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1.
Plast Reconstr Surg Glob Open ; 12(10): e6242, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39399806

RESUMEN

The deep inferior epigastric perforator (DIEP) flap is the preferred method for autologous breast reconstruction after mastectomy, but risks the development of hernia, bulge, and decreased core strength. Robotic harvest of DIEP vessels may limit abdominal wall morbidity through smaller fascial incisions and preservation of motor nerves. This study shows the expected learning curve (LC) for robotic harvest and compares the LC between a general surgeon (GS) and a plastic surgeon (PS). A retrospective cohort study was performed for patients who underwent bilateral robotic DIEP flap harvest from October 2021 to September 2022. We evaluated robotic pedicle dissection time (DT) and compared the times between GS and PS. We calculated LC for each surgeon using the cumulative sum (CUSUM) method, C U S U M = ∑ i = 1 n ( x i - µ - ) . The LC was identified as the peak of the CUSUM graph. Forty-four flap dissections were recorded during the collection period: 27 by the PS and 17 by the GS. There was no significant difference in DT between the GS and the PS (P = 0.366), and both surgeons saw a decrease in DT over time. Using the CUSUM method, we see the peak of the plot at patient 9 for the PS and the peak of the plot at patient 5 for the GS, after which cumulative DT decreased. As robotic harvest of DIEP flaps becomes accepted, plastic surgeons who wish to incorporate it into their practice may achieve proficiency in their DT within 10 flap harvests and a similar DT compared with robotic-trained GSs.

2.
Appl Environ Microbiol ; : e0102624, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39248464

RESUMEN

Interactions between plants and soil microbial communities that benefit plant growth and enhance nutrient acquisition are driven by the selective release of metabolites from plant roots, or root exudation. To investigate these plant-microbe interactions, we developed a photoaffinity probe based on sorgoleone (sorgoleone diazirine alkyne for photoaffinity labeling, SoDA-PAL), a hydrophobic secondary metabolite and allelochemical produced in Sorghum bicolor root exudates. We applied SoDA-PAL to the identification of sorgoleone-binding proteins in Acinetobacter pittii SO1, a potential plant growth-promoting microbe isolated from sorghum rhizosphere soil. Competitive photoaffinity labeling of A. pittii whole cell lysates with SoDA-PAL identified 137 statistically enriched proteins, including putative transporters, transcriptional regulators, and a subset of proteins with predicted enzymatic functions. We performed computational protein modeling and docking with sorgoleone to prioritize candidates for experimental validation and then confirmed binding of sorgoleone to four of these proteins in vitro: the α/ß fold hydrolase SrgB (OH685_09420), a fumarylacetoacetase (OH685_02300), a lysophospholipase (OH685_14215), and an unannotated hypothetical protein (OH685_18625). Our application of this specialized sorgoleone-based probe coupled with structural bioinformatics streamlines the identification of microbial proteins involved in metabolite recognition, metabolism, and toxicity, widening our understanding of the range of cellular pathways that can be affected by a plant secondary metabolite.IMPORTANCEHere, we demonstrate that a photoaffinity-based chemical probe modeled after sorgoleone, an important secondary metabolite released by sorghum roots, can be used to identify microbial proteins that directly interact with sorgoleone. We applied this probe to the sorghum-associated bacterium Acinetobacter pittii and showed that probe labeling is dose-dependent and sensitive to competition with purified sorgoleone. Coupling the probe with proteomics and computational analysis facilitated the identification of putative sorgoleone binders, including a protein implicated in a conserved pathway essential for sorgoleone catabolism. We anticipate that discoveries seeded by this workflow will expand our understanding of the molecular mechanisms by which specific metabolites in root exudates shape the sorghum rhizosphere microbiome.

3.
Trends Cancer ; 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39341697

RESUMEN

Cancer researchers tend to be well-versed in communicating research and research results to scientific audiences. To maintain momentum and progress against cancer, they must acquire and nurture skills allowing for better engagement with the lay public.

