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Fresh produce is traditionally labeled with plastic price lookup (PLU) stickers that are attached to the produce surface using edible glue. However, both the stickers and glue are environmental contaminants, and the stickers can still easily detach from the produce surface during handling and disrupt traceability. An alternative method of labeling, the CO2 laser-labeling technology (LLT), has been gaining attention in recent years. However, engraving Quick Response (QR) code using LLT is unique, and the performance of this technology varies from produce item to produce item, and information on its effects on postharvest quality, microbial safety, and economic feasibility has not been reported. The objectives of this study were to investigate the effect of laser-labeling technology on (1) postharvest quality, (2) microbial safety, and (3) economic analysis of this technology. Three horticultural crops, 'Red Delicious' apple (Malus pumila), green bell pepper (Capsicum annuum), and cucumber (Cucumis sativus) were procured from a local grocery store. Each produce was engraved with a Quick Response (QR) code or 6-digit alphanumerical (text) code using the commercially available Trotec Speedy 300 CO2 laser engraver, followed by the application of edible wax. Fresh weight loss for laser-printed produce was higher compared to controls, but no difference in visual quality ratings was observed. The laser-labeled produce was assessed for microbial contamination by artificially inoculating rifampicin-resistant Escherichia coli (E. coli) log10 6 CFU/mL to the labeled fruit. The results showed that the population of rifampicin-resistant E. coli was statistically higher in all three products labeled with text code compared to the nontreated controls. The QR-coded treatments were similar to the controls. The wax application did not affect the microbial attachment on the laser-labeled produce. The CO2 laser labeling technology has the potential for industrial application.
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Microbiología de Alimentos , Humanos , Seguridad de Productos para el Consumidor , Contaminación de Alimentos/análisis , Dióxido de Carbono , Recuento de Colonia Microbiana , Manipulación de Alimentos , Capsicum/microbiologíaRESUMEN
OBJECTIVES: Intimal sarcomas are rare, aggressive neoplasms that arise from large blood vessels. Characterization of the tumor immune microenvironment may suggest new treatment strategies. METHODS: Seventeen specimens from 7 patients were labeled by immunohistochemistry for programmed cell death 1 ligand 1 (PD-L1), CD45, CD8, CD4, FOXP3, CD20, CD68, and LAG3. The immune cell density was scored as a percentage of the tumor area (1+ [<5%], 2+ [5%-50%], 3+ [>50%]); PD-L1 expression was scored on tumor cells and on intratumoral immune cells. Immune marker density was quantified using image analysis software. RESULTS: All intimal sarcomas showed immune cell infiltration (41% were 1+, 53% were 2+, 6% were 3+). Tumor and immune cell PD-L1 labeling was seen in 35% and 76% of cases, respectively; PD-L1+ intimal sarcomas had higher CD45+, CD8+, FOXP3+, CD68+, and leukocyte activation gene 3 (LAG3)+ cell densities (P ≤ .01). Similarly, PD-L1 expression on immune cells correlated with higher densities of CD8+ and FOXP3+ cells (P < .04). Higher LAG3+ cell density correlated with higher CD68+ cell density and necrosis (P < .05). One patient with prolonged survival had the highest immune cell density and PD-L1 expression. CONCLUSIONS: These data show that intimal sarcomas have an active tumor microenvironment with an adaptive pattern of PD-L1 expression. Our results suggest that immunotherapy may be an effective treatment option.
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Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Antígeno B7-H1 , Sarcoma/terapia , Factores de Transcripción Forkhead , Procesamiento de Imagen Asistido por Computador , Microambiente TumoralRESUMEN
Systemic treatment options for patients with locally advanced or metastatic basal cell carcinoma (BCC) are limited, particularly when tumors are refractory to anti-programmed cell death protein-1 (PD-1). A better understanding of immune checkpoint expression within the BCC tumor microenvironment may inform combinatorial treatment strategies to optimize response rates. CD3, PD-1, programmed death ligand-1 (PD-L1), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3)+ cell densities within the tumor microenvironment of 34 archival, histologically aggressive BCCs were assessed. Tumor infiltrating lymphocyte (TIL) expression of PD-1, PD-L1, and LAG-3, and to a lesser degree TIM-3, correlated with increasing CD3+ T-cell densities (Pearson's r=0.89, 0.72, 0.87, and 0.63, respectively). 100% of BCCs (34/34) demonstrated LAG-3 and PD-1 expression in >1% TIL; and the correlation between PD-1 and LAG-3 densities was high (Pearson's r=0.89). LAG-3 was expressed at ~50% of the level of PD-1. Additionally, we present a patient with locally-advanced BCC who experienced stable disease during and after 45 weeks of first-line anti-PD-1 (nivolumab), followed by a partial response after the addition of anti-LAG-3 (relatlimab). Longitudinal biopsies throughout the treatment course showed a graduated increase in LAG-3 expression after anti-PD-1 therapy, lending support for coordinated immunosuppression and suggesting LAG-3 as a co-target for combination therapy to augment the clinical impact of anti-PD-(L)1.
