Control of lipolysis by a population of oxytocinergic sympathetic neurons.

Oxytocin (OXT), a nine-amino-acid peptide produced in the hypothalamus and released by the posterior pituitary, has well-known actions in parturition, lactation and social behaviour1, and has become an intriguing therapeutic target for conditions such as autism and schizophrenia2. Exogenous OXT has also been shown to have effects on body weight, lipid levels and glucose homeostasis1,3, suggesting that it may also have therapeutic potential for metabolic disease1,4. It is unclear, however, whether endogenous OXT participates in metabolic homeostasis. Here we show that OXT is a critical regulator of adipose tissue lipolysis in both mice and humans. In addition, OXT serves to facilitate the ability of ß-adrenergic agonists to fully promote lipolysis. Most surprisingly, the relevant source of OXT in these metabolic actions is a previously unidentified subpopulation of tyrosine hydroxylase-positive sympathetic neurons. Our data reveal that OXT from the peripheral nervous system is an endogenous regulator of adipose and systemic metabolism.

Associations Among Adipose Tissue Immunology, Inflammation, Exosomes and Insulin Sensitivity in People With Obesity and Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIMS: Insulin resistance is a key factor in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We evaluated the importance of subcutaneous abdominal adipose tissue (SAAT) inflammation and both plasma and SAAT-derived exosomes in regulating insulin sensitivity in people with obesity and NAFLD. METHODS: Adipose tissue inflammation (macrophage and T-cell content and expression of proinflammatory cytokines), liver and whole-body insulin sensitivity (assessed using a hyperinsulinemic-euglycemic clamp and glucose tracer infusion), and 24-hour serial plasma cytokine concentrations were evaluated in 3 groups stratified by adiposity and intrahepatic triglyceride (IHTG) content: (1) lean with normal IHTG content (LEAN; N = 14); (2) obese with normal IHTG content (OB-NL; N = 28); and (3) obese with NAFLD (OB-NAFLD; N = 28). The effect of plasma and SAAT-derived exosomes on insulin-stimulated Akt phosphorylation in human skeletal muscle myotubes and mouse primary hepatocytes was assessed in a subset of participants. RESULTS: Proinflammatory macrophages, proinflammatory CD4 and CD8 T-cell populations, and gene expression of several cytokines in SAAT were greater in the OB-NAFLD than the OB-NL and LEAN groups. However, with the exception of PAI-1, which was greater in the OB-NAFLD than the LEAN and OB-NL groups, 24-hour plasma cytokine concentration areas-under-the-curve were not different between groups. The percentage of proinflammatory macrophages and plasma PAI-1 concentration areas-under-the-curve were inversely correlated with both hepatic and whole-body insulin sensitivity. Compared with exosomes from OB-NL participants, plasma and SAAT-derived exosomes from the OB-NAFLD group decreased insulin signaling in myotubes and hepatocytes. CONCLUSIONS: Systemic insulin resistance in people with obesity and NAFLD is associated with increased plasma PAI-1 concentrations and both plasma and SAAT-derived exosomes. ClinicalTrials.gov number: NCT02706262 (https://clinicaltrials.gov/ct2/show/NCT02706262).

Do lifestyle factors and quality of life differ in people with metabolically healthy and unhealthy obesity?

