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1.
Support Care Cancer ; 32(6): 349, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744744

RESUMO

PURPOSE: Quality of life (QoL), appetite, cachexia, and biomarkers [albumin, hemoglobin (Hb), neutrophils, lymphocytes, platelets, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), interleukin 8 (IL-8), C-X-C motif chemokine ligand 5 (CXCL5) and citrullinated histoneH3 (H3Cit)] were compared for 40 cases with advanced cancer and 40 healthy controls. Baseline differences and significant relationships were explored for biomarkers with QoL, appetite, and cachexia. METHODS: In a prospective case-control, age and sex matched study, the European Organisation for the Research and Treatment of Cancer Quality of Life-C30 questionnaire (EORTC-QLQ-C30) for QoL, the Functional Assessment of Anorexia and Cachexia Therapy assessment (FAACT A/CS-12) for appetite, and a five-factor cachexia assessment tool for cachexia assessment were performed. Routine hematological measurements and blood chemistry analyses together with ELISA procedures and a Multiplex® bead array platform, were used for biomarker analysis. Descriptive statistics and regression analyses were undertaken. P < 0.05 defined statistical significance. RESULTS: Global health status (QL-G), functional scales (QL-FS), and symptom scales (QL-SS) differed for cases and controls (p < 0.01). In cases, differences were observed for QL-G (p < 0.01), QL-FS (p < 0.01), and QL-SS (p = 0.01) compared to standardized references values. FAACT A/CS-12 scores differed significantly between cases and controls (p < 0.01) and 30% of cases scored "poor" appetites. Cachexia was present in 60% of cases. Albumin, lymphocytes, platelets, Hb, platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), CRP, TNFα, all at p < 0.01, neutrophil to lymphocyte ratio (NLR) (p = 0.02), IL-6 (p < 0.04), and IL-8 (p = 0.02) differed significantly between cases and controls. No difference was found for CXCL5 or H3Cit. Albumin NLR, Hb, PLR, SII, TNFα, IL-8, and CRP showed significant relationships with all aspects of QoL. QL-FS was significantly related to CXCL5 (p = 0.04), significant relationships with FAACT A/CS-12 included: NLR (p = 0.002), Hb (p < 0.001), and PLR (p < 0.01). NLR, PLR, SII, TNFα, IL-6, IL-8, and CRP correlated positively to cachexia and albumin while Hb and lymphocyte count correlated negatively to cachexia. CONCLUSION: CXCL5 and H3Cit were not reliable biomarkers for cancer cachexia, nor significantly related to QoL, appetite or cachexia. Albumin, NLR, Hb, PLR, SII, TNFα, IL-8, and CRP were reliable indicators of QoL, appetite, and cachexia. Future research should include other novel biomarkers namely growth differentiation factor-15 (GDF-15), fibroblast growth factor 21 (FGF-21), fractakline, interferon gamma (IFN-y), IL-16, macrophage colony stimulating factor (M-CSF), and macrophage procoagulant-inducing factor (MPIF).


Assuntos
Apetite , Biomarcadores , Caquexia , Neoplasias , Qualidade de Vida , Humanos , Caquexia/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias/complicações , Estudos de Casos e Controles , Estudos Prospectivos , Idoso , Apetite/fisiologia , Biomarcadores/sangue , Inquéritos e Questionários , Adulto
2.
J Am Coll Cardiol ; 83(15): 1370-1381, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38599713

RESUMO

BACKGROUND: An ABCD-GENE (age, body mass index, chronic kidney disease, diabetes, and CYP2C19 genetic variants) score ≥10 predicts reduced clopidogrel effectiveness, but its association with response to alternative therapy remains unclear. OBJECTIVES: The aim of this study was to evaluate the association between ABCD-GENE score and the effectiveness of clopidogrel vs alternative P2Y12 inhibitor (prasugrel or ticagrelor) therapy after percutaneous coronary intervention (PCI). METHODS: A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y12 inhibitor treatment were included. The primary outcome was major atherothrombotic events (MAE) within 1 year after PCI. Cox regression was performed to assess event risk in clopidogrel-treated (reference) vs alternatively treated patients, with stabilized inverse probability weights derived from exposure propensity scores after stratifying by ABCD-GENE score and further by CYP2C19 loss-of-function (LOF) genotype. RESULTS: Among patients with scores <10 (n = 3,200), MAE was not different with alternative therapy vs clopidogrel (weighted HR: 0.89; 95% CI: 0.65-1.22; P = 0.475). The risk for MAE also did not significantly differ by treatment among patients with scores ≥10 (n = 1,135; weighted HR: 0.75; 95% CI: 0.51-1.11; P = 0.155). Among CYP2C19 LOF allele carriers, MAE risk appeared lower with alternative therapy in both the group with scores <10 (weighted HR: 0.50; 95% CI: 0.25-1.01; P = 0.052) and the group with scores ≥10 (weighted HR: 0.48; 95% CI: 0.29-0.80; P = 0.004), while there was no difference in the group with scores <10 and no LOF alleles (weighted HR: 1.03; 95% CI: 0.70-1.51; P = 0.885). CONCLUSIONS: These data support the use of alternative therapy over clopidogrel in CYP2C19 LOF allele carriers after PCI, regardless of ABCD-GENE score, while clopidogrel is as effective as alternative therapy in non-LOF patients with scores <10.


