectively. One of the most frequent drug-related adverse events was keratopathy observed in nine (32%) patients, leading to therapy discontinuation in only three (11%) of them. Moreover, 22 out of 28 total patients who were treated with at least two administrations achieved an ORR of 50% (CR, 14%; VGPR, 14%; and PR, 22%) with a median PFS and OS of 5 and 11 months, respectively. In conclusion, our multicentric study confirmed efficacy and safety of belantamab-mafodotin in triple-refractory MM patients even in the real-life setting.

Tyrosol-Enriched Tomatoes by Diffusion across the Fruit Peel from a Chitosan Coating: A Proposal of Functional Food.

Chitosan is receiving increasing attention from the food industry for being a biodegradable, non-toxic, antimicrobial biopolymer able to extend the shelf life of, and preserve the quality of, fresh food. However, few studies have investigated the ability of chitosan-based coatings to allow the diffusion of bioactive compounds into the food matrix to improve its nutraceutical quality. This research is aimed at testing whether a hydrophilic molecule (tyrosol) could diffuse from the chitosan-tyrosol coating and cross the tomato peel. To this end, in vitro permeation tests using excised tomato peel and an in vivo application of chitosan-tyrosol coating on tomato fruit, followed by tyrosol quantification in intact fruit, peel and flesh during a seven-day storage at room temperature, were performed. Both approaches demonstrated the ability of tyrosol to permeate across the fruit peel. Along with a decreased tyrosol content in the peel, its concentration within the flesh was increased, indicating an active transfer of tyrosol into this tissue. This finding, together with the maintenance of constant tyrosol levels during the seven-day storage period, is very promising for the use of chitosan formulations to produce functional tomato fruit.

Immune profiling of breast milk from mothers with treated celiac disease.

BACKGROUND: The protective effect of breastfeeding on celiac disease (CD) onset is controversial. We studied a wide range of milk components in milk produced by celiac mothers following long-term gluten-free diet (GFD) in comparison to milk produced by healthy mothers. METHODS: Breast-milk samples from celiac (n = 33) and healthy (n = 41) mothers were obtained during the first year of lactation. A panel of bioactive components was analyzed by enzyme-linked immunosorbent assay in the aqueous fraction. We studied molecules involved in defenses, immunoregulation, and strengthening of the gut-epithelial barrier. RESULTS: During late lactation (from 6 to 12 months after delivery), the content of total immunoglobulin A (IgA) and IgM was significantly lower in the milk produced by celiac patients. Nevertheless, gliadin (GFD)-specific IgA relative contribution was higher in this group, in contrast to tetanus toxoid-specific antibodies. The balance between pro-inflammatory and anti-inflammatory molecules was different. While interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 were most frequently found in samples from celiac mothers, soluble Toll-like receptor-2 prevalence was lower. CONCLUSIONS: We describe differences between the innate and adaptive immune profile of milk produced by celiac and healthy mothers. These results might explain previous controversial reports about breastfeeding and CD protection. IMPACT: In spite of a long-term adherence to GFD, the milk produced by mothers with CD exhibit a different immune profile, in relation with some immunoregulatory factors and antibody content. This work shows a more comprehensive characterization of milk from celiac mothers, including macronutrients, lysozymes, growth factors, and immunoregulatory components that had not been studied before. The present study widens the available data regarding the characteristics of human milk of celiac mothers following GFD. Further follow-up studies of the health of children who were breastfed by celiac mothers will be necessary in order to also estimate the impact of the present results therein.

Impact of Holder pasteurization on immunological properties of human breast milk over the first year of lactation.

BACKGROUND: The timing of milk donations to human milk banks ranges from a few days to more than 1 year after delivery, and the Holder method is used for pasteurization. We evaluated the effect of temporal variation and thermal treatment on the immunological properties of milk. METHODS: We analyzed 73 milk samples, raw and after pasteurization, donated at different lactation stages. We studied antibodies, lysozyme, cytokines, soluble receptors, and factors with impact on barrier function. We also evaluated in vitro the capacity of milk to modulate nuclear factor-κB (NF-κB) signaling in an HT-29 epithelial cell line stimulated with tumor necrosis factor-α (TNF-α). RESULTS: With few exceptions, immune components exhibited their highest levels in colostrum, and were stable in the various stages of mature milk. Pasteurization altered the immunological composition of milk, and very drastically for some components. Raw milk of the first year reduced NF-κB activation in HT-29 cells treated with TNF-α to approximately the same extent, and Holder pasteurization significantly affected this capacity. CONCLUSIONS: Overall, the present work reports that mature donated milk is equally valuable over the first year of lactation, but warns about drastic losses of anti-inflammatory properties during Holder pasteurization that could be critical for the health of preterm infants.