BACKGROUND AND OBJECTIVES: Although obesity is typically associated with metabolic co-morbidities, some people with obesity do not develop metabolic abnormalities. We evaluated whether modifiable lifestyle factors (i.e., physical activity, dietary composition, and sleep characteristics) can help explain why some people with obesity are metabolically healthy (MHO) and whether metabolically unhealthy obesity (MUO) affects quality of life (QOL). SUBJECTS/METHODS: Physical activity and sleep characteristics were assessed by using tri-axial accelerometers and dietary intake, sleep quality, and QOL were evaluated by using validated questionnaires in people stratified into three groups: (1) lean with normal glucose tolerance, plasma triglyceride (TG) concentration and intrahepatic TG (IHTG) content (metabolically healthy lean [MHL]; n = 20); (2) obesity and normal glucose tolerance, plasma TG concentration and IHTG content (MHO; n = 36); and (3) obesity with abnormal glucose metabolism and hepatic steatosis (MUO; n = 43). RESULTS: People with MHO performed ~45-min more light-intensity physical activity/day than the MHL and MUO groups (P < 0.05). QOL, particularly the physical function domain, was higher in the MHO than the MUO group (P < 0.05). Although self-reported intake of starch, dairy, and cured meats were higher in the MUO than the MHO group (P < 0.02), the absolute differences were small and unlikely to have metabolic effects. No differences were found in sleep duration or quality between groups. CONCLUSIONS: These data suggest physical activity, but not sleep or dietary intake, contribute to better metabolic health in people with MHO than those with MUO, and that QOL is lower in people with MUO than those with MHO.

Increased Adipose Tissue Fibrogenesis, Not Impaired Expandability, Is Associated With Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIMS: It is proposed that impaired expansion of subcutaneous adipose tissue (SAT) and an increase in adipose tissue (AT) fibrosis causes ectopic lipid accumulation, insulin resistance (IR), and metabolically unhealthy obesity. We therefore evaluated whether a decrease in SAT expandability, assessed by measuring SAT lipogenesis (triglyceride [TG] production), and an increase in SAT fibrogenesis (collagen production) are associated with NAFLD and IR in persons with obesity. APPROACH AND RESULTS: In vivo abdominal SAT lipogenesis and fibrogenesis, expression of SAT genes involved in extracellular matrix (ECM) formation, and insulin sensitivity were assessed in three groups of participants stratified by adiposity and intrahepatic TG (IHTG) content: (1) healthy lean with normal IHTG content (Lean-NL; n = 12); (2) obese with normal IHTG content and normal glucose tolerance (Ob-NL; n = 25); and (3) obese with NAFLD and abnormal glucose metabolism (Ob-NAFLD; n = 25). Abdominal SAT TG synthesis rates were greater (P < 0.05) in both the Ob-NL (65.9 ± 4.6 g/wk) and Ob-NAFLD groups (71.1 ± 6.7 g/wk) than the Lean-NL group (16.2 ± 2.8 g/wk) without a difference between the Ob-NL and Ob-NAFLD groups. Abdominal SAT collagen synthesis rate and the composite expression of genes encoding collagens progressively increased from the Lean-NL to the Ob-NL to the Ob-NAFLD groups and were greater in the Ob-NAFLD than the Ob-NL group (P < 0.05). Composite expression of collagen genes was inversely correlated with both hepatic and whole-body insulin sensitivity (P < 0.001). CONCLUSIONS: AT expandability is not impaired in persons with obesity and NAFLD. However, SAT fibrogenesis is greater in persons with obesity and NAFLD than in those with obesity and normal IHTG content, and is inversely correlated with both hepatic and whole-body insulin sensitivity.

The Basic Shoulder Arthroplasty: Simple Shoulder Replacement for the Generalist.

Shoulder arthroplasty was first introduced through the developments of Dr. Charles Neer and over the past decade has seen several advancements. Improved recognition and training have heightened the awareness of arthroplasty as a treatment alternative both for surgeons and patients. The addition of reverse shoulder arthroplasty has been the driving force behind the explosive growth of arthroplasty and is now performed more often than anatomic shoulder arthroplasty. Although revision shoulder arthroplasty is primarily of interest to the subspecialist, it is a skill sought by the general orthopaedic surgeon. It is important for the orthopaedic surgeon to be knowledgeable about the planning, necessary skills, and management of basic shoulder arthroplasty.

Small bowel adenocarcinoma in Crohn's disease: a rare but devastating complication.

