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1.
Foot (Edinb) ; 59: 102099, 2024 May 13.
Article En | MEDLINE | ID: mdl-38744063

OBJECTIVES: Persons with intellectual disabilities frequently have podiatric conditions. Findings from the 2018 United States Summer games (USA) venues are compared to those from athletes screened at the 2019 Special Olympics World Summer Games in Abu Dhabi, United Arab Emirates (UAE). METHODS: Data from Fit Feet screenings from 2445 United Arab Emirates (UAE) participants were compared to 1244 US participants. RESULTS: A sampling of results that reflect significant differences in findings between the USA cohort and Abu Dhabi cohort include ankle joint range of motion, excessive abduction, hallux abducto valgus and pes planus. The overall shoe to foot mismatch was found to be 52.2%. A professional referral was recommended 27.7% of the time in the USA data and 28.5% in the Abu Dhabi data. An urgent referral was requested 5.1% of the time for the USA data and 3.7% of the time in the Abu Dhabi data. CONCLUSION: Special Olympics athletes experience a greater prevalence of identifiable podiatric conditions as compared to the general population. Several of the conditions investigated in this study differed significantly between the international Special Olympics cohort and the USA cohort. Assessment of the feet of Special Olympics athletes can help to better appreciate the podiatric conditions in a population of individuals with intellectual disabilities. The variance identified between populations of Special Olympics athletes may be a reflection on the lack of standardization of conditions that are assessed for as well as the disparate characteristics of the clinical volunteers. Future Fit Feet events may wish to consider significant improvements in objectivity and standardization as it pertains to the conditions that are evaluated for in the Fit Feet exam.

2.
Inorg Chem ; 63(19): 8816-8821, 2024 May 13.
Article En | MEDLINE | ID: mdl-38696708

While intensive studies have focused on the synthesis and characterization of new metal-organic nanotube (MONT) structures, the lack of size and morphology control remains an obstacle in broadening applications for this class of materials. Herein, we demonstrate control of MONT crystallite size and morphology by tuning polarity and the protic/aprotic nature of solvents, including dimethylformamide, N-methyl-2-pyrrolidone, ethanol, and 2-methyltetrahydrofuran, for the isostructural syntheses of two MONTs. Through a combination of transmission electron microscopy, powder X-ray diffraction, and selected area electron diffraction, we find that MONT crystallite sizes can be tuned while maintaining control over the relative dispersity without significantly altering the underlying crystal structure.

3.
J Cardiothorac Surg ; 19(1): 288, 2024 May 14.
Article En | MEDLINE | ID: mdl-38745263

Pulmonary arterial sarcomas (PAS) are rare aggressive tumours occurring mainly in the pulmonary trunk. We report a case of PAS involving the pulmonary trunk wall and valve, with uniform wall thickening which represents an atypical imaging manifestation of this tumour. A 63-year-old male presented with vague respiratory symptoms with rapid progression. CTPA showed low density filling defects in both pulmonary arteries and PET scan showed increased uptake in the pulmonary trunk, which along with raised ESR suggested Pulmonary Vasculitis. Echo imaging showed Right ventricular hypertrophy and pulmonary stenosis. Response to steroid therapy was minimal and his symptoms worsened. A referral for second opinion was made and he was diagnosed with PAS. He underwent Pulmonary thromboendarterectomy with Pulmonary valve replacement. Post-operative histopathology confirmed the diagnosis. PAS is rare and frequently misdiagnosed. Surgical resection is not curative, but together with chemotherapy can prolong survival.


Pulmonary Artery , Pulmonary Valve , Sarcoma , Vascular Neoplasms , Humans , Male , Middle Aged , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/surgery , Pulmonary Artery/pathology , Sarcoma/diagnosis , Sarcoma/surgery , Pulmonary Valve/diagnostic imaging , Vascular Neoplasms/diagnosis , Vascular Neoplasms/surgery , Vascular Neoplasms/diagnostic imaging , Diagnosis, Differential , Vasculitis/diagnosis , Diagnostic Errors
4.
Curr Dev Nutr ; 8(5): 102145, 2024 May.
Article En | MEDLINE | ID: mdl-38693966

