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1.
J Evol Biol ; 37(6): 642-652, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38513126

ABSTRACT

Phenotypic variation within species can affect the ecological dynamics of populations and communities. Characterizing the genetic variation underlying such effects can help parse the roles of genetic evolution and plasticity in "eco-evolutionary dynamics" and inform how genetic variation may shape patterns of evolution. Here, we employ genome-wide association (GWA) methods in Timema cristinae stick insects and their co-occurring arthropod communities to identify genetic variation associated with community-level traits. Previous studies have shown that maladaptation (i.e., imperfect crypsis) of T. cristinae can reduce the abundance and species richness of other arthropods due to an increase in bird predation. Whether genetic variation that is independent of crypsis has similar effects is unknown and was tested here using genome-wide genotyping-by-sequencing data of stick insects, arthropod community information, and GWA mapping with Bayesian sparse linear mixed models. We find associations between genetic variation in stick insects and arthropod community traits. However, these associations disappear when host-plant traits are accounted for. We thus use path analysis to disentangle interrelationships among stick-insect genetic variation, host-plant traits, and community traits. This revealed that host-plant size has large effects on arthropod communities, while genetic variation in stick insects has a smaller, but still significant effect. Our findings demonstrate that (1) genetic variation in a species can be associated with community-level traits but that (2) interrelationships among multiple factors may need to be analyzed to disentangle whether such associations represent causal relationships. This work helps to build a framework for genomic studies of eco-evolutionary dynamics.


Subject(s)
Genetic Variation , Animals , Insecta/genetics , Genome-Wide Association Study , Bayes Theorem
2.
Diabet Med ; 41(4): e15273, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38191796

ABSTRACT

This paper describes the protocol to test the feasibility of the Safe management of people with Type 1 diabetes and EAting Disorders studY (STEADY) intervention. STEADY is a novel complex intervention for people with type 1 diabetes and disordered eating (T1DE) of mild to moderate severity. The STEADY intervention integrates cognitive behavioural therapy (CBT) with diabetes education, and was developed using Experience-Based Co-Design. METHODS: The feasibility of STEADY will be tested using a randomised controlled feasibility trial. Forty adults with T1DE will be recruited and randomised into the STEADY intervention or treatment as usual control group. We will collect demographic, biomedical and psychometric data, routine glucose metrics and conduct the Structured Clinical Interview for DSM-5. Participants randomised to the STEADY intervention will receive 12 STEADY therapy sessions with a diabetes specialist nurse trained in CBT, delivered via videoconference and an optional smartphone app. The main outcome at 6 months will be the feasibility of STEADY (recruitment, dropout rates, feasibility of delivery). The secondary outcomes are biomedical (HbA1c and glucose time in range) and psychological (person-reported outcome measures in disordered eating, diabetes distress, depression and anxiety). A process evaluation will evaluate the fidelity, feasibility, acceptability and appropriateness of STEADY, and participant experiences. ETHICS AND DISSEMINATION: The protocol was approved by the East of England-Essex Research Ethics Committee (21/EE/0235). Study findings will be shared with study participants and disseminated through peer-reviewed publications and conference presentations.


Subject(s)
Diabetes Mellitus, Type 1 , Feeding and Eating Disorders , Adult , Humans , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/therapy , Feeding and Eating Disorders/therapy , Anxiety , Anxiety Disorders , Glucose , Randomized Controlled Trials as Topic
3.
Diabet Med ; 41(5): e15287, 2024 May.
Article in English | MEDLINE | ID: mdl-38379243

ABSTRACT

AIMS: This qualitative study aimed to develop the first cognitive behavioural (CBT) model outlining the development and maintenance of disordered eating in adult men living with Type 1 diabetes to improve on previous theoretical models of Type 1 diabetes and disordered eating and to draw comparisons to women with Type 1 diabetes and disordered eating. METHODS: Twenty-seven men (n = 16 with Type 1 diabetes and disordered eating, n = 11 with Type 1 diabetes without disordered eating) participated in semi-structured interviews. Data were analysed using thematic analysis and individual CBT formulations were developed for each participant to inform the model. RESULTS: Men with Type 1 diabetes and disordered eating experience negative thoughts about food, insulin, weight/shape and diabetes itself, which cause negative emotions such as fear and vulnerability and difficulties with diabetes self care such as problems with hyper and hypoglycaemia and problems accessing structured education and technology result in men feeling more dissatisfied about their body weight/shape. CONCLUSIONS: This CBT model of disordered eating in men with Type 1 diabetes can guide new interventions.