4.
J Evol Biol ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250679

RESUMEN

Individual vital rates are key determinants of lifetime reproductive success, and variability in these rates shapes population dynamics. Previous studies have found that this vital rate hetero- geneity can influence demographic properties including population growth rates, however, the explicit effects of the amount of variation within and the covariance between vital rates that can also vary throughout the lifespan on population growth remains unknown. Here, we explore the analytical consequences of nongenetic heterogeneity on long-term population growth rates and rates of evolution by modifying traditional age-structured population projection matrices to incorporate variation among individual vital rates. The model allows vital rates to be permanent throughout life ("fixed condition") or to change over the lifespan ("dynamic condition"). We reduce the complexity associated with adding individual heterogeneity to age-structured models through a novel application of matrix collapsing ("phenotypic collapsing"), showing how to col- lapse in a manner that preserves the asymptotic and transient dynamics of the original matrix. The main conclusion is that nongenetic individual heterogeneity can strongly impact the long-term growth rate and rates of evolution. The magnitude and sign of this impact depends heavily on how the heterogeneity covaries across the lifespan of an organism. Our results emphasize that nongenetic variation cannot simply be viewed as random noise, but rather that it has consistent, predictable effects on fitness and evolvability.

5.
J Reconstr Microsurg ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39102843

RESUMEN

BACKGROUND: Traditional deep inferior epigastric artery perforator (DIEP) flap harvest splits the anterior sheath, weakening the abdominal wall and predisposing patients to bulge or hernia. Abdominal wall morbidity may be decreased using minimally invasive techniques. We refined a transabdominal approach to the robotic harvest of bilateral DIEP flaps. METHODS: A retrospective medical record study involving all patients who underwent bilateral or bipedicled robotic DIEP (rDIEP) or standard DIEP (sDIEP) flap harvest between July 2021 and September 2022. Outcomes included abdominal wall morbidity, total operative time, length of stay (LOS), and complications. RESULTS: Forty-seven patients were included (48 sDIEP flaps, 46 rDIEP flaps) with no significant difference in patient characteristics. Fascial incision length in the rDIEP group was shorter (4.1 vs. 11.7 cm, p < 0.001). Mesh reinforcement of the abdominal wall was used in 13/24 sDIEP and none in rDIEP patients (p < 0.001). Operative time was longer in the rDIEP cohort (739 vs. 630 minutes, p = 0.013), although subanalysis showed no difference in the second half of the cohort. The average robotic dissection time was 135 minutes, which decreased significantly with the surgeon's experience. There were no intraoperative complications from using the robot. LOS was shorter with rDIEP but not statistically significant (3.9 vs. 4.3 days, p = 0.157). CONCLUSION: This study represents the most extensive cohort analysis of bilateral rDIEP flap harvest, offering a comprehensive comparison to traditional sDIEP. The initial results underscore the viability of robotic techniques for flap harvesting, highlighting potential advantages including reduced fascial incision length and decreased abdominal disruption. Furthermore, using robotics may obviate the necessity for fascial reinforcement with mesh.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39105892

RESUMEN

Women with primary mitral insufficiency have a smaller regurgitant volume at the same regurgitant fraction than men. We hypothesized that normalizing regurgitant volume with left ventricular end-diastolic volume or allometric scaling would eliminate the difference in regurgitant volume between women and men. The study cohort consisted of 101 patients with mitral valve prolapse undergoing cardiac MRI. Descriptive statistics and linear regression were performed to assess differences between sexes. Of the 101 patients, 46 (46%) were women. Women had a significantly smaller left and right ventricular end-diastolic volume, end-systolic volume, and stroke volume. While there was no difference in regurgitant fraction between women and men (34 ± 13% vs. 35 ± 14%; p = 0.71), women had a significantly smaller regurgitant volume (36 ± 18 ml vs. 49 ± 26 ml; p = 0.005). The slope-intercept relationship between regurgitant fraction and regurgitant volume revealed unique slopes and y-intercept values for men and women (p-value < 0.0001). Normalizing regurgitant volume to left ventricular end-diastolic volume (RVol/LVEDV), body surface area1.5 (RVol/BSA1.5) and height2.7 (RVol/height2.7) all had essentially identical slope-intercept relationships with regurgitant fraction for men and women, but RVol/LVEDV had the smallest effect size. In mitral insufficiency secondary to mitral valve prolapse women have a significantly smaller regurgitant volume than men despite no difference in regurgitant fraction. The significant difference in regurgitant volume between women and men is secondary to women having a smaller left ventricular end-diastolic volume.

