The Breast Milk Immunoglobulinome

Breast milk components contribute to the infant's immune development and protection, and among other immune factors, immunoglobulins (Igs) are the most studied. The presence of IgA in milk has been known for a long time; however, less information is available about the presence of other Igs such as IgM, IgG, and their subtypes (IgG1, IgG2, IgG3, and IgG4) or even IgE or IgD. The total Ig concentration and profile will change during the course of lactation; however, there is a great variability among studies due to several variables that limit establishing a clear pattern. In this context, the aim of this review was firstly to shed light on the Ig concentration in breast milk based on scientific evidence and secondly to study the main factors contributing to such variability. A search strategy provided only 75 studies with the prespecified eligibility criteria. The concentrations and proportions found have been established based on the intrinsic factors of the study¿such as the sampling time and quantification technique¿as well as participant-dependent factors, such as lifestyle and environment. All these factors contribute to the variability of the immunoglobulinome described in the literature and should be carefully addressed for further well-designed studies and data interpretation

Galectins-1, -3 and -9 Are Present in Breast Milk and Have a Role in Early Life Development

Galectins (Gal) are a family of conserved soluble proteins with high affinity for β-galactoside structures. They have been recognized as important proteins for successful pregnancy. However, little is known about their presence in breast milk and their role in early infancy. Gal-1, -3 and -9 concentrations were evaluated by Multiplex immunoassays in mother-infant pairs from the MAMI cohort in maternal plasma (MP) (n = 15) and umbilical cord plasma (UCP) (n = 15) at birth and in breast milk samples (n = 23) at days 7 and 15 postpartum. Data regarding mother and infant characteristics were collected. Gal-9 was present in a lower concentration range than Gal-1 and Gal-3 in plasma, specifically in UCP. A major finding in the current study is that Gal-1, -3 and -9 were detected for the first time in all the transitional breast milk samples and no differences were found when comparing the two breastfeeding time points. Finally, Gal levels were associated with some maternal and infant characteristics, such as gestational age, pregnancy weight gain, maternal diet, the gender, infant growth and infant infections. In conclusion, Gal levels seem to be involved in certain developmental aspects of early life. Keywords: galectin; breast milk; umbilical cord plasma; maternal plasm

Evaluation of Medicine Abuse Trends in Community Pharmacies: The Medicine Abuse Observatory (MAO) in a Region of Southern Europe

The misuse of medicines is a global public health concern that needs to be taken into consideration and requires actions across all government sectors and society. The aim of this study is to identify trends of drug abuse in Catalonia, a region of Spain located in the South of Europe. For this purpose, a questionnaire-based detection tool was created and implemented in 60 community pharmacies. Out of 548 questionnaires (98.4%), 64.2% of participants were men and the highest age proportion was 25-35 years (31.4%). Potential drug abuse was the highest in urban pharmacies (84.9%). The main drug class involved were benzodiazepines (31.8%), codeine (19.3%), tramadol (7.5%), methylphenidate (5.8%), gabapentinoids (5.8%), cycloplegic drops (4.4%), z-drugs (2.6%), piracetam (2.2%), dextromethorphan (1.6%) and clomethiazole (1.1%). The majority of drugs were requested without prescription (58.6%) and through probably forged prescriptions (23.7%). Slightly less than half (49.8%) of the patients request frequently to the pharmacist, especially in rural and mountain pharmacies (73.3% and 88.5%, respectively). A small proportion (10.8%) were requested with intimidation. Pharmacists only supplied in 21.7% of the cases. This study has demonstrated the suitability of the new detection system, being a useful approach to replicate in other locations with similar needs

Association of Maternal Microbiota and Diet in Cord Blood Cytokine and Immunoglobulin Profiles

Mothers confer natural passive immunization to their infants through the transplacental pathway during the gestation period. The objective of the present study was to establish at birth the maternal and cord plasma concentration and relationship of immunoglobulins (Igs), cytokines (CKs), and adipokines. In addition, the impact of the maternal microbiota and diet was explored. The plasma profile of these components was different between mothers and babies, with the levels of many CKs, IgM, IgG2a, IgE, IgA, and leptin significantly higher in mothers than in the cord sample. Moreover, the total Igs, all IgG subtypes, IgE, and the Th1/Th2 ratio positively correlated in the mother-infant pair. Maternal dietary components such as monounsaturated fatty acids-polyunsaturated fatty acids and fiber were positively associated with some immune factors such as IgA in cord samples. The microbiota composition clustering also influenced the plasma profile of some factors (i.e., many CKs, some Ig, and adiponectin). In conclusion, we have established the concentration of these immunomodulatory factors in the maternal-neonatal pair at birth, some positive associations, and the influence of maternal diet and the microbiota composition, suggesting that the immune status during pregnancy, in terms of CKs and Igs levels, can influence the immune status of the infant at birth. Keywords: breast milk; cord blood; cytokine; diet; enterotype; immunoglobulin; microbiota