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Carcinoma Basocelular , Neoplasias Cutáneas , Humanos , Antígeno B7-H1 , Receptor 2 Celular del Virus de la Hepatitis A , Receptor de Muerte Celular Programada 1 , Carcinoma Basocelular/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Microambiente TumoralRESUMEN
Neoadjuvant immunotherapy is thought to produce long-term remissions through induction of antitumor immune responses before removal of the primary tumor. Tertiary lymphoid structures (TLS), germinal center-like structures that can arise within tumors, may contribute to the establishment of immunological memory in this setting, but understanding of their role remains limited. Here, we investigated the contribution of TLS to antitumor immunity in hepatocellular carcinoma (HCC) treated with neoadjuvant immunotherapy. We found that neoadjuvant immunotherapy induced the formation of TLS, which were associated with superior pathologic response, improved relapse free survival, and expansion of the intratumoral T and B cell repertoire. While TLS in viable tumor displayed a highly active mature morphology, in areas of tumor regression we identified an involuted TLS morphology, which was characterized by dispersion of the B cell follicle and persistence of a T cell zone enriched for ongoing antigen presentation and T cell-mature dendritic cell interactions. Involuted TLS showed increased expression of T cell memory markers and expansion of CD8+ cytotoxic and tissue resident memory clonotypes. Collectively, these data reveal the circumstances of TLS dissolution and suggest a functional role for late-stage TLS as sites of T cell memory formation after elimination of viable tumor.
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Ultraviolet-C (UV-C) light-assisted water treatment systems are an increasingly investigated alternative to chemical sanitizers for agricultural surface water decontamination. However, the relatively high concentration of particulate matter in surface water is a major challenge to expanding its application in the production of fresh produce. The objective of this project was to test the efficacy of two commercial UV-C devices to reduce the microbial risk of agricultural water in order to develop a web application to assist growers in decision-making related to the on-farm implementation of UV-C technologies for agricultural water treatment. An on-farm study using three agricultural water sources was performed to determine the microbial reduction efficacy of a low power, low flow (LP/LF; 1-9 gallons per minute (GPM), 1.34-gallon capacity) and a high powered, high flow (HP/HF; 1-110 GPM, 4.75-gallon capacity) device at flow rates of 6, 7, and 9 GPM. A threshold of 30% UVT for the HP/HF device was observed, wherein lower water transmissibility significantly impacted microbial inactivation. Although less effective at lower %UVT, the LP/LF device costs less to install, maintain, and operate. The observations were used to design an online tool for growers to calculate the predicted reduction of generic Escherichia coli using either device based on the %UVT of their water source. However, because this study utilized an exploratory and proof-of-concept approach, the experimental flow rates were limited to reflect the capacities of the smaller unit (9 GPM) for direct comparison to the larger unit. Thus, the preliminary model and tool are largely limited to the experimental conditions. Yet, these results of this study demonstrate the utility of UV-C light in reducing the microbial risk of agricultural water, and future studies using different UV-C devices and higher flow rates will expand the use of the decision-making tool.