7.
J Reconstr Microsurg ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191380

RESUMEN

BACKGROUND: The deep inferior epigastric artery perforator (DIEP) flap is the gold standard for autologous breast reconstruction. However, the conventional procedure's anterior sheath division, from perforating vessels to the pedicle origin, risks weakening the abdominal wall's primary strength layer. Employing the da Vinci Xi Surgical System with indocyanine green dye and near-infrared fluorescence imaging, we refined a robotic technique for bilateral DIEP flap harvest. This approach enhances safety during vessel dissection, utilizing smaller fascial incisions. This study will present this technique in detail to microsurgeons interested in robotic DIEP flaps. METHODS: In a retrospective cohort study spanning July 2021 to September 2022, female patients undergoing robotic bilateral DIEP flap reconstruction were analyzed. Following suprafascial flap dissection, the surgical robot was docked to target the pelvis, identifying and exposing deep inferior epigastric vessels intracorporeally. Mobilization and division occurred at their bases, with retrieval through a minimal anterior fascial incision, minimizing disruption to the abdominal wall and its motor innervation. RESULTS: The study comprised 23 patients (46 flaps), with a mean fascial length of 4.1 cm and mean pedicle length of 12.82 cm. Mesh usage was absent. Robotic time averaged 139 minutes, overall case length was 739 minutes, and the average length of stay was 3.9 days. Notably, no pedicle or intra-abdominal injuries were reported. CONCLUSION: This technique ensures safe and efficient pedicle dissection in robotic DIEP flap harvests. Given the limited number of plastic surgeons adept in minimally invasive abdominal surgeries, we recommend collaborative efforts, with general surgeons initially assisting microsurgeons in adopting the robotic approach. This strategy facilitates a smooth transition until plastic surgeons attain confidence and competence in independent robotic dissection.

8.
Nat Commun ; 15(1): 7414, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198404

RESUMEN

How prostate cancer cells and their precursors mediate changes in the tumor microenvironment (TME) to drive prostate cancer progression is unclear, in part due to the inability to longitudinally study the disease evolution in human tissues. To overcome this limitation, we perform extensive single-cell RNA-sequencing (scRNA-seq) and molecular pathology of the comparative biology between human prostate cancer and key stages in the disease evolution of a genetically engineered mouse model (GEMM) of prostate cancer. Our studies of human tissues reveal that cancer cell-intrinsic activation of MYC signaling is a common denominator across the well-known molecular and pathological heterogeneity of human prostate cancer. Cell communication network and pathway analyses in GEMMs show that MYC oncogene-expressing neoplastic cells, directly and indirectly, reprogram the TME during carcinogenesis, leading to a convergence of cell state alterations in neighboring epithelial, immune, and fibroblast cell types that parallel key findings in human prostate cancer.


Asunto(s)
Neoplasias de la Próstata , Proteínas Proto-Oncogénicas c-myc , Microambiente Tumoral , Masculino , Microambiente Tumoral/genética , Humanos , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Animales , Ratones , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Regulación Neoplásica de la Expresión Génica , Transducción de Señal , Análisis de la Célula Individual , Modelos Animales de Enfermedad , Comunicación Celular , Carcinogénesis/genética , Carcinogénesis/patología , Ratones Transgénicos , RNA-Seq
9.
JAMA Netw Open ; 7(5): e249474, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38696166