Subject(s)
Diabetes Mellitus, Type 1 , Feeding and Eating Disorders , Adult , Male , Humans , Female , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/psychology , Self Care , Feeding and Eating Disorders/complications , Feeding and Eating Disorders/epidemiology , Feeding and Eating Disorders/therapy , Emotions , Cognition
4.
Diabet Med ; 41(5): e15259, 2024 May.
Article in English | MEDLINE | ID: mdl-38017616

ABSTRACT

OBJECTIVE: Standardised person-reported outcomes (PRO) data can contextualise clinical outcomes enabling precision diabetes monitoring and care. Comprehensive outcome sets can guide this process, but their implementation in routine diabetes care has remained challenging and unsuccessful at international level. We aimed to address this by developing a person-centred outcome set for Type 1 and Type 2 diabetes, using a methodology with prospects for increased implementability and sustainability in international health settings. METHODS: We used a three-round questionnaire-based Delphi study to reach consensus on the outcome set. We invited key stakeholders from 19 countries via purposive snowball sampling, namely people with diabetes (N = 94), healthcare professionals (N = 65), industry (N = 22) and health authorities (N = 3), to vote on the relevance and measurement frequency of 64 previously identified clinical and person-reported outcomes. Subsequent consensus meetings concluded the study. RESULTS: The list of preliminary outcomes was shortlisted via the consensus process to 46 outcomes (27 clinical outcomes and 19 PROs). Two main collection times were recommended: (1) linked to a medical visit (e.g. diabetes-specific well-being, symptoms and psychological health) and (2) annually (e.g. clinical data, general well-being and diabetes self management-related outcomes). CONCLUSIONS: PROs are often considered in a non-standardised way in routine diabetes care. We propose a person-centred outcome set for diabetes, specifically considering psychosocial and behavioural aspects, which was agreed by four international key stakeholder groups. It guides standardised collection of meaningful outcomes at scale, supporting individual and population level healthcare decision making. It will be implemented and tested in Europe as part of the H2O project.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/therapy , Delphi Technique , Consensus , Research Design , Mental Health
5.
J Surg Oncol ; 129(6): 1025-1033, 2024 May.
Article in English | MEDLINE | ID: mdl-38305061

ABSTRACT

Previously reported upgrade rates for benign breast intraductal papilloma (IDP) are widely variable. However, many previous studies have failed to consider radiologic-pathologic discordance of lesions. This review aims to synthesize malignant upgrade data for benign, concordant IDP at surgical excision. Thirteen studies were included in our meta-analysis. The pooled estimate for percentage underestimation of carcinoma was 1.4% (95% CI: 0.8%-2.0%). We conclude that these lesions can be safely managed by active surveillance.


Subject(s)
Breast Neoplasms , Papilloma, Intraductal , Humans , Papilloma, Intraductal/pathology , Papilloma, Intraductal/surgery , Papilloma, Intraductal/diagnostic imaging , Female , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Breast Neoplasms/diagnostic imaging
6.
J Reconstr Microsurg ; 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39134048