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Descontaminación , Rayos Ultravioleta , Recuento de Colonia Microbiana , Descontaminación/métodos , Escherichia coli , Viabilidad MicrobianaRESUMEN
OBJECTIVE: To describe the causes and distribution of lameness in beef and dairy cattle presenting to either a primary care ambulatory or in-house clinical service at a veterinary teaching hospital. SAMPLE: This retrospective clinical case study was conducted by reviewing hospital admissions of beef and dairy cattle seen by in-house or ambulatory clinicians at a veterinary teaching hospital from 2001 to 2021. PROCEDURES: Final diagnosis was recorded and, when available, the affected limb, whether a lesion was localized to the digit, and the affected claw were also recorded. Data were stratified by location of initial evaluation (ambulatory vs in hospital), period of presentation, production class, age, sex, and whether the final diagnosis was infectious or noninfectious. RESULTS: Overall, 2,220 animals met criteria for inclusion in the study. The most common diagnoses were noninfectious in nature and affected a hind limb more often than a forelimb. More than 82% of all cattle had lameness localized to the digit, with the lateral claw being affected more than 80% of the time. CLINICAL RELEVANCE: Lameness is an important concern from both a humane and economic standpoint. The results of this study will help with the diagnosis and prevention of lameness in beef and dairy cattle of different ages and production classes.
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Enfermedades de los Bovinos , Pezuñas y Garras , Bovinos , Animales , Estudios Retrospectivos , Hospitales Veterinarios , Hospitales de Enseñanza , Cojera Animal/diagnóstico , Enfermedades de los Bovinos/diagnóstico , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/patología , Pezuñas y Garras/patología , América del NorteRESUMEN
The removal of intramyocardial masses has long been thought of as a surgical procedure and is generally reserved for patients with obstructive symptoms when the mass is thought to be benign. Thus, many patients who are incidentally diagnosed with intracardiac masses are either subjected to protracted follow-up with serial imaging awaiting tumor growth before surgical excision is ultimately offered. We report a novel procedure in which a 54-year-old man with an atrial myxoma underwent successful percutaneous resection using electrosurgery followed by removal with a novel endovascular retrieval system. This approach provides an alternative to either surgical excision or watchful waiting in patients with small- to medium-sized intracardiac tumors. (Level of Difficulty: Advanced.).
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Staphylococcus aureus is a medically important pathogen with high metabolic versatility allowing it to infect various niches within a host. S. aureus utilizes two major transcriptional regulators, namely, CodY and CcpA, to remodel metabolic and virulence gene expression in response to changing environmental conditions. Previous studies revealed that inactivation of either codY or ccpA has a pronounced impact on different aspects of staphylococcal physiology and pathogenesis. To determine the contribution and interplay of these two regulators in modulating central metabolism, virulence, and biofilm development, we constructed and characterized the codY ccpA double mutant in S. aureus UAMS-1. In line with previous studies, we found that CcpA and CodY control the cellular metabolic status by altering carbon flux through the central and overflow metabolic pathways. Our results demonstrate that ccpA inactivation impairs biofilm formation and decreases incorporation of extracellular DNA (eDNA) into the biofilm matrix, whereas disrupting codY resulted in a robust structured biofilm tethered together with eDNA and polysaccharide intercellular adhesin (PIA). Interestingly, inactivation of both codY and ccpA decreases biofilm biomass and reduces eDNA release in the double mutant. Compared with the inactivation of codY, the codY ccpA mutant did not overexpress toxins but maintained overexpression of amino acid metabolism pathways. Furthermore, the codY ccpA mutant produced large amounts of PIA, in contrast to the wild-type strain and ccpA mutant. Combined, the results of this study suggest that the coordinated action of CodY and CcpA modulate central metabolism, virulence gene expression, and biofilm-associated genes to optimize growth on preferred carbon sources until starvation sets in. IMPORTANCE Staphylococcus aureus is a leading cause of biofilm-associated infections, including infective endocarditis, worldwide. A greater understanding of metabolic forces driving biofilm formation in S. aureus is essential for the identification of novel therapeutic targets and for the development of new strategies to combat this medically important pathogen. This study characterizes the interplay and regulation of central metabolism and biofilm development by two global transcriptional regulators, CodY and CcpA. We found that the lack of CcpA and/or CodY have different impacts on intracellular metabolic status leading to a formation of morphologically altered biofilms. Overall, the results of this study provide new insights into our understanding of metabolism-mediated regulation of biofilm development in S. aureus.
