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1.
Ecol Food Nutr ; 63(2): 112-134, 2024.
Article in English | MEDLINE | ID: mdl-38421255

ABSTRACT

Our intersectional research explored food insecurity and job insecurity as predictors of healthcare insecurity and mental health challenges among households living in economic instability since the COVID19 pandemic began. The New York City COVID19 Research Team adapted a validated, web based, anonymous survey questionnaire using a Social Determinants of Health Framework. The study oversampled underserved populations with a total of 2,099 participants. We report strong associations between food insecurity and job insecurity among healthcare insecure households, and significant mental health challenges among food insecure and healthcare insecure households. This underscores the need for integrated social policies to protect underserved urban populations.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Mental Health , Job Security , Intersectional Framework , Food Supply , Food Insecurity , Delivery of Health Care
3.
Ir Med J ; 116(8): 830, 2023 09 21.
Article in English | MEDLINE | ID: mdl-37791649
4.
Ir J Med Sci ; 192(4): 1573-1579, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36369600

ABSTRACT

BACKGROUND: In May 2021, the B.1.617 variant of SARS-CoV-2 emerged in Ireland, and both Delta and Kappa sub-lineages were initially deemed variants of concern (VOCs) on a precautionary basis. We describe a large outbreak of SARS-CoV-2 B.1.617.1 (Kappa mutation) linked to a private gathering among third level students in Cork, Ireland. METHODS: Surveillance data were available from the Health Service Executive COVID Care Tracker. The epidemiological sequence of infection for each new case in this outbreak was tracked and whole genome sequencing was requested on all linked cases. Enhanced public health control measures were implemented by the Department of Public Health HSE-South to contain onward spread of VOCs, including retrospective contact tracing, lengthy isolation and quarantine periods for cases and close contacts. Extensive surveillance efforts were used to describe and control onward transmission. RESULTS: There were 146 confirmed SARS-CoV-2 cases linked to the outbreak. All sequenced cases (53/146; 36%) confirmed Kappa mutation. The median age was 21 years (range 17-65). The majority (88%) had symptoms of SARS-CoV-2 infection. There were 407 close contacts; the median was 3 per case (range 0-14). There were no known hospitalisations, ICU admissions or deaths. Vaccination data was unavailable, but the outbreak pre-dated routine availability of COVID-19 vaccines among younger adults in Ireland. CONCLUSION: Enhanced public health control measures for new and emerging variants of SARS-CoV-2 may be burdensome for cases and close contacts. The overall public health benefit of enhanced controls may only become apparent when evidence on disease transmissibility and severity becomes more complete.


Subject(s)
COVID-19 , Adult , Humans , Adolescent , Young Adult , Middle Aged , Aged , COVID-19/epidemiology , SARS-CoV-2/genetics , COVID-19 Vaccines , Ireland/epidemiology , Retrospective Studies , Disease Outbreaks , Mutation
5.
J Racial Ethn Health Disparities ; 10(4): 1703-1720, 2023 08.
Article in English | MEDLINE | ID: mdl-35831703

ABSTRACT

BACKGROUND: COVID-19 revealed and broadened existing disparities in large cities. This article interprets the early impacts of COVID-19 on food insecurity (FI) in the Chicago and New York City (NYC) metropolitan areas for Black, Indigenous, and People of Color (BIPOC) and provides a study using a Social Determinants of Health (SDOH) framework. METHODS: A cross-sectional survey adapted from the National Food Access and COVID Research Team (NFACT) was deployed in Chicago (N = 680) and in NYC (N = 525) during summer 2020 and oversampled for race, ethnicity, and socioeconomic status. Multivariate binary logistic regression generated adjusted odds ratios (aOR) and 95% CIs for FI and select SDOH variables, which was conducted on each dataset. RESULTS: The prevalence of FI in NYC increased to 66.8% (from 57.8%) and in Chicago to 44.8% (from 41.0%). While higher income protected against FI before, protection was diminished or eliminated since COVID-19. FI declined for households with children in NYC while odds increased and became significant in Chicago. Respondents with chronic health conditions experienced increased odds of FI since COVID. In Chicago, this variable had the highest odds of FI. Respondents with depression or anxiety had increased odds of FI. In NYC, depression had the highest odds of FI. Females in NYC were protected against FI. Hispanics in NYC lost protection against FI from before to since COVID-19. CONCLUSIONS: Results support the observed rise of FI for BIPOC and its association with health status. The analysis has multifaceted, structural policy implications for reducing FI in urban centers.