Background: A significant aspect of the SARS-CoV-2 pathology involves oxidative stress, characterized by an imbalance between the production of harmful free radicals and the body's antioxidant defenses. With the ongoing evolution of SARS-CoV-2, the investigation into non-virus-specific therapeutic options, such as antioxidant therapy, has gained importance. Objectives: This systematic review and meta-analysis aimed to summarize data from randomized control trials (RCTs) to evaluate the effectiveness and safety of antioxidant therapy in patients with SARS-CoV-2 infection. Methods: We searched the peer-reviewed indexed literature on MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, EMBASE, International Pharmaceutical Abstracts, and Scopus, from inception to July 2023. Results: The search identified 3306 articles from which 25 were included for quantitative synthesis, with 5 studies eligible for meta-analysis. Antioxidant therapies included zinc, vitamin A, vitamin C, and combination treatments. Zinc interventions showed mixed results regarding intensive care unit admissions and hospital stays. Vitamin A studies indicated improvements in inflammatory markers. Vitamin C studies displayed inconsistent effects on clinical improvement and hospitalization. Combination treatments suggested benefits in symptom clearance and cytokine storm reduction. Meta-analysis of vitamin C studies found no significant difference in C-reactive protein concentrations (-0.50; 95% CI: -3.63, 2.63; I2 = 0%), intensive care unit stay duration (pooled mean difference: 1.44; 95% CI: 0.07, 2.81; I2 = 0%), or mortality (pooled odds ratio: 0.55; 95% CI: 0.28, 1.09; I2 = 0%), with a slight trend favoring reduced hospitalization duration (pooled mean difference: -2.37; 95% CI: -2.99, -1.76; I2 = 49%). Of the 25 studies, 8 were high quality with low bias, 6 had some concerns, and 11 were low quality with high bias. Conclusions: The review presents mixed efficacy of antioxidant therapies for SARS-CoV-2, with some studies indicating potential benefits. Further well-designed large-scale RCTs are warranted to determine the definitive role of antioxidants in SARS-CoV-2 treatment.This systematic review was registered at PROSPERO as CRD42023430805.

5.
RMD Open ; 10(2)2024 May 20.
Article En | MEDLINE | ID: mdl-38772680

OBJECTIVES: Fibromyalgia is frequently treated with opioids due to limited therapeutic options. Long-term opioid use is associated with several adverse outcomes. Identifying factors associated with long-term opioid use is the first step in developing targeted interventions. The aim of this study was to evaluate risk factors in fibromyalgia patients newly initiated on opioids using machine learning. METHODS: A retrospective cohort study was conducted using a nationally representative primary care dataset from the UK, from the Clinical Research Practice Datalink. Fibromyalgia patients without prior cancer who were new opioid users were included. Logistic regression, a random forest model and Boruta feature selection were used to identify risk factors related to long-term opioid use. Adjusted ORs (aORs) and feature importance scores were calculated to gauge the strength of these associations. RESULTS: In this study, 28 552 fibromyalgia patients initiating opioids were identified of which 7369 patients (26%) had long-term opioid use. High initial opioid dose (aOR: 31.96, mean decrease accuracy (MDA) 135), history of self-harm (aOR: 2.01, MDA 44), obesity (aOR: 2.43, MDA 36), high deprivation (aOR: 2.00, MDA 31) and substance use disorder (aOR: 2.08, MDA 25) were the factors most strongly associated with long-term use. CONCLUSIONS: High dose of initial opioid prescription, a history of self-harm, obesity, high deprivation, substance use disorder and age were associated with long-term opioid use. This study underscores the importance of recognising these individual risk factors in fibromyalgia patients to better navigate the complexities of opioid use and facilitate patient-centred care.


Analgesics, Opioid , Fibromyalgia , Machine Learning , Opioid-Related Disorders , Humans , Fibromyalgia/epidemiology , Analgesics, Opioid/therapeutic use , Analgesics, Opioid/adverse effects , Female , Male , Middle Aged , Risk Factors , Retrospective Studies , Adult , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/etiology , United Kingdom/epidemiology , Aged
6.
J Cardiothorac Surg ; 19(1): 294, 2024 May 18.
Article En | MEDLINE | ID: mdl-38762548

Spontaneous retroperitoneal hematoma (SRH) is a rare complication of anticoagulation therapy. Presentation may vary from limb paresis to hypovolemic shock due to blood loss. The optimal treatment is controversial. It can be managed conservatively or surgically. We report a case of a 73-year-old man presenting with progressively worsening abdominal pain and severe pain radiating to his left lower limb twenty-five days after his pulmonary endarterectomy (PEA) surgery. He was on anticoagulation per our institutional protocol for PEA patients. Investigations revealed a large, spontaneously occurring iliopsoas hematoma. Our patient was treated conservatively, and the SRH stabilised.