BACKGROUND: Small bowel adenocarcinoma (SBA) remains a rare entity but occurs at increased frequency in the setting of chronic Crohn's disease (CD). Our aim was to study the presentation, diagnosis and prognosis of SBA in patients undergoing surgery for CD at a single institution. METHODS: We reviewed the medical records of all patients with CD complicated by adenocarcinoma of the small bowel from 2000 to 2017. Descriptive statistics and Kaplan-Meier overall survival estimates were calculated. RESULTS: In total, 22 patients (14 males) with CD (median duration of Crohn's diagnosis 32 years) were diagnosed with SBA and underwent surgical resection (8 isolated small bowel resections, 12 ileocolic resections, and 2 total proctocolectomies). The median patient age at the time of diagnosis was 54 years (range 22-82 years). A total of 17 patients (77%) underwent cross-sectional CT imaging within 3 months of surgery, a cancer diagnosis was suggested in only one patient. In one other patient, SBA was diagnosed preoperatively on endoscopic biopsy of the terminal ileum. The remaining patients were operated on for obstruction (n = 17), abscess or fistulizing disease (n = 2), and sigmoid cancer (n = 1). For these 20 (90%) patients not suspected to have SBA on preoperative assessment, 5 (25%) were diagnosed intraoperatively on frozen section and 15 (75%) were unexpectedly diagnosed postoperatively on final pathology. T staging was characterized by more advanced tumors (T4: 59%, T3: 27%, T2: 9%, and T1: 5%). Nine patients (41%) had nodal involvement and five patients (23%) had hepatic and/or peritoneal carcinomatosis. The 1-, 3-, and 5-year survival estimates for our cohort were 84%, 30%, and 10%, respectively. Median survival was 30.5 months with median follow-up of 23 months (range 6-84 months). CONCLUSIONS: SBA in the setting of CD is most commonly found incidentally after surgical resection for benign indications. As such, any suspicious finding at the time of surgery in a patient with chronic CD should warrant careful investigation with frozen section and/or resection. Prognosis for CD complicated by SBA remains poor even in the modern era.

One and two-year clinical outcomes for a polyethylene glenoid with a fluted peg: one thousand two hundred seventy individual patients from eleven centers.

PURPOSE: Clinical shoulder science lacks a benchmark against which the early clinical value of new glenoid components can be compared; such a benchmark may be derived from a multicenter study of patients receiving an established, internationally used design of glenoid component. METHODS: We obtained data from 11 centers on 1270 patients having total shoulder arthroplasty using an all-polyethylene component with a fluted central peg. We analyzed individual patient outcomes at 1 and 2 years after surgery. We compared the improvement for each patient to the minimal clinically important difference (MCID) and calculated each patient's improvement as a percent of maximal possible improvement (MPI). RESULTS: The preoperative scores improved from SST 3 ± 2, ASES 37 ± 15, Constant score 36 ± 16, and Penn score 30 ± 19 to SST 10 ± 2, ASES 90 ± 12, Constant 76 ± 13, and Penn 80 ± 24 (p < 0.001 for each). A high percentage of patients improved by more than the MCID (SST 96%, ASES 98%, Constant 94%, Penn 93%) and obtained improvement of at least 30% of the MPI (SST 95%, ASES 98%, Constant 91%, Penn 87%). The clinical outcomes realized with this glenoid design were not worse for the 41% of shoulders with preoperative type B glenoids or for the 30% of shoulders with more than 15 degrees of glenoid retroversion. CONCLUSIONS: Individual patients from 11 international practices having total shoulder arthroplasty using a basic glenoid component design obtained highly significant clinical outcomes, providing a benchmark against which the early outcomes of new designs can be compared to determine whether they provide increased clinical value.

The muscle anabolic effect of protein ingestion during a hyperinsulinaemic euglycaemic clamp in middle-aged women is not caused by leucine alone.