Subject(s)
COVID-19 , Child , Female , Humans , COVID-19/epidemiology , Cities , New York City/epidemiology , Chicago/epidemiology , Socioeconomic Factors , Cross-Sectional Studies , Pandemics , Food Insecurity , Food Supply
6.
Cureus ; 14(4): e24030, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35573506

ABSTRACT

Polycythemia rubra vera (PRV) is a clonal myeloproliferative neoplasm characterized by autonomous production of erythrocytes, neutrophils, and platelets. Angiomyolipomas (AMLs) are benign renal perivascular epithelioid cell neoplasms of which approximately 80% are sporadic. Here, we report synchronous diagnoses of PRV and asymptomatic sporadic bilateral renal AMLs in a 71-year-old woman. We describe her treatment with phlebotomy and hydroxyurea for PRV and surveillance for renal AMLs. We compare the features and treatment of the present case with those of two previously reported women who also had PRV and sporadic renal AMLs. Finally, we discuss the management and acquired genetic basis of both neoplasms.

7.
Eur Heart J Cardiovasc Pharmacother ; 8(6): 578-586, 2022 Sep 03.
Article in English | MEDLINE | ID: mdl-34448822

ABSTRACT

AIMS: Many patients are unable to achieve guideline-recommended LDL cholesterol (LDL-C) targets, despite taking maximally tolerated lipid-lowering therapy. Bempedoic acid, a competitive inhibitor of ATP citrate lyase, significantly lowers LDL-C with or without background statin therapy in diverse populations. Because pharmacodynamic interaction between statins and bempedoic acid is complex, a dose-response model was developed to predict LDL-C pharmacodynamics following administration of statins combined with bempedoic acid. METHODS AND RESULTS: Bempedoic acid and statin dosing and LDL-C data were pooled from 14 phase 1-3 clinical studies. Dose-response models were developed for bempedoic acid monotherapy and bempedoic acid-statin combinations using previously published statin parameters. Simulations were performed using these models to predict change in LDL-C levels following treatment with bempedoic acid combined with clinically relevant doses of atorvastatin, rosuvastatin, simvastatin, and pravastatin. Dose-response models predicted that combining bempedoic acid with the lowest statin dose of commonly used statins would achieve a similar degree of LDL-C lowering as quadrupling that statin dose; for example, the predicted LDL-C lowering was 54% with atorvastatin 80 mg compared with 54% with atorvastatin 20 mg + bempedoic acid 180 mg, and 42% with simvastatin 40 mg compared with 46% with simvastatin 10 mg + bempedoic acid 180 mg. CONCLUSION: These findings suggest bempedoic acid combined with lower statin doses offers similar LDL-C lowering compared with statin monotherapy at higher doses, potentially sparing patients requiring additional lipid-lowering therapies from the adverse events associated with higher statin doses.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Atorvastatin , Cholesterol, LDL , Dicarboxylic Acids , Fatty Acids , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Simvastatin/therapeutic use
8.
J Surg Res ; 269: 51-58, 2022 01.
Article in English | MEDLINE | ID: mdl-34520982

ABSTRACT

BACKGROUND: Use of routine chest x-rays (CXR) following thoracostomy tube (TT) removal is highly variable and its utility is debated. We hypothesize that routine post-pull chest x-ray (PP-CXR) findings following TT removal in pediatric trauma would not guide the decision for TT reinsertion. METHODS: Patients ≤ 18 y who were not mechanically ventilated and undergoing final TT removal for a traumatic hemothorax (HTX) and/or pneumothorax (PTX) at a level I pediatric trauma center from 2010 to 2020 were retrospectively reviewed. The outcomes of interest were rate of PP-CXR and TT reinsertion rate following PP-CXR. Clinical predictors for worsened findings on PP-CXR were also assessed. RESULTS: Fifty-nine patients were included. A CXR after TT removal was performed in 57 patients (97%), with 28% demonstrating worsened CXR findings compared to the prior film. Except for higher ISS (p = 0.033), there were no demographic or clinical predictors for worsened CXR findings. However, they were more likely to have additional films following the TT removal (p = 0.008) than those with stable or improved PP-CXR findings. One (1.8%) asymptomatic child with worsened PP-CXR findings had TT reinsertion based purely on their worsened PP-CXR findings. CONCLUSIONS: The vast majority of PP-CXR did not guide TT reinsertion after pediatric thoracic trauma. Treatment algorithms may aid to reduce variability and potentially unnecessary routine films.


