Search

BACKGROUND: Human milk oligosaccharides (HMOs) are an abundant class of compounds found in human milk and have been linked to the development of the infant, and specifically the brain, immune system, and gut microbiome. OBJECTIVES: Advanced analytical methods were used to obtain relative quantitation of many structures in approximately 2000 samples from over 1000 mothers in urban, semirural, and rural sites across geographically diverse countries. METHODS: LC-MS−based analytical methods were used to profile the compounds with broad structural coverage and quantitative information. The profiles revealed their structural heterogeneity and their potential biological roles. Comparisons of HMO compositions were made between mothers of different age groups, lactation periods, infant sexes, and residing geographical locations. RESULTS: A common behavior found among all sites was a decrease in HMO abundances during lactation until approximately postnatal month 6, where they remained relatively constant. The greatest variations in structural abundances were associated with the presence of α(1,2)-fucosylated species. Genomic analyses of the mothers were not performed; instead, milk was phenotyped according to the abundances of α(1,2)-fucosylated structures. Mothers from the South American sites tended to have higher proportions of phenotypic secretors [mothers with relatively high concentrations of α(1,2)-fucosylated structures] in their populations compared to the rest of the globe, with Bolivia at ∼100% secretors, Peru at ∼97%, Brazil at ∼90%, and Argentina at ∼85%. Conversely, the cohort sampled in Africa manifested the lowest proportion of secretors (South Africa ∼ 63%, the Gambia ∼ 64%, and Malawi ∼ 75%). Furthermore, we compared total abundances of HMOs in secretors compared with nonsecretors and found that nonsecretors have lower abundances of HMOs compared to secretors, regardless of geographical location. We also observed compositional differences of the 50+ most abundant HMOs between milk types and geographical locations. CONCLUSIONS: This study represents the largest structural HMO study to date and reveals the general behavior of HMOs during lactation among different populations.

Motoneurons are one of the highest energy demanding cell types and a primary target in Amyotrophic lateral sclerosis (ALS), a debilitating and lethal neurodegenerative disorder without currently available effective treatments. Disruption of mitochondrial ultra-structure, transport and metabolism is a commonly reported phenotype in ALS models and can critically affect survival and proper function of motor neurons. However, how changes in metabolic rates contribute to ALS progression are not fully understood yet. Here we utilize hiPCS derived motoneuron cultures and live imaging quantitative techniques to evaluate metabolic rates in Fused in Sarcoma (FUS)-ALS model cells. We show that differentiation and maturation of motoneurons is accompanied by an overall upregulation of mitochondrial components and significant increase in metabolic rates that corresponds to their high energy-demanding state. Detailed compartment-specific live measurements using a fluorescent ATP sensor and FLIM imaging show significantly lower levels of ATP in the somas of cells carrying FUS-ALS mutations. These changes lead to the increased vulnerability of disease motoneurons to further metabolic challenges with mitochondrial inhibitors and could be due to the disruption of mitochondrial inner membrane integrity and an increase in its proton leakage. Furthermore, our measurements demonstrate heterogeneity between axonal and somatic compartments with lower relative levels of ATP in axons. Our observations strongly support the hypothesis that mutated FUS impacts metabolic states of motoneurons and makes them more susceptible to further neurodegenerative mechanisms.

Previous methods used to infer axon diameter distributions using magnetic resonance imaging (MRI) primarily use single diffusion encoding sequences such as pulsed gradient spin echo (PGSE) and are thus sensitive to axons of diameters >5 μm. We applied oscillating gradient spin echo (OGSE) sequences to study human axons in the 1–2 μm range in the corpus callosum, which include the majority of axons constituting cortical connections. The ActiveAx model was applied to calculate the fitted mean effective diameter for axons (AxD) and was compared with values found using histology. Axon diameters from histological data were calculated using three different datasets; true diameters (minimum diameter), a combination of minimum and maximum diameters, and diameters measured across a consistent diffusion direction. The AxD estimates from MRI were 1.8 ± 0.1 μm to 2.34 ± 0.04 μm with an average of 2.0 ± 0.2 μm for the ActiveAx model. The histology AxD values were 1.43 ± 0.02 μm when using the true minimum axon diameters, 5.52 ± 0.02 μm when using the combination of minimum and maximum axon diameters, and 2.20 ± 0.02 μm when collecting measurements across a consistent diffusion direction. This experiment demonstrates the first known usage of OGSE to calculate axon diameters in the human corpus callosum on a 1–2 μm scale. The importance for the model to account for axonal orientation dispersion is indicated by histological results which more closely match the MRI model results depending on the direction of axon diameter measurements. These initial steps using this non-invasive imaging method can be applied to future methodology to develop in vivo axon diameter measurements in human brain tissue.

