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BackgroundIgA and its secretory form sIgA impact protection from infection and necrotising enterocolitis but little is known about quantities in preterm mums own milk (MOM) or infant stool, onset of endogenous production in the preterm gut, and what affects these.MethodsWe measured by ELISA in MOM and stool from healthy preterm infants total IgA and sIgA longitudinally and additionally in MOM fresh, refrigerated, frozen, and after traversing feeding systems.ResultsIn 42 MOM (median gestation 26 weeks), we showed total IgA levels and sIgA were highest in colostrum, fell over 3 weeks, and were not impacted by gestation. Median IgA values matched previous term studies (700 mcg/ml). In MOM recipients stool IgA was detected in the first week, at around 30% of MOM quantities. Formula fed infants did not have detectable stool IgA until the third week. Levels of IgA and sIgA were approximately halved by handling processes.ConclusionsMOM in the 3 weeks after preterm delivery contains the highest concentrations of IgA and sIgA. Endogenous production after preterm birth occurs from the 3 week meaning preterm infants are dependent on MOM for IgA which should be optimised. Routine NICU practices halve the amount available to the infant.Impact(Secretory) Immunoglobulin A (IgA) is present in colostrum of maternal milk from infants as preterm as 23–24 weeks gestational age, falling over the first 3 weeks to steady levels similar to term.Gestation at birth does not impact (secretory) IgA levels in breast milk.IgA is present in very preterm infant stools from maternal milk fed infants from the first week of life, but not in formula milk fed preterm infants until week three, suggesting endogenous production from this point.Refrigeration, freezing, and feeding via plastic tubing approximately halved the amount of IgA available.

ObjectiveNecrotising enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm infants. The underlying mechanisms are poorly understood: mother’s own breast milk (MOM) is protective, possibly relating to human milk oligosaccharide (HMO) and infant gut microbiome interplay. We investigated the interaction between HMO profiles and infant gut microbiome development and its association with NEC.DesignWe performed HMO profiling of MOM in a large cohort of infants with NEC (n=33) with matched controls (n=37). In a subset of 48 infants (14 with NEC), we also performed longitudinal metagenomic sequencing of infant stool (n=644).ResultsConcentration of a single HMO, disialyllacto-N-tetraose (DSLNT), was significantly lower in MOM received by infants with NEC compared with controls. A MOM threshold level of 241 nmol/mL had a sensitivity and specificity of 0.9 for NEC. Metagenomic sequencing before NEC onset showed significantly lower relative abundance of Bifidobacterium longum and higher relative abundance of Enterobacter cloacae in infants with NEC. Longitudinal development of the microbiome was also impacted by low MOM DSLNT associated with reduced transition into preterm gut community types dominated by Bifidobacterium spp and typically observed in older infants. Random forest analysis combining HMO and metagenome data before disease accurately classified 87.5% of infants as healthy or having NEC.ConclusionThese results demonstrate the importance of HMOs and gut microbiome in preterm infant health and disease. The findings offer potential targets for biomarker development, disease risk stratification and novel avenues for supplements that may prevent life-threatening disease.

Placement of gastric feeding tubes in preterm babies should be without excessive force and by, or under the supervision of, experienced staff. Conservative management of oesophageal perforation is treatment of choice after removal of the gastric tube.1 The diagnosis can be confirmed using water-soluble contrast (figure 2A). Oesophageal surgery in extremely preterm babies is technically challenging and not tolerated as well as by more mature babies.2 Healing is usually rapid in preterm babies and so conservative management is feasible, using parenteral nutrition and antibiotics, without major impact on the baby.3 Healing of the perforation (at 7–10 days) can be confirmed by carefully instilling oral water-soluble contrast (oesophagraphy).