Endarterectomy , Hematoma , Humans , Male , Aged , Endarterectomy/adverse effects , Retroperitoneal Space , Hematoma/etiology , Hematoma/surgery , Pulmonary Artery/surgery , Tomography, X-Ray Computed , Pulmonary Embolism/etiology , Pulmonary Embolism/surgery , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Postoperative Complications
7.
Lancet Planet Health ; 8 Suppl 1: S18, 2024 04.
Article En | MEDLINE | ID: mdl-38632913

BACKGROUND: Given the urgency of transitioning towards sustainable nutrition, dietary shifts that provide co-benefits to human health and the environment are imperative. There is currently no database of the environmental impacts of foods that reflects Canada's unique geographical and agri-climatic context and regional inputs and emissions. To determine sustainable diets, harmonising nutritional considerations with environmental impacts is also essential for an equitable comparison of foods. We aimed to develop a Canadian Food Life Cycle Inventory database and a multidimensional index to enable a joint assessment of the health and environmental impacts of foods in Canada. METHODS: The Canadian Food Life Cycle Inventory database uses life cycle assessment methodology to evaluate environmental impacts. The datasets mirror Canada's food consumption patterns, averaging the spectrum of agricultural practices weighted by domestic production and import shares. The database is structured according to the nomenclature and categorisation of the Canadian Nutrient File. Environmental sustainability is assessed using a cradle-to-grave approach, including indicators such as greenhouse gas emissions, eutrophication, particulate matter, freshwater usage, land use, non-renewable energy consumption, and food loss and waste. Environmental impacts are quantified through an environmental impact score (EIS) assigned to each impact category for a given food. The EIS-nutrition (EIS-N) integrates the evaluation of nutritional quality with environmental impacts using Nutri-Score, a validated food nutrient-profiling tool. The EIS-N is modelled as a ratio of the EIS to the Nutri-Score values. FINDINGS: Preliminary results show the greatest environmental impacts for animal-based foods, particularly beef, in agreement with current literature. Foods with greater nutritional quality also generally show greater environmental sustainability, with some exceptions for particular impact categories. INTERPRETATION: The database and index have potential to serve as powerful tools to support researchers, policy makers, and consumers, harnessing big data to drive efficient food and climate solutions for systems transformation. FUNDING: Province of Ontario and University of Toronto, CIHR SMART Healthy Cities Training Platform, and University of Toronto's Temerty Faculty of Medicine.


Environment , Food , Animals , Cattle , Humans , Diet , Life Cycle Stages , Ontario
8.
BMJ Open ; 14(4): e079316, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38643005

INTRODUCTION: Prehospital identification of intracerebral haemorrhage (ICH) in suspected stroke cases may enable the initiation of appropriate treatments and facilitate better-informed transport decisions. This scoping review aims to examine the literature to identify early clinical features and portable devices for the detection of ICH in the prehospital setting. METHODS: Three databases were searched via Ovid (MEDLINE, EMBASE and CENTRAL) from inception to August 2022 using prespecified search strategies. One reviewer screened all titles, abstracts and full-text articles for eligibility, while a second reviewer independently screened 20% of the literature during each screening stage. Data extracted were tabulated to summarise the key findings. RESULTS: A total of 6803 articles were screened for eligibility, of which 22 studies were included for analysis. Among them, 15 studies reported on early clinical features, while 7 considered portable devices. Associations between age, sex and comorbidities with the presence of ICH varied across studies. However, most studies reported that patients with ICH exhibited more severe neurological deficits (n=6) and higher blood pressure levels (n=11) at onset compared with other stroke and non-stroke diagnoses. Four technologies were identified for ICH detection: microwave imaging technology, volumetric impedance phase shift spectroscopy, transcranial ultrasound and electroencephalography. Microwave and ultrasound imaging techniques showed promise in distinguishing ICH from other diagnoses. CONCLUSION: This scoping review has identified potential clinical features for the identification of ICH in suspected stroke patients. However, the considerable heterogeneity among the included studies precludes meta-analysis of available data. Moreover, we have explored portable devices to enhance ICH identification. While these devices have shown promise in detecting ICH, further technological development is required to distinguish between stroke subtypes (ICH vs ischaemic stroke) and non-stroke diagnoses.