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Infecciones Estafilocócicas , Staphylococcus aureus , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biopelículas , Regulación Bacteriana de la Expresión Génica , Humanos , Staphylococcus aureus/metabolismoRESUMEN
The marine feather duster, Bispira melanostigma (Schmarda, 1861), is a tube-dwelling annelid that contributes to ecological and biogeochemical processes in benthic communities. Due to the lack of scientific data, B. melanostigma is often difficult to distinguish from other species of marine worms through morphological characteristics alone. In this study, we report the complete mitochondrial genome of Bispira melanostigma. The complete mitogenome contained 20,624 bp length with a total of 13 protein-encoding genes, 21 tRNA, and 2 rRNA genes. Phylogenetic analysis of the complete mitochondrial DNA of B.melanostigma can aid in the understanding of evolutionary relationships within Sabellidae.
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This article reports the results of an ethics survey of professional members of the Society for Industrial and Organizational Psychology (SIOP/APA-Div. 14) conducted in 2019, and compares its findings with those of a similar survey conducted in 2009. In 2019, but not 2009, international members and associates were included. A total of 680 survey responses were received in 2019, with 157 of them describing a narrative incident of a recently experienced ethical situation. In 2009, 228 of 661 respondents described a total of 292 incidents. Respondents were asked to categorize and rate their incidents on a variety of attributes. Demographic subgroup analyses showed more similarities than differences in the nature and outcomes of ethical issues reported. However, differences were observed as a function of work domain (academe, internal practice, external practice), membership status (member/fellow/associate), career stage (years since highest degree), and field of highest degree (I-O psychology, other psychology area, and business), suggesting caution if generalizing to the entire field. Respondents who actually faced the ethical issue described viewed it as somewhat less serious than those who occupied some other (observer) role in the situation, and also reported more successful resolutions. Comparing 2019 with 2009 data revealed overall consistency in the relative incidence of different forms of ethical challenges and the work activity areas in which they arise. However, in 2019 there were more covert incidents (e.g., role conflicts, values conflicts, conflicts of interest) and fewer overt incidents (e.g., coercion, corruption). Implications for improving ethics education and training are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Principios Morales , Psicología Industrial , Estudios de Seguimiento , HumanosRESUMEN
Gender differences in adolescent social media use are often documented in the research literature, yet few studies delve into why they occur. Accordingly, we investigated whether gender identification and gender ideologies are associated with five major purposes of social media use in adolescence (emotion and activity bonding with friends, social compensation, appearance validation, and bullying). Participants were 309 cisgender U.S. high school students (Mageâ=â15.74; 59% girls; 53% white) primarily using Instagram and Snapchat but also TikTok (more popular with girls) and Discord (more popular with boys) in 2019. Girls reported greater use of social media for emotion bonding, appearance validation, and social compensation compared to boys, who reported greater competitive activity bonding. Girls and boys did not differ in their use of social media for bullying. In linear regressions, masculinity ideology predicted purposes associated with girls (appearance validation, social compensation), as well as those associated with boys (competitive activity bonding), regardless of gender. Femininity ideology uniquely predicted emotion bonding and social compensation but only mediated the effect of gender for the latter. Findings illustrate that gender is important for understanding uses and gratifications of social media in adolescence, but traditional masculinity ideology is similar across genders and relates to multiple functions of social media in boys' and girls' lives. More work is needed to conceptualize gender beliefs and values in Gen Z, given recent challenges to gender binary ideology and low reliability of the scales in this study, which were developed before social media.
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BACKGROUND: The progression of clinical manifestations in patients with coronavirus disease 2019 (COVID-19) highlights the need to account for symptom duration at the time of hospital presentation in decision-making algorithms. METHODS: We performed a nested case-control analysis of 4103 adult patients with COVID-19 and at least 28 days of follow-up who presented to a New York City medical center. Multivariable logistic regression and classification and regression tree (CART) analysis were used to identify predictors of poor outcome. RESULTS: Patients presenting to the hospital earlier in their disease course were older, had more comorbidities, and a greater proportion decompensated (<4 days, 41%; 4-8 days, 31%; >8 days, 26%). The first recorded oxygen delivery method was the most important predictor of decompensation overall in CART analysis. In patients with symptoms for <4, 4-8, and >8 days, requiring at least non-rebreather, age ≥ 63 years, and neutrophil/lymphocyte ratio ≥ 5.1; requiring at least non-rebreather, IL-6 ≥ 24.7 pg/mL, and D-dimer ≥ 2.4 µg/mL; and IL-6 ≥ 64.3 pg/mL, requiring non-rebreather, and CRP ≥ 152.5 mg/mL in predictive models were independently associated with poor outcome, respectively. CONCLUSION: Symptom duration in tandem with initial clinical and laboratory markers can be used to identify patients with COVID-19 at increased risk for poor outcomes.
