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1.
Foods ; 13(11)2024 May 25.
Article in English | MEDLINE | ID: mdl-38890883

ABSTRACT

Listeria (L.) monocytogenes is an opportunistic foodborne pathogen that causes listeriosis in humans and animals, reaching up to 30% case mortality. There are only a few reports in Mexico about the L. monocytogenes strains found in various foods. The aim of this study was to determine the prevalence of L. monocytogenes, serogroups, virulence genes, and antimicrobial resistance in different foods from Reynosa, Tamaulipas, Mexico. L. monocytogenes strains were characterized by microbiological and molecular methods. Susceptibility to 12 antibiotics was determined according to CLSI and EUCAST. A total of 300 samples of seafood, pasteurized and raw milk, cheese, beef, and chicken were collected from supermarkets and retail markets. The presence of L. monocytogenes was detected in 5.6% of the samples. Most strains belonged to serogroups 4b, 4d, and 4e (68.4%). All strains presented a minimum of four virulence genes; the most common were actA, hly, and plcB (92.1%). A high percentage of antimicrobial susceptibility was observed, with resistance only to STX-TMP (78.9%), STR (26.3%), MEM (21.0%), and E (2.6%). These results show that the foods in Reynosa, Tamaulipas, are a reservoir of L. monocytogenes and represent a potential health risk.

2.
Front Public Health ; 12: 1364323, 2024.
Article in English | MEDLINE | ID: mdl-38774047

ABSTRACT

Background: This study examines the lasting impact of historical redlining on contemporary neurosurgical care access, highlighting the need for equitable healthcare in historically marginalized communities. Objective: To investigate how redlining affects neurosurgeon distribution and reimbursement in U.S. neighborhoods, analyzing implications for healthcare access. Methods: An observational study was conducted using data from the Center for Medicare and Medicaid Services (CMS) National File, Home Owner's Loan Corporation (HOLC) neighborhood grades, and demographic data to evaluate neurosurgical representation across 91 U.S. cities, categorized by HOLC Grades (A, B, C, D) and gentrification status. Results: Of the 257 neighborhoods, Grade A, B, C, and D neighborhoods comprised 5.40%, 18.80%, 45.8%, and 30.0% of the sample, respectively. Grade A, B, and C neighborhoods had more White and Asian residents and less Black residents compared to Grade D neighborhoods (p < 0.001). HOLC Grade A (OR = 4.37, 95%CI: 2.08, 9.16, p < 0.001), B (OR = 1.99, 95%CI: 1.18, 3.38, p = 0.011), and C (OR = 2.37, 95%CI: 1.57, 3.59, p < 0.001) neighborhoods were associated with a higher representation of neurosurgeons compared to Grade D neighborhoods. Reimbursement disparities were also apparent: neurosurgeons practicing in HOLC Grade D neighborhoods received significantly lower reimbursements than those in Grade A neighborhoods ($109,163.77 vs. $142,999.88, p < 0.001), Grade B neighborhoods ($109,163.77 vs. $131,459.02, p < 0.001), and Grade C neighborhoods ($109,163.77 vs. $129,070.733, p < 0.001). Conclusion: Historical redlining continues to shape access to highly specialized healthcare such as neurosurgery. Efforts to address these disparities must consider historical context and strive to achieve more equitable access to specialized care.


Subject(s)
Neurosurgeons , Humans , United States , Neurosurgeons/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Neighborhood Characteristics , Residence Characteristics/statistics & numerical data , Healthcare Disparities/statistics & numerical data
3.
Front Public Health ; 12: 1341212, 2024.
Article in English | MEDLINE | ID: mdl-38799679