Pràctiques d'hematologia a Fisiologia: de l'aprenentatge presencial a l'aprenentatge virtual: Adaptació de l'aprenentatge presencial al virtual

S'ha confeccionat una eina virtual complementària a les pràctiques de laboratori que permet assegurar l'aprenentatge així com treballar competències transversals. A través de l'eina 'Lliçó' del Moodle s'ha elaborat una seqüència de pàgines de contingut i de preguntes de diferent tipologia que es treballen de forma virtual i síncrona en grups de 2-3 estudiants sota la supervisió del professorat connectats a través del BB Collaborate. L'alumnat valora positivament l'eina virtual

Association of Maternal Microbiota and Diet in Cord Blood Cytokine and Immunoglobulin Profiles

Mothers confer natural passive immunization to their infants through the transplacental pathway during the gestation period. The objective of the present study was to establish at birth the maternal and cord plasma concentration and relationship of immunoglobulins (Igs), cytokines (CKs), and adipokines. In addition, the impact of the maternal microbiota and diet was explored. The plasma profile of these components was different between mothers and babies, with the levels of many CKs, IgM, IgG2a, IgE, IgA, and leptin significantly higher in mothers than in the cord sample. Moreover, the total Igs, all IgG subtypes, IgE, and the Th1/Th2 ratio positively correlated in the mother–infant pair. Maternal dietary components such as monounsaturated fatty acids-polyunsaturated fatty acids and fiber were positively associated with some immune factors such as IgA in cord samples. The microbiota composition clustering also influenced the plasma profile of some factors (i.e., many CKs, some Ig, and adiponectin). In conclusion, we have established the concentration of these immunomodulatory factors in the maternal–neonatal pair at birth, some positive associations, and the influence of maternal diet and the microbiota composition, suggesting that the immune status during pregnancy, in terms of CKs and Igs levels, can influence the immune status of the infant at birth.This work was supported by the research grant from LaMarató-TV3 (DIM-2-ELI, ref. 2018-27/30-31) and also by the European Research Council under the European Union’s Horizon 2020 research and innovation program (ERC starting grant, no. 639226). MS-R was supported by a Predoctoral Fellowship from Generalitat Valenciana—European Social Fund (ASCII2016). K.R-A holds a fellowship from the Spanish Ministry of Economy, Industry and Competitiveness (FPU 19/05150).Peer reviewe

Com desenvolupar un escaperoom educatiu per a l'aprenentatge d'immunologia: BreakOut Educatiu

Els BreakOut Educatius tenen com a finalitat que l'estudiant aprengui jugant a través de la resolució d'una sèrie d'enigmes que es troben en una caixa o similar. Per introduir continguts d'immunologia s'ha dissenyat un BreakOut educatiu recreant una tecnologia basada en nanobots capaç de curar qualsevol tipus d'infecció. L'experiència, tot i necessitar d'una inversió de temps important, ha estat gratificant per a estudiants i professors

Maternal diet and breast milk: shaping the newborn immune system to fight early life infections