Subject(s)
Pneumothorax , Thoracic Injuries , Chest Tubes/adverse effects , Child , Humans , Pneumothorax/etiology , Pneumothorax/surgery , Retrospective Studies , Thoracic Injuries/surgery , Thoracostomy/adverse effects
9.
Lett Appl Microbiol ; 74(3): 302-310, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34826143

ABSTRACT

The human oral cavity is host to a diverse microbiota. Much of what is known about the behaviour of oral microbes derives from studies of individual or several cultivated species, situations which do not totally reflect the function of organisms within more complex microbiota or multispecies biofilms. The number of validated models that allow examination of the role that biofilms play during oral cavity colonization is also limited. The CDC biofilm reactor is a standard method that has been deployed to study interactions between members of human microbiotas allowing studies to be completed during an extended period under conditions where nutrient availability, and washout of waste products are controlled. The objective of this work was to develop a robust in vitro biofilm-model system from a pooled saliva inoculum to study the development, reproducibility and stability of the oral microbiota. By employing deep sequencing of the variable regions of the 16S rRNA gene, we found that the CDC biofilm reactor could be used to efficiently cultivate microbiota containing all six major phyla previously identified as the core saliva microbiota. After an acclimatisation period, communities in each reactor stabilised. Replicate reactors were predominately populated by a shared core microbiota; variation between replicate reactors was primarily driven by shifts in abundance of shared operational taxonomic units. We conclude that the CDC biofilm reactor can be used to cultivate communities that replicate key features of the human oral cavity and is a useful tool to facilitate studies of the dynamics of these communities.


Subject(s)
Microbiota , Biofilms , Humans , Mouth , RNA, Ribosomal, 16S/genetics , Reproducibility of Results
10.
J Cyst Fibros ; 21(1): 70-77, 2022 01.
Article in English | MEDLINE | ID: mdl-34635459

ABSTRACT

BACKGROUND: CF is traditionally assessed in clinic. It is unclear if home monitoring of young people with CF is feasible or acceptable. The COVID-19 pandemic has made home monitoring more of a necessity. We report the results of CLIMB-CF, exploring home monitoring's feasibility and potential obstacles. METHODS: We designed a mobile app and enrolled participants with CF aged 2-17 years and their parents for six months. They were asked to complete a variety of measures either daily or twice a week. During the study, participants and their parents completed questionnaires exploring depression, anxiety and quality of life. At the end of the study parents and participants completed acceptability questionnaires. RESULTS: 148 participants were recruited, 4 withdrew prior to starting the study. 82 participants were female with median (IQR) age 7.9 (5.2-12 years). Median data completeness was 40.1% (13.6-69.9%) for the whole cohort; when assessed by age participants aged ≥ 12 years contributed significantly less (15.6% [9.8-30%]). Data completeness decreased over time. There was no significant difference between parental depression and anxiety scores at the start and the end of the study nor in CFQ-R respiratory domain scores for participants ≥ 14 years. The majority of participants did not feel the introduction of home monitoring impacted their daily lives. CONCLUSIONS: Most participants felt home monitoring did not negatively impact their lives and it did not increase depression, anxiety or decrease quality of life. However, uptake was variable, and not well sustained. The teenage years pose a particular challenge and further work is required.