ABSTRACT

Background and objectives: This study investigates geographic disparities in aneurysmal subarachnoid hemorrhage (aSAH) care for Black patients and aims to explore the association with segregation in treatment facilities. Understanding these dynamics can guide efforts to improve healthcare outcomes for marginalized populations. Methods: This cohort study evaluated regional differences in segregation for Black patients with aSAH and the association with geographic variations in disparities from 2016 to 2020. The National Inpatient Sample (NIS) database was queried for admission data on aSAH. Black patients were compared to White patients. Segregation in treatment facilities was calculated using the dissimilarity (D) index. Using multivariable logistic regression models, the regional disparities in aSAH treatment, functional outcomes, mortality, and end-of-life care between Black and White patients and the association of geographical segregation in treatment facilities was assessed. Results: 142,285 Black and White patients were diagnosed with aSAH from 2016 to 2020. The Pacific division (D index = 0.55) had the greatest degree of segregation in treatment facilities, while the South Atlantic (D index = 0.39) had the lowest. Compared to lower segregation, regions with higher levels of segregation (global F test p < 0.001) were associated a lower likelihood of mortality (OR 0.91, 95% CI 0.82-1.00, p = 0.044 vs. OR 0.75, 95% CI 0.68-0.83, p < 0. 001) (p = 0.049), greater likelihood of tracheostomy tube placement (OR 1.45, 95% CI 1.22-1.73, p < 0.001 vs. OR 1.87, 95% CI 1.59-2.21, p < 0.001) (p < 0. 001), and lower likelihood of receiving palliative care (OR 0.88, 95% CI 0.76-0.93, p < 0.001 vs. OR 0.67, 95% CI 0.59-0.77, p < 0.001) (p = 0.029). Conclusion: This study demonstrates regional differences in disparities for Black patients with aSAH, particularly in end-of-life care, with varying levels of segregation in regional treatment facilities playing an associated role. The findings underscore the need for targeted interventions and policy changes to address systemic healthcare inequities, reduce segregation, and ensure equitable access to high-quality care for all patients.


Subject(s)
Black or African American , Healthcare Disparities , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/mortality , Subarachnoid Hemorrhage/therapy , United States , Female , Male , Middle Aged , Healthcare Disparities/statistics & numerical data , Black or African American/statistics & numerical data , Adult , Aged , Cohort Studies , White People/statistics & numerical data , Social Segregation
4.
Article in English | MEDLINE | ID: mdl-38568393

ABSTRACT

We tested the hypothesis that children in New York City (NYC) with an immigrant parent were more likely to lack health insurance and report poorer parent-rated health compared to those of US-born parents in this serial, cross-sectional study using existing data from 2009 to 2017 among children age < 12 years in two NYC health surveys. Main outcomes were parent-reported responses for (1) child insurance coverage and (2) child general health status. In multivariable logistic regression models, we estimated likelihood of outcomes for children of immigrants compared to those of US-born parents, adjusting for child, parent, and household characteristics. We included 2,637 children in 2009 and 7,042 in 2017 in NYC. In 2017, children of immigrant parents were more likely to experience uninsurance than children of US-born parents [adjusted odds ratio (AOR) 2.36 (95% CI: 1.05-5.31)]. Compared to children of US-born parents, children with an immigrant parent were more likely to have a gap in insurance coverage in both 2009 (AOR 1.88; 95% CI: 1.08-3.27) and 2017 (AOR 1.60; 95% CI: 1.06-2.41). Although more children of immigrants had poor/fair health than those of US-born parents in both years, differences were not statistically significant after adjusting for covariates. Our findings among a sample of children eligible for health insurance suggest policies intended to expand child health care access did not equitably reach children of immigrants despite their eligibility for health insurance. Tailored interventions for children of immigrants are needed to mitigate disparities in health insurance coverage.

5.
Article in English | MEDLINE | ID: mdl-38528179

ABSTRACT

Stroke is a major health concern in the USA, disproportionately affecting socioeconomically disadvantaged groups. This study investigates the link between persistent poverty and stroke mortality rates in residents aged 65 and above, positing that sustained economic challenges at the county level correlate with an increase in stroke-related deaths. Persistent poverty refers to a long-term state where a significant portion of a population lives below the poverty threshold for an extended period, typically measured over several decades. It captures the chronic nature of economic hardship faced by a community across multiple generations. Utilizing data from the CDC Wonder database and the American Community Survey, we conducted a comprehensive analysis across US counties, differentiating them by persistent poverty status. Our results indicate a statistically significant link between persistent poverty and increased mortality from ischemic and hemorrhagic strokes; counties afflicted by long-standing poverty were associated with an additional 33.49 ischemic and 8.16 hemorrhagic stroke deaths per 100,000 residents annually compared to their wealthier counterparts. These disparities persisted when controlling for known stroke risk factors and other socioeconomic variables. These results highlight the need for targeted public health strategies and interventions to address the disparities in stroke mortality rates and the broader implications for healthcare equity. The study underscores the vital role of socioeconomic context in health outcomes and the urgency of addressing long-term poverty as a key determinant of public health.