KEY POINTS: It has been suggested that leucine is primarily responsible for the increase in muscle protein synthesis after protein ingestion because leucine uniquely activates the mTOR-p70S6K signalling cascade. We compared the effects of ingesting protein or an amount of leucine equal to that in the protein during a hyperinsulinaemic-euglycaemic clamp (to eliminate potential confounding as a result of differences in the insulinogenic effect of protein and leucine ingestion) on muscle anabolic signalling and protein turnover in 28 women. We found that protein, but not leucine, ingestion increased muscle p-mTORSer2448 and p-p70S6KThr389 , although only protein, and not leucine, ingestion decreased muscle p-eIF2αSer51 and increased muscle protein synthesis. ABSTRACT: It has been suggested that leucine is primarily responsible for the increase in muscle protein synthesis (MPS) after protein ingestion because leucine uniquely activates the mTOR-p70S6K signalling cascade. We tested this hypothesis by measuring muscle p-mTORSer2448 , p-p70S6KThr389 and p-eIF2αSer51 , as well as protein turnover (by stable isotope labelled amino acid tracer infusion in conjunction with leg arteriovenous blood and muscle tissue sampling), in 28 women who consumed either 0.45 g protein kg-1 fat-free mass (containing 0.0513 g leucine kg-1 fat-free mass) or a control drink (n = 14) or 0.0513 g leucine kg-1 fat-free mass or a control drink (n = 14) during a hyperinsulinaemic-euglycaemic clamp procedure (HECP). Compared to basal conditions, the HECP alone (without protein or leucine ingestion) suppressed muscle protein breakdown by ∼20% and increased p-mTORSer2448 and p-p70S6KThr389 by >50% (all P < 0.05) but had no effect on p-eIF2αSer51 and MPS. Both protein and leucine ingestion further increased p-mTORSer2448 and p-p70S6KThr389 , although only protein, and not leucine, ingestion decreased (by ∼35%) p-eIF2αSer51 and increased (by ∼100%) MPS (all P < 0.05). Accordingly, leg net protein balance changed from negative (loss) during basal conditions to equilibrium during the HECP alone and the HECP with concomitant leucine ingestion and to positive (gain) during the HECP with concomitant protein ingestion. These results provide new insights into the regulation of MPS by demonstrating that leucine and mTOR signalling alone are not responsible for the muscle anabolic effect of protein ingestion during physiological hyperinsulinaemia, most probably because they fail to signal to eIF2α to initiate translation and/or additional amino acids are needed to sustain translation.

Coinheritance of 2 New Potentially Damaging Heterozygous COL7A1 Variants in a Family With Autosomal Dominant Epidermolysis Bullosa Pruriginosa.

Epidermolysis bullosa pruriginosa (EBP) is a rare subtype of EB which is characterized by intense pruritus with blistering and nodular or lichenoid lesions most prominent on the lower extremities. It is caused by variants in COL7A1 which encodes for type VII collagen. There is wide phenotypic and genotypic variability between affected individuals. We report 2 potentially pathogenic variants in COL7A1 occurring on the same allele in a family with EBP and autosomal dominant inheritance. Late-onset EBP and incomplete penetrance may lead to delayed presentation in affected family members with the same variants. The broad phenotypic variability seen in EBP suggests that further genotypic and environmental factors may influence presentation. Genetic and histopathological diagnosis is essential, given the considerable overlap with clinically similar presentations such as hypertrophic lichen planus.

A randomised controlled trial of peri-operative lidocaine infusions for open radical prostatectomy.

We allocated 76 men scheduled for radical retropubic prostatectomy to peri-operative lidocaine 2% or saline 0.9%: a pre-operative 0.075 ml.kg(-1) intravenous bolus; an intra-operative intravenous infusion at 0.075 ml.kg(-1) .h(-1) ; and 24 hours' postoperative subcutaneous infusion at 0.075 ml.kg(-1) .h(-1) . Lidocaine reduced the postoperative hospital stay by a mean (95% CI) of 1.3 (0.3-2.4) days, p = 0.017, from a mean (SD) of 4.6 (3.2) days with saline. There were no significant differences in pain at rest or on coughing at 24 h. [corrected]. Lidocaine reduced 24-h morphine consumption by a mean (95% CI) of 13.9 (2.2-25.7) mg, p = 0.021, from a mean (SD) of 52.3 (26.9) mg with saline. There were no differences in other outcomes.