[eng] Newborns have limited ability to fight infections due to an immature adaptative immune response. As a result, they depend on mechanisms of maternal immune transfer, such as placental transfer and intake of breast milk (BM) during lactation. These processes also play a vital role in the proper development of the infant immune system. The overall composition of BM changes through the lactation period and so does the content of immune components. Diet as well as other factors can influence the composition of BM. It is of considerable interest to investigate the potential of the maternal diet during gestation and lactation to contribute to the maturation of the infant immune system. This influence could confer benefits in terms of preventing and mitigating infections during the early stages of life. Thus, the aim of this thesis was to examine the effect of maternal diet during pregnancy and lactation on the immune profile of BM and on the infant’s capacity to fight against infections in the early stages of life. Additionally, the effect on the umbilical cord plasma (UCP) and maternal plasma (MP) immune composition was also studied. The levels of UCP immune factors were significantly different from those found in MP. Moreover, the levels of UCP IgE and IgG are highly associated with those found in MP. With regard to the composition of bioactive components in BM in the transition stage, a different profile between day 7 and day 15 was observed, with day 7 exhibiting the highest concentration of the analyzed immune factors. Furthermore, two groups of mothers were identified based on the evolution of their BM immune composition (BM immunotypes) between those days, primarily attributed to differences in specific types of Ig. This highlights the importance of considering the individual variations in BM immune factors for future studies. Another noteworthy finding was the identification of Gal-1, -3, and -9 for the first time in BM, which exhibited similar levels at both time points in the transitional stage. Finally, being a first-time mother or not, and a maternal infection, such as the SARS-CoV-2 infection, have shown to play a role in immune composition. Next, the influence of maternal diet and other perinatal factors during pregnancy and lactation on these bioactive components and the incidence of infections in the offspring was evaluated at clinical level. It was observed that maternal intake of dietary fiber, plant protein, and polyunsaturated fatty acids could potentially contribute to the development of the neonate's immune defense. This effect may be mediated through modifications in the maternal intestinal microbiota during pregnancy. The occurrence of early-life infections, both gastrointestinal and respiratory, within the first year of life was observed to be lower when mothers followed a dietary pattern rich in dietary fiber and vegetable protein and low in lipids during pregnancy and breastfeeding. In contrast, a maternal diet high in animal protein and lipids had the opposite effect, increasing the incidence of infant infections. This effect was associated with specific immune factors found in BM and on the infant microbiota diversity. Then, the maternal dietary profiles from the clinical cohort were adapted to conduct a preclinical nutritional intervention in dams to study the neonatal immune response in a model of acute rotavirus-induced gastroenteritis. The maternal diet fortified with vegetable protein, fiber, and fish oil had a beneficial impact on both the mothers and the infected offspring, as well as in the BM. Firstly, it was found to enhance maternal mucosal immunity and in addition, an an-obesogenic effect of the adipose tissue was also found. With regard to the offspring, the maternal diet contributed to an improvement of the RV-induced gastroenteritis, to the development of the immune system of the infant, to an enhanced RV-specific response and to changes in the microbiota composition. The present thesis gained insight into the influence of maternal nutrition during gestation and lactation on the enhancement of the newborn immune function to fight against infections. While this study revealed some evidence of the immunomodulatory effects of maternal diet on the BM and the offspring, further research is necessary to fully comprehend the underlying mechanisms.[cat] Els nounats tenen respostes immunitàries limitades i depenen dels mecanismes de transferència immunitària materna per a la defensa i el correcte desenvolupament immunitari. La investigació sobre la dieta materna i el seu impacte en la maduració del sistema immunitari infantil té una especial rellevància, ja que es creu que pot ajudar a prevenir i mitigar les infeccions durant la infància. Aquesta tesi té com a objectiu investigar els efectes de la dieta materna durant l'embaràs i la lactància en el desenvolupament immunitari del nadó i la seva capacitat per combatre les infeccions en el primer any de vida, així com explorar el paper dels components immunitaris de la llet materna en aquest context. En un estudi clínic, es van caracteritzar els nivells de factors immunitaris en el plasma matern i del nounat (cordó umbilical), així com en la llet materna. A més, es va investigar per una banda, l'impacte de la dieta materna durant l'embaràs i la lactància en les infeccions dels descendents a partir del registre de les infeccions fins a un any de vida. Per l’altra banda, a partir de l’anàlisi de les dietes maternes de l’estudi clínic es van establir dues dietes que es van administrar a rates gestants i lactants per tal d’avaluar el seu efecte sobre una infecció per rotavirus en les cries. Es va constatar que la llet materna presenta variabilitat en la composició immunitària (immunoglobulines, citocines i adipocines) durant l'etapa de transició, i aquests components no evolucionen de la mateixa manera en totes les mares. S'ha establert per una banda l’existència de dos immunotips de la llet materna en funció d’aquesta evolució i, per l’altra, la concentració de tres galectines en la llet de transició. A més, factors com el fet de tenir un fill previ i la infecció materna, com la de SARS-CoV-2, van influir en la composició d'aquests factors, especialment en les immunoglobulines. El consum matern de fibra dietètica, proteïna vegetal i àcids grassos poliinsaturats va disminuir la incidència d'infeccions en l'estudi clínic. Aquesta observació es va confirmar en la intervenció preclínica amb aquesta dieta, ja que va potenciar la resposta immunitària del binomi mare-fill, incloent la llet, i va reduir el curs de la infecció amb rotavirus. Així, dieta i llet materna, són factors que juguen un paper clau en les infeccions dels descendents. En conclusió, aquesta tesi doctoral tesi proporciona evidències sobre l'impacte de la nutrició materna en la funció immunitària del nounat i la prevenció d'infeccions