6.
Cureus ; 15(5): e38765, 2023 May.
Article in English | MEDLINE | ID: mdl-37303418

ABSTRACT

Endometriosis is a benign gynecological condition that elicits chronic pain in 2-10% of reproductive-age women in the United States and exists in approximately 50% of women with infertility. It creates complications such as hemorrhage and uterine rupture. Historically, the gynecologic symptoms of endometriosis have been associated with economic strain and inferior quality of life. It is suspected that endometriosis diagnosis and treatment are affected by health disparities throughout gynecological care. The goal of this review was to collate and report the current evidence on potential healthcare disparities related to endometriosis diagnosis, treatment, and care across race, ethnicity, and socioeconomic status. This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched the Excerpta Medica Database (EMBASE), Medline Ovid, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and PsycInfo databases for relevant articles on the topic. Eligibility was established a priori to include articles written in English, published between 2015-2022, and reported on cohort, cross-sectional, or experimental studies conducted in the United States. Initially, 328 articles were found, and after screening and quality assessment, four articles were retained for the final review. Results indicated that White women had higher rates of minimally invasive procedures versus open abdominal surgeries than non-White women. White women also had fewer surgical complications compared to all other races and ethnicities. Black women had higher rates of perioperative complications, higher mortality, and spent more time in the perioperative stage than any other race or ethnicity. In the management of endometriosis, the limited research available showed that all non-White women encountered an increased risk of perioperative and postoperative complications compared to White women. More research is needed to explore diagnostic and treatment disparities beyond surgical management, socioeconomic barriers, and improved representation of racial and ethnic minority women.

7.
Curr Issues Mol Biol ; 45(4): 2965-2971, 2023 Apr 03.
Article in English | MEDLINE | ID: mdl-37185718

ABSTRACT

Alopecia Areata (AA) is a multifactorial, dermatological disease characterized by non-scarring hair loss. Alterations in candidate genes, such as HR (Hairless), could represent a risk factor for its development. The aim of this study was to search for and analyze variants in exons 3, 15 and 17 of the HR gene in Mexican patients with AA. A total of 30 samples from both AA patients and healthy donors were analyzed in this study. Exons were amplified and sequenced using the Sanger method. Descriptive statistics and χ2 tests were used in the analysis of clinical-demographic characteristics and the comparison of allelic/genotypical frequencies between groups, respectively. The effect on protein function for the non-synonymous variants was determined with three bioinformatics servers. Three gene variants were identified in the HR gene of the evaluated patients. The benign polymorphism c.1010G > A p.(Gly337Asp) (rs12675375) had been previously reported, whereas the variants c.750G > A p.(Gln250Gln) and c.3215T > A (Val1072AGlu) have not been described in other world populations. Both non-synonymous variants proved to be significant (p ≤ 0.05). The variant c.3215T > A p.(Val1072Glu) is of particular interest due to its deleterious effect on the structure and function of the protein; therefore, it could be considered a risk factor for the development of AA.