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Oxygen consumption is a fundamental characteristic of staphylococcal physiology reflecting the energy and metabolic state of the bacterial cell. During aerobic growth, oxygen consumption rates (OCR) depend on nutrient availability and vary at different growth stages. The measurement of oxygen consumption rates provides a versatile tool to characterize the impact of various mutations, environmental cues, and antibiotics on bacterial growth and fitness. In this chapter, we describe a MitoXpress® Xtra-based oxygen consumption assay for fast and reliable determination of respiration rates in Staphylococcus aureus. This highly reproducible and simple method requires a minimal set of reagents and allows rapid screening of multiple samples through real-time determination of the OCR with an oxygen-sensing probe and fluorescence plate reader.
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Antibacterianos/farmacología , Oxígeno/análisis , Staphylococcus aureus/crecimiento & desarrollo , Técnicas Biosensibles , Fluoroinmunoensayo , Aptitud Genética , Mutación , Consumo de Oxígeno , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genéticaRESUMEN
Two strains, H8/1T and H16/1AT, of Gram-stain-positive, coagulase-negative staphylococci were isolated from separate healthy domestic dogs in Scotland. Both strains were genome sequenced and their inferred DNA-DNA hybridisation indicates that H8/1T and H16/1AT represent two novel species of the genus Staphylococcus. On the basis of the results of genome sequence analysis (genome blast distance phylogeny and single nucleotide polymorphism analysis) H8/1T is most closely related to Staphylococcus devriesei and H16/1AT most closely related to Staphylococcus felis. Also, average nucleotide identity distinguished H8/1T and H16/1AT from S. devriesei and S. felis as did minor phenotypic differences. On the basis of these results, it is proposed that H8/1T and H16/1AT represent novel species with the respective names Staphylococcus caledonicus and Staphylococcus canis. The type strain of S. caledonicus is H8/1T (=NCTC 14452T=CCUG 74789T). The type strain of S. canis is H16/1AT (=NCTC 14451T=CCUG 74790T).
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Perros/microbiología , Filogenia , Staphylococcus/clasificación , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Escocia , Análisis de Secuencia de ADN , Staphylococcus/aislamiento & purificaciónRESUMEN
Blood and faecal samples from 2086 Sahelian and Djallonke sheep have been collected to assess the epidemiology and spatio-temporal distribution of gastrointestinal parasites. A survey with a questionnaire allowed collecting data on individual animal and farms. Faecal samples were analysed using the McMaster technique, while anaemia was assessed using FAMACHA score test and packed cell volume. The overall prevalence of gastrointestinal parasites was 91%, and strongyles (70.7%), Eimeria sp. (60.4%), Moniezia sp. (5.7%), Stronyloides sp. (0.9%) were identified. There was no significant association between the region and strongyles infection (P Ë 0.05). Animals sampled during the rainy season (n = 565; P = 82.2%, mean EPG = 154.8 ± 12.02) were mostly and heavily infected than those from the hot dry (n = 518; P = 74.2%; mean EPG = 97.7 ± 17.4) and the cold dry season (n = 392; P = 55.5%; mean EPG = 24.5 ± 19.5) (P Ë 0.05). Females (n = 1027; P = 72.1%; mean EPG = 77.6 ± 17) were most infected than males (n = 448; P = 67.7%; mean EPG = 61.6 ± 19.5) (P Ë 0.05). Animals that were treated, at most 3 months before sampling (n = 166; P = 61.5%; mean EPG = 41.7 ± 21.4), were less infected than those, which received this treatment after three months before sampling (n = 199; P = 74.8%; mean EPG = 89.1 ± 15.8) (P Ë 0.05). Data from blood samples indicate that 6.5% of sheep was anaemic (PCV ≤ 19%), while 59.7% was noted anaemic regarding FAMACHA scores. PCV values varied significantly for FAMACHA scores, and the highest mean value was noted for score 1 (27.6) (P Ë 0.05). The Cohen's kappa score between FAMACHA and PCV was 0.02. These findings suggest that strongyles infections are significantly associated with season, and heavier infections were noted during rainy season.