Brain Ischemia , Emergency Medical Services , Stroke , Humans , Stroke/diagnosis , Cerebral Hemorrhage/diagnostic imaging
9.
Lancet Diabetes Endocrinol ; 12(5): 330-338, 2024 May.
Article En | MEDLINE | ID: mdl-38588684

BACKGROUND: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets. METHODS: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs). FINDINGS: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030). INTERPRETATION: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes. FUNDING: Full funding sources are listed at the end of the Article.


Diabetes Mellitus, Type 2 , Glycemic Index , Glycemic Load , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/blood , Middle Aged , Female , Male , Glycemic Index/physiology , Prospective Studies , Adult , Aged , Risk Factors , Incidence , Blood Glucose/analysis , Diet , Cohort Studies
10.
Sci Rep ; 14(1): 7297, 2024 03 27.
Article En | MEDLINE | ID: mdl-38538664

Cystic echinococcosis is caused by the zoonotic tapeworm Echinococcus granulosus. There has been ongoing controversy over whether it causes weight loss in cattle. Recently implemented recording of comorbidities at processors has provided opportunity to investigate this effect. Using prevalence-based observational data from 1,648,049 adult cattle processed in seven states and territories in Australia (2019-2022), we explored associations between carcase weight, hydatid cysts, comorbidities, sex, age, and region. Linear mixed-effect regression models estimated the effect of cystic echinococcosis on carcase weight, guided by directed acyclic graphs to reduce bias. The highest, previously unreported, prevalence was in the southeast Queensland region. The estimated effect of cystic echinococcosis cysts on carcase weight ranged from a gain of 0.32 kg/carcase (standard error [se] 0.58 kg; two-tooth 2022) to a loss of -5.45 kg/carcase (se 0.63 kg; six-tooth 2019) with most point estimates (11/16) between 0 and -2.5 kg across all cattle grouped by year and dentition. This effect size would be practically undetectable in live cattle which is an important finding; cattle producers are unlikely to observe increased productivity through weight gain from cystic echinococcosis prevention in cattle, and awareness to strengthen prevention in domestic dogs around cattle properties to reduce human risk remains a public health focus.


Cattle Diseases , Echinococcosis , Echinococcus granulosus , Echinococcus , Dogs , Animals , Cattle , Humans , Cattle Diseases/epidemiology , Echinococcosis/epidemiology , Echinococcosis/veterinary , Australia/epidemiology
11.
Cancer Discov ; 14(5): 846-865, 2024 May 01.
Article En | MEDLINE | ID: mdl-38456804

Oncology drug combinations can improve therapeutic responses and increase treatment options for patients. The number of possible combinations is vast and responses can be context-specific. Systematic screens can identify clinically relevant, actionable combinations in defined patient subtypes. We present data for 109 anticancer drug combinations from AstraZeneca's oncology small molecule portfolio screened in 755 pan-cancer cell lines. Combinations were screened in a 7 × 7 concentration matrix, with more than 4 million measurements of sensitivity, producing an exceptionally data-rich resource. We implement a new approach using combination Emax (viability effect) and highest single agent (HSA) to assess combination benefit. We designed a clinical translatability workflow to identify combinations with clearly defined patient populations, rationale for tolerability based on tumor type and combination-specific "emergent" biomarkers, and exposures relevant to clinical doses. We describe three actionable combinations in defined cancer types, confirmed in vitro and in vivo, with a focus on hematologic cancers and apoptotic targets. SIGNIFICANCE: We present the largest cancer drug combination screen published to date with 7 × 7 concentration response matrices for 109 combinations in more than 750 cell lines, complemented by multi-omics predictors of response and identification of "emergent" combination biomarkers. We prioritize hits to optimize clinical translatability, and experimentally validate novel combination hypotheses. This article is featured in Selected Articles from This Issue, p. 695.