ABSTRACT

BACKGROUND: The rising clinical importance of assessing frailty is driven by its predictive capability for postoperative outcomes. This study assesses the effectiveness of RAI-rev (Revised Risk Analysis Index) in predicting adverse outcomes in lower extremity (LE) flap reconstruction. METHODS: Analyzing NSQIP (National Surgical Quality Improvement Program) data from 2015 to 2020, we compared demographics, perioperative factors, and 30-day outcomes in all locoregional and free-flap cases. Frailty scores, calculated using RAI-rev, were categorized with <15 as nonfrail and >35 as the most frail. Adjusted odds ratios (aORs) for specific complications were calculated using nonfrail as the reference group. Frailty scores in locoregional flaps were compared with those in free flaps. RESULTS: We identified 270 locoregional and 107 free-flap cases. Higher RAI-rev scores in locoregional flaps correlated with increased complications, such as deep surgical site infection (1% nonfrail vs. 20% RAI 31-35), stroke (0% nonfrail vs. 17% most frail), and mortality (0% nonfrail vs. 17% most frail). Locoregional flap cases with RAI-rev scores in the most frail group had a significantly elevated aOR for stroke (51.0, 95% confidence interval [CI]: 1.8-1402.5, p = 0.02), mortality (43.1, 95% CI: 1.6-1167.6, p = 0.03), and any complication (6.8, 95% CI: 1.2-37.4, p = 0.03). In free-flap cases, higher RAI-rev scores were associated with increased complications, with only sepsis showing a statistically significant difference (6% nonfrail vs. 100% most frail; aOR: 42.3, CI: 1.45-1245.3, p = 0.03). Free-flap cases had a significantly lower RAI-rev score compared with locoregional flap cases (14.91 vs. 17.64, p = 0.01). CONCLUSION: Elevated RAI-rev scores (>35) correlated with more complications in locoregional flaps, while free-flap reconstruction patients had generally low RAI-rev scores. This suggests that free flaps are less commonly recommended for presumed higher risk patients. The study demonstrates that RAI-rev may be able to serve as a risk calculator in LE reconstruction, aiding in the assessment of candidates for limb salvage versus amputation.

7.
J Reconstr Microsurg ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39191416

ABSTRACT

BACKGROUND: Free flap (FF) reconstruction is frequently required for soft-tissue coverage after significant orthopaedic trauma of the lower extremity (LE). While usually the final step in limb salvage, re-elevation of the previously inset FF may be necessary to restore a functional limb. In this study, we present our algorithm for LE FF re-elevation and review our experience to identify factors associated with successful limb salvage and return to ambulation. METHODS: A retrospective, single-institution review was conducted of adult patients with LE wounds who required FF reconstruction from 2016 to 2021. From this cohort, patients who required re-elevation of their LE FF were identified. Successful FF re-elevation was defined by limb salvage and return to ambulation. RESULTS: During the study period, 412 patients with LE wounds required flap reconstruction. Of these patients, 205 (49.8%) underwent free tissue transfer, and 39 (9.5%) met our inclusion criteria. From this cohort, 34 had successful FF re-elevation, while 1 was non-weight bearing and 4 were elected for amputation due to chronic complications unrelated to their FF. Univariate analysis revealed the total number of FF re-elevations (p < 0.001), the frequency of re-elevation indicated for orthopaedic access (p < 0.001), and infections necessitating return to the operating room (p = 0.001) were each negatively associated with limb salvage and return to ambulation. CONCLUSION: The described algorithm highlights the preoperative planning and meticulous flap preservation necessary for the successful coverage of critical structures following FF re-elevation. Our data demonstrate that LE FFs can be safely re-elevated for hardware access or flap revision. In these complex cases of LE trauma, management by a multidisciplinary team is essential for successful limb salvage.

8.
Br J Haematol ; 202(4): 796-800, 2023 08.
Article in English | MEDLINE | ID: mdl-37357380

ABSTRACT

Management of classical Hodgkin lymphoma in older patients is challenging due to poor tolerance of the chemotherapy regimens used in younger patients. We modified the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone), whereby bleomycin and etoposide were removed and cyclophosphamide dose was reduced, for older patients with co-morbidities. Here we present data from the first 41 patients treated with 'ACOPP' across 3 centres, demonstrating that it can be delivered, with a favourable toxicity profile (TRM 2%) and promising efficacy (2-year PFS and OS, 73% (95% CI: 52-94) and 93% (95% CI: 80-100) respectively).


Subject(s)
Hodgkin Disease , Humans , Aged , Hodgkin Disease/pathology , Vincristine/adverse effects , Retrospective Studies , Procarbazine/adverse effects , Etoposide/adverse effects , Cyclophosphamide/adverse effects , Doxorubicin/adverse effects , Bleomycin/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Prednisone/adverse effects
9.
HIV Med ; 24(4): 380-388, 2023 04.
Article in English | MEDLINE | ID: mdl-36196017

ABSTRACT

Obesity is a chronic disease with multiple adverse effects on health. The prevalence of obesity is increasing worldwide, and people of African ancestry are disproportionally affected. Several widely used antiretrovirals have been associated with weight gain and contribute to the rising burden of obesity in people with HIV. Obesity and weight gain on antiretroviral therapy are risk factors for the development of type 2 diabetes mellitus, a condition which also disproportionally affects black populations. In this review, we discuss recent data on weight gain in relation to initiating or switching antiretroviral therapy and advances in the management of obesity. Availability of highly effective treatments for obesity have the potential to address, and potentially reverse, the epidemics of obesity and diabetes mellitus in people with HIV.