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Hemoncosis , Haemonchus , Parásitos , Enfermedades de las Ovejas , Agricultura , Animales , Burkina Faso/epidemiología , Granjas , Heces , Femenino , Hemoncosis/diagnóstico , Hemoncosis/epidemiología , Hemoncosis/veterinaria , Masculino , Recuento de Huevos de Parásitos/veterinaria , Ovinos , Enfermedades de las Ovejas/diagnóstico , Enfermedades de las Ovejas/epidemiologíaRESUMEN
Milk fats are vital to neonate survival and development, but vary highly by diet, maternal metabolic state and stage of lactation. To gain a better understanding of changes in lipid composition of sow milk across lactation, milk was collected from nine multiparous sows on days 0, 3, 7, and 14, relative to birth and lipids were profiled using multiple reaction monitoring (MRM) profiling. Percent fat was determined by creamatocrit, and found to be different (P < 0.05) between day 0 (12.36 ± 5.90%) and day 3 (16.22 ± 3.65%) but not between day 7 (13.13 ± 2.19%) and day 14 (12.13 ± 2.45%). Fat was extracted from milk (n = 6/day) using the Bligh-Dyer method and profiled using tandem mass spectrometry MRM to determine the abundance of lipids defined by class and fatty acyl residue composition. Lipid species relative concentration was calculated from internal standards, and data analysis was performed using Metaboanalyst 4.0. Concentration of phosphatidyl-choline, -serine, -ethanolamine, -inositol, cholesteryl ester and sphingomyelin did not vary across lactation days, nor did the distribution of associated fatty acyl residues. The total abundance of triacylglycerides (TGs) and phosphatidylglycerols (PGs) increased (P < 0.05) from colostrum (day 0) to transitional (days 3 and 7) and mature milk (day 14). As lactation days increased from day 0 to day 14, the number of carbons and unsaturation within fatty acyl residues decreased (P < 0.05) in both TGs and PGs. The proportion of TGs and PGs increased (P < 0.05) relative to other lipid classes. Changes in composition of milk triglycerides and phosphatidylglycerols likely reflect the metabolic activity of the mammary gland and developmental needs of neonates.
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Leche , Fosfolípidos , Animales , Membrana Celular , Calostro , Dieta , Femenino , Lactancia , Lipidómica , Fosfatidilgliceroles , Embarazo , Porcinos , TriglicéridosRESUMEN
Two juvenile alpacas, 1 male and 1 female, were presented for evaluation of grade V/VI bilateral basilar systolic heart murmurs. Both animals were ultimately diagnosed with severe valvular pulmonic stenosis and a small ventricular septal defect. Transvenous balloon valvuloplasty was performed in each animal using methods described in the dog. A double balloon technique was employed in the first case, with a balloon-annulus ratio of ~1.55. For the second case, a high-pressure dilatation balloon catheter with a balloon-annulus ratio of ~1.33 was selected. Experience with both procedures indicates that balloon pulmonary valvuloplasty is technically feasible in alpacas using techniques extrapolated from those used in dogs. Furthermore, accepted criteria for procedural success were fulfilled for both alpacas, with more than a 50% reduction in the echocardiographically derived transpulmonic pressure gradient after intervention.