Assuntos
Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Clopidogrel , Citocromo P-450 CYP2C19/genética , Intervenção Coronária Percutânea/efeitos adversos , Ticagrelor/uso terapêutico , Resultado do Tratamento , Genótipo
3.
FASEB J ; 38(8): e23585, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38661043

RESUMO

Fractional laser ablation is a technique developed in dermatology to induce remodeling of skin scars by creating a dense pattern of microinjuries. Despite remarkable clinical results, this technique has yet to be tested for scars in other tissues. As a first step toward determining the suitability of this technique, we aimed to (1) characterize the response to microinjuries in the healthy and cirrhotic liver, and (2) determine the underlying cause for any differences in response. Healthy and cirrhotic rats were treated with a fractional laser then euthanized from 0 h up to 14 days after treatment. Differential expression was assessed using RNAseq with a difference-in-differences model. Spatial maps of tissue oxygenation were acquired with hyperspectral imaging and disruptions in blood supply were assessed with tomato lectin perfusion. Healthy rats showed little damage beyond the initial microinjury and healed completely by 7 days without scarring. In cirrhotic rats, hepatocytes surrounding microinjury sites died 4-6 h after ablation, resulting in enlarged and heterogeneous zones of cell death. Hepatocytes near blood vessels were spared, particularly near the highly vascularized septa. Gene sets related to ischemia and angiogenesis were enriched at 4 h. Laser-treated regions had reduced oxygen saturation and broadly disrupted perfusion of nodule microvasculature, which matched the zones of cell death. Our results demonstrate that the cirrhotic liver has an exacerbated response to microinjuries and increased susceptibility to ischemia from microvascular damage, likely related to the vascular derangements that occur during cirrhosis development. Modifications to the fractional laser tool, such as using a femtosecond laser or reducing the spot size, may be able to prevent large disruptions of perfusion and enable further development of a laser-induced microinjury treatment for cirrhosis.


Assuntos
Isquemia , Cirrose Hepática , Animais , Ratos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Isquemia/metabolismo , Isquemia/patologia , Fígado/metabolismo , Fígado/patologia , Terapia a Laser/métodos , Ratos Sprague-Dawley , Hepatócitos/metabolismo
4.
Nurs Inq ; : e12635, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558441

RESUMO

Our goal was to explore self-care practices among men who have sex with men in the context of Mpox in Brazil. This study used qualitative research methods, including interviews and thematic analysis, to collect and analyze data from male participants across the Brazilian territory. The narratives unveil men's perspectives on self-care, risk reduction, and health beliefs during the Mpox pandemic. Our findings highlight a multifaceted approach to self-care among men, encompassing hygiene, physical contact management, mask usage, skin lesion vigilance, and adherence to official guidelines. Men's attitudes toward sexual behaviors emphasize the importance of reducing sexual partners, practicing safe sex, and combating misinformation through accurate information dissemination. The development of these behaviors and self-care practices can be facilitated by nurses guided by Dorothea Orem's Self-Care Theory, supported by patient-centered care, with strategies to address and confront the stigma associated with the disease and provide emotional support. Thus, the study underscores the pivotal role of self-care in mitigating infection risks, especially in the context of emerging infectious diseases. It acknowledges the impact of socio-cultural factors and healthcare policies on men's preventive measures. However, it also recognizes limitations, such as potential bias due to stigma concerns and a nonrepresentative sample. Ultimately, the research advocates for tailored education, promotion of gender equity, and healthcare empowerment to effectively manage health risks in such contexts.