8.
Genet Med ; 24(5): 1008-1016, 2022 05.
Article in English | MEDLINE | ID: mdl-35227607

ABSTRACT

PURPOSE: Pancreatic cancer (PC) risk is increased in families, but PC risk and risk perception have been understudied when both parents have cancer. METHODS: An unbiased method defining cancer triads (proband with PC and both parents with cancer) in a prospective registry estimated risk of PC to probands' siblings in triad group 1 (no parent with PC), group 2 (1 parent with PC), and group 3 (both parents with PC). We estimated standardized incidence ratios (SIRs) using a Surveillance, Epidemiology, and End Results (SEER) reference. We also estimated the risk when triad probands carried germline pathogenic/likely pathogenic variants in any of the 6 PC-associated genes (ATM, BRCA1, BRCA2, CDKN2A, MLH1, and TP53). PC risk perception/concern was surveyed in siblings and controls. RESULTS: Risk of PC was higher (SIR = 3.5; 95% CI = 2.2-5.2) in 933 at-risk siblings from 297 triads. Risk increased by triad group: 2.8 (95% CI = 1.5-4.5); 4.5 (95% CI = 1.6-9.7); and 21.2 (95% CI = 4.3-62.0). SIR in variant-negative triads was 3.0 (95% CI = 1.6-5.0), whereas SIR in variant-positive triads was 10.0 (95% CI = 3.2-23.4). Siblings' perceived risk/concern of developing PC increased by triad group. CONCLUSION: Sibling risks were 2.8- to 21.2-fold higher than that of the general population. Positive variant status increased the risk in triads. Increasing number of PC cases in a triad was associated with increased concern and perceived PC risk.


Subject(s)
Pancreatic Neoplasms , Siblings , Family , Genetic Predisposition to Disease , Humans , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms
9.
Dermatol Ther ; 35(5): e15432, 2022 05.
Article in English | MEDLINE | ID: mdl-35266258

ABSTRACT

The widespread use of PD-1 inhibitors to treat various solid tumors has brought certain challenges for the clinician, including immune-related adverse events (irAEs). Cutaneous toxicities are among the most observed irAEs. Bullous and lichenoid dermatoses following PD-1 inhibitor therapy have been described. Here we report a novel case of lichen planus pemphigoides, featuring characteristics of both bullous pemphigoid and lichen planus, in a patient treated with nivolumab for renal cell carcinoma. We subsequently review all three cutaneous conditions which may arise in the context of PD-1 inhibitor therapy.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Lichen Planus , Lichenoid Eruptions , Carcinoma, Renal Cell/drug therapy , Female , Humans , Immune Checkpoint Inhibitors , Lichen Planus/chemically induced , Lichen Planus/diagnosis , Lichen Planus/drug therapy , Lichenoid Eruptions/chemically induced , Lichenoid Eruptions/diagnosis , Male , Nivolumab/adverse effects
10.
J Gen Intern Med ; 37(2): 298-307, 2022 02.
Article in English | MEDLINE | ID: mdl-33939079

ABSTRACT

BACKGROUND: Despite substantial research on medical student mistreatment, there is scant quantitative data on microaggressions in US medical education. OBJECTIVE: To assess US medical students' experiences of microaggressions and how these experiences influenced students' mental health and medical school satisfaction. DESIGN AND PARTICIPANTS: We conducted a cross-sectional, online survey of US medical students' experiences of microaggressions. MAIN MEASURES: The primary outcome was a positive depression screen on the 2-item Patient Health Questionnaire (PHQ-2). Medical school satisfaction was a secondary outcome. We used logistic regression to model the association between respondents' reported microaggression frequency and the likelihood of a positive PHQ-2 screen. For secondary outcomes, we used the chi-squared statistic to test associations between microaggression exposure and medical school satisfaction. KEY RESULTS: Out of 759 respondents, 61% experienced at least one microaggression weekly. Gender (64.4%), race/ethnicity (60.5%), and age (40.9%) were the most commonly cited reasons for experiencing microaggressions. Increased microaggression frequency was associated with a positive depression screen in a dose-response relationship, with second, third, and fourth (highest) quartiles of microaggression frequency having odds ratios of 2.71 (95% CI: 1-7.9), 3.87 (95% CI: 1.48-11.05), and 9.38 (95% CI: 3.71-26.69), relative to the first quartile. Medical students who experienced at least one microaggression weekly were more likely to consider medical school transfer (14.5% vs 4.7%, p<0.001) and withdrawal (18.2% vs 5.7%, p<0.001) and more likely to believe microaggressions were a normal part of medical school culture (62.3% vs 32.1%) compared to students who experienced microaggressions less frequently. CONCLUSIONS: To our knowledge, this is the largest study on the experiences and influences of microaggressions among a national sample of US medical students. Our major findings were that microaggressions are frequent occurrences and that the experience of microaggressions was associated with a positive depression screening and decreased medical school satisfaction.