All Things Clavicle: From Acromioclavicular to Sternoclavicular and All Points in Between.

The clavicle is the most frequently injured bone in the human body. In most cases, fractures that occur in the midshaft of the clavicle can be managed nonsurgically. An increasing number of studies suggest that displaced midshaft clavicle fractures have improved outcomes after surgical management, and equivalent outcomes can be achieved with both plating and intramedullary techniques. Distal clavicle fractures are managed according to the disruption of the coracoclavicular ligaments. Fractures with disruption of the ligaments usually will require fixation, whereas fractures with intact ligaments may be treated with closed management. Multiple techniques of reconstruction appear to yield similar outcomes; however, hook-plating techniques result in the highest complication rates. The evaluation process for acromioclavicular joint injuries is moving from a static two-dimensional evaluation to a three-dimensional evaluation that involves an assessment for scapular dyskinesis. Surgical reconstruction is indicated for patients who exhibit scapular dyskinesis. Anterior sternoclavicular injuries can typically be managed nonsurgically, whereas posterior sternoclavicular dislocations always require urgent surgical management. Newer techniques of ligament reconstruction for sternoclavicular injuries yield improved biomechanical stability.

Effect of hyperinsulinaemia-hyperaminoacidaemia on leg muscle protein synthesis and breakdown: reassessment of the two-pool arterio-venous balance model.

Accurate measurement of muscle protein turnover is critical for understanding the physiological processes underlying muscle atrophy and hypertrophy. Several mathematical approaches, used in conjunction with a tracer amino acid infusion, have been described to derive protein synthesis and breakdown rates from a two-pool (artery-vein) model. Despite apparently common underlying principles, these approaches differ significantly (some seem to not take into account arterio-venous shunting of amino acids, which comprises ∼80-90% of amino acids appearing in the vein) and most do not specify how tracer enrichment (i.e. mole percent excess (MPE) or tracer-to-tracee ratio (TTR)) and amino acid concentration (i.e. unlabelled only or total labelled plus unlabelled) should be expressed, which could have a significant impact on the outcome when using stable isotope labelled tracers. We developed equations that avoid these uncertainties and used them to calculate leg phenylalanine (Phe) kinetics in subjects who received a [(2) H5 ]Phe tracer infusion during postabsorptive conditions and during a hyperinsulinaemic-euglycaemic clamp with concomitant protein ingestion. These results were compared with those obtained by analysing the same data with previously reported equations. Only some of them computed the results correctly when used with MPE as the enrichment measure and total (tracer+tracee) Phe concentrations; errors up to several-fold in magnitude were noted when the same approaches were used in conjunction with TTR and/or unlabelled concentration only, or when using the other approaches (irrespective of how concentration and enrichment are expressed). Our newly developed equations should facilitate accurate calculation of protein synthesis and breakdown rates.

Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults.

VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 µg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 µg/ml for the same two doses. Over the 5-40 mg/kg i.v. dose range (n = 18), the clearance was 0.016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies.

The impact of patient narratives on self-efficacy and self-care in Australians with type 2 diabetes: stage 1 results of a randomized trial.

UNLABELLED: A randomized-controlled trial (RCT) was conducted from September 2009 to June 2011. National Diabetes Services Scheme registrants diagnosed with type 2 diabetes and aged 30-70 years were invited to participate in a 3-week intervention programme with follow-up at 4 weeks and 6 months. Data were collected using self-report questionnaires in the participant's homes. The intervention group received diabetes factsheets and a DVD comprising patient stories (narratives) of type 2 diabetes management. The control group (CG) received factsheets only. The RCT evaluated the impact of patient narratives on the study outcomes, self-efficacy and self-care, using the Aust/English Diabetes Management Self-efficacy Scale and the Summary Diabetes Self-care Activities measure. Participants were randomly assigned to the intervention or CG using block randomization. The study was not blinded. Six hundred and seventy people enrolled into the study with 335 allocated to each group. At 4 weeks, data were available for 598 participants. t-tests were used to analyse the results. The mean difference between the groups for self-efficacy was 7.2 units (P < 0.001, 95% Confidence Interval (CI) 3.8, 10.7) favouring the intervention group. Change in self-care behaviours during the previous 7 days was also significantly greater for the intervention group: general diet (0.31 days, 95% CI 0.13, 0.48), specific diet (0.26 days, 95% CI 0.05, 0.46), exercise (0.51 days, 95% CI 0.23, 0.80), blood glucose (0.52 days, 95% CI 0.19, 0.85) and foot care (0.38 days, 95% CI 0.06, 0.71). Narrative communication shows promise as a valuable component of type 2 diabetes self-management programmes. REGISTRATION: ACTRN 12609000210279.