RESUMEN

Importance: The National Cancer Institute comprehensive cancer centers (CCCs) lack spatial and temporal evaluation of their self-designated catchment areas. Objective: To identify disparities in cancer stage at diagnosis within and outside a CCC's catchment area across a 10-year period using spatial and statistical analyses. Design, Setting, and Participants: This cross-sectional, population-based study conducted between 2010 and 2019 utilized cancer registry data for the Johns Hopkins Sidney Kimmel CCC (SKCCC). Eligible participants included patients with cancer in the contiguous US who received treatment for cancer, a diagnosis of cancer, or both at SKCCC. Patients were geocoded to zip code tabulation areas (ZCTAs). Individual-level variables included sociodemographic characteristics, smoking and alcohol use, treatment type, cancer site, and insurance type. Data analysis was performed between March and July 2023. Exposures: Distance between SKCCC and ZCTAs were computed to generate a catchment area of the closest 75% of patients and outer zones in 5% increments for comparison. Main Outcomes and Measures: The primary outcome was cancer stage at diagnosis, defined as early-stage, late-stage, or unknown stage. Multinomial logistic regression was used to determine associations of catchment area with stage at diagnosis. Results: This study had a total of 94 007 participants (46 009 male [48.94%] and 47 998 female [51.06%]; 30 195 aged 22-45 years [32.12%]; 4209 Asian [4.48%]; 2408 Hispanic [2.56%]; 16 004 non-Hispanic Black [17.02%]; 69 052 non-Hispanic White [73.45%]; and 2334 with other or unknown race or ethnicity [2.48%]), including 47 245 patients (50.26%) who received a diagnosis of early-stage cancer, 19 491 (20.73%) who received a diagnosis of late-stage cancer , and 27 271 (29.01%) with unknown stage. Living outside the main catchment area was associated with higher odds of late-stage cancers for those who received only a diagnosis (odds ratio [OR], 1.50; 95% CI, 1.10-2.05) or only treatment (OR, 1.44; 95% CI, 1.28-1.61) at SKCCC. Non-Hispanic Black patients (OR, 1.16; 95% CI, 1.10-1.23) and those with Medicaid (OR, 1.65; 95% CI, 1.46-1.86) and no insurance at time of treatment (OR, 2.12; 95% CI, 1.79-2.51) also had higher odds of receiving a late-stage cancer diagnosis. Conclusions and Relevance: In this cross-sectional study of CCC data from 2010 to 2019, patients residing outside the main catchment area, non-Hispanic Black patients, and patients with Medicaid or no insurance had higher odds of late-stage diagnoses. These findings suggest that disadvantaged populations and those living outside of the main catchment area of a CCC may face barriers to screening and treatment. Care-sharing agreements among CCCs could address these issues.


Asunto(s)
Instituciones Oncológicas , Áreas de Influencia de Salud , Estadificación de Neoplasias , Neoplasias , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Neoplasias/epidemiología , Instituciones Oncológicas/estadística & datos numéricos , Áreas de Influencia de Salud/estadística & datos numéricos , Adulto , Anciano , Disparidades en Atención de Salud/estadística & datos numéricos , Estados Unidos , Sistema de Registros
10.
HEC Forum ; 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38231425

RESUMEN

Organizational ethics-defined as the alignment of an institution's practices with its mission, vision, and values-is a growing field in health care not well characterized in empirical literature. To capture the scope and context of organizational ethics work in United States healthcare institutions, we conducted a nationwide convenience survey of ethicists regarding the scope of organizational ethics work, common challenges faced, and the organizational context in which this work is done. In this article, we report substantial variability in the structure of organizational ethics programs and the settings in which it is conducted. Notable findings included disagreement about the activities that comprise organizational ethics and a lack of common metrics used to assess organizational ethics activities. A frequently cited barrier to full engagement in these activities was poor institution-wide understanding about the role and function of organizational ethics resources. These data suggest a tension in the trajectory of organizational ethics' professionalization: while some variability is appropriate to the field's relative youth, inadequate attention to definitions of organizational ethics practice and metrics for success can impede discussions about appropriate institutional support, leadership context, and training for practitioners.