Purpose To identify, evaluate and synthesise studies examining the barriers and enablers for survivors of critical illness to participate in physical activity in the ICU and post-ICU settings from the perspective of patients, caregivers and healthcare providers. Methods Systematic review of articles using five electronic databases: MEDLINE, CINAHL, EMBASE, Cochrane Library, Scopus. Quantitative and qualitative studies that were published in English in a peer-reviewed journal and assessed barriers or enablers for survivors of critical illness to perform physical activity were included. Prospero ID: CRD42016035454. Results Eighty-nine papers were included. Five major themes and 28 sub-themes were identified, encompassing: (1) patient physical and psychological capability to perform physical activity, including delirium, sedation, illness severity, comorbidities, weakness, anxiety, confidence and motivation; (2) safety influences, including physiological stability and concern for lines, e.g. risk of dislodgement; (3) culture and team influences, including leadership, interprofessional communication, administrative buy-in, clinician expertise and knowledge; (4) motivation and beliefs regarding the benefits/risks; and (5) environmental influences, including funding, access to rehabilitation programs, staffing and equipment. Conclusions The main barriers identified were patient physical and psychological capability to perform physical activity, safety concerns, lack of leadership and ICU culture of mobility, lack of interprofessional communication, expertise and knowledge, and lack of staffing/equipment and funding to provide rehabilitation programs. Barriers and enablers are multidimensional and span diverse factors. The majority of these barriers are modifiable and can be targeted in future clinical practice.

A 3-year-old neutered male Posavac Hound presented with rapidly progressive cervical swelling, respiratory distress, and systemic inflammation. Diagnostics confirmed severe hypothyroidism [total thyroxine (TT4) < 0.5 μg/dL, thyroid-stimulating hormone (TSH) 5.54 ng/dL], elevated thyroglobulin autoantibodies (TgAA 131%), hyperglobulinemia, hypoalbuminemia, and mild ionized hypercalcemia. Imaging showed bilateral thyroid enlargement with cavitated necrosis, pulmonary nodules, and lymphadenopathy. Cytology revealed pyogranulomatous inflammation without infectious organisms, and infectious disease screening was negative. Protein electrophoresis and immunofixation revealed elevated IgG4, suggesting immune-mediated dysregulation. The dog responded rapidly to prednisolone and thyroid hormone supplementation, with resolution of clinical signs and normalization of inflammatory markers by ~60 days. This report describes a unique case of immune-mediated thyroiditis with systemic inflammatory involvement that responded to steroids, emphasizing the importance of considering immune-mediated thyroiditis as a differential diagnosis for acute cervical neck swelling in a young dog with concurrent pulmonary involvement.

Background Haematological cancer affects more than 1.3 million people around the world annually and accounted for almost 800,000 deaths globally in 2020. The number of patients with these cancers undergoing bone marrow transplant is increasing. Of note, this intensive treatment is associated with complex and multifactorial side effects, often impacting nutritional status, physical functioning and overall health-related quality of life. The primary aim of this study is to investigate the effectiveness of an eight-week multidisciplinary rehabilitation intervention compared with usual care on the physical function domain of the European Organisation for the Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30 version 3) in patients with haematological cancer following bone marrow transplant. Methods This is a multisite, pragmatic two-arm parallel-group, randomised controlled trial (RCT) with stratified randomisation, powered for superiority, recruiting 170 participants at 30 days following either allogeneic or autologous bone marrow transplant (ACTRN12622001071718). Recruitment sites include three Australian university affiliated teaching hospitals. Participants are eligible if aged ≥ 18 years, treated for haematological cancer with allogeneic or autologous bone marrow transplant and can walk independently. The intervention group will receive eight weeks of twice weekly telehealth-based exercise classes, an initial and follow up dietetics consult, post exercise protein supplements, and a home-based physical activity program, all with embedded behaviour change strategies. The primary outcome is patient reported physical function measured using the EORTC QLQ-C30 version 3. Secondary outcomes include other domains of the EORTC QLQ-C30, fatigue, physical function, physical activity levels, frailty, body composition, sarcopenia and nutrition assessment. We will also undertake a health economic analysis alongside the trial and a process evaluation exploring intervention fidelity, causal mechanisms as well as contextual influences through qualitative enquiry. Discussion The REBOOT trial will add RCT-evidence from a rigorously conducted, statistically powered multi-site trial to existing limited knowledge on the effects of multi-disciplinary rehabilitation for people with haematological cancer. If effectiveness is supported, then implementation of rehabilitation into care pathways for people having bone marrow transplant can be considered. Trial registration ACTRN12622001071718 prospectively registered 03/08/2022, last updated 08/03/2024.