5.
Am Heart J Plus ; 41: 100390, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38600957

RESUMO

Background: Heart failure with preserved ejection fraction (HFpEF) is the most common cardiac complication in patients with coronary microvascular dysfunction (CMD), yet its underlying pathways remain unclear. Aortic pulse-wave velocity (aPWV) is an indicator of large artery stiffness and a predictor for cardiovascular disease. However, aPWV in CMD and HFpEF is not well characterized and may provide understanding of disease progression. Methods: Among participants without obstructive coronary artery disease, we evaluated 51 women with suspected CMD and 20 women and men with evidence of HFpEF. All participants underwent aPWV measurement (SphygmoCor, Atcor Medical) with higher aPWV indicating greater vascular stiffness. Cardiac magnetic resonance imaging (CMRI) assessed left ventricular (LV) ejection fraction, CMD via myocardial perfusion reserve index (MPRI), and ventricular remodeling via LV mass-volume ratio. . Statistical analysis was performed using Wilcoxon rank sum tests, Pearson correlations and linear regression analysis. Results: Compared to the suspected CMD group, the HFpEF participants were older (65 ± 12 vs 56 ± 11 yrs., p = 0.002) had higher BMI (31.0 ± 4.3 vs 27.8 ± 6.7 kg/m2, p = 0.013), higher aPWV (10.5 ± 2.0 vs 8.0 ± 1.6 m/s, p = 0.05) and lower MPRI (1.5 ± 0.3 vs1.8 ± 0.3, p = 0.02), but not remodeling. In a model adjusted for cardiovascular risk factors, the HFpEF group had a lower LVEF (estimate -4.78, p = 0.0437) than the suspected CMD group. Conclusions: HFpEF participants exhibit greater arterial stiffness and lower myocardial perfusion reserve, with lower LVEF albeit not remodeling, compared to suspected CMD participants. These findings suggest arterial stiffness may contribute to progression from CMD to HFpEF. Prospective work is needed and ongoing.

6.
J Immunotoxicol ; 21(1): 2345152, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38659406

RESUMO

The recent global resurgence of severe infections caused by the Group A streptococcus (GAS) pathogen, Streptococcus pyogenes, has focused attention on this microbial pathogen, which produces an array of virulence factors, such as the pore-forming toxin, streptolysin O (SOT). Importantly, the interactions of SOT with human neutrophils (PMN), are not well understood. The current study was designed to investigate the effects of pretreatment of isolated human PMN with purified SOT on several pro-inflammatory activities, including generation of reactive oxygen species (ROS), degranulation (elastase release), influx of extracellular calcium (Ca2+) and release of extracellular DNA (NETosis), using chemiluminescence, spectrophotometric and fluorimetric procedures, respectively. Exposure of PMN to SOT alone caused modest production of ROS and elastase release, while pretreatment with the toxin caused significant augmentation of chemoattractant (fMLP)-activated ROS generation and release of elastase by activated PMN. These effects of treatment of PMN with SOT were associated with both a marked and sustained elevation of cytosolic Ca2+concentrations and significant increases in the concentrations of extracellular DNA, indicative of NETosis. The current study has identified a potential role for SOT in augmenting the Ca2+-dependent pro-inflammatory interactions of PMN, which, if operative in a clinical setting, may contribute to hyper-activation of PMN and GAS-mediated tissue injury.


Assuntos
Armadilhas Extracelulares , Neutrófilos , Streptococcus pyogenes , Estreptolisinas , Humanos , Proteínas de Bactérias/metabolismo , Cálcio/metabolismo , Degranulação Celular/efeitos dos fármacos , Células Cultivadas , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Inflamação/imunologia , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Elastase Pancreática/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Infecções Estreptocócicas/imunologia , Streptococcus pyogenes/imunologia , Estreptolisinas/metabolismo
7.
Dermatol Surg ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518178

RESUMO

BACKGROUND: Autofluorescence photography can detect specific light-tissue interactions and record important pathophysiological changes associated with nonmelanoma skin cancer (NMSC), which has been ascribed to the fluorescence of an aromatic amino acid, tryptophan. OBJECTIVE: To assess the impact of a novel, autofluorescence imaging (AFI) device on margin control for NMSCs before Mohs micrographic surgery (MMS) in an effort to decrease overall operating time. METHODS: Before the initial stage of MMS, NMSCs were measured with a 2-mm margin as standard of care (normal margin). The tumor was then imaged with the AFI device. A 2-mm margin was drawn around the fluorescent area captured by the AFI device and was referred to as the camera margin. The tumor was excised based on the normal margin and evaluated on frozen histological section. RESULTS: Imaging based on the AFI device resulted in appropriate recommendations for margin control in 8 of 11 tumors. Four of these tumors did not fluoresce and demonstrated a lack of tumor residuum on stage I specimen, as anticipated. There were no side effects from the AFI device. CONCLUSION: This is an initial pilot study that supports the use of a novel, noninvasive imaging device to help with margin assessment before MMS. On optimization, this device has potential to extend applicability to surgical excisions for tumors that do not fulfill criteria for MMS.