Einleitung Seit Mai 2020 wurden die ersten POC Tests für die SARS-CoV-2 Diagnostik angeboten, welche mit der Notwendigkeit des nasopharyngealen Abstrichs verbunden waren. Aufgrund des langen Arbeitskanals durch die Nasenhaupthöhle besteht das Risiko einer Schleimhautverletzung mit konsekutiver Epistaxis. Methodik Wir beschreiben den Krankheitsverlauf zweier Patientinnen, bei denen es nach extern durchgeführtem nasopharyngealen Test zu einer massiven interventionspflichtigen Epistaxis nasi kam. Ergebnisse Bei einer Patientin musste nach frustraner Nasentamponade eine endonasale Blutstillung in Intubationsnarkose durchgeführt werden. Bei einer zweiten Patientin kam es zu einer Hb-relevanten Epistaxis nasi mit hämorrhagischem Schock. Sie wurde intubiert und beatmet stationär übernommen. Schlussfolgerung Der transnasale Test in der SARS-CoV-2 Diagnostik führt in seltenen Fällen zu lebensbedrohlichen Komplikationen. Aufgrund der weltweit über 5 Millionen täglich durchgeführten Tests im Rahmen der aktuellen Pandemie sind Komplikationen nicht zu vernachlässigen. Es ist unverzichtbar, dass die den Abstrich durchführende Person die Anatomie detailliert kennt. Alternative Testmethoden werden bezüglich ihrer Sensitivität weiter beurteilt. Hinsichtlich der auch zukünftig bestehenden Notwendigkeit von SARS-CoV-2-Tests ist eine weitere Etablierung alternativer und risikoärmerer Testverfahren unerlässlich.

In recent decades, Bolivia has expanded maternal and child health insurance coverage to improve access to prenatal and early life health care. Nationally, however, maternal and child health disparities persist along a rural-urban divide. Research is needed among rural populations to better understand local barriers to health care access and usage. Particularly among Indigenous populations, disparities may be compounded by differences in preferences for and access to traditional versus biomedical health care. We examined prenatal care and birth practices among Tsimane forager-farmers of El Beni, Bolivia. From 2012–2013, we interviewed 151 Tsimane mothers (0–35 months postpartum) from nine villages about birth and neonatal care practices, prenatal care, and pharmaceutical usage during labour and postpartum recovery. Results demonstrate local disparities in biomedical care usage by ease of access (e.g. proximity to market town, Spanish fluency), and maternal experience (e.g. parity and prior offspring death or miscarriage). While 59% of interviewed mothers had received at least one prenatal screening, services performed in screenings were limited. Nearly all women continue to birth at home with family assistance. Inconsistent access to health care services may be exacerbated by regional, generational, and educational disparities within the population.

The aim of the study was to explore children’s conceptions of morality, specifically the meanings children assigned to situations of morality. The participants were eight to eleven-year-old childre...

