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Angelo Antonini Thaís Armangué Caroline Arquizan Scott Ayton William Banks Brenda Banwell Giuseppe Barisano Frederik Barkhof Karen Barlow Erin Beck Heleen Beckerman Alim Louis Benabid Selim Benbadis James Bernat Geert Jan Biessels Laurent Billot Niels Birbaumer Gretchen Birbeck Bradley Boeve Hayrunnisa Bolay Carsten Bonnemann Marie-Germaine Bousser Carol Brayne Xandra Owen Breakefield Alexis Brice Vera Bril Fabienne Brilot Matthijs Brouwer Adrian Budhram Jean Marc Burgunder Paolo Calabresi Bruce Campbell Cheryl Carcel Francisco Cardoso Sandra Morais Cardoso María Carmona-Iragui Jean-Laurent Casanova Neil Cashman Valeria Caso Fernando Cendes Piu Chan Andreas Charidimou Jeremy Chataway K Ray Chaudhuri Lei Chen Adriano Chiò Tanuja Chitnis Soo-jin Cho Shu-Ling Chong Leonid Churilov Paola Cinque Hans Clusmann Jeffrey Cohen Johnathan Cooper-Knock John Corboy Philippe Corcia Dennis Cordato Mario Cornejo-Olivas Irene Cortese Ana Sofia Costa Shelagh Coutts Maria L Cuadrado Merit Cudkowicz Russell C Dale Kristen Dams-O’Connor Yves Dauvilliers Mamede de Carvalho Bart De Strooper Marianne de Visser Joris de Wit Sophie Demeret Christel Depienne Pascal Derkinderen Jean-Francois Desaphy Orrin Devinsky David Devos Massimiliano Di Filippo Vincenzo Di Lazzaro Ramon Diaz-Arrastia Sulayman D Dib-hajj Hans-Christoph Diener Birger Victor Dieriks Ding Ding Ruth Dobson Matthew Dodd Qiang Dong Anne Ducros Jaroslaw Dulski John Duncan Alexandra Durr H Henrik Ehrsson David Eidelberg Alberto Espay Paolo Eusebi Amelia Evoli Margherita Fabbri Dongsheng Fan Forough Farrokhyar Alfonso Fasano Camille Fauchon Michael Fehlings Anthony Feinstein Eva Feldman Wuwei Feng Luigi Ferini Strambi Pierre-Olivier Fernagut Clarissa Ferrari Thalia Field Anthony Figaji Massimo Filippi Richard Finkel Urs Fischer Kathryn C Fitzgerald Agnès Fleury Jennifer Fogarty Brent Fogel Gary A Ford Juan Fortea Nick Fox Jacqueline French Giovanni Frisoni Kaiming G Fu Qiushi Fu Cynthia Gagnon Marialuisa Gandolfi Ziv Gan-Or Justo Garcĺa de Yébenes Angela Genge Marco Geraci Markus Glatzel Joseph Gleeson Jennifer Goldman Philip B Gorelick Rebecca Gottesman Mayank Goyal Francesc Graus Ribas Lea Grinberg James C Grotta James Guest Tanya Gurevich Mark Hallett Roy H Hamilton Adam Handel Graeme Hankey Oskar Hansson Orla Hardiman Michael Harhay David Hasan Nobutaka Hattori Jeffrey Hausdorff Yulei He Jacqueline S Hebert Michael Heckman Luke Henderson Bettina Henzi Amanda Heslegrave Michael Hill Marius Hoeper Günter Höglinger Reinhard Hohlfeld Rita Horvath Michael Howell Salvador Ibáñez Micó Sarosh Irani Muireann Irish Rigmor Højland Jensen Yong Ji Jiyao Jiang Liqun Jiao Peng Jin Anne Joutel Steven Julious Larry Junck Angela Kaindl Lorraine Kalia Anita Kamondi Takashi Kanda Kejal Kantarci Mark Kelson Zoe Kelson Ashvini Keshavan Pooja Khatri Joep Killestein Han-Joon Kim Helen Kim Jun-ichi Kira Christine Klein Benzi Kluger Martin Kocher Masatoshi Koga Daniel Kondziella Igor Koralnik Diana Krause Florian Krismer Kishore Kumar Shenghan Kuo Gert Kwakkel Jean-Charles Lambert Gert Jan Lammers Susan Landau Anthony Lang Simona Lattanzi Weidong Le Victoria Leavitt Christine Lebrun Frenay Edward Lee Min Ae Lee-Kirsch Andrew J Lees Robin Lemmens Elizabeth Leroux Johannes Levin Simon John Geoffrey Lewis David Liebeskind Shen-Yang Lim Hester Lingsma Ming Liu Tobias Loddenkemper Andres Lozano Madia Lozupone Liming Lu Wei Luo Andrew Maas Antoinette MaassenVanDenBrink R Loch Macdonald Pedro Machado Priyanka Madaan Walter Maetzler Melinda Magyari Shumei Man Mohammad