Subject(s)
Students, Medical , Cross-Sectional Studies , Depression/diagnosis , Depression/epidemiology , Humans , Microaggression , Personal Satisfaction
11.
Cureus ; 14(12): e32437, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36644033

ABSTRACT

The prolonged coronavirus disease 2019 (COVID-19) pandemic has raised concerns about the failures in the public health measures used to manage the spread of this deadly virus. This review focuses its attention on research papers that at their core highlight the individual public health measures instituted by organizations, institutions, and the government of the United States (US) since the start of the COVID-19 pandemic and that were published in 2019 to 2022. Together, these sources help paint a well-rounded view of the US management of this pandemic so that conclusions may be drawn from mistakes that were made and this country may respond better in the future to such situations. This paper is unique because it highlights the areas where improvement is needed, whereas other published work describes the measures taken and how they were carried out, not the failures, which leaves a gap in the literature that this paper hopes to fill. Through a deep dive into public health measures, seven areas in which improvements could be made were pinpointed by the authors. Such measures included mask mandates, social distancing, lockdown/quarantine, hand hygiene, COVID-19 testing, travel screening, and vaccine hesitancy. In exploring each measure, a discussion was carried out about its benefits and shortcomings in alleviating the ramifications of a global pandemic. In addition to the poor supply chain for critical products like personal protective equipment (PPE), the miscommunication between states and federal policies did not allow for the entirety of the US to respond cohesively in the face of the COVID-19 pandemic. This general review is crucial to know what is working and what needs to be changed to increase the benefits provided to the population.

12.
Int. j. med. surg. sci. (Print) ; 8(4): 1-12, dic. 2021. ilus, tab
Article in Spanish | LILACS | ID: biblio-1348221

ABSTRACT

Uno de los métodos más universales empleados para predecir el ancho mesiodistal de caninos y premolares no erupcionados es el diseñado por el Dr. Edison Moyers, quien tomando como referencia la población anglosajona creó tablas de percentiles para estimar dichos valores en maxilar y mandíbula. Durante la última década varios investigadores han descubierto que, al aplicarlo en diversas poblaciones, existen diferencias significativas entre las predicciones y los valores reales. En Cuba, el método de Moyers es muy utilizado al 50% de probabilidades para la predicción en ambos sexos, pero existen pocos reportes de estudios que validen su confiablidad y los que existen utilizan muestras pequeñas de pacientes. Es por ello por lo que el objetivo de esta investigación es determinar la aplicabilidad del método de Moyers al 50% de probabilidades para la estimación del diámetro mesiodistal de caninos y premolares en pacientes de 12-18 años. Se desarrolló un estudio descriptivo y transversal desde julio de 2019 hasta febrero de 2020 con una población de 125 pacientes, 62 del sexo femenino y 63 del masculino, de entre 12 y 18 años de Cuba. Se efectuaron las mediciones de los anchos mesiodistales de los incisivos inferiores, todos los caninos y premolares. Se realizaron distribuciones de frecuencia a las variables estudiadas y los resultados se presentaron en tablas estadísticas. Para comprobar la existencia de diferencias significativas se utilizó la prueba estadística t-Student. Los resultados principales obtenidos fueron que el método de Moyers tiende a subestimar los valores para el sexo femenino entre los 0,4-0,5 mm, y para el sexo masculino entre los 0,6-0,7 mm, siendo esta diferencia significativa para los hombres. Se concluye que el método de Moyers no puede ser aplicado en la población estudiada para la predicción del ancho mesiodistal de caninos y premolares