11.
Cardiology ; 149(3): 266-274, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38290490

RESUMEN

INTRODUCTION: Despite contemporary practice guidelines, a substantial number of post-acute coronary syndrome (ACS) patients fail to achieve guideline-recommended LDL-C thresholds. Our study aimed to investigate this guideline recommendations-to-practice care gap. Specifically, we aimed to identify opportunities where additional lipid-lowering therapies are indicated and explore reasons for the non-prescription of guideline-recommended therapies. METHODS: ACS patients with LDL-C ≥1.81 mmol/L (70 mg/dL) despite maximally tolerated statin ± ezetimibe therapy (including those intolerant of ≥2 statins) were enrolled 1-12 months post-event from 27 Canadian and US sites from September 2018 to October 2020 and followed up for three visits during the 12 months post-event. We determined the proportion of patients who did not achieve Canadian/US guideline-recommended LDL-C thresholds, the number of patients who would have been eligible for additional lipid-lowering therapies, and reasons behind lack of escalation in lipid-lowering therapies when indicated. Individual patient and aggregate practice feedback, including guideline-recommended intensification suggestions, were provided to each physician. RESULTS: Of the 248 patients enrolled in the pilot study (median age 64 [57, 73] years, 31.5% female and STEMI 27.4%), 75.4% were on high-intensity statins on the first visit. A total of 18.5% of those who attended all 3 visits had an LDL-C measured only at the first visit which was above the threshold. After 1 year of follow-up, 51.9% of patients achieved LDL-C thresholds at either visit 2 or 3. In the context of feedback reminding physicians about guideline-directed LDL-C-modifying therapy in their individual participating patients, we observed an increase in the use of ezetimibe and PCSK9 inhibitor therapy at 3-12 months. This was associated with a significant lowering of the mean LDL-C (from 2.93 mmol/L [baseline] to 2.09 mmol/L [3-6 months] to 1.87 mmol/L [6-12 months]) and a significantly greater proportion of patients (from 0% [baseline] to 38.6% [3-6 months] to 53.4% [6-12 months]) achieving guideline-recommended LDL-C thresholds. The most prevalent reasons behind the non-intensification of LDL-C-lowering therapy with ezetimibe and/or PCSK9i were LDL-C levels being close to target, the pre-existing use of other lipid-lowering therapies, patient refusal, and cost. CONCLUSION: Although most patients post-ACS were on high-intensity statin therapy, almost 50% failed to achieve guideline-recommended LDL-C thresholds by 1-year follow-up. Furthermore, additional lipid-lowering therapies in this high-risk group were underprescribed, and this might be linked to several factors including potential gaps in physician knowledge, treatment inertia, patient refusal, and cost.


Asunto(s)
Síndrome Coronario Agudo , LDL-Colesterol , Dislipidemias , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Anciano , Dislipidemias/tratamiento farmacológico , Dislipidemias/sangre , Dislipidemias/complicaciones , LDL-Colesterol/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Canadá , Ezetimiba/uso terapéutico , Guías de Práctica Clínica como Asunto , Adhesión a Directriz , Proyectos Piloto , Estados Unidos , Anticolesterolemiantes/uso terapéutico
12.
Plast Reconstr Surg ; 153(4): 796-798, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37335588

RESUMEN

SUMMARY: Indocyanine green-guided near-infrared fluorescence imaging has gained clinical acceptance lately. This technology can be particularly advantageous in the case of robotic flap harvest. This article presents a new approach to deep epigastric pedicle dissection using indocyanine green-guided near-infrared fluorescence in the setting of robot-assisted deep inferior epigastric perforator flaps.


Asunto(s)
Mamoplastia , Colgajo Perforante , Robótica , Humanos , Verde de Indocianina , Imagen Óptica/métodos , Colgajos Quirúrgicos , Colgajo Perforante/irrigación sanguínea
13.
Nat Rev Urol ; 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37907729

RESUMEN

The stromal component of the tumour microenvironment in primary and metastatic prostate cancer can influence and promote disease progression. Within the prostatic stroma, fibroblasts are one of the most prevalent cell types associated with precancerous and cancerous lesions; they have a vital role in the structural composition, organization and integrity of the extracellular matrix. Fibroblasts within the tumour microenvironment can undergo cellular senescence, which is a stable arrest of cell growth and a phenomenon that is emerging as a recognized hallmark of cancer. Supporting the idea that cellular senescence has a pro-tumorigenic role, a subset of senescent cells exhibits a senescence-associated secretory phenotype (SASP), which, along with increased inflammation, can promote prostate cancer cell growth and survival. These cellular characteristics make targeting senescent cells and/or modulating SASP attractive as a potential preventive or therapeutic option for prostate cancer.