Ali Mansournia Niklas Marklund Raúl Martínez-Fernández Sheila Martins Mario Masellis Clio Mavragani Mikael Mazighi Kimford Meador Martin I Meltzer Benedict Michael Timothy Miller Wendy Mitchell Biswadev Mitra John Mitrofanis Dimos-Dimitrios Mitsikostas Javadpour Mohsen Brit Mollenhauer Rikke Møller Xavier Montalban Teshamae Monteith Lewis Morgenstern Takeshi Morimoto Elena Moro Meg Morris Robert W Motl Tahseen Mozaffar Susanne Muehlschlegel Keith Muir Thomas Müller Praveen V Mummaneni Srikanth Muppidi Merrilee Needham Virginia Newcombe Thanh Nguyen Agneta Nordberg John Norrie Jose Obeso John O’Brien Neil Edward O’Connell Hirokazu Oguni Adesola Ogunniyi Michael Okun Verónica Olavarría Osamu Onodera Simona Orcesi Johanna Ospel Michael O’Sullivan Mayowa Owolabi Jacqueline Palace Lina Palaiodimou Elizabeth Emma Palmer Jeyaraj Pandian Deborah Pareto Lucilla Parnetti Mark Parsons Patrizio Pasqualetti Archana Patel Jean-Francois Payen Lillian Pazvakawambwa Ekaterina Pechenkova Yann Péréon Alexandra Pérez Emilio Perucca Piero Perucca Susanne Petri Dzung Pham Fredrik Piehl Yolande Pijnenburg Jennie Ponsford Lawrence Poree Kathleen Poston Marie-Claude Potier Andrea Domenico Pratico Christopher Price Federica Provini Alejandro Rabinstein Bianca Raffaelli Michael Rafii Yusuf Rajabally Tarek Rajji Sudarshini Ramanathan Olivier Rascol Sabrina Ravaglia Paola Rebora Irena Rektorová Uwe Reuter Katy Rezvani Marc Ribo Alan S Rigby Peter Ringleb Gabriël Rinkel Nilo Riva Chiara Robba Maria Rocca María Rodríguez-Oroz Michele Romoli Jonathan Rosand Clark Rosen Owen Ross Xavier Rossello Jeffrey Rothstein Peter Rothwell Àlex Rovira Christopher Rowe Annemieke J M Rozemuller Peter Rudge Ruediger Rupp Altaf Saadi Simona Sacco Mohammad Ali Sahraian Christian Saleh Cristina Sampaio Rujipat Samransamruajkit Ley Sander Else Charlotte Sandset Patrick Santens Naveed Sattar Ingrid E Scheffer Nicholas Schiff Julie Schneider Lon Schneider Christiane Schneider-Gold Andreas Schulze-Bonhage Giorgio Scivoletto Barry Seemungal James Sejvar Gustavo Sevlever Pankaj Sharma Christopher Shaw Pamela Shaw Kevin Sheth Fu-Dong Shi Holly A Shill Ashkan Shoamanesh Andew Siderowf Vincenzo Silani Robert Silbergleit Andrew Singleton Pyry Sipilä Claudia Sommer Lili Song Maria Grazia Spillantini Tara L Spires-Jones Luciano A Sposato Werner Stenzel Katharina Stibrant Sunnerhagen A Jon Stoessl Pasquale Striano Stephen Strittmatter José Ignacio Suárez Thyagarajan Subramanian John Suckling Antonio Suppa Heidi Sutherland Shigeaki Suzuki Kevin Talbot Eng-King Tan Keiko Tanaka Cristina Tassorelli Hudson Gerry Taylor John-Paul Taylor Hélio Afonso Teive Charlotte Teunissen Avner Thaler Madhav Thambisetty Sudhin Thayyil Eric Peter Thelin Roland Thijs Götz Thomalla Alan Thompson Lars Timmermann Mathias Toft Antonio Toscano Kazunori Toyoda Anthony Traboulsee Georgios Tsivgoulis Shoji Tsuji Arianna Tucci Guillaume Turc Andrew Udy Osamu Uemura Akiyuki Uzawa Pedro Valdes-Sosa Leonard van den Berg Ingrid A F van der Mei Anneke Van der Walt Ruben van Eijk Thomas Van Essen Sampsa Vanhatalo Lidia Vaqué Rosario Vasta Vinata Vedam-Mai Elisa Vegezzi Marie Vidailhet Aleksandar Videnovic Sylvia Villeneuve John Vissing Antonio Vitobello Sabine Voigt Victor Volovici Ostoja (Steve) Vucic Waqar Waheed Mitch Wallin Sebastian Walsh Jithangi Wanigasinghe Steven Warach Joanna Wardlaw Jason Warren Mike Wattjes Rimona Weil Paul Weiss Patrick Wen Marieke Wermer A Clinton White Robyn N Whitney Heinz S Wiendl Tissa Wijeratne Edward Wild Zachary Wills Nina Wilson Andrea Winkler Thomas Wisniewski Max Wiznitzer Nicole Wolf Jean Woo Anna Woodbury John A Woolmore Selina Wray Weili Xu Shadi Yaghi Pinar Yalinay-Dikmen Chuanzhu Yan Riqiang Yan Pengfei Yang Yin Yang Gerald W Zamponi Phyllis Zee Inga Zerr Xin Zhang Zhentao Zhang Dong Zhou Wendy Ziai