Antineoplastic Combined Chemotherapy Protocols , Neoplasms , Humans , Cell Line, Tumor , Neoplasms/drug therapy , Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Screening Assays, Antitumor/methods , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
12.
Article En | MEDLINE | ID: mdl-38470220

RATIONALE: Chronic Thromboembolic Pulmonary Hypertension involves formation and non-resolution of thrombus, dysregulated inflammation, angiogenesis and the development of a small vessel vasculopathy. OBJECTIVES: We aimed to establish the genetic basis of chronic thromboembolic pulmonary hypertension to gain insight into its pathophysiological contributors. METHODS: We conducted a genome-wide association study on 1907 European cases and 10363 European controls. We co-analysed our results with existing results from genome-wide association studies on deep vein thrombosis, pulmonary embolism and idiopathic pulmonary arterial hypertension. MEASUREMENTS AND MAIN RESULTS: Our primary association study revealed genetic associations at the ABO, FGG, F11, MYH7B, and HLA-DRA loci. Through our co-analysis we demonstrate further associations with chronic thromboembolic pulmonary hypertension at the F2, TSPAN15, SLC44A2 and F5 loci but find no statistically significant associations shared with idiopathic pulmonary arterial hypertension. CONCLUSIONS: Chronic thromboembolic pulmonary hypertension is a partially heritable polygenic disease, with related though distinct genetic associations to pulmonary embolism and to deep vein thrombosis.

13.
Ecol Evol ; 14(3): e11046, 2024 Mar.
Article En | MEDLINE | ID: mdl-38487746

Reference conditions are difficult to find in the Anthropocene but essential for effective biodiversity conservation. Aquatic ecosystems in the Andes-Amazon transition zone of Colombia are now at high risk due to expanded human activities after peace agreements in 2016 ended armed conflict because lands formerly controlled by FARC and other armed groups are now prone to agricultural and urban expansion. Particularly, expanding human land use may reduce fish diversity across the altitudinal gradient, especially in the premontane streams (i.e., <500 m a.s.l.) because lands are more amenable to human use than at greater altitudes. We evaluated fish α-diversity (measured as species richness, total abundance, and effective species number) and ß-diversity (spatial and temporal) in 12 sites over 8 years bracketing the end of armed conflict. All α-diversity and ß-diversity analyses were evaluated relative to categorical altitude (< or >500 m) and continuous altitude. Strong differences in fish community structure among sites occurred as a function of altitude. Fish communities exhibit altitudinal biodiversity gradients that are consistent in space and time, and that need to be accounted for conservation and management considerations. Our results provide a reference to identify short- and long-term changes due to impending human land use at a critical moment for the conservation of tropical fish diversity. Similar studies in other areas of the upper Amazon Basin are needed to evaluate effects of subsequent human activities on diversity patterns and our study area to compare to reference conditions reported here.

14.
Lancet Respir Med ; 12(4): e21-e30, 2024 04.
Article En | MEDLINE | ID: mdl-38548406

BACKGROUND: Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. METHODS: The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm5 and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292. FINDINGS: Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 71·5% of baseline in the macitentan group and to 87·6% in the placebo group (geometric means ratio 0·81, 95% CI 0·70-0·95, p=0·0098). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]). INTERPRETATION: In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. FUNDING: Actelion Pharmaceuticals Ltd.


Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Pyrimidines , Humans , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/etiology , Pulmonary Arterial Hypertension/drug therapy , Treatment Outcome , Sulfonamides/therapeutic use , Familial Primary Pulmonary Hypertension , Double-Blind Method
15.
JAC Antimicrob Resist ; 6(1): dlae007, 2024 Feb.
Article En | MEDLINE | ID: mdl-38304721

Accreditation of healthcare services provides quality assurance of hospital practice to support safe and effective care for patients. Accreditation programmes focused on antimicrobial stewardship (AMS) have been developed in high-income countries (HIC) and recently the WHO has developed a toolkit to support AMS practice in low and middle-income (LMIC) countries. BSAC has developed their Global Antimicrobial Stewardship Accreditation Scheme (GAMSAS) for hospitals based on globally applicable standards. GAMSAS aims to support healthcare organizations to build measurable AMS programmes and to support spread of best practice. GAMSAS involves a desktop assessment by BSAC experts followed by a hospital visit to gather further insight into how a hospital's AMS programme operates. A final report of compliance with the GAMSAS standards and a recommendation about accreditation at one of three levels is formally approved at a GAMSAS panel meeting involving well-established global experts in AMS. The BSAC GAMSAS team reflect on progress during the first year and ambitions for future spread.

16.
Am J Obstet Gynecol ; 2024 Feb 07.
Article En | MEDLINE | ID: mdl-38336125

BACKGROUND: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. OBJECTIVE: This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. STUDY DESIGN: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF10-DEIA-LiPA25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model. RESULTS: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups. CONCLUSION: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.