The advent of highly effective treatments targeting the disease biology of chronic lymphocytic leukemia (CLL) has transformed the therapeutic field tremendously. However, transformation into an aggressive B-cell lymphoma, called Richter syndrome (RS), remains highly challenging since the treatment options for this condition are still insufficient. Exploratory drug testing and experimental studies are restricted by the lack of satisfactory models. We have established U-RT1, a cell line derived from a highly proliferating RS clonally related to the patient's underlying CLL. The cell line shows morphological features and an immunophenotype of RS-DLBCL (non-GCB). Molecular analysis revealed a complex karyotype with driver aberrations characteristic for RS such as loss of TP53 and CDKN2A. Furthermore, U-RT1 displays a chromosomal gain of the NOTCH1 gene locus and strong immunoreactivity for BCL-2. These features suggest that U-RT1 is the first eligible model system for investigations on the pathogenesis of RS and novel treatment options. CA extern

Background/Aims The Bath Ankylosing Spondylitis Metrology Index (BASMI) is used in the monitoring of those living with axial spondyloarthritis (axSpA); it is the recommended and validated measure of movement in this patient group. As a physical outcome measure its use has been challenging during the COVID-19 pandemic. The aim of this project is to assess the current application of the BASMI in axSpA services across the UK. Methods A survey was devised to explore when the BASMI is used, by whom and the reasons for its use. The AStretch committee reviewed and re-drafted the questions. The survey was shared across multiple platforms and email professional distribution lists, and was open 2nd-12th October 2021. Results 74 UK healthcare professionals completed the survey. It is mostly physiotherapists who undertake the BASMI (69%); some other clinicians also measure: nurses (10%), medics (9%), physiotherapy support workers (10%), healthcare support workers (2%). Confidence in performing the BASMI averaged at 3.5/5. The majority of respondents record the BASMI in the electronic record (73%); app-based solutions are developing (7%) and paper-only recording diminishing (20%). When asked about frequency, most respondents (73%) recorded “it depends”, implying that the BASMI is used on an individual patient basis. Table 1 presents data with regards to why the BASMI is undertaken, scored by participant ranking, and free text responses about reasons for use. Conclusion A large sample size was recruited for this survey, implying a good level of interest in better understanding the current application of the BASMI. It is evident clinicians use the BASMI on newly-diagnosed patients as a priority in their assessment and shared-decision making. Other aspects such as addressing poor movement and adherence to exercise are ranked highly. The reported reasons for BASMI use are varied, and its application not standardised across UK rheumatology teams. This might reflect the diverse trajectory of axSpA and the importance of seeing patients as individuals. How and why we undertake physical outcome measures is crucial for consideration as we currently consider remote versus face-to-face consult pathways for our axSpA cohort. There is enough evidence here to recommend ongoing, regular application of the BASMI in a traditional face-to-face setting. Disclosure K. Weight: None. W.J. Gregory: Honoraria; W.G. has received speaker, conference registration and advisory board fees from Abbvie, Pfizer Novartis and UCB. H. Chambers: None. E. Clarke: Honoraria; E. C. has received speaker fees from Novartis UK. M. Daly: None. A. Davie: None. J.C. Elkins: None. S. Gaikwad: None. H. Harrison: None. C. Longton: Shareholder/stock ownership; C.L. is a shareholder in Astra Zeneca. Honoraria; C.L. has received speaker fees from Novartis. M. Martin: Honoraria; M.M. has received speaker, conference registration and advisory board fees from Abbvie, Novartis (not since 2018). Grants/research support; M.M. received grant monies from the National Axial Spondyloarthritis Society in 2017. M. Motion: None. S. Voules: None. M. McDonald: None. C. Jeffries: Honoraria; C.J. has received speaker, conference registration and advisory board fees from Abbvie, Pfizer, Novartis and UBC.