The food enzyme rennet paste containing chymosin (EC 3.4.23.4), pepsin A (EC 3.4.23.1) and triacylglycerol lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) is prepared from the abomasum of suckling goats, lambs and calves by Caglificio Clerici S.p.A. The food enzyme is intended to be used in milk processing for cheese production. As no concerns arise from the animal source of the food enzyme, from its manufacture, and based on the history of safe use and consumption, the Panel considers that toxicological data were not required and no exposure assessment was necessary. On the basis of literature data, the Panel considers that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure could not be excluded, but the likelihood is considered to be low. Based on the data provided, the Panel concludes that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Exosomes participate in cell-to-cell communication, facilitated by the transfer of RNAs, proteins and lipids from donor to recipient cells. Exosomes and their RNA cargos do not exclusively originate from endogenous synthesis but may also be obtained from dietary sources such as the inter-species transfer of exosomes and RNAs in bovine milk to humans. Here, we assessed the bioavailability and distribution of exosomes and their microRNA cargos from bovine, porcine and murine milk within and across species boundaries. Milk exosomes labeled with fluorophores or fluorescent fusion proteins accumulated in liver, spleen and brain following suckling, oral gavage and intravenous administration in mice and pigs. When synthetic, fluorophore-labeled microRNAs were transfected into bovine milk exosomes and administered to mice, distinct species of microRNAs demonstrated unique distribution profiles and accumulated in intestinal mucosa, spleen, liver, heart or brain. Administration of bovine milk exosomes failed to rescue Drosha homozygous knockout mice, presumably due to low bioavailability or lack of essential microRNAs.

Oxytocin is a neuropeptide that is important for maternal physiology and childcare, including parturition and milk ejection during nursing 1 – 6 . Suckling triggers the release of oxytocin, but other sensory cues—specifically, infant cries—can increase the levels of oxytocin in new human mothers 7 , which indicates that cries can activate hypothalamic oxytocin neurons. Here we describe a neural circuit that routes auditory information about infant vocalizations to mouse oxytocin neurons. We performed in vivo electrophysiological recordings and photometry from identified oxytocin neurons in awake maternal mice that were presented with pup calls. We found that oxytocin neurons responded to pup vocalizations, but not to pure tones, through input from the posterior intralaminar thalamus, and that repetitive thalamic stimulation induced lasting disinhibition of oxytocin neurons. This circuit gates central oxytocin release and maternal behaviour in response to calls, providing a mechanism for the integration of sensory cues from the offspring in maternal endocrine networks to ensure modulation of brain state for efficient parenting. Experiments in mice identify a neural circuit that relays information about infant cries from the maternal auditory thalamus to hypothalamic oxytocin neurons to induce the release of oxytocin and modulate maternal behaviour.