Subject(s)
Diabetes Mellitus, Type 2 , HIV Infections , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Obesity/complications , Obesity/epidemiology , Risk Factors , Weight Gain
10.
Diabet Med ; 40(3): e14952, 2023 03.
Article in English | MEDLINE | ID: mdl-36054221

ABSTRACT

AIM: To explore if novel non-invasive diagnostic technologies identify early small nerve fibre and retinal neurovascular pathology in prediabetes. METHODS: Participants with normoglycaemia, prediabetes or type 2 diabetes underwent an exploratory cross-sectional analysis with optical coherence tomography angiography (OCT-A), handheld electroretinography (ERG), corneal confocal microscopy (CCM) and evaluation of electrochemical skin conductance (ESC). RESULTS: Seventy-five participants with normoglycaemia (n = 20), prediabetes (n = 29) and type 2 diabetes (n = 26) were studied. Compared with normoglycaemia, mean peak ERG amplitudes of retinal responses at low (16-Td·s: 4.05 µV, 95% confidence interval [95% CI] 0.96-7.13) and high (32-Td·s: 5·20 µV, 95% CI 1.54-8.86) retinal illuminance were lower in prediabetes, as were OCT-A parafoveal vessel densities in superficial (0.051 pixels/mm2 , 95% CI 0.005-0.095) and deep (0.048 pixels/mm2 , 95% CI 0.003-0.093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA1c and peak ERG amplitude at 32-Td·s (r = -0.256, p = 0.028), implicit time at 32-Td·s (r = 0.422, p < 0.001) and 16-Td·s (r = 0.327, p = 0.005), OCT parafoveal vessel density in the superficial (r = -0.238, p = 0.049) and deep (r = -0.3, p = 0.017) retinal layers, corneal nerve fibre length (CNFL) (r = -0.293, p = 0.017), and ESC-hands (r = -0.244, p = 0.035) were observed. HOMA-IR was a predictor of CNFD (ß = -0.94, 95% CI -1.66 to -0.21, p = 0.012) and CNBD (ß = -5.02, 95% CI -10.01 to -0.05, p = 0.048). CONCLUSIONS: The glucose threshold for the diagnosis of diabetes is based on emergent retinopathy on fundus examination. We show that both abnormal retinal neurovascular structure (OCT-A) and function (ERG) may precede retinopathy in prediabetes, which require confirmation in larger, adequately powered studies.


Subject(s)
Diabetes Mellitus, Type 2 , Prediabetic State , Retinal Diseases , Humans , Prediabetic State/diagnosis , Diabetes Mellitus, Type 2/diagnosis , Cross-Sectional Studies , Retina
11.
Eur Arch Otorhinolaryngol ; 280(4): 1555-1563, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36542113

ABSTRACT

BACKGROUND: The thyroid gland plays an important endocrine function regulating metabolism, growth and development. A variety of benign and malignant conditions necessitate surgical removal of the thyroid gland, either in its entirety, or partially. Thyroidectomy is the most commonly undertaken endocrine surgery. Hypocalcaemia, occurring at a rate of approximately 25%, is the most common complication following total thyroidectomy. Hypocalcaemia can increase healthcare costs requiring further investigations, treatment and delaying discharge. Severe hypocalcaemia can be potentially life threatening. It has been demonstrated that routine post-operative supplementation with Vitamin D and calcium, can reduce post-operative hypocalcaemia, at present it is unclear whether preoperative supplementation has a similar effect. METHODS: This systematic review includes randomised controlled trials on human adult subjects, who received preoperative Vitamin D and/or calcium, and which studied the effect on post-operative hypocalcaemia following total or near total thyroidectomy. There were no restrictions in respect of post-operative supplementation regimen. Studies were limited to those published in English. RESULT: Seven of the eleven trials demonstrated a reduction in either laboratory or clinical hypocalcaemia with preoperative supplementation. This benefit was most likely to be seen when postoperative supplementation was performed on an as needed basis. IV calcium was required to treat resistant or severe hypocalcaemia, in five of the eleven trials, in each of these five trials, rates of IV replacement were lower in the preoperative supplementation group. CONCLUSION: The use of preoperative Vitamin D, with or without calcium, may provide a modest reduction in the incidence of laboratory and clinic hypocalcaemia following total or near total thyroidectomy. There is a trend toward a reduced requirement for IV calcium with preoperative supplementation. Larger robust randomised trials are needed to provide a definitive answer. Preoperative supplementation can be considered in patients undergoing total or near total thyroidectomy.