Distinct breast milk microbiota, cytokine, and adipokine profiles are associated with infant growth at 12 months: an in vitro host-microbe interaction mechanistic approach

Breast milk (BM) is important for adequate infant development, and it contains bioactive compounds, such as bacteria, cytokines and some adipokines which play a role in infant microbial, metabolic, and immunological maturation. However, little is known about its impact on growth and development in early life. The objective of this study was to evaluate the impact of milk microbiota, cytokine, and adipokine profiles on the risk of overweight at 12 months of life to find the possible mechanisms of host-microbe interactions. In this study, BM samples from 100 healthy women collected during 15 d after birth were included. BM microbiota was analysed by 16S rRNA gene sequencing, and cytokine and adipokine levels were measured by the Luminex approach. In addition, infant weight and length were recorded during the first 12 months and z-scores were obtained according to the WHO databases. Infants were classified as risk of overweight (ROW) and no-risk of overweight (NOROW) based on their body mass index z-score (BMIZ) and infant weight-for-length z-score (WLZ) at 12 months. In order to study host-microbe interactions, epithelial intestinal and mammary cell lines were exposed to milk microbes to assess the host response by interleukin (IL)-6 production as a potential inflammatory marker. BM was dominated by Staphylococcus and Streptococcus genera, and the most abundant cytokines were IL-6 and IL-18. Leptin levels were positively correlated with the pregestational body mass index (BMI). Higher relative abundance of the Streptococcus genus was associated with higher IL-10 and higher relative abundance of the Bifidobacterium genus was associated with lower IL-6 concentrations in milk. Infant WLZ at 12 months could be partially predicted by Streptococcus genus proportions and IL-10 and IL-18 levels in BM. BM microbiota significantly induced cytokine responses in mammary epithelial cells. Higher levels of IL-6 production were observed in mammary cells exposed to BM microbiota from mothers with ROW offspring compared to mothers with NOROW offspring. In conclusion, BM microbiota is related to the cytokine profile. IL-10 and IL-18 levels and the abundance of the Streptococcus genus could affect early infant development. Further research is needed to clarify the specific impact of BM microbiota and cytokines on infant growth and the risk of overweight.This work was supported by the research grant from the European Research Council under the European Union's Horizon 2020 research and innovation program (ERC starting grant, no. 639226) and La Marató-TV3 (DIM-2-ELI, ref. 2018-27/30-31). E. C.-M. was supported by a predoctoral fellowship from the Generalitat Valenciana—European Social Fund (GRISOLÍA2019). K. R.-A. holds a fellowship from the Spanish Ministry of Economy, Industry, and Competitiveness (FPU19/05150).Peer reviewe

Evaluation of Medicine Abuse Trends in Community Pharmacies: The Medicine Abuse Observatory (MAO) in a Region of Southern Europe

The misuse of medicines is a global public health concern that needs to be taken into consideration and requires actions across all government sectors and society. The aim of this study is to identify trends of drug abuse in Catalonia, a region of Spain located in the South of Europe. For this purpose, a questionnaire-based detection tool was created and implemented in 60 community pharmacies. Out of 548 questionnaires (98.4%), 64.2% of participants were men and the highest age proportion was 25–35 years (31.4%). Potential drug abuse was the highest in urban pharmacies (84.9%). The main drug class involved were benzodiazepines (31.8%), codeine (19.3%), tramadol (7.5%), methylphenidate (5.8%), gabapentinoids (5.8%), cycloplegic drops (4.4%), z-drugs (2.6%), piracetam (2.2%), dextromethorphan (1.6%) and clomethiazole (1.1%). The majority of drugs were requested without prescription (58.6%) and through probably forged prescriptions (23.7%). Slightly less than half (49.8%) of the patients request frequently to the pharmacist, especially in rural and mountain pharmacies (73.3% and 88.5%, respectively). A small proportion (10.8%) were requested with intimidation. Pharmacists only supplied in 21.7% of the cases. This study has demonstrated the suitability of the new detection system, being a useful approach to replicate in other locations with similar needs