Lactation is critical to infant short-term and long-term health and protects mothers from breast cancer, ovarian cancer and type 2 diabetes mellitus. The mammary gland is a dynamic organ, regulated by the coordinated actions of reproductive and metabolic hormones. These hormones promote gland development from puberty onwards and induce the formation of a branched, epithelial, milk-secreting organ by the end of pregnancy. Progesterone withdrawal following placental delivery initiates lactation, which is maintained by increased pituitary secretion of prolactin and oxytocin, and stimulated by infant suckling. After weaning, local cytokine production and decreased prolactin secretion trigger large-scale mammary cell loss, leading to gland involution. Here, we review advances in the molecular endocrinology of mammary gland development and milk synthesis. We discuss the hormonal functions of the mammary gland, including parathyroid hormone-related peptide secretion that stimulates maternal calcium mobilization for milk synthesis. We also consider the hormonal composition of human milk and its associated effects on infant health and development. Finally, we highlight endocrine and metabolic diseases that cause lactation insufficiency, for example, monogenic disorders of prolactin and prolactin receptor mutations, maternal obesity and diabetes mellitus, interventions during labour and delivery, and exposure to endocrine-disrupting chemicals such as polyfluoroalkyl substances in consumer products and other oestrogenic compounds.The mammary gland is responsible for lactation and is regulated by the coordinated actions of reproductive and metabolic hormones. This Review discusses the hormonal regulation of lactation, hormonal functions of the mammary gland, the hormone composition of human milk, and endocrine and metabolic diseases that cause lactation insufficiency.

Social behavior is a key component of pig welfare on farms, but little is known on the development of social behaviors in piglets. This study aimed to explore social behaviors and identify early social styles in suckling piglets. Social behaviors of 68 piglets from 12 litters were scored continuously for 8 h per day at 21 and 42 days of age, and were included in a Hierarchical Clustering on Principal Components analysis to identify clusters of pigs with similar social styles. Social nosing represented 78% of all social interactions given. Three social styles were identified: low-solicited inactive animals (inactive), active animals (active), and highly-solicited avoiders (avoiders). Belonging to a cluster was independent of age, but was influenced by sex, with females being more represented in the 'inactive' cluster, and males in the 'active' cluster, whereas both sexes were equally represented in the 'avoider' cluster. Stability of piglets' allocation to specific clusters over age was high in the 'inactive' (59%) and 'active' (65%) clusters, but low in the 'avoider' cluster (7%). Haptoglobin and growth rate were higher in 'active' than 'inactive' pigs, and intermediate in 'avoiders'. Our findings suggest the existence of transient social styles in piglets, likely reflective of sexual dimorphism or health status.

Early cow-calf separation prevents much of cows’ natural maternal behaviour. Early separation is thought to prevent the development of a cow-calf bond. To assess this bond, we measured motivation of dairy cows to reunite with their calf. To vary the degree of bonding, some cows were allowed continued contact with their calf and others were separated from their calf soon after birth, following standard practice on most farms. Among cows allowed continued contact, some were able to suckle their calf and others were prevented from suckling (by covering the cow’s udder with an udder net). Cows were habituated to the weighted-gate apparatus before calving by daily training with the (un-weighted) gate. After calving, cow willingness to use the gate was assessed by determining if she would push open the gate to access to her own calf. Testing occurred once daily, with weight on the gate gradually increased. After passing through the gate, the dam’s calf-directed behaviour was recorded. Suckled cows pushed a greater maximum weight (45.8 ± 7.8 kg) than separated cows (21.6 ± 6.7 kg) and non-suckled cows (24.3 ± 4.5 kg), with no differences between separated and non-suckled cows. Once reunited, latency to make nose contact and duration of licking did not differ between treatments. We conclude that motivation for calf contact is greater for cows that are suckled.

Abstract This study was conducted to compare the effects of adding sodium butyrate (SB), medium-chain fatty acids (MCFAs), or n-3 polyunsaturated fatty acids (n-3 PUFAs) to the diet of sows during late gestation and lactation on the reproductive performance of sows and the growth performance and intestinal health of suckling piglets. Twenty-four sows (Landrace × Large-White hybrid; third parity; 200 ± 15 kg) were randomly assigned to receive 1 of 4 diets: basal diet (control group), basal diet + 1 g SB/kg (SB group), basal diet + 7.75 g MCFA/kg (MCFA group), or basal diet + 68.2 g n-3 PUFA/kg (n-3 PUFA group). The experiment began on day 85 of gestation and ended day 22 of lactation. Colostrum samples were collected from each sow. After the experiment, blood and tissue samples were collected from 1 randomly selected piglet. The results showed that the weaning-to-estrus interval of sows in the SB, MCFA, and n-3 PUFA groups was shorter than that of sows in the control group (P < 0.05). The incidence of diarrhea in suckling piglets in the SB, MCFA, and n-3 PUFA groups was lower than that of piglets in the control group (P < 0.05). The fat, protein, IgA, IgG, and IgM concentration in colostrum from sows increased following dietary supplementation with SB, MCFA, or n-3 PUFA (P < 0.05). Comparison with the control group, the mRNA expression of claudin-1, zona occludens 1, and interleukin-10 increased in the jejunum mucosa of suckling piglets in the SB, MCFA, and n-3 PUFA groups, while that of TLR4 decreased (P < 0.05). Compared with the control group, the Chao1 and ACE indexes of microbial flora in the colon contents of piglets in the SB, MCFA, and MCFA groups increased (P < 0.05), while the relative abundance of Firmicutes, Actinobacteria, and Synergistetes decreased at the phylum level (P < 0.05). In conclusion, during late pregnancy and lactation, dietary SB supplementation had a greater effect on intestinal health and caused a greater decrease in preweaning mortality of suckling piglets than did dietary MCFA or n-3 PUFA supplementation; dietary MCFA supplementation shortened the weaning-to-estrus interval of sows to a greater extent than did dietary SB or n-3 PUFA supplementation; and dietary n-3 PUFA supplementation increased the fat and protein content in the colostrum to the greatest extent.