Subject(s)
Calcium , Hypocalcemia , Adult , Humans , Calcium/therapeutic use , Hypocalcemia/etiology , Hypocalcemia/prevention & control , Vitamin D/therapeutic use , Thyroidectomy/adverse effects , Thyroidectomy/methods , Vitamins/therapeutic use , Postoperative Complications/prevention & control
12.
Gut ; 71(2): 254-264, 2022 02.
Article in English | MEDLINE | ID: mdl-33597157

ABSTRACT

OBJECTIVE: Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D). DESIGN: Eligible patients (haemoglobin A1c (HbA1c) 59-86 mmol/mol, body mass index≥24 and ≤40 kg/m2, fasting insulin >48.6 pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks. RESULTS: Overall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was -10.4 (18.6) mmol/mol in DMR group versus -7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was -5.4 (5.6)% in DMR group versus -2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was -6.6 mmol/mol (17.5 mmol/mol) versus -3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was -5.4% (6.1%) versus -2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient. CONCLUSIONS: DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, particularly in patients with high FPG. TRIAL REGISTRATION NUMBER: NCT02879383.


Subject(s)
Catheter Ablation , Diabetes Mellitus, Type 2/therapy , Duodenum/surgery , Endoscopic Mucosal Resection , Hyperthermia, Induced , Intestinal Mucosa/surgery , Adult , Aged , Diabetes Mellitus, Type 2/blood , Double-Blind Method , Feasibility Studies , Female , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Treatment Outcome
13.
Diabet Med ; 39(4): e14749, 2022 04.
Article in English | MEDLINE | ID: mdl-34821402

ABSTRACT

AIMS: To develop a cognitive behavioural therapy-based intervention for people with type 1 diabetes and disordered eating using Experience-Based Co-Design as part of the Safe management of people with Type 1 diabetes and EAting Disorders studY (STEADY). METHODS: Fifteen people with type 1 diabetes and experience of disordered eating (33 ± 11 years old, 22 ± 12 years diabetes duration) and 25 healthcare professionals working in type 1 diabetes or eating disorders (44 ± 9 years old; 14 ± 10 years of professional experience) attended six Experience-Based Co-Design workshops from July 2019 to March 2020 to collaboratively develop intervention content. RESULTS: We developed a cognitive behaviour therapy intervention 'toolkit' that can be tailored for individual patient needs. Participants designed and revised toolkit materials to ensure acceptability and relevance for people with diabetes and disordered eating by engaging in guided discussion, brainstorming, and rapid testing to review toolkit prototypes in an iterative process. Workshop themes were 'Insulin titration'; 'Hypoglycaemia'; 'Coming to terms with diabetes'; 'Fear of weight gain'; 'Toolkit revision'; and 'Practical elements of STEADY therapy'. The intervention is focussed on improving diabetes self-care and embedded in a multidisciplinary healthcare approach. The intervention will be delivered in 12 sessions by a diabetes specialist nurse trained in cognitive behavioural therapy. CONCLUSIONS: Through an iterative co-design process, people with type 1 diabetes and healthcare professionals collaboratively developed a novel intervention toolkit that can be used with a wide range of disordered eating presentations. The intervention will be tested in the STEADY feasibility randomised controlled trial.