14.
Nat Commun ; 14(1): 7666, 2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-37996432

RESUMEN

Bacteriophages are abundant in soils. However, the majority are uncharacterized, and their hosts are unknown. Here, we apply high-throughput chromosome conformation capture (Hi-C) to directly capture phage-host relationships. Some hosts have high centralities in bacterial community co-occurrence networks, suggesting phage infections have an important impact on the soil bacterial community interactions. We observe increased average viral copies per host (VPH) and decreased viral transcriptional activity following a two-week soil-drying incubation, indicating an increase in lysogenic infections. Soil drying also alters the observed phage host range. A significant negative correlation between VPH and host abundance prior to drying indicates more lytic infections result in more host death and inversely influence host abundance. This study provides empirical evidence of phage-mediated bacterial population dynamics in soil by directly capturing specific phage-host interactions.


Asunto(s)
Bacteriófagos , Bacteriófagos/genética , Metagenoma , Suelo , Bacterias/genética , Lisogenia/genética
15.
bioRxiv ; 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37905029

RESUMEN

The tissue microenvironment in prostate cancer is profoundly altered. While such alterations have been implicated in driving prostate cancer initiation and progression to aggressive disease, how prostate cancer cells and their precursors mediate those changes is unclear, in part due to the inability to longitudinally study the disease evolution in human tissues. To overcome this limitation, we performed extensive single-cell RNA-sequencing (scRNA-seq) and rigorous molecular pathology of the comparative biology between human prostate cancer and key time points in the disease evolution of a genetically engineered mouse model (GEMM) of prostate cancer. Our studies of human tissues, with validation in a large external data set, revealed that cancer cell-intrinsic activation of MYC signaling was the top up-regulated pathway in human cancers, representing a common denominator across the well-known molecular and pathological heterogeneity of human prostate cancer. Likewise, numerous non-malignant cell states in the tumor microenvironment (TME), including non-cancerous epithelial, immune, and fibroblast cell compartments, were conserved across individuals, raising the possibility that these cell types may be a sequelae of the convergent MYC activation in the cancer cells. To test this hypothesis, we employed a GEMM of prostate epithelial cell-specific MYC activation in two mouse strains. Cell communication network and pathway analyses suggested that MYC oncogene-expressing neoplastic cells, directly and indirectly, reprogrammed the TME during carcinogenesis, leading to the emergence of cascading cell state alterations in neighboring epithelial, immune, and fibroblast cell types that paralleled key findings in human prostate cancer. Importantly, among these changes, the progression from a precursor-enriched to invasive-cancer-enriched state was accompanied by a cell-intrinsic switch from pro-immunogenic to immunosuppressive transcriptional programs with coinciding enrichment of immunosuppressive myeloid and Treg cells in the immune microenvironment. These findings implicate activation of MYC signaling in reshaping convergent aspects of the TME of prostate cancer as a common denominator across the otherwise well-documented molecular heterogeneity of human prostate cancer.