Subject(s)
Cystic Fibrosis/therapy , Mobile Applications , Monitoring, Physiologic/methods , Monitoring, Physiologic/psychology , Quality of Life , Adolescent , Anxiety , COVID-19/epidemiology , Child , Child, Preschool , Depression , Feasibility Studies , Female , Humans , Male , Pandemics , SARS-CoV-2
11.
Curr Dev Nutr ; 5(12): nzab135, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34934898

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic profoundly affected food systems including food security. Understanding how the COVID-19 pandemic impacted food security is important to provide support and identify long-term impacts and needs. OBJECTIVE: The National Food Access and COVID research Team (NFACT) was formed to assess food security over different US study sites throughout the pandemic, using common instruments and measurements. This study presents results from 18 study sites across 15 states and nationally over the first year of the COVID-19 pandemic. METHODS: A validated survey instrument was developed and implemented in whole or part through an online survey of adults across the sites throughout the first year of the pandemic, representing 22 separate surveys. Sampling methods for each study site were convenience, representative, or high-risk targeted. Food security was measured using the USDA 6-item module. Food security prevalence was analyzed using ANOVA by sampling method to assess statistically significant differences. RESULTS: Respondents (n = 27,168) indicate higher prevalence of food insecurity (low or very low food security) since the COVID-19 pandemic, compared with before the pandemic. In nearly all study sites, there is a higher prevalence of food insecurity among Black, Indigenous, and People of Color (BIPOC), households with children, and those with job disruptions. The findings demonstrate lingering food insecurity, with high prevalence over time in sites with repeat cross-sectional surveys. There are no statistically significant differences between convenience and representative surveys, but a statistically higher prevalence of food insecurity among high-risk compared with convenience surveys. CONCLUSIONS: This comprehensive study demonstrates a higher prevalence of food insecurity in the first year of the COVID-19 pandemic. These impacts were prevalent for certain demographic groups, and most pronounced for surveys targeting high-risk populations. Results especially document the continued high levels of food insecurity, as well as the variability in estimates due to the survey implementation method.

12.
PLoS Comput Biol ; 17(10): e1009474, 2021 10.
Article in English | MEDLINE | ID: mdl-34662342

ABSTRACT

The role of heating, ventilation, and air-conditioning (HVAC) systems in the transmission of SARS-CoV-2 is unclear. To address this gap, we simulated the release of SARS-CoV-2 in a multistory office building and three social gathering settings (bar/restaurant, nightclub, wedding venue) using a well-mixed, multi-zone building model similar to those used by Wells, Riley, and others. We varied key factors of HVAC systems, such as the Air Changes Per Hour rate (ACH), Fraction of Outside Air (FOA), and Minimum Efficiency Reporting Values (MERV) to examine their effect on viral transmission, and additionally simulated the protective effects of in-unit ultraviolet light decontamination (UVC) and separate in-room air filtration. In all building types, increasing the ACH reduced simulated infections, and the effects were seen even with low aerosol emission rates. However, the benefits of increasing the fraction of outside air and filter efficiency rating were greatest when the aerosol emission rate was high. UVC filtration improved the performance of typical HVAC systems. In-room filtration in an office setting similarly reduced overall infections but worked better when placed in every room. Overall, we found little evidence that HVAC systems facilitate SARS-CoV-2 transmission; most infections in the simulated office occurred near the emission source, with some infections in individuals temporarily visiting the release zone. HVAC systems only increased infections in one scenario involving a marginal increase in airflow in a poorly ventilated space, which slightly increased the likelihood of transmission outside the release zone. We found that improving air circulation rates, increasing filter MERV rating, increasing the fraction of outside air, and applying UVC radiation and in-room filtration may reduce SARS-CoV-2 transmission indoors. However, these mitigation measures are unlikely to provide a protective benefit unless SARS-CoV-2 aerosol emission rates are high (>1,000 Plaque-forming units (PFU) / min).


Subject(s)
Air Conditioning , COVID-19/transmission , Heating , SARS-CoV-2 , Ventilation , Aerosols , Air Microbiology , Air Movements , COVID-19/prevention & control , COVID-19/virology , Computational Biology , Computer Simulation , Humans , Models, Biological , Pandemics , SARS-CoV-2/radiation effects , Social Interaction , Ultraviolet Rays , Workplace
13.
Metabolism ; 124: 154887, 2021 11.
Article in English | MEDLINE | ID: mdl-34508741