Complications rates, reoperation rates, and the learning curve in reverse shoulder arthroplasty.

BACKGROUND: Reverse shoulder arthroplasty (RSA) has ushered a new era in shoulder surgery. However, the results of RSA also described the complication rates associated with the procedure as inordinate and a learning curve associated with the incidence of complications. METHODS: The records of 112 patients who underwent 114 RSA procedures by the senior author (G.I.G.) were reviewed for complications related to a RSA. Of these, 93 RSA procedures were the primary treatment for the shoulder, and 21 were revisions. RESULTS: The total complication rate for the entire group was 7%. Complications included 3 periprosthetic fractures, 3 hematomas, 1 acromion fracture, and 1 deep infection. The complication rate was 19% in the revision RSA group and 4.3% in the primary RSA group (P ≤ .02). Complication rates in the initial RSA patients in this series did not differ from the final procedures in this series (P = .96). The total reoperation rate was 5.3%, and was 19% in the revision RSA group vs 2.2% in the primary RSA group (P ≤ .02). CONCLUSION: Complications and reoperations associated with a RSA, although significant, occurred at much lower rate than in previous reports. This series demonstrates a significant difference in complication rates and reoperation rates between primary and revision RSA. Revision RSA complications and reoperations were far more common than in primary RSA procedures. No evidence of a learning curve related to surgical experience was demonstrated in this series.

Influence of Nest Box Color and Release Sites on Osmia lignaria (Hymenoptera: Megachilidae) Reproductive Success in a Commercial Almond Orchard.

Intensively managed, commercial orchards offer resources for managed solitary bees within agricultural landscapes and provide a means to study bee dispersal patterns, spatial movement, nest establishment, and reproduction. In 2012, we studied the impact of 1) the color of nest boxes covaried with four nest box density treatments and 2) the number of bee release sites covaried with two nest box density treatments on the reproductive success of Osmia lignaria Say in a California almond orchard pollinated by a mixture of O. lignaria and Apis mellifera L. Nest box color influenced the number of nests, total cells, and cells with male and female brood. More nests and cells were produced in light blue nest boxes than in orange or yellow nest boxes. The covariate nest box density also had a significant effect on brood production. The number of release sites did not affect O. lignaria nesting and reproduction, but the number of cavities in nest boxes influenced reproduction. Overall, the color of nest boxes and their distribution, but not the number of release sites, can greatly affect O. lignaria nest establishment and reproductive success in a commercial almond orchard. The ability to locate nesting sites in a homogenous, large orchard landscape may also be facilitated by the higher frequency of nest boxes with low numbers of cavities, and by the ability to detect certain nest box colors that best contrast with the blooming trees.

Impaired plasma glucose clearance is a key determinant of fasting hyperglycemia in people with obesity.