16.
Cancer Prev Res (Phila) ; 16(8): 449-460, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37347938

RESUMEN

Glutathione S-transferase pi 1 (GSTP1) is lowly expressed in normal prostate luminal cells and becomes induced in most proliferative inflammatory atrophy (PIA) lesions. GSTP1 becomes silenced in prostatic intraepithelial neoplasia (PIN) and prostate adenocarcinoma (CaP) via cytosine-phospho-guanine (CpG) island promoter hypermethylation. However, GSTP1 methylation patterns in PIA and PIN, and their relationship to patterns in CaP are poorly understood. We used bisulfite genomic sequencing to examine patterns of GSTP1 promoter CpG island methylation in laser capture microdissected benign, PIA, PIN, and CaP regions from 32 subjects that underwent radical prostatectomy. We analyzed 908 sequence clones across 24 normal epithelium, 37 PIA, 18 PIN, and 23 CaP regions, allowing assessment of 34,863 CpG sites with allelic phasing. Normal and PIA lesions were mostly unmethylated with 0.52 and 1.3% of total CpG sites methylated, respectively. PIN and CaP lesions had greater methylation with 24% and 51% of total CpG sites methylated, respectively. The degree of GSTP1 methylation showed progression from PIA << PIN < CaP. PIN lesions showed more partial methylation compared with CaP lesions. Partially methylated lesions were enriched for methylation changes at AP1 and SP1 transcription factor binding sites. These results demonstrate that methylation density in the GSTP1 CpG island in PIN was intermediate relative to that in normal prostate epithelium/PIA and CaP lesions. These results are consistent with gradual spreading of DNA methylation centered at the SP1/AP1 transcription factor binding sites in precursor lesions, with subsequent spreading of methylation across the entire CpG island in transition to CaP. PREVENTION RELEVANCE: DNA hypermethylation at the GSTP1 promoter progressively spreads from being unmethylated in normal prostate to intermediate levels in precursor lesions to extensive methylation in cancer. This molecular progression of GSTP1 promoter methylation patterns in early prostate carcinogenesis could be useful for identification and interception of prostate cancer precursors.


Asunto(s)
Neoplasia Intraepitelial Prostática , Neoplasias de la Próstata , Masculino , Humanos , Gutatión-S-Transferasa pi/genética , Gutatión-S-Transferasa pi/metabolismo , Metilación de ADN , Islas de CpG/genética , Glutatión Transferasa/genética , Neoplasias de la Próstata/patología , Neoplasia Intraepitelial Prostática/genética , Neoplasia Intraepitelial Prostática/patología
17.
Pest Manag Sci ; 79(7): 2581-2590, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36869740

RESUMEN

BACKGROUND: Tebufenozide is widely used to control populations of the smaller tea tortrix, Adoxophyes honmai. However, A. honmai has evolved resistance such that straightforward pesticide application is an untenable long-term approach for population control. Evaluating the fitness cost of resistance is key to devising a management strategy that slows the evolution of resistance. RESULTS: We used three approaches to assess the life-history cost of tebufenozide resistance with two strains of A. honmai: a tebufenozide-resistant strain recently collected from the field in Japan and a susceptible strain that has been maintained in the laboratory for decades. First, we found that the resistant strain with standing genetic variation did not decline in resistance in the absence of insecticide over four generations. Second, we found that genetic lines that spanned a range of resistance profiles did not show a negative correlation between their LD50 , the dosage at which 50 % of individuals died, and life-history traits that are correlates of fitness. Third, we found that the resistant strain did not manifest life-history costs under food limitation. Our crossing experiments indicate that the allele at an ecdysone receptor locus known to confer resistance explained much of the variance in resistance profiles across genetic lines. CONCLUSION: Our results indicate that the point mutation in the ecdysone receptor, which is widespread in tea plantations in Japan, does not carry a fitness cost in the tested laboratory conditions. The absence of a cost of resistance and the mode of inheritance have implications for which strategies may be effective in future resistance management efforts. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Asunto(s)
Insecticidas , Mariposas Nocturnas , Animales , Mariposas Nocturnas/genética , Hidrazinas , Insecticidas/farmacología , , Resistencia a los Insecticidas/genética
18.
Sci Rep ; 13(1): 3528, 2023 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-36864085