ABSTRACT

Dysregulated lipoprotein metabolism is a major cause of atherosclerotic cardiovascular disease (ASCVD). Use of stable isotope tracers and compartmental modelling have provided deeper understanding of the mechanisms underlying lipid disorders in patients at high risk of ASCVD, including familial hypercholesterolemia (FH), elevated lipoprotein(a) [Lp(a)] and metabolic syndrome (MetS). In patients with FH, deficiency in low-density lipoprotein (LDL) receptor activity not only impairs the catabolism of LDL, but also induces hepatic overproduction and decreases catabolism of triglyceride-rich lipoproteins (TRLs). Patients with elevated Lp(a) are characterized by increased hepatic secretion of Lp(a) particles. Atherogenic dyslipidemia in MetS patients relates to a combination of overproduction of very-low density lipoprotein-apolipoprotein (apo) B-100, decreased catabolism of apoB-100-containing particles, and increased catabolism of high-density lipoprotein-apoA-I particles, as well as to impaired clearance of TRLs in the postprandial state. Kinetic studies show that weight loss, fish oils, statins and fibrates have complementary modes of action that correct atherogenic dyslipidemia. Defining the kinetic mechanisms of action of proprotein convertase subtilisin/kexin type 9 and angiopoietin-like 3 inhibitors on lipid and lipoprotein mechanism in dyslipidemic subjects will further our understanding of these therapies in decreasing the development of ASCVD. "Everything changes but change itself. Everything flows and nothing remains the same... You cannot step twice into the same river, for other waters and yet others go flowing ever on." Heraclitus (c.535- c. 475 BCE).


Subject(s)
Cardiovascular Diseases/metabolism , Dyslipidemias/metabolism , Lipoproteins/metabolism , Cardiovascular Diseases/etiology , Dyslipidemias/complications , Humans , Isotope Labeling
14.
Preprint in English | medRxiv | ID: ppmedrxiv-21260280

ABSTRACT

BackgroundThe COVID-19 pandemic profoundly affected food systems including food security. Understanding how the COVID-19 pandemic impacted food security is important to provide support, and identify long-term impacts and needs. ObjectiveOur team- the National Food Access and COVID research Team (NFACT) was formed to assess food security over different U.S. study sites throughout the pandemic, using common instruments and measurements. Here we present results from 18 study sites across 15 states and nationally over the first year of the COVID-19 pandemic. MethodsA validated survey instrument was developed and implemented in whole or part across the sites throughout the first year of the pandemic, representing 22 separate surveys. Sampling methods for each study site were convenience, representative, or high-risk targeted. Food security was measured using the USDA six-item module. Food security prevalence was analyzed using analysis of variance by sampling method to statistically significant differences. ResultsIn total, more than 27,000 people responded to the surveys. We find higher prevalence of food insecurity (low or very low food security) since the COVID-19 pandemic, as compared to before the pandemic. In nearly all study sites, we find higher prevalence of food insecurity among Black, Indigenous, and People of Color (BIPOC), households with children, and those with job disruptions. We also demonstrate lingering food insecurity, with high or increased prevalence over time in sites with repeat surveys. We find no statistically significant differences between convenience and representative surveys, but statistically higher prevalence of food insecurity among high-risk compared to convenience surveys. ConclusionsThis comprehensive multi-study site effort demonstrates higher prevalence of food insecurity since the beginning of the COVID-19 pandemic, which in multiple survey sites continues throughout the first year of the pandemic. These impacts were prevalent for certain demographic groups, and most pronounced for surveys targeting high-risk populations.

15.
Occup Med (Lond) ; 71(2): 95-98, 2021 04 09.
Article in English | MEDLINE | ID: mdl-33585881

ABSTRACT

BACKGROUND: It is recognized that healthcare workers (HCWs) are at high risk of contracting Covid-19. It is incumbent on occupational health staff to recognize potential symptoms of Covid-19 among HCWs. AIMS: The aims of the study were to describe the presenting symptoms of HCWs who developed Covid-19 in Ireland, and to estimate the odds of specific symptoms being associated with a positive Covid-19 polymerase chain reaction (PCR) result. METHODS: A retrospective chart review of all symptomatic HCWs who self-presented for Covid-19 testing in Cork from March to May 2020 was conducted. A sex-matched case-control study was carried out to compare presenting features among those who tested positive compared to those who tested negative. Univariate and multivariable-adjusted conditional logistic regression models were run using Stata 15.0 to identify the symptoms associated with positive Covid-19 swab results. RESULTS: Three hundred and six HCWs were included in the study; 102 cases and 204 controls. Common presenting features among cases were fever/chills (55%), cough (44%) and headache (35%). The symptoms which were significantly associated with a positive Covid-19 swab result were loss of taste/smell (adjusted odds ratio [aOR] 12.15, 95% confidence interval [CI] 1.36-108.79), myalgia (aOR 2.36, 95% 1.27-4.38), fatigue (aOR 2.31, 95% CI 1.12-4.74), headache (aOR 2.11, 95% CI 1.19-3.74) and fever/chills (aOR 1.88, 95% CI 1.12-3.15). CONCLUSIONS: Fever, fatigue, myalgia, loss of taste/smell and headache were associated with increased odds of a Covid-19 diagnosis among symptomatic self-referred HCWs compared with those had negative swab results. Testing criteria for HCWs should reflect the broad range of possible symptoms of Covid-19.