Subject(s)
Cognitive Behavioral Therapy , Diabetes Mellitus, Type 1 , Feeding and Eating Disorders , Adult , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/psychology , Diabetes Mellitus, Type 1/therapy , Feeding and Eating Disorders/therapy , Health Personnel , Humans , Middle Aged , Self Care , Young Adult
14.
Diabetes Obes Metab ; 24(10): 2038-2050, 2022 10.
Article in English | MEDLINE | ID: mdl-35676820

ABSTRACT

AIM: This study investigated whether therapeutically relevant concentrations of fluoxetine, which have been shown to reduce plasma glucose and glycated haemoglobin independent of changes in food intake and body weight, regulate beta-cell function and improve glucose homeostasis. METHODS: Cell viability, insulin secretion, beta-cell proliferation and apoptosis were assessed after exposure of MIN6 beta cells or isolated mouse and human islets to 0.1, 1 or 10 µmol/L fluoxetine. The effect of fluoxetine (10 mg/kg body weight) administration on glucose homeostasis and islet function was also examined in ob/ob mice. RESULTS: Exposure of MIN6 cells and mouse islets to 0.1 and 1 µmol/L fluoxetine for 72 hours did not compromise cell viability but 10 µmol/L fluoxetine significantly increased Trypan blue uptake. The dose of 1 µmol/L fluoxetine significantly increased beta-cell proliferation and protected islet cells from cytokine-induced apoptosis. In addition, 1 µmol/L fluoxetine induced rapid and reversible potentiation of glucose-stimulated insulin secretion from islets isolated from mice, and from lean and obese human donors. Finally, intraperitoneal administration of fluoxetine to ob/ob mice over 14 days improved glucose tolerance and resulted in significant increases in beta-cell proliferation and enhanced insulin secretory capacity. CONCLUSIONS: These data are consistent with a role for fluoxetine in regulating glucose homeostasis through direct effects on beta cells. Fluoxetine thus demonstrates promise as a preferential antidepressant for patients with concomitant occurrence of depression and diabetes.


Subject(s)
Fluoxetine , Islets of Langerhans , Animals , Body Weight , Fluoxetine/metabolism , Fluoxetine/pharmacology , Glucose/metabolism , Humans , Insulin/metabolism , Insulin Secretion , Islets of Langerhans/metabolism , Mice , Selective Serotonin Reuptake Inhibitors/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacology
15.
Retina ; 42(3): 442-449, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35188489

ABSTRACT

PURPOSE: To explore the association between retinal neurodegeneration and metabolic parameters in progressive dysglycemia. METHOD: A cross-sectional study was performed on 68 participants: normal glucose tolerance (n = 23), prediabetes (n = 25), and Type 2 diabetes without diabetic retinopathy (n = 20). Anthropometric assessment and laboratory sampling for HbA1c, fasting glucose, insulin, c-peptide, lipid profile, renal function, and albumin-to-creatinine ratio were conducted. Central and pericentral macular thicknesses on spectral domain optical coherence tomography were compared with systemic parameters. RESULTS: Baseline demographic characteristics were similar across all groups. Cuzick's trend test revealed progressive full-thickness macular thinning with increasing dysglycemia across all three groups (P = 0.015). The urinary albumin-to-creatinine ratio was significantly correlated with full-thickness superior (R = -0.435; P = 0.0002), inferior (R = -0.409; P = 0.0005), temporal (R = -0.429; P = 0.003), and nasal (R = -0.493; P < 0.0001) pericentral macular thinning, after post hoc Bonferroni adjustment. There was no association between macular thinning and waist circumference, body mass index, blood pressure, lipid profile, or insulin resistance. CONCLUSION: Progressive dysglycemia is associated with macular thinning before the onset of visible retinopathy and occurs alongside microalbuminuria. Retinal neurodegenerative changes may help identify those most at risk from dysglycemic end-organ damage.


Subject(s)
Albuminuria/diagnosis , Diabetes Mellitus, Type 2/diagnosis , Glucose Metabolism Disorders/diagnosis , Prediabetic State/diagnosis , Retinal Degeneration/diagnosis , Aged , Blood Glucose/metabolism , C-Peptide/blood , Cross-Sectional Studies , Female , Glycated Hemoglobin/metabolism , Humans , Insulin/blood , Lipids/blood , Male , Middle Aged , Tomography, Optical Coherence
16.
Postgrad Med J ; 98(1161): e13, 2022 Jul.
Article in English | MEDLINE | ID: mdl-33782204