OBJECTIVE: The objective of this study was to evaluate the relative importance of the basal rate of glucose appearance (Ra) in the circulation and the basal rate of plasma glucose clearance in determining fasting plasma glucose concentration in people with obesity and different fasting glycemic statuses. METHODS: The authors evaluated basal glucose kinetics in 33 lean people with normal fasting glucose (<100 mg/dL; Lean < 100 group) and 206 people with obesity and normal fasting glucose (Ob < 100 group, n = 118), impaired fasting glucose (100-125 mg/dL; Ob 100-125 group, n = 66), or fasting glucose diagnostic of diabetes (≥126 mg/dL; Ob ≥ 126 group, n = 22). RESULTS: Although there was a large (up to three-fold) range in glucose Ra within each group, the ranges in glucose concentration in the Lean < 100, Ob < 100, and Ob 100-125 groups were small because of a close relationship between glucose Ra and clearance rate. However, the glucose clearance rate at any Ra value was lower in the hyperglycemic than the normoglycemic groups. In the Ob ≥ 126 group, plasma glucose concentration was primarily determined by glucose Ra, because glucose clearance was markedly attenuated. CONCLUSIONS: Fasting hyperglycemia in people with obesity represents a disruption of the precisely regulated integration of glucose production and clearance rates.

Perception, acceptability and challenges of digital adherence technology among TB healthcare workers.

INTRODUCTION: Successful treatment of TB requires high levels of adherence to treatment. This has been found to be below optimal with directly observed therapy (DOT), and digital adherence technologies (DATs) offer a promising approach to non-adherence to medication and improving treatment outcomes. This study explores the perception, acceptability, and challenges of DATs among healthcare workers (HCWs). METHODS: The study was conducted in eight states in Nigeria among Health Care workers involved in treating patients with TB. This was a descriptive cross-sectional study using an open questionnaire and analysed using IBM SPSS v25. RESULTS: Twenty-three HCWs (95.8%) agreed that DATs helped them provide better support and counselling to their patients. All of them would recommend DATs to their patients and found it easy to explain them. Eleven (45.8%) of them were not able to use DATs on a few occasions; their reasons were poor network (n = 9, 37.5%) and (n = 1, 4.2%) power failure. CONCLUSION: DATs help HCWs provide better support and care regarding real-time tracking of their patients' adherence to treatment and possibly reduction of attrition. This implies that DATs are a suitable alternative to DOT to help HCWs provide the best care and support to their patients towards achieving the End TB targets.

INTRODUCTION: Le traitement réussi de la TB nécessite des niveaux élevés d'observance du traitement. Cela s'est avéré inférieur à l'optimal avec le traitement sous observation directe, et les technologies d'observance numérique (DAT) offrent une approche prometteuse de la non-observance des médicaments et de l'amélioration des résultats du traitement. Cette étude explore la perception, l'acceptabilité et les défis des DAT chez les travailleurs de la santé (HCW, pour l'anglais « healthcare worker ¼). MÉTHODES: L'étude a été menée dans huit États du Nigeria auprès de travailleurs de la santé impliqués dans le traitement des patients atteints de TB. Il s'agissait d'une étude transversale descriptive utilisant un questionnaire ouvert et analysée à l'aide d'IBM SPSS v25. RÉSULTATS: Vingt-trois HCW (95,8%) ont convenu que les DAT les aidaient à fournir un meilleur soutien et des conseils à leurs patients. Tous recommandaient les fichiers DAT à leurs patients et trouvaient facile de les expliquer. Onze d'entre eux (45,8%) n'ont pas pu utiliser les fichiers DAT à quelques reprises, en raison d'une mauvaise qualité du réseau (n = 9 ; 37,5%) et d'une panne de courant (n = 1 ; 4,2%). CONCLUSION: Les DAT aident les HCW à fournir un meilleur soutien et des soins en ce qui concerne le suivi en temps réel de l'observance du traitement par leurs patients et éventuellement la réduction de l'attrition. Cela implique que les DAT sont une alternative appropriée au DOT pour aider les travailleurs de la santé à fournir les meilleurs soins et le meilleur soutien à leurs patients pour atteindre les objectifs de l'éradication de la TB.

Appraising perception, accessibility and uptake of DAT among patients with TB.