Background Modern treat-to-target approaches to rheumatoid arthritis (RA) involve frequent monitoring of disease activity with the goal of disease remission or a low disease activity. The Rheumatoid Arthritis Impact of Disease (RAID) is a multidimensional, validated patient-reported outcome measure that covers seven domains, which has been found to discriminate between active and non-active disease. Applying smartphone apps to monitoring of RA is described as an innovation which has been implemented in the UK and USA. The proposed study will evaluate the feasibility of scaled implementation of a remote monitoring service based on RAID for eligible patients with RA at three NHS organisations (trusts) in south east London, UK. Methods Pragmatic formative service evaluation study informed by implementation theory and incorporating the perspectives of RA service users throughout. The study will follow a multi-method approach. Rapid evidence review will be carried out to identify implementation approaches used in similar services. Quantitative data will be collected from a cross-sectional sample of service users through a web-based questionnaire assessing patient satisfaction, as well as service-level data routinely collected by trusts and from the remote monitoring system and documentation produced in developing and implementing the remote monitoring service. Qualitative data will be collected from approximately 30 clinical and non-clinical staff and 20-30 patients purposively sampled to conduct semi-structured interviews to explore their perspectives on remote monitoring in RA. The evaluation will be supported by established implementation frameworks, including EPIS (Exploration, Preparation, Implementation and Sustainment) and COM-B (Capability-Opportunity-Motivation-Behaviour), which will be used to guide data generation and to inform the framework analysis of qualitative data. Discussion This pragmatic study will enhance the understanding of implementation process and outcomes and will explore the potential to scale up the remote monitoring system in RA. A larger scale hybrid study can be designed based on the dataset the current study will produce to offer definitive clinical and implementation evaluation.

This study examines the care work of teachers employed at two schools in situations of severe deprivation. At the teachers’ places of employment, basic amenities and complementary support structure...

Since May 2020, the first nasopharyngeal POC tests for SARS-CoV-2 diagnostic have been available. Due to the long passage through the nasal cavity, there is a risk of injury with subsequent epistaxis.We describe the course of disease of two female patients who suffered from massive epistaxis requiring intervention after an externally performed nasopharyngeal swab.After nasal tamponade, one patient underwent clipping of the sphenopalatine artery under general anesthesia. The other patient suffered from nasal bleeding with hemorrhagic shock requiring transfusion. She was intubated and admitted to our hospital.The nasopharyngeal swab for diagnosis of SARS-CoV-2 can lead to life-threatening complications in rare cases. Considering that daily more than 5 million corona tests are being carried out worldwide as part of the current pandemic, complications should not be neglected. It is necessary that the person performing the swab has a detailed understanding of the anatomy involved. Alternative test methods were further assessed with regard to their sensitivity. With regard to the future need for SARS-CoV-2 tests, alternative and lower-risk test procedures must be investigated and established.Seit Mai 2020 wurden die ersten POC Tests für die SARS-CoV-2 Diagnostik angeboten, welche mit der Notwendigkeit des nasopharyngealen Abstrichs verbunden waren. Aufgrund des langen Arbeitskanals durch die Nasenhaupthöhle besteht das Risiko einer Schleimhautverletzung mit konsekutiver Epistaxis.Wir beschreiben den Krankheitsverlauf zweier Patientinnen, bei denen es nach extern durchgeführtem nasopharyngealen Test zu einer massiven interventionspflichtigen Epistaxis nasi kam.Bei einer Patientin musste nach frustraner Nasentamponade eine endonasale Blutstillung in Intubationsnarkose durchgeführt werden. Bei einer zweiten Patientin kam es zu einer Hb-relevanten Epistaxis nasi mit hämorrhagischem Schock. Sie wurde intubiert und beatmet stationär übernommen.Der transnasale Test in der SARS-CoV-2 Diagnostik führt in seltenen Fällen zu lebensbedrohlichen Komplikationen. Aufgrund der weltweit über 5 Millionen täglich durchgeführten Tests im Rahmen der aktuellen Pandemie sind Komplikationen nicht zu vernachlässigen. Es ist unverzichtbar, dass die den Abstrich durchführende Person die Anatomie detailliert kennt. Alternative Testmethoden werden bezüglich ihrer Sensitivität weiter beurteilt. Hinsichtlich der auch zukünftig bestehenden Notwendigkeit von SARS-CoV-2-Tests ist eine weitere Etablierung alternativer und risikoärmerer Testverfahren unerlässlich.