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Valvuloplastia con Balón , Camélidos del Nuevo Mundo , Enfermedades de los Perros , Estenosis de la Válvula Pulmonar , Animales , Valvuloplastia con Balón/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/terapia , Perros , Femenino , Masculino , Estenosis de la Válvula Pulmonar/diagnóstico por imagen , Estenosis de la Válvula Pulmonar/terapia , Estenosis de la Válvula Pulmonar/veterinariaRESUMEN
BACKGROUND: Deep brain stimulation (DBS) is a treatment option for Parkinson's disease patients when medication does not sufficiently manage their symptoms. DBS can be a highly effect therapy, but only after a time-consuming trial-and-error stimulation parameter adjustment process that is susceptible to clinician bias. This trial-and-error process will be further prolonged with the introduction of segmented electrodes that are now commercially available. New approaches to optimizing a patient's stimulation parameters, that can also handle the increasing complexity of new electrode and stimulator designs, is needed. METHODS: To improve DBS parameter programming, we explored two semi-automated optimization approaches: a Bayesian optimization (BayesOpt) algorithm to efficiently determine a patient's optimal stimulation parameter for minimizing rigidity, and a probit Gaussian process (pGP) to assess patient's preference. Quantified rigidity measurements were obtained using a robotic manipulandum in two participants over two visits. Rigidity was measured, in 5Hz increments, between 10-185Hz (total 30-36 frequencies) on the first visit and at eight BayesOpt algorithm-selected frequencies on the second visit. The participant was also asked their preference between the current and previous stimulation frequency. First, we compared the optimal frequency between visits with the participant's preferred frequency. Next, we evaluated the efficiency of the BayesOpt algorithm, comparing it to random and equal interval selection of frequency. RESULTS: The BayesOpt algorithm estimated the optimal frequency to be the highest tolerable frequency, matching the optimal frequency found during the first visit. However, the participants' pGP models indicate a preference at frequencies between 70-110 Hz. Here the stimulation frequency is lowest that achieves nearly maximal suppression of rigidity. BayesOpt was efficient, estimating the rigidity response curve to stimulation that was almost indistinguishable when compared to the longer brute force method. CONCLUSIONS: These results provide preliminary evidence of the feasibility to use BayesOpt for determining the optimal frequency, while pGP patient's preferences include more difficult to measure outcomes. Both novel approaches can shorten DBS programming and can be expanded to include multiple symptoms and parameters.
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Algoritmos , Teorema de Bayes , Estimulación Encefálica Profunda/métodos , Enfermedad de Parkinson/terapia , Adulto , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Concerns over radiation exposure are ubiquitous to all interventional cardiologists; however, fear of exposure during childbearing years disproportionately deters women from entering the field. This review summarizes the available data on occupational radiation exposure during pregnancy with an emphasis on radiation quantification, the impact of exposure at various stages of fetal development, societal recommendations for safe levels of exposure during gestation, threshold levels necessary to induce fetal harm, and safe practices for the pregnant interventionalist. Reconciling the available information, we conclude that pregnancy in the cardiac catheterization laboratory is both safe and feasible. This review also highlights new technologies that may augment standard radiation safety techniques and are of particular interest to the pregnant interventional cardiologist. Finally, we propose steps to improve female representation in this field, underscoring the importance of a sex-balanced workforce.
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Cardiología , Exposición Profesional , Exposición a la Radiación , Cateterismo Cardíaco/efectos adversos , Femenino , Humanos , Laboratorios , Exposición Profesional/efectos adversos , Embarazo , Dosis de Radiación , Exposición a la Radiación/efectos adversos , Exposición a la Radiación/prevención & control , Radiografía IntervencionalRESUMEN
BACKGROUND: Mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have immunomodulatory properties that are of interest to treat novel coronavirus disease 2019 (COVID-19). Leng et al. recently reported that hUC-MSCs derived from one donor negatively expressed Angiotensin-Converting Enzyme 2 (ACE2), a key protein for viral infection along with Transmembrane Serine Protease 2 (TMPRSS2). The purpose of this study was to quantify the expression of ACE2 and TMPRSS2 in hUC-MSCs lots derived from multiple donors using molecular-based techniques in order to demonstrate their inability to be a host to SARS-CoV-2. METHODS: Expression of ACE2 and TMPRSS2 was analyzed in 24 lots of hUC-MSCs derived from Wharton's jelly via quantitative polymerase chain reaction (qPCR), Western Blot, immunofluorescence and flow cytometry using 24 different donors. RESULTS: hUC-MSCs had significantly lower ACE2 (p = 0.002) and TMPRSS2 (p = 0.008) expression compared with human lung tissue homogenates in Western blot analyses. Little to no expression of ACE2 was observed in hUC-MSC by qPCR, and they were not observable with immunofluorescence in hUC-MSCs cell membranes. A negative ACE2 and TMPRSS2 population percentage of 95.3% ± 15.55 was obtained for hUC-MSCs via flow cytometry, with only 4.6% ACE2 and 29.5% TMPRSS2 observable positive populations. CONCLUSIONS: We have demonstrated negative expression of ACE2 and low expression of TMPRSS2 in 24 lots of hUC-MSCs. This has crucial implications for the design of future therapeutic options for COVID-19, since hUC-MSCs would have the ability to "dodge" viral infection to exert their immunomodulatory effects.