17.
Am J Clin Nutr ; 119(2): 496-510, 2024 Feb.
Article En | MEDLINE | ID: mdl-38309832

BACKGROUND: Inulin-type fructans (ITF) are the leading prebiotics in the market. Available evidence provides conflicting results regarding the beneficial effects of ITF on cardiovascular disease risk factors. OBJECTIVES: This study aimed to evaluate the effects of ITF supplementation on cardiovascular disease risk factors in adults. METHODS: We searched MEDLINE, EMBASE, Emcare, AMED, CINAHL, and the Cochrane Library databases from inception through May 15, 2022. Eligible randomized controlled trials (RCTs) administered ITF or placebo (for example, control, foods, diets) to adults for ≥2 weeks and reported one or more of the following: low, very-low, or high-density lipoprotein cholesterol (LDL-C, VLDL-C, HDL-C); total cholesterol; apolipoprotein A1 or B; triglycerides; fasting blood glucose; body mass index; body weight; waist circumference; waist-to-hip ratio; systolic or diastolic blood pressure; or hemoglobin A1c. Two reviewers independently and in duplicate screened studies, extracted data, and assessed risk of bias. We pooled data using random-effects model, and assessed the certainty of evidence (CoE) using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: We identified 1767 studies and included 55 RCTs with 2518 participants in meta-analyses. The pooled estimate showed that ITF supplementation reduced LDL-C [mean difference (MD) -0.14 mmol/L, 95% confidence interval (95% CI: -0.24, -0.05), 38 RCTs, 1879 participants, very low CoE], triglycerides (MD -0.06 mmol/L, 95% CI: -0.12, -0.01, 40 RCTs, 1732 participants, low CoE), and body weight (MD -0.97 kg, 95% CI: -1.28, -0.66, 36 RCTs, 1672 participants, low CoE) but little to no significant effect on other cardiovascular disease risk factors. The effects were larger when study duration was ≥6 weeks and in pre-obese and obese participants. CONCLUSION: ITF may reduce low-density lipoprotein, triglycerides, and body weight. However, due to low to very low CoE, further well-designed and executed trials are needed to confirm these effects. PROSPERO REGISTRATION NUMBER: CRD42019136745.


Cardiovascular Diseases , Inulin , Adult , Humans , Inulin/pharmacology , Inulin/therapeutic use , Cardiovascular Diseases/prevention & control , Fructans/pharmacology , Fructans/therapeutic use , Cholesterol, LDL , Randomized Controlled Trials as Topic , Body Weight , Obesity , Triglycerides
18.
Nutrients ; 16(4)2024 Feb 08.
Article En | MEDLINE | ID: mdl-38398819

BACKGROUND: A cholesterol-lowering diet score was previously developed for epidemiological studies; its association with serum lipid profile was not confirmed yet. METHODS: The score was developed as an adaptation of the dietary portfolio for cholesterol reduction, assigning one point for adherence to seven dietary indicators and ranging from 0 (null adherence) to 7 (highest adherence). The score was calculated for breast cancer patients enrolled in the DEDiCa study using a 7-day food record; serum lipid profile, including total and low-density lipoprotein cholesterol (LDL-C), was evaluated in serum at baseline. RESULTS: Patients with the highest adherence to the cholesterol-lowering diet (i.e., score ≥ 4) reported lower LDL-C level than women with score 0-1 (median: 107 mg/dL and 122 mg/dL, respectively; p < 0.01). The proportion of women with LDL-C above the recommended limit of 116 mg/dL was 60.0% with score 0-1 and 42.6% with score ≥4. Although the score directly correlates with consumption of foods from vegetal sources, it was mildly associated with the healthful plant-based diet index (r-Spearman = 0.51) and the Mediterranean Diet Adherence Screener (r-Spearman = 0.30) Conclusions: These results provide experimental evidence that the cholesterol-lowering diet score is capable of detecting a specific plant-based dietary pattern that affects circulating cholesterol levels.