One of the most universal methods used to predict the mesiodistal width of non-erupted canines and premolars is the one designed by Dr. Edison Moyers, an American orthodontist who, taking the Anglo-Saxon population as a reference, created percentile tables to estimate these values in the maxilla and mandible. During the last decade, several researchers have discovered that, when applied to various populations, there are significant differences between predictions and actual values. In Cuba, it is widely used at a 50% probability for prediction in both sexes, but there are few reports of studies that validate its reliability and those that do exist use small samples of patients. For this reason, the objective of this research is to determine the applicability of the Moyers method at 50% probabilities for estimating the mesiodistal diameter of canines and premolars in patients 12-18 years of age. A descriptive and cross-sectional study was developed from July 2019 to February 2020 with a population of 125 patients, 62 females and 63 males, between 12 and 18 years old from Cuba. Measurements were made of the mesiodistal widths of the lower incisors, all the canines and premolars. Frequency distributions were made to the variables studied and the results were presented in statistical tables. To verify the existence of significant differences, the statistical t-Student test was used. The main results obtained were that the Moyers method tends to underestimate the values for the female sex between 0.4-0.5 mm, and for the male sex between 0.6 and 0.7 mm, this difference being significant for men. It is concluded that the Moyers method cannot be applied in the population studied for the prediction of the mesiodistal width of canines and premolars


Subject(s)
Humans , Child , Adolescent , Bicuspid/anatomy & histology , Cuspid/anatomy & histology , Odontometry , Cuba
14.
eNeuro ; 8(2)2021.
Article in English | MEDLINE | ID: mdl-33472866

ABSTRACT

While it is well established that there are robust circadian rhythms of arginine vasopressin (AVP) in the cerebrospinal fluid (CSF), the route whereby the peptide reaches the CSF is not clear. A , AVP neurons constitute the largest fraction of the SCN neuronal population. Here, we show that processes of AVP-expressing SCN neurons cross the epithelium of the 3rd ventricular wall to reach the CSF (black arrows). Additionally, we report rostro-caudal differences in AVP neuron size and demonstrate that the localization of cells expressing the clock protein PER2 extend beyond the AVP population, thereby indicating that the size of this nucleus is somewhat larger than previously understood. B , Following lateral ventricle (LV) injection of cholera toxin ß subunit (CTß ; magenta) the retrograde tracer is seen in AVP neurons of the SCN, supporting the anatomical evidence that AVP neuronal processes directly contact the CSF.Arginine vasopressin (AVP) expressing neurons form the major population in the brain's circadian clock located in the hypothalamic suprachiasmatic nucleus (SCN). They participate in inter-neuronal coupling and provide an output signal for synchronizing daily rhythms. AVP is present at high concentrations in the cerebrospinal fluid (CSF) and fluctuates on a circadian timescale. While it is assumed that rhythms in CSF AVP are of SCN origin, a route of communication between these compartments has not been delineated. Using immunochemistry (ICC) and cell filling techniques, we determine the morphology and location of AVP neurons in mouse and delineate their axonal and dendritic processes. Cholera toxin ß subunit (CTß) tracer injected into the lateral ventricle tests whether AVP neurons communicate with CSF. Most importantly, the results indicate that AVP neurons lie in close proximity to the third ventricle, and their processes cross the ventricular wall into the CSF. We also report that contrary to widely held assumptions, AVP neurons do not fully delineate the SCN borders as PER2 expression extends beyond the AVP region. Also, AVP neurons form a rostral prong originating in the SCN medial-most and ventral-most aspect. AVP is lacking in the mid-dorsal shell but does occur at the base of the SCN just above the optic tract. Finally, neurons of the rostral SCN are smaller than those lying caudally. These findings extend our understanding of AVP signaling potential, demonstrate the heterogeneity of AVP neurons, and highlight limits in using this peptide to delineate the mouse SCN.