Objective: We tested qualitative metasynthesis of a series of Hermeneutic Single Case Efficacy Design (HSCED) studies as a method for comparing within-session processes that may explain good and poor therapeutic outcome. Method: We selected eight HSCED studies according to change in clients' scores on the Strathclyde Inventory (SI), a brief self-report instrument used to measure outcome in person-centered psychotherapy. Four of the case studies investigated the experience of clients whose pre-post change in SI scores showed improvement by the end of therapy, and the other four focused on clients whose change in SI scores indicated deterioration. We conducted a qualitative metasynthesis, adopting a generic descriptive-interpretive approach to analyze and compare the data generated by the HSCED studies. Results: In contrast to improvers, deteriorators appeared to be less ready to engage in therapeutic work at the beginning of therapy, and found the process more difficult; their therapists were less able to respond to these difficulties in a responsive, empathic manner; deteriorators were less able to cope successfully with changes of therapist and, eventually, gave up on therapy. Conclusion: We found that our qualitative metasynthesis of a series of HSCED studies produced a plausible explanation for the contrasting outcomes that occurred.

Background and objectives Cesarean section may lead to suboptimal breastfeeding outcomes, though evidence has been mixed. Factors, such as premature birth, birth weight and maternal age may independently increase risk of cesarean and hinder breastfeeding initiation, while maternal preferences, support and sociostructural barriers may influence breastfeeding practices beyond the immediate postpartum period. Methodology We assessed impacts of cesarean section and gestational factors on breastfeeding duration among Indigenous Qom mothers in Argentina who have strong traditional breastfeeding support. We modeled transitions from exclusive breastfeeding to complementary feeding and from complementary feeding to full weaning in a Bayesian time-to-event framework with birth mode and gestational covariates (n = 89 infants). Results Estimated median time to full weaning was 30 months. Cesarean-delivered babies were weaned an average of 5 months later adjusting for gestational age, maternal parity and infant sex. No factors were associated with time-to-complementary feeding, and time-to-complementary feeding was not associated with time-to-full weaning. Conclusions and implications Among Indigenous Qom mothers in Argentina, cesarean section was not associated with suboptimal breastfeeding outcomes. Although some Qom mothers do experience early breastfeeding problems, particularly following first birth, problems are not more frequent following cesarean delivery. Traditional postpartum kin and community support during prolonged postpartum periods may be instrumental in helping mothers to overcome early breastfeeding problems due to cesarean or other risk factors.

Mutations in SOCS1 are frequent in primary mediastinal B-cell lymphoma and classical Hodgkin lymphoma. In the latter, SOCS1 mutations affect the length of the encoded protein (major mutations) and are associated with shorter patient survival. Two independent studies examined the prognostic impact of SOCS1 mutations in diffuse large B-cell lymphoma (DLBCL) and showed differing results. This may be due to the small number of included patients, the heterogeneity of patients' demographics and the distinct treatment schemes in these studies. To overcome the size limitations of these previous studies, we assessed SOCS1 mutations in the RICOVER-60 cohort. The cohort uniformly consists of elderly patients (aged 61-80 years) treated with the CHOP-14 scheme (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisolone at 14-day intervals) with or without an additional rituximab treatment. Patient outcomes were analysed with regard to overall SOCS1 mutation frequency, major and minor mutations and a novel impact-based classifier - against the treatment modalities. Patients harbouring putative pathogenic SOCS1 mutations showed significant reduced overall survival within the CHOP plus rituximab group. Hence, putative pathogenic SOCS1 mutations seem to efface the beneficial effect of the therapeutic CD20 antibody. Comparing published data of whole exome and transcriptome sequencing of a large DLBCL cohort confirmed that predicted deleterious SOCS1 mutations forecast pre-eminent survival in early onset DLBCL. peerReviewed

Gastric bypass surgery leads to significant and sustained weight loss and a reduction in associated health risks in individuals with severe obesity. While reduced energy intake (EI) is the primary driver of weight loss following surgery, the underlying mechanisms accounting for this energy deficit are not well understood. The evidence base has been constrained by a lack of fit-for-purpose methodology in assessing food intake coupled with follow-up studies that are relatively short-term. This paper describes the underlying rationale and protocol for an observational, fully residential study using covert, objective methodology to evaluate changes in 24-hr food intake in patients (n = 31) at 1-month pre-surgery and 3-, 12- and 24-months post-surgery, compared to weight-stable controls (n = 32). The main study endpoints included change in EI, macronutrient intake, food preferences, and eating behaviours (speed, frequency, and duration of eating). Other physiological changes that may influence EI and weight regulation including changes in body composition, circulating appetite hormones, resting metabolic rate, total energy expenditure and gastrointestinal symptoms were also evaluated. Understanding which mechanisms contribute to a reduction in EI and weight loss post-surgery could potentially help to identify those individuals who are most likely to benefit from gastric bypass surgery as well as those that may need more targeted intervention to optimise their weight loss post-surgery. Furthermore, clarification of these mechanisms may also inform targeted approaches for non-surgical treatments of obesity.