IntroductionConsensus guidelines on sedation in breastfeeding were published by the Association of Anaesthetists in 2020. This was in response to concerns about breastfeeding women receiving inconsistent advice, and breastfeeding being interrupted unnecessarily. This can put women at risk of complications such as mastitis and issues with milk supply, and can cause undue distress to both mother and child. Breastfeeding can continue uninterrupted after single doses of midazolam or fentanyl, and expressing and discarding milk is not required. This survey assessed the confidence and knowledge of endoscopy staff encountering breastfeeding patients, with specific attention to sedation and bowel preparation.MethodsAn online survey was distributed to gastroenterology and endoscopy services and to gastroenterology specialty trainees in the North Western Deanery, between June and September 2023.ResultsThirty-three endoscopists and 17 endoscopy nursing staff responded. Confidence in managing sedation was favourable in both staff groups, although nurses reported lower confidence in advising about bowel preparation. Across both staff groups, between a third and one half of respondents believed feeding should be delayed following midazolam or fentanyl, and 39% of endoscopists stated that they routinely advise breastfeeding patients to express and discard milk after having sedation. Of the respondents who agreed with expressing and discarding, 69% felt that this should be done for 24 hours or more. Only 3 respondents were aware of the Association of Anaesthetists guidelines, and awareness of prescribing resources specific to breastfeeding was poor. Only 52% of endoscopists and 35% of endoscopy nurses correctly stated that feeding could continue uninterrupted after sedation.ConclusionsConfidence and practices in both bowel preparation and sedation for breastfeeding patients are variable in both endoscopists and endoscopy nursing staff. Adherence to guidelines is inconsistent. Endoscopy services should consider improving staff awareness of these guidelines and developing local policy to ensure consistent and evidence-based care is being delivered to this patient group. Since the completion of this study, up to date recommendations have been made in the British Society of Gastroenterology guidelines on sedation in gastrointestinal endoscopy (2023). In response to our results, a Standard Operating Procedure is being developed for our Trust to ensure consistent care delivery.

Enteric viruses like norovirus, rotavirus and astrovirus have long been accepted as spreading in the population through fecal–oral transmission: viruses are shed into feces from one host and enter the oral cavity of another, bypassing salivary glands (SGs) and reaching the intestines to replicate, be shed in feces and repeat the transmission cycle 1 . Yet there are viruses (for example, rabies) that infect the SGs 2 , 3 , making the oral cavity one site of replication and saliva one conduit of transmission. Here we report that enteric viruses productively and persistently infect SGs, reaching titres comparable to those in the intestines. We demonstrate that enteric viruses get released into the saliva, identifying a second route of viral transmission. This is particularly significant for infected infants, whose saliva directly transmits enteric viruses to their mothers’ mammary glands through backflow during suckling. This sidesteps the conventional gut–mammary axis route 4 and leads to a rapid surge in maternal milk secretory IgA antibodies 5 , 6 . Lastly, we show that SG-derived spheroids 7 and cell lines 8 can replicate and propagate enteric viruses, generating a scalable and manageable system of production. Collectively, our research uncovers a new transmission route for enteric viruses with implications for therapeutics, diagnostics and importantly sanitation measures to prevent spread through saliva. Enteric viruses replicate in salivary glands, can be propagated in salivary gland-derived spheroids and cell lines, and are released into saliva, which is a new transmission route having implications for therapeutics, diagnostics and sanitation measures.