ABSTRACT

PURPOSE: Despite the associations between workhours, fatigue and motor vehicle accidents, driving abilities for residents post-call have been infrequently analysed. Our purpose was to compare orthopaedic surgery resident performance on a driving simulator after a night of call compared with their baseline. STUDY DESIGN: All residents from a single orthopaedic programme were asked to complete baseline and post-call driving simulator assessments and surveys. The primary outcome measure was brake reaction time (BRT) and secondary outcome measures included lane variance, speed variance and accidents on the driving simulator. RESULTS: All 19 orthopaedic residents agreed to participate. Compared with the baseline assessment, residents demonstrated significantly higher levels of sleepiness on the Stanford Sleepiness Scale post-call (1.6 vs 3.4; p<0.0001). Despite higher levels of fatigue post-call, there was no statistically significant differences between baseline and post-call assessments for mean BRT, accidents, lane variation and speed variation. CONCLUSIONS: These data suggest that for orthopaedic residents, driving simulator performance does not appear to be worse after a single night of call compared with baseline. Future collaborative, multicentre investigations on post-call driving safety that incorporate different call types and frequencies are necessary to better define the impact of post-call fatigue on driving performance. Recognising that motor vehicle accidents remain the leading cause of death for people under the age of 30 years, these continued areas of study are necessary to truly establish a culture of resident safety.


Subject(s)
Automobile Driving , Internship and Residency , Orthopedic Procedures , Orthopedics , Adult , Fatigue , Humans , Orthopedics/education , Sleepiness
17.
J Environ Manage ; 303: 114270, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-34906832

ABSTRACT

Increasing metal demand is accelerating the mining and processing of minerals, however to ensure sustainable growth innovative approaches are required to better manage associated effluents. Biochar from the fast pyrolysis of residues from fishery and forestry operations has been studied as a low-cost, environmentally and economically friendly method for treating mine tailings and processing effluents. However, the bulk of the studies focus on terrestrial biomass (e.g. wood) and do not include potential inhibition/enhancement of adsorption due to pH controlling compounds. In this work biochar generated from snow crab (Chionoecetes Opilio) processing was studied as an adsorbent for copper solutions containing sulfate (a key compound in sulfide ore mining waters) with the objective of assessing adsorption capacity and the impact of sulfate on copper adsorption. The biochar, a porous structure comprised of calcite (CaCO3), was alkaline and has a negative zeta potential under neutral and basic conditions. The crab biochar removed over 99% of Cu2+ from a 100 mg/L solution (sourced as CuSO4) at a dosage of 5 g/L, which was higher than lignocellulosic biochar at the same biochar dosage. While metal adsorption can often be impacted at acidic conditions, Cu2+ adsorption was not impacted by initial acidic pH due to the biochar's buffering capacity. The Pseudo-Second Order (PSO) model fit the adsorption rate with maximum adsorption achieved in approximately 2 h. The maximum adsorption isotherm capacity was 184.8 ± 10.2 mg/g for Cu2+, much higher than existing commercial activated carbons and previously studied lignocellulosic biochars and followed the Freundlich isotherm. The adsorption mechanism responsible for removal of Cu2+ was found to be precipitation, in the form of the mineral posnjakite (Cu4[(OH)6SO4]·H2O). These results indicate for the first time that crab-based biochars are capable of adsorbing large quantities of Cu2+ from sulfate-rich solution, while also buffering solution pH, demonstrating promise as an acid mine drainage treatment for removal of harmful metals and reduction of acidity.


Subject(s)
Brachyura , Water Pollutants, Chemical , Adsorption , Animals , Charcoal , Copper/analysis , Kinetics , Sulfates , Water Pollutants, Chemical/analysis
18.
Circulation ; 142(11): e160-e166, 2020 09 15.
Article in English | MEDLINE | ID: mdl-32787451