Dopamine function and reward processing are highly interrelated and involve common brain regions afferent to the nucleus accumbens, within the mesolimbic pathway. Although dopamine function and reward system neural activity are impaired in most psychiatric disorders, it is unknown whether alterations in the dopamine system underlie variations in reward processing across a continuum encompassing health and these disorders. We explored the relationship between dopamine function and neural activity during reward anticipation in 27 participants including healthy volunteers and psychiatric patients with schizophrenia, depression, or cocaine addiction, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) multimodal imaging with a voxel-based statistical approach. Dopamine transporter (DAT) availability was assessed with PET and [11 C]PE2I as a marker of presynaptic dopamine function, and reward-related neural response was assessed using fMRI with a modified Monetary Incentive Delay task. Across all the participants, DAT availability in the midbrain correlated positively with the neural response to anticipation of reward in the nucleus accumbens. Moreover, this relationship was conserved in each clinical subgroup, despite the heterogeneity of mental illnesses examined. For the first time, a direct link between DAT availability and reward anticipation was detected within the mesolimbic pathway in healthy and psychiatric participants, and suggests that dopaminergic dysfunction is a common mechanism underlying the alterations of reward processing observed in patients across diagnostic categories. The findings support the use of a dimensional approach in psychiatry, as promoted by the Research Domain Criteria project to identify neurobiological signatures of core dysfunctions underling mental illnesses.

Streptococcus agalactiae (Group B Streptococcus , GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates. Group B streptococci (GBS) started causing serious infections in newborn babies in the 1960s. Here, the authors show that the emergence of GBS diseases was associated with worldwide dissemination of a few clones that were resistant to tetracycline, an antibiotic that became widely used in the 1950s.

Objective Hundreds of scientific publications are produced annually that involve the measurement of cortisol in saliva. Intra- and inter-laboratory variation in salivary cortisol results has the potential to contribute to cross-study inconsistencies in findings, and the perception that salivary cortisol results are unreliable. This study rigorously estimates sources of measurement variability in the assay of salivary cortisol within and between established international academic-based laboratories that specialize in saliva analyses. One hundred young adults ( Mean age : 23.10 years; 62 females) donated 2 mL of whole saliva by passive drool. Each sample was split into multiple- 100 µL aliquots and immediately frozen. One aliquot of each of the 100 participants’ saliva was transported to academic laboratories (N = 9) in the United States, Canada, UK, and Germany and assayed for cortisol by the same commercially available immunoassay. Results 1.76% of the variance in salivary cortisol levels was attributable to differences between duplicate assays of the same sample within laboratories, 7.93% of the variance was associated with differences between laboratories, and 90.31% to differences between samples. In established - qualified laboratories, measurement error of salivary cortisol is minimal, and inter-laboratory differences in measurement are unlikely to have a major influence on the determined values.

Emergency medical services (EMS) are critical in the treatment of ST-segment elevation myocardial infarction (STEMI). Prehospital system delays are an important target for improving timely STEMI care, yet few limited data are available. Using a deterministic approach, we merged EMS data from the North Carolina Pre-hospital Medical Information System (PreMIS) with data from the Reperfusion of Acute Myocardial Infarction in Carolina Emergency Departments—Emergency Response (RACE-ER) Project. Our sample included all patients with STEMI from June 2008 to October 2010 who arrived by EMS and who had primary percutaneous coronary intervention (PCI). Prehospital system delays were compared using both RACE-ER and PreMIS to examine agreement between the 2 data sources. Overall, 8,680 patients with STEMI in RACE-ER arrived at a PCI hospital by EMS; 21 RACE-ER hospitals and 178 corresponding EMS agencies across the state were represented. Of these, 6,010 (69%) patients were successfully linked with PreMIS. Linked and notlinked patients were similar. Overall, 2,696 patients were treated with PCI only and were taken directly to a PCI-capable hospital by EMS; 1,750 were transferred from a non-PCI facility. For those being transported directly to a PCI center, 53% reached the 90-minute target guideline goal. For those transferred from a non-PCI facility, 24% reached the 120-minute target goal for primary PCI. We successfully linked prehospital EMS data with inhospital clinical data. With this linked STEMI cohort, less than half of patients reach goals set by guidelines. Such a data source could be used for future research and quality improvement interventions.