8.
Pigment Cell Melanoma Res ; 37(3): 403-410, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38361478

RESUMO

Post-inflammatory hyperpigmentation (PIH) is a hypermelanosis that often occurs secondary to skin irritation or injury, especially in darker skin tones, for which there is currently a lack of effective treatment options. Few preclinical models are available to study PIH. Here, we show that the Yucatan miniature pig consistently develops PIH after skin injuries. Skin wounds were produced on Yucatan pigs by needle punches, full-thickness excisions, or burns. Wound sites were monitored and photographed regularly. Tissue samples were collected after 24 weeks and processed for histology/immunohistochemistry. Skin pigmentation and histologic changes were quantified by computer-assisted image analyses. All injury methods resulted in hyperpigmentation. Melanin content at the histologic level was quantified in the larger (burn and excision) wounds, showing a significant increase compared to uninjured skin. Increased melanin was found for both epidermal and dermal regions. Dermal melanin deposits were primarily clustered around the papillary vasculature, and were associated not with melanocytes but with leukocytes. The Yucatan miniature pig model recapitulates key clinical and histologic features of PIH in humans, including skin hyperpigmentation at both gross and histologic levels, and persistence of dermal melanin subsequent to injury. This model could be used to further our understanding of the etiology of PIH, and for new therapy development.


Assuntos
Modelos Animais de Doenças , Hiperpigmentação , Melaninas , Porco Miniatura , Animais , Suínos , Hiperpigmentação/patologia , Hiperpigmentação/metabolismo , Melaninas/metabolismo , Pele/patologia , Pele/metabolismo , Inflamação/patologia , Pigmentação da Pele , Feminino , Humanos
9.
Int J Radiat Biol ; : 1-11, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319708

RESUMO

PURPOSE: The purpose of this paper was to conduct a review of the studies published between 2018 and 2022 to investigate radiation-related effects in the offspring of human individuals exposed to ionizing radiation. METHODS: The search identified 807 publications, from which 9 studies were selected for detailed analysis to examine for effects in children whose parents were exposed to various types and doses of radiation. RESULTS: The review does not yield substantial evidence supporting intergenerational effects of radiation exposure in humans. However, caution is required when interpreting the results due to limitations in the majority of the published articles. CONCLUSION: This review, covering the period 2018-2022, serves as an extension of the previous systematic review conducted by Stephens et al. (2024), which encompassed the years 1988-2018. Together, these two papers offer a comprehensive overview of the available evidence regarding the intergenerational effects of parental pre-conceptional exposure to ionizing radiation. Overall, the findings do not provide strong evidence supporting a significant association between adverse (or other) outcomes in unexposed children and parental preconception radiation exposure.

10.
J Infect Dis ; 229(4): 947-958, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38324758

RESUMO

BACKGROUND: Malarial infections are often missed by microscopy, and most parasite carriers are asymptomatic in low-endemicity settings. Whether parasite detectability and its ability to elicit symptoms change as transmission declines remains unclear. METHODS: We performed a prospective panel survey with repeated measurements on the same participants over 12 months to investigate whether Plasmodium vivax detectability by microscopy and risk of symptoms upon infection varied during a community-wide larviciding intervention in the Amazon basin of Brazil that markedly reduced vector density. We screened 1096 to 1400 residents in the intervention site for malaria by microscopy and quantitative TaqMan assays at baseline and twice during intervention. RESULTS: We found that more P vivax infections than expected from their parasite densities measured by TaqMan assays were missed by microscopy as transmission decreased. At lower transmission, study participants appeared to tolerate higher P vivax loads without developing symptoms. We hypothesize that changes in the ratio between circulating parasites and those that accumulate in the bone marrow and spleen, by avoiding peripheral blood microscopy detection, account for decreased parasite detectability and lower risk of symptoms under low transmission. CONCLUSIONS: P vivax infections are more likely to be subpatent and remain asymptomatic as malaria transmission decreases.


Assuntos
Malária Falciparum , Malária Vivax , Malária , Humanos , Malária Vivax/parasitologia , Brasil/epidemiologia , Estudos Prospectivos , Malária Falciparum/parasitologia , Prevalência , Plasmodium vivax