Subject(s)
COVID-19/complications , Health Personnel , Occupational Health , Pandemics , Adult , COVID-19/diagnosis , COVID-19/virology , COVID-19 Testing , Cough/diagnosis , Cough/etiology , Fatigue/diagnosis , Fatigue/etiology , Female , Fever/diagnosis , Fever/etiology , Headache/diagnosis , Headache/etiology , Humans , Ireland , Logistic Models , Male , Middle Aged , Myalgia/diagnosis , Myalgia/etiology , Odds Ratio , Olfaction Disorders/diagnosis , Olfaction Disorders/etiology , Retrospective Studies , SARS-CoV-2 , Taste Disorders/diagnosis , Taste Disorders/etiology , Young Adult
16.
Metabolism ; 107: 154221, 2020 06.
Article in English | MEDLINE | ID: mdl-32240727

ABSTRACT

BACKGROUND: Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) particle containing apolipoprotein(a) (apo(a)) covalently linked to apolipoprotein B-100 (apoB). Statin-treated patients with elevated Lp(a) have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Recent trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition decreases Lp(a) and cardiovascular events, particularly in high risk patients with elevated Lp(a). We investigated the kinetic mechanism whereby alirocumab, a PCSK9 inhibitor, lowers Lp(a) in statin-treated patients with high Lp(a) and ASCVD. METHODS: The effects of 12-week alirocumab treatment (150 mg every 2 weeks) on apo(a) kinetics were studied in 21 patients with elevated Lp(a) concentration (>0.5 g/L). Apo(a) fractional catabolic rate (FCR) and production rate (PR) were determined using intravenous D3-leucine administration, mass spectrometry and compartmental modelling. All patients were on long-term statin treatment. RESULTS: Alirocumab significantly decreased plasma concentrations of total cholesterol (-39%), LDL-cholesterol (-67%), apoB (-56%), apo(a) (-25%) and Lp(a) (-22%) (P< 0.001 for all). Alirocumab also significantly lowered plasma apo(a) pool size (-26%, P <0.001) and increased the FCR of apo(a) (+28%, P< 0.001), but did not alter apo(a) PR, which remained significantly higher relative to a reference group of patients on statins with normal Lp(a) (P< 0.001). CONCLUSIONS: In statin-treated patients, alirocumab lowers elevated plasma Lp(a) concentrations by accelerating the catabolism of Lp(a) particles. This may be consequent on marked upregulation of hepatic receptors (principally for LDL) and/or reduced competition between Lp(a) and LDL particles for these receptors; the mechanism could contribute to the benefit of PCSK9 inhibition with alirocumab on cardiovascular outcomes.


Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipidemias/blood , Hyperlipidemias/drug therapy , Hypolipidemic Agents/pharmacology , Lipoprotein(a)/metabolism , PCSK9 Inhibitors , Adolescent , Adult , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Apoprotein(a)/blood , Cholesterol/blood , Coronary Artery Disease/drug therapy , Female , Humans , Hypolipidemic Agents/therapeutic use , Male , Middle Aged , Young Adult
17.
Br J Dermatol ; 182(1): 156-165, 2020 01.
Article in English | MEDLINE | ID: mdl-31056744