Selective and neutral forces shape human microbiota assembly in early life. The Tsimane are an indigenous Bolivian population with infant care-associated behaviors predicted to increase mother-infant microbial dispersal. Here, we characterize microbial community assembly in 47 infant-mother pairs from six Tsimane villages, using 16S rRNA gene amplicon sequencing of longitudinal stool and tongue swab samples. We find that infant consumption of dairy products, vegetables, and chicha (a fermented drink inoculated with oral microbes) is associated with stool microbiota composition. In stool and tongue samples, microbes shared between mothers and infants are more abundant than non-shared microbes. Using a neutral model of community assembly, we find that neutral processes alone explain the prevalence of 79% of infant-colonizing microbes, but explain microbial prevalence less well in adults from river villages with more regular access to markets. Our results underscore the importance of neutral forces during microbiota assembly. Changing lifestyle factors may alter traditional modes of microbiota assembly by decreasing the role of neutral processes., Selective and neutral forces shape human microbiota assembly in early life. Here, Sprockett et al. study microbial community assembly in 47 infant-mother pairs from the Tsimane, an indigenous Bolivian population, highlighting the importance of neutral forces during microbiota assembly.

Aims In the pathogenesis of several diseases, neo-angiogenesis is increased (e.g. tumour growth). The peptide L-glutamyl-L-tryptophan (EW/IM862) has been claimed to exhibit inhibitory effects on tumour growth in vivo. However, the potential role of natural peptides with respect to anti-angiogenic properties is unsettled. The current study explores anti-angiogenic effects of the dipeptides WL, EW, IW and WE. Methods and results Using a bottom-up strategy, we first evaluated the effects of the peptides on VEGFR-2 signalling and quantified their effects in different angiogenesis assays. WL consistently had the strongest effects on phosphorylation of VEGFR-2 and downstream signalling. Therefore, this peptide was chosen in comparison with EW to further assess anti-angiogenic properties. However, sprout formation in three-dimensional (3D) fibrin gel bead assay was significantly inhibited by EW only. Furthermore, vessel sprouting in the mouse aortic ring assay was decreased by the presence of WL and EW compared to control. Results from a chorioallantoic membrane assay showed that under vascular endothelial growth factor (VEGF) stimulation WL and EW decreased the number of blood vessels versus control. These results were in line with those obtained in a matrigel plug assay. The VEGF-induced increase in the haemoglobin content was nearly abolished when treatment was combined with either WL or EW application. In the murine model of oxygen-induced retinopathy, WL exhibited a small albeit significant anti-angiogenic effect. Conclusion Comprehensive screening of WL suggests an anti-angiogenic effect, demonstrated in in vitro, ex vivo and in vivo models. Thus, WL is a dipeptide with potential anti-angiogenic effects and is worthy for further exploration.