INTRODUCTION: Poor adherence to TB treatment poses a significant public health threat to TB control programmes. The sustainability of directly observed treatment has been questioned because of its non-patient-centred approach and resource-intensive nature, and Digital Adherence Technologies (DATs) provide a suitable alternative. This study assessed the feasibility and acceptability of DATs among patients with TB. METHODS: This descriptive study was conducted in eight states in Nigeria among all patients with drug-susceptible TB. RESULT: A total of 230 patients (89.1%) own a phone that no one else uses, and 18 (7.0%) use a family phone. A higher proportion of 189 (73.3%) have airtime credit and 119 (46.1%) have internet credit on their phone. In addition, 216 (83.7%) stated that the reminders they received on their phone helped them remember to take their medicine. Only 11 (4.3%) patients missed a dose of the TB medicine. Equally, 11 (4.3%) patients had taken their TB medicine without using DAT. Of these, 7 (63.3%) did not use DATs because they forgot to text medication labels, and 3 (27.6%) did so because of poor network. Only four (1.6%) purchased additional items to support the use of DATs. CONCLUSION: DATs are acceptable in a wide variety of settings, even with reported challenges. Implementation efforts should ensure access, address technical challenges, and minimise additional cost to patients.

INTRODUCTION: La mauvaise observance du traitement antituberculeux constitue une menace importante pour la santé publique pour les programmes de lutte contre la TB. La durabilité du traitement sous observation directe a été remise en question en raison de son approche non centrée sur le patient et de sa nature gourmande en ressources, et les technologies d'observance numérique (DAT) constituent une alternative appropriée. Cette étude a évalué la faisabilité et l'acceptabilité des DAT chez les patients atteints de TB. MÉTHODES: Cette étude descriptive a été menée dans huit États du Nigeria auprès de tous les patients atteints de TB pharmacosensible. RÉSULTAT: Un total de 230 patients (89,1%) possèdent un téléphone que personne d'autre n'utilise, et 18 (7,0%) utilisent un téléphone familial. Une proportion plus élevée de 189 (73,3%) ont du crédit de temps d'antenne et 119 (46,1%) ont du crédit Internet sur leur téléphone. De plus, 216 (83,7%) ont déclaré que les rappels qu'ils ont reçus sur leur téléphone les ont aidés à se rappeler de prendre leurs médicaments. Seuls 11 patients (4,3%) ont manqué une dose du médicament antituberculeux. De même, 11 patients (4,3%) avaient pris leur médicament antituberculeux sans utiliser de DAT. De ce nombre, 7 (63,3%) n'ont pas utilisé de fichiers DAT parce qu'ils ont oublié d'envoyer des étiquettes de médicaments par texto, et 3 (27,6%) l'ont fait en raison d'un réseau médiocre. Seulement quatre (1,6%) ont acheté des articles supplémentaires pour soutenir l'utilisation des fichiers DAT. CONCLUSION: Les fichiers DAT sont acceptables dans une grande variété de contextes, même en cas de problèmes signalés. Les efforts de mise en œuvre doivent garantir l'accès, relever les défis techniques et minimiser les coûts supplémentaires pour les patients.

Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity.

There is considerable heterogeneity in the cardiometabolic abnormalities associated with obesity. We evaluated multi-organ system metabolic function in 20 adults with metabolically healthy obesity (MHO; normal fasting glucose and triglycerides, oral glucose tolerance, intrahepatic triglyceride content, and whole-body insulin sensitivity), 20 adults with metabolically unhealthy obesity (MUO; prediabetes, hepatic steatosis, and whole-body insulin resistance), and 15 adults who were metabolically healthy lean. Compared with MUO, people with MHO had (1) altered skeletal muscle biology (decreased ceramide content and increased expression of genes involved in BCAA catabolism and mitochondrial structure/function); (2) altered adipose tissue biology (decreased expression of genes involved in inflammation and extracellular matrix remodeling and increased expression of genes involved in lipogenesis); (3) lower 24-h plasma glucose, insulin, non-esterified fatty acids, and triglycerides; (4) higher plasma adiponectin and lower plasma PAI-1 concentrations; and (5) decreased oxidative stress. These findings provide a framework of potential mechanisms responsible for MHO and the metabolic heterogeneity of obesity. This study was registered at ClinicalTrials.gov (NCT02706262).