ABSTRACT

BACKGROUND: The updated American Joint Committee on Cancer (AJCC) staging criteria for melanoma remain unable to identify high-risk stage I tumour subsets. OBJECTIVES: To determine the utility of epidermal autophagy and beclin 1 regulator 1 (AMBRA1)/loricrin (AMLo) expression as a prognostic biomarker for AJCC stage I cutaneous melanoma. METHODS: Peritumoral AMBRA1 expression was evaluated in a retrospective discovery cohort of 76 AJCC stage I melanomas. AMLo expression was correlated with clinical outcomes up to 12 years in two independent powered, retrospective validation and qualification cohorts comprising 379 AJCC stage I melanomas. RESULTS: Decreased AMBRA1 expression in the epidermis overlying primary melanomas in a discovery cohort of 76 AJCC stage I tumours was associated with a 7-year disease-free survival (DFS) rate of 81·5% vs. 100% survival with maintained AMBRA1 (P < 0·081). Following an immunohistochemistry protocol for semi-quantitative analysis of AMLo, analysis was undertaken in validation (n = 218) and qualification cohorts (n = 161) of AJCC stage I melanomas. Combined cohort analysis revealed a DFS rate of 98·3% in the AMLo low-risk group (n = 239) vs. 85·4% in the AMLo high-risk cohort (n = 140; P < 0·001). Subcohort multivariate analysis revealed that an AMLo hazard ratio (HR) of 4·04 [95% confidence interval (CI) 1·69-9·66; P = 0·002] is a stronger predictor of DFS than Breslow depth (HR 2·97, 95% CI 0·93-9·56; P = 0·068) in stage IB patients. CONCLUSIONS: Loss of AMLo expression in the epidermis overlying primary AJCC stage I melanomas identifies high-risk tumour subsets independently of Breslow depth. What's already known about this topic? There is an unmet clinical need for biomarkers of early-stage melanoma. Autophagy and beclin 1 regulator 1 (AMBRA1) is a proautophagy regulatory protein with known roles in cell proliferation and differentiation, and is a known tumour suppressor. Loricrin is a marker of epidermal terminal differentiation. What does this study add? AMBRA1 has a functional role in keratinocyte/epidermal proliferation and differentiation. The combined decrease/loss of peritumoral AMBRA1 and loricrin is associated with a significantly increased risk of metastatic spread in American Joint Committee on Cancer (AJCC) stage I tumours vs. melanomas, in which peritumoral AMBRA1 and loricrin are maintained, independently of Breslow depth. What is the translational message? The integration of peritumoral epidermal AMBRA1/loricrin biomarker expression into melanoma care guidelines will facilitate more accurate, personalized risk stratification for patients with AJCC stage I melanomas, thereby facilitating stratification for appropriate follow-up and informing postdiagnostic investigations, including sentinel lymph node biopsy, ultimately resulting in improved disease outcomes and rationalization of healthcare costs.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Melanoma , Membrane Proteins/genetics , Skin Neoplasms , Autophagy , Epidermis/pathology , Humans , Melanoma/pathology , Neoplasm Staging , Prognosis , Retrospective Studies , Skin Neoplasms/pathology , United States
18.
Clin Exp Dermatol ; 45(1): 48-55, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31265150

ABSTRACT

BACKGROUND: We conducted a re-audit of the surgical practice of UK dermatologists for the treatment of nonmelanoma skin cancer and examined changes with reference to our previous audit in 2014. The audit was supplemented by a detailed assessment of completeness of the histopathology reports for each tumour. METHODS: UK dermatologists collected data on 10 consecutive nonmicrographic excisions for basal cell carcinoma (BCC) and 5 for squamous cell carcinoma (SCC). Data were collected on site, preoperative diagnosis, histological diagnosis, proximity to previous scars, and histological deep and peripheral margins. RESULTS: In total, 222 responses were received from 135 centres, reporting on 3290 excisions. Excisions from the head and neck accounted for 56.7% of cases. Tumour diameter (mean ± SD) was 11.4 ± SD 7.1 mm (maximum size 100 mm) and 97% of cases were primary excisions. BCCs and SCCs respectively accounted for 65.7% and 26.8% of total cases. Of the suspected BCCs and SCCs, 95.8% and 80.4%, respectively, were confirmed histologically. All margins for any tumour were clear in 97.0% of cases, and complication rate in the audit was < 1%. Of the 2864 histology reports evaluated, only 706 (24.6%) contained all core data items; 95% of these were structure (synoptic) reports. Commonly omitted items were level of invasion, risk and T stage, which were absent from 35.7%, 64.2% and 44.1% of reports, respectively. CONCLUSIONS: Diagnostic accuracy and complete excision rates remain high. Complication rates may be under-reported owing to lack of follow-up. Histopathology reporting has a greater chance of being complete if reports are generated on a field-based platform (synoptic reporting).