RESUMEN

Parasitoids are small insects, (e.g., small wasps or flies) that reproduce by laying eggs on or within host arthropods. Parasitoids make up a large proportion of the world's biodiversity and are popular agents of biological control. Idiobiont parasitoids paralyze their hosts upon attack and thus are expected to only target hosts large enough to support offspring development. Host resources generally impact host attributes and life histories including size, development, and life span. Some argue slow host development in response to resource quality increases parasitoid efficacy (i.e., a parasitoid's ability to successfully reproduce on or within a host) due to longer host exposure to parasitoids. However, this hypothesis is not always supported and does not consider variation in other host traits in response to resources that may be important for parasitoids (e.g., variation in host size is known to impact parasitoid efficacy). In this study we test whether trait variation within host developmental stages in response to host resources is more important for parasitoid efficacy and life histories than trait variation across host developmental stages. We exposed seed beetle hosts raised on a food quality gradient to mated female parasitoids and measured the number of hosts parasitized and parasitoid life history traits at the scale of host stage- and age-structure. Our results suggest host food quality does not cascade to impact idiobiont parasitoid life histories despite large food quality effects on host life history. Instead, variation in host life histories across host developmental stages better predicts parasitoid efficacy and life histories, suggesting finding a host in a specific instar is more important for idiobiont parasitoids than finding hosts on or within higher quality resources.


Asunto(s)
Artrópodos , Escarabajos , Femenino , Animales , Humanos , Biodiversidad , Desarrollo Infantil , Calidad de los Alimentos
19.
Orthop Clin North Am ; 54(2): 169-192, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36894290

RESUMEN

Artificial intelligence (AI) is used in the clinic to improve patient care. While the successes illustrate AI's impact, few studies have led to improved clinical outcomes. In this review, we focus on how AI models implemented in nonorthopedic fields of corrosion science may apply to the study of orthopedic alloys. We first define and introduce fundamental AI concepts and models, as well as physiologically relevant corrosion damage modes. We then systematically review the corrosion/AI literature. Finally, we identify several AI models that may be implemented to study fretting, crevice, and pitting corrosion of titanium and cobalt chrome alloys.


Asunto(s)
Inteligencia Artificial , Cuerpo Humano , Humanos , Corrosión , Aleaciones de Cromo , Titanio
20.
Front Vet Sci ; 10: 1079918, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36908521

RESUMEN

Introduction: Diagnostic test evaluation for African swine fever (ASF) in field settings like Vietnam is critical to understanding test application in intended populations for surveillance and control strategies. Bayesian latent class analysis (BLCA) uses the results of multiple imperfect tests applied to an individual of unknown disease status to estimate the diagnostic sensitivity and specificity of each test, forgoing the need for a reference test. Methods: Here, we estimated and compared the diagnostic sensitivity and specificity of a novel indirect ELISA (iELISA) for ASF virus p30 antibody (Innoceleris LLC.) and the VetAlert™ ASF virus DNA Test Kit (qPCR, Tetracore Inc.) in field samples from Vietnam by assuming that disease status 1) is known and 2) is unknown using a BLCA model. In this cross-sectional study, 398 paired, individual swine serum/oral fluid (OF) samples were collected from 30 acutely ASF-affected farms, 37 chronically ASF-affected farms, and 20 ASF-unaffected farms in Vietnam. Samples were tested using both diagnostic assays. Diagnostic sensitivity was calculated assuming samples from ASF-affected farms were true positives and diagnostic sensitivity by assuming samples from unaffected farms were true negatives. ROC curves were plotted and AUC calculated for each test/sample combination. For comparison, a conditionally dependent, four test/sample combination, three population BLCA model was fit. Results: When considering all assumed ASF-affected samples, qPCR sensitivity was higher for serum (65.2%, 95% Confidence Interval [CI] 58.1-71.8) and OF (52%, 95%CI 44.8-59.2) compared to the iELISA (serum: 42.9%, 95%CI 35.9-50.1; OF: 33.3%, 95%CI 26.8-40.4). qPCR-serum had the highest AUC (0.895, 95%CI 0.863-0.928). BLCA estimates were nearly identical to those obtained when assuming disease status and were robust to changes in priors. qPCR sensitivity was considerably higher than ELISA in the acutely-affected population, while ELISA sensitivity was higher in the chronically-affected population. Specificity was nearly perfect for all test/sample types. Discussion: The effect of disease chronicity on sensitivity and specificity could not be well characterized here due to limited data, but future studies should aim to elucidate these trends to understand the best use of virus and antibody detection methods for ASF. Results presented here will help the design of surveillance and control strategies in Vietnam and other countries affected by ASF.

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