Bariatric surgery, including Gastric Bypass (GBP) Surgery, is the most efficient modality to manage severe obesity. Resting Energy Expenditure (REE) is an area of interest in the context of weight loss (WL) as it has been postulated to be an independent predictor of WL success following GBP. As such, the aim of this study is to investigate the impact of REE on WL following GBP. 31 GBP patients (77.4% females BMI 45.5 ± 7.0kg/m2 ; 47.3 ± 11.6y) and 32 weight-stable controls (46.9% females; BMI 27.0 ± 4.6kg/m2 ; 41.1 ± 13.5y) were assessed at one-month pre-surgery and at 3 and 12-months post-surgery. Fat mass (FM) and fat-free mass (FFM) were measured using dual energy X-ray absorptiometry (Lunar iDXA, GE Healthcare). REE was measured under standardised conditions using indirect calorimetry (ECAL, Metabolic Health Solutions). Statistical analyses were performed with SPSS v24.0, Armonk, NY. Multiple regression analysis showed that FM (P = 0.001), FFM (P < 0.0001) and gender (P = 0.012) significantly predicted the interindividual variability in REE. Total body weight (TBW) was removed from the model due to collinearity. Adjusted-REE values were then generated using the above predictor variables. Low-REE and high-REE groups were created using within-group adjusted-REE split. At both follow-ups (3- and 12-months post-surgery), patients had a greater reduction in TBW, FM, FFM, measured-REE and adjusted-REE values compared with controls (P < 0.0001). There was also no significant difference between measured and adjusted-REE values at all time-points (P > 0.05). Patients with high REEs at baseline lost more TBW than those in the low-REE group at 3-months post-surgery (-24.9 ± 6.5 kg vs. -16.6 ± 7.0 kg; P = 0.005) and 12-months post-surgery (-41.3 ± 12.5 kg vs. -25.8 ± 10.4.0 kg; P = 0.003). There was no significant difference in mean TBW changes for controls in the low-and high-REE groups at both follow-ups. Patients with high REEs at 3-months post-surgery did not lose more TBW than those in the low-REE group at 12-months post-surgery (-30.1 ± 12.8 kg vs. -38.6 ± 14.4 kg; P = 0.155). Similarly, there was no difference in mean TBW reduction between controls in the low- and high-REE groups (P = 0.115). Thus while patients with a high adjusted-REE value at baseline (> 9746.6kJ/day) lost more weight at 3- and 12-months post-GBP, it is plausible that from the third to the 12th month post-surgery, other key drivers of weight loss, particularly the reduction in energy intake are more important in predicting WL. Further research with a larger sample size is required to increase the chances of detecting a true effect.

Alzheimer’s disease (AD) pathology causes microstructural changes in the brain. These changes, if quantified with magnetic resonance imaging (MRI), could be studied for use as an early biomarker for AD. The aim of our study was to determine if T(1) relaxation, diffusion tensor imaging (DTI), and quantitative magnetization transfer imaging (qMTI) metrics could reveal changes within the hippocampus and surrounding white matter structures in ex vivo transgenic mouse brains overexpressing human amyloid precursor protein with the Swedish mutation. Delineation of hippocampal cell layers using DTI color maps allows more detailed analysis of T(1)-weighted imaging, DTI, and qMTI metrics, compared with segmentation of gross anatomy based on relaxation images, and with analysis of DTI or qMTI metrics alone. These alterations are observed in the absence of robust intracellular Aβ accumulation or plaque deposition as revealed by histology. This work demonstrates that multiparametric quantitative MRI methods are useful for characterizing changes within the hippocampal substructures and surrounding white matter tracts of mouse models of AD.

Pubertal timing is in part mediated by environmental factors, with greater energy availability often associated with earlier or more rapid development. Many indigenous populations are undergoing socioeconomic change that may affect pubertal development and related health risks, necessitating fundamental longitudinal research on growth and development in these populations.Growth velocity and time to menarche among peri-urban indigenous Qom (Toba) girls in Argentina are described.From 2011-2015, monthly anthropometrics and menstrual status were collected from 61 Qom girls aged 7-14. Growth velocity curves were generated using the 'Super-imposition by translation and rotation' (SITAR) method. Median time to menarche was estimated by Kaplan-Meier survival analysis.Mean ages at peak height, weight and BMI velocity were estimated at 10.8, 10.5 and 10.7 years and median age at menarche at 11.6 years (95% CI = 11.4-11.9). At menarche, 45% of girls were overweight or obese and only one participant was short-statured by international standards.Qom participants in this study exhibit relatively fast pubertal development as compared to other Latin American indigenous populations studied previously by others. Genetic and environmental factors influencing body size, diet and/or activity levels should be investigated further in this population.