Subject(s)
Dermatologists , Pathologists , Practice Patterns, Physicians'/statistics & numerical data , Skin Neoplasms/surgery , Carcinoma, Basal Cell/surgery , Carcinoma, Squamous Cell/surgery , Clinical Audit , Dermatologic Surgical Procedures/statistics & numerical data , Margins of Excision , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Societies, Medical , United Kingdom
19.
Limnol Oceanogr ; 64(3): 1333-1346, 2019 May.
Article in English | MEDLINE | ID: mdl-31741542

ABSTRACT

Arsenic contamination of lakebed sediments is widespread due to a range of human activities, including herbicide application, waste disposal, mining, and smelter operations. The threat to aquatic ecosystems and human health is dependent on the degree of mobilization from sediments into overlying water columns and exposure of aquatic organisms. We undertook a mechanistic investigation of arsenic cycling in two impacted lakes within the Puget Sound region, a shallow weakly-stratified lake and a deep seasonally-stratified lake, with similar levels of lakebed arsenic contamination. We found that the processes that cycle arsenic between sediments and the water column differed greatly in shallow and deep lakes. In the shallow lake, seasonal temperature increases at the lakebed surface resulted in high porewater arsenic concentrations that drove larger diffusive fluxes of arsenic across the sediment-water interface compared to the deep, stratified lake where the lakebed remained ~10#x00B0;C cooler. Plankton in the shallow lake accumulated up to an order of magnitude more arsenic than plankton in the deep lake due to elevated aqueous arsenic concentrations in oxygenated waters and low phosphate: arsenate ratios in the shallow lake. As a result, strong arsenic mobilization from sediments in the shallow lake was countered by large arsenic sedimentation rates out of the water column driven by plankton settling.

20.
J Clin Endocrinol Metab ; 104(12): 6247-6255, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31393573

ABSTRACT

BACKGROUND: Lipoprotein(a) [Lp(a)] is a low-density lipoprotein‒like particle containing apolipoprotein(a) [apo(a)]. Patients with elevated Lp(a), even when treated with statins, are at increased risk of cardiovascular disease. We investigated the kinetic basis for elevated Lp(a) in these patients. OBJECTIVES: Apo(a) production rate (PR) and fractional catabolic rate (FCR) were compared between statin-treated patients with and without elevated Lp(a). METHODS: The kinetics of apo(a) were investigated in 14 patients with elevated Lp(a) and 15 patients with normal Lp(a) levels matched for age, sex, and body mass index using stable isotope techniques and compartmental modeling. All 29 patients were on background statin treatment. Plasma apo(a) concentration was measured using liquid chromatography-mass spectrometry. RESULTS: The plasma concentration and PR of apo(a) were significantly higher in patients with elevated Lp(a) than in patients with normal Lp(a) concentration (all P < 0.01). The FCR of apo(a) was not significantly different between the groups. In univariate analysis, plasma concentration of apo(a) was significantly associated with apo(a) PR in both patient groups (r = 0.699 and r = 0.949, respectively; all P < 0.01). There was no significant association between plasma apo(a) concentration and FCR in either of the groups (r = 0.160 and r = -0.137, respectively). CONCLUSION: Elevated plasma Lp(a) concentration is a consequence of increased hepatic production of Lp(a) particles in these patients. Our findings provide a kinetic rationale for the use of therapies that target the synthesis of apo(a) and production of Lp(a) particles in patients with elevated Lp(a).


Subject(s)
Apoprotein(a)/metabolism , Biomarkers/analysis , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipidemias/metabolism , Lipoprotein(a)/blood , Adolescent , Adult , Aged , Apoprotein(a)/drug effects , Female , Follow-Up Studies , Humans , Hyperlipidemias/drug therapy , Kinetics , Lipoprotein(a)/drug effects , Male , Middle Aged , Prognosis , Young Adult
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