ABSTRACT

Engaging in regular physical activity is one of the most important things people can do to improve their cardiovascular health; however, population levels of physical activity remain low in the United States. Effective population-based approaches implemented in communities can help increase physical activity among all Americans. Evidence suggests that built environment interventions offer one such approach. These interventions aim to create or modify community environmental characteristics to make physical activity easier or more accessible for all people in the places where they live. In 2016, the Community Preventive Services Task Force released a recommendation for built environment approaches to increase physical activity. This recommendation is based on a systematic review of 90 studies (search period, 1980-June 2014) conducted using methods outlined by the Guide to Community Preventive Services. The Community Preventive Services Task Force found sufficient evidence of effectiveness to recommend combined built environment strategies. Specifically, these strategies combine interventions to improve pedestrian or bicycle transportation systems with interventions to improve land use and environmental design. Components of transportation systems can include street pattern design and connectivity, pedestrian infrastructure, bicycle infrastructure, and public transit infrastructure and access. Components of land use and environmental design can include mixed land use, increased residential density, proximity to community or neighborhood destinations, and parks and recreational facility access. Implementing this Community Preventive Services Task Force recommendation in communities across the United States can help promote healthy and active living, increase physical activity, and ultimately improve cardiovascular health.


Subject(s)
American Heart Association , Built Environment , Cardiovascular Diseases/prevention & control , Exercise , Health Promotion , Humans , United States
19.
Environ Microbiol ; 23(11): 6377-6390, 2021 11.
Article in English | MEDLINE | ID: mdl-34347349

ABSTRACT

The loss of cellular water (desiccation) and the resulting low cytosolic water activity are major stress factors for life. Numerous prokaryotic and eukaryotic taxa have evolved molecular and physiological adaptions to periods of low water availability or water-limited environments that occur across the terrestrial Earth. The changes within cells during the processes of desiccation and rehydration, from the activation (and inactivation) of biosynthetic pathways to the accumulation of compatible solutes, have been studied in considerable detail. However, relatively little is known on the metabolic status of organisms in the desiccated state; that is, in the sometimes extended periods between the drying and rewetting phases. During these periods, which can extend beyond decades and which we term 'anhydrobiosis', organismal survival could be dependent on a continued supply of energy to maintain the basal metabolic processes necessary for critical functions such as macromolecular repair. Here, we review the state of knowledge relating to the function of microorganisms during the anhydrobiotic state, highlighting substantial gaps in our understanding of qualitative and quantitative aspects of molecular and biochemical processes in desiccated cells.


Subject(s)
Desiccation , Eukaryota , Adaptation, Physiological , Eukaryota/metabolism , Water/metabolism
20.
Diabet Med ; 38(7): e14578, 2021 07.
Article in English | MEDLINE | ID: mdl-33797072

ABSTRACT

AIMS: This qualitative study aimed to develop the first cognitive behavioural therapy model outlining the development and maintenance of disordered eating in type 1 diabetes and report on recovery strategies and resilience factors to improve previous theoretical models of type 1 diabetes and disordered eating. METHODS: Twenty-three women (n = 9 with type 1 diabetes and disordered eating, n = 5 with type 1 diabetes recovering from disordered eating, and n = 9 with type 1 diabetes without disordered eating) participated in semi-structured interviews. Data were analysed using grounded theory and individual cognitive-behavioural formulations were developed for each participant to inform the development/maintenance and resilience models. RESULTS: The development/maintenance model summarises commonly experienced vicious cycles of thoughts, feelings and behaviours in type 1 diabetes and disordered eating. The resilience model summarises strategies and knowledge acquired by those with type 1 diabetes in recovery from disordered eating and individuals with type 1 diabetes who did not develop disordered eating. Early adverse life events, past psychiatric history, perfectionist personality traits, difficult experiences around type 1 diabetes diagnosis and its relentless daily management sensitise individuals to eating, weight and shape cues. Alongside physical symptoms/complications, unhelpful interpersonal reactions and inadequate healthcare, vicious cycles of thoughts, feelings and behaviours develop. 'Good enough' psychological adaptation to type 1 diabetes, integrating type 1 diabetes into one's identity, self care and compassion around eating, weight and shape were key protective/post-traumatic resilience factors. CONCLUSIONS: This first cognitive behavioural therapy model of type 1 diabetes and disordered eating informed by personal experience will inform an intervention for type 1 diabetes and disordered eating.


Subject(s)
Diabetes Mellitus, Type 1/psychology , Feeding and Eating Disorders/psychology , Models, Psychological , Adaptation, Psychological , Adolescent , Cognitive Behavioral Therapy , Cross-Sectional Studies , Female , Humans , Interviews as Topic , Self Care
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