Subject(s)
Arginine Vasopressin , Circadian Clocks , Animals , Arginine Vasopressin/metabolism , Circadian Rhythm , Mice , Neurons/metabolism , Suprachiasmatic Nucleus/metabolism
15.
IEEE/ACM Trans Comput Biol Bioinform ; 18(6): 2823-2827, 2021.
Article in English | MEDLINE | ID: mdl-33242309

ABSTRACT

Tree-based phylogenetic networks, which may be roughly defined as leaf-labeled networks built by adding arcs only between the original tree edges, have elegant properties for modeling evolutionary histories. We answer an open question of Francis, Semple, and Steel about the complexity of determining how far a phylogenetic network is from being tree-based, including non-binary phylogenetic networks. We show that finding a phylogenetic tree covering the maximum number of nodes in a phylogenetic network can be computed in polynomial time via an encoding into a minimum-cost flow problem.


Subject(s)
Algorithms , Computational Biology/methods , Evolution, Molecular , Phylogeny , Models, Genetic
17.
Cancer Epidemiol Biomarkers Prev ; 29(10): 1870-1875, 2020 10.
Article in English | MEDLINE | ID: mdl-33004408

ABSTRACT

The 2010 report of the President's Cancer Panel concluded that the burden of cancer from chemical exposures is substantial, while the programs for testing and regulation of carcinogens remain inadequate. New research on the role of early life exposures and the ability of chemicals to act via multiple biological pathways, including immunosuppression, inflammation, and endocrine disruption as well as mutagenesis, further supports the potential for chemicals and chemical mixtures to influence disease. Epidemiologic observations, such as higher leukemia incidence in children living near roadways and industrial sources of air pollution, and new in vitro technologies that decode carcinogenesis at the molecular level, illustrate the diverse evidence that primary prevention of some cancers may be achieved by reducing harmful chemical exposures. The path forward requires cross-disciplinary approaches, increased environmental research investment, system-wide collaboration to develop safer economic alternatives, and community engagement to support evidence-informed action. Engagement by cancer researchers to integrate environmental risk factors into prevention initiatives holds tremendous promise for reducing the rates of disease.See all articles in this CEBP Focus section, "Environmental Carcinogenesis: Pathways to Prevention."


Subject(s)
Carcinogenesis/pathology , Environmental Exposure/adverse effects , Humans
18.
Metab Eng ; 61: 389-396, 2020 09.
Article in English | MEDLINE | ID: mdl-32771628

ABSTRACT

Traditionally engineered to produce novel bioactive molecules, Type I modular polyketide synthases (PKSs) could be engineered as a new biosynthetic platform for the production of de novo fuels, commodity chemicals, and specialty chemicals. Previously, our investigations manipulated the first module of the lipomycin PKS to produce short chain ketones, 3-hydroxy acids, and saturated, branched carboxylic acids. Building upon this work, we have expanded to multi-modular systems by engineering the first two modules of lipomycin to generate unnatural polyketides as potential biofuels and specialty chemicals in Streptomyces albus. First, we produce 20.6 mg/L of the ethyl ketone, 4,6 dimethylheptanone through a reductive loop exchange in LipPKS1 and a ketoreductase knockouts in LipPKS2. We then show that an AT swap in LipPKS1 and a reductive loop exchange in LipPKS2 can produce the potential fragrance 3-isopropyl-6-methyltetrahydropyranone. Highlighting the challenge of maintaining product fidelity, in both bimodular systems we observed side products from premature hydrolysis in the engineered first module and stalled dehydration in reductive loop exchanges. Collectively, our work expands the biological design space and moves the field closer to the production of "designer" biomolecules.


Subject(s)
Bacterial Proteins , Escherichia coli , Metabolic Engineering , Polyketide Synthases , Streptomyces/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Escherichia coli/enzymology , Escherichia coli/genetics , Polyketide Synthases/genetics , Polyketide Synthases/metabolism , Streptomyces/enzymology
20.
Sci Immunol ; 5(48)2020 06 05.
Article in English | MEDLINE | ID: mdl-32503879

ABSTRACT

Pathogenic autoantibodies causing encephalopathy modify the expression of the glucose transporter in oligodendrocytes.


Subject(s)
Autoantibodies/immunology , Oligodendroglia/immunology , Sugars/immunology , Glucose Transport Proteins, Facilitative/genetics , Glucose Transport Proteins, Facilitative/immunology , Humans , Oligodendroglia/pathology
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