Antibody Profile of Colostrum and the Effect of Processing in Human Milk Banks: Implications in Immunoregulatory Properties.

BACKGROUND: When feeding preterm infants, donor milk is preferred if the mother's own milk is unavailable. Pasteurization may have detrimental effects on bioactivity, but more information is needed about its effects on the immunological compounds. Research aim: This work has two main aims: evaluate the antibody profile of colostrum and study the quantitative variations in the antibodies' level and specific reactivity after undergoing Holder pasteurization. The authors focused on immunoregulatory components of colostrum (antidietary antibodies and TGF-ß2) in the neonatal gut. METHODS: This is a descriptive cross-sectional study of a convenience sample of 67 donated colostrum samples at different days after delivery, both raw and pasteurized. Antibody profiles were analyzed at different times during breastfeeding, and total and specific antibodies (IgM, IgA, and IgG subclasses) were compared with tetanus toxoid and ovalbumin using enzyme-linked immunosorbent assay. The processing effect on total and specific antibodies, as well as TGF-ß2, was evaluated by paired analyses. RESULTS: No variations in immunological compounds were observed throughout the colostrum stage. The TGF-ß2, antibodies' concentrations, and antibodies' specific reactivity after pasteurization did not vary significantly as days of lactation varied. Changes in antibody levels were dependent on isotype and IgG subclass, and IgG4 showed remarkable resistance to heating. Moreover, the effect of the pasteurization on specific reactivity was antigen dependent. CONCLUSION: The supply of relevant immunological components is stable throughout the colostrum stage. The effects of pasteurization on antibodies depend on isotype, subclass, and specificity. This information is relevant to improving the immunological quality of colostrum, especially for preterm newborns.

Gastrointestinal stromal tumour (GIST) in a young man with unprovoked haematemesis.

This case involves a 27-year-old Hispanic man who presented to the emergency department with two episodes of haematemesis with no other associated symptoms. In addition, he has no medical history, denies alcohol abuse, denies non-steroidal anti-inflammatory drug use and has never experienced these episodes before. Esophagogastroduodenoscopy evaluation showed a large gastric mass, and histological results obtained from several biopsies of the mass supported a diagnosis of gastrointestinal stromal tumour. His abdominal CT scan also supported this finding. However, the unprovoked haematemesis and young age of the patient does not fit the typical presentation of a gastrointestinal stromal tumour.

Criminalization of stalking in Italy: one of the last among the current European member states' anti-stalking laws.

This article illustrates the state of knowledge on stalking in Italy from the first scientific review published in 2001 to the recent anti-stalking law, which became effective in February 2009, introducing a new article in the existing Italian Penal Code. In recent years the interest in stalking has increased progressively, such that it is now possible to find official data on the prevalence of the phenomenon in Italy. At the same time, European research activity has moved from the recognition of the phenomenon to analysis of pathways for a victim's assessment of stalking risk and enactment of legal regulation. The new law is described and analyzed.

Association between colonic screening, subject characteristics, and stage of colorectal cancer.

OBJECTIVES: Colorectal cancer remains a significant cause of mortality and morbidity in North America. Colorectal cancer survival is highly dependent on stage at diagnosis, therefore it is important to identify factors related to stage. This study evaluated the association between subject factors (e.g., colonic screening, family history) and stage of colorectal cancer at diagnosis. METHODS: Population-based colorectal cancer cases recruited by the Ontario Familial Colon Cancer Registry between 1997 and 1999 were staged according to the tumor-nodal-metastasis (TNM) staging system and classified as early (TNM I/II) or late (TNM III/IV) stage. Epidemiologic information and stage was available for 768 cases. Multivariate logistic regression was used to obtain odds ratios (OR) estimates. RESULTS: Having had screening endoscopy reduced the risk of late stage diagnosis (OR = 0.46, 95% CI 0.22-0.98). Being older (>45 yr) was associated with a reduced risk of late stage cancer (OR = 0.36, 95% CI 0.18-0.74), as was having a first degree relative with colorectal cancer (OR =0.66, 95% CI 0.46-0.95). Rural residence (OR = 1.48, 95% CI 1.01-2.17) and non-white ethnicity (OR = 3.34, 95% CI 1.20-9.36) were associated with an increased risk of late stage cancer. CONCLUSIONS: Several factors are independently associated with late stage colorectal cancer. Colorectal cancer screening awareness and education programs need to consider targeting persons most likely to present with late stage colorectal cancer.