Cholesterol , Diet, Mediterranean , Humans , Female , Cholesterol, LDL , Diet, Healthy
19.
Lancet Diabetes Endocrinol ; 12(2): 107-118, 2024 Feb.
Article En | MEDLINE | ID: mdl-38272606

BACKGROUND: There is debate over whether the glycaemic index of foods relates to chronic disease. We aimed to assess the associations between glycaemic index (GI) and glycaemic load (GL) and type 2 diabetes, cardiovascular disease, diabetes-related cancers, and all-cause mortality. METHODS: We did a meta-analysis of large cohorts (≥100 000 participants) identified from the Richard Doll Consortium. We searched the Cochrane Library, MEDLINE, PubMed, Embase, Web of Science, and Scopus for cohorts that prospectively examined associations between GI or GL and chronic disease outcomes published from database inception to Aug 4, 2023. Full-article review and extraction of summary estimates data were conducted by three independent reviewers. Primary outcomes were incident type 2 diabetes, total cardiovascular disease (including mortality), diabetes-related cancers (ie, bladder, breast, colorectal, endometrial, hepatic, pancreatic, and non-Hodgkin lymphoma), and all-cause mortality. We assessed comparisons between the lowest and highest quantiles of GI and GL, adjusting for dietary factors, and pooling their most adjusted relative risk (RR) estimates using a fixed-effects model. We also assessed associations between diets high in fibre and whole grains and the four main outcomes. The study protocol is registered with PROSPERO, CRD42023394689. FINDINGS: From ten prospective large cohorts (six from the USA, one from Europe, two from Asia, and one international), we identified a total of 48 studies reporting associations between GI or GL and the outcomes of interest: 34 (71%) on various cancers, nine (19%) on cardiovascular disease, five (10%) on type 2 diabetes, and three (6%) on all-cause mortality. Consumption of high GI foods was associated with an increased incidence of type 2 diabetes (RR 1·27 [95% CI 1·21-1·34]; p<0·0001), total cardiovascular disease (1·15 [1·11-1·19]; p<0·0001), diabetes-related cancer (1·05 [1·02-1·08]; p=0·0010), and all-cause mortality (1·08 [1·05-1·12]; p<0·0001). Similar associations were seen between high GL and diabetes (RR 1·15 [95% CI 1·09-1·21]; p<0·0001) and total cardiovascular disease (1·15 [1·10-1·20]; p<0·0001). Associations between diets high in fibre and whole grains and the four main outcomes were similar to those for low GI diets. INTERPRETATION: Dietary recommendations to reduce GI and GL could have effects on health outcomes that are similar to outcomes of recommendations to increase intake of fibre and whole grain. FUNDING: Banting and Best and the Karuna Foundation.


Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Glycemic Load , Neoplasms , Humans , Glycemic Index , Diabetes Mellitus, Type 2/epidemiology , Cardiovascular Diseases/epidemiology , Prospective Studies , Neoplasms/epidemiology , Diet , Chronic Disease , Dietary Carbohydrates , Risk Factors
20.
Sci Rep ; 14(1): 811, 2024 Jan 08.
Article En | MEDLINE | ID: mdl-38191916

Quantum light emitters (also known as single photon emitters) are known to be the heart of quantum information technologies. Irrespective of possessing ideal single photon emitter properties, quantum emitters in 2-D hBN defect structures, exhibit constrained quantum light emission within the 300-700 nm range. However, this emission range cannot fully satisfy the needs of an efficient quantum communication applications such as quantum key distribution (QKD), which demands the quantum light emission in fiber optic telecom wavelength bands (from 1260 to 1625 nm) and the free space optical (FSO) (UV-C-solar blind band-100 to 280 nm) wavelength ranges. Hence, there is a necessity to tune the quantum light emission into these two bands. However, the most promising technique to tune the quantum light emitters in hBN here, is still a matter of debate and till date there is no experimental and theoretical assurances. Hence, this work will focus on one of the most promising simple techniques known as Stark electrical tuning of the quantum light emission of hBN defect structures (NBVN, VB, CB, CBVN, CBCN, CBCNCBCN complex, and VBO2). These hBN defects are designed and sandwiched as metal/graphene/hBN defect structure/graphene/metal heterostructure and electrically tuned towards FSO and fiber optic bands (tuning range from UV-C to O-band IR region) region, using constrained DFT computations. The external electric field predicted to yield an atomic bond angle tilt associated with this point defect structure creates out-of-plane dipole moments, enabling the tuning of quantum emission. This electrical tuning technique leads to a simple passive photonic component which enables easier compatibility with quantum circuits and it is found to be one of the perfect alternative solutions, which does not require much external hardware setup to implement as compared to earlier published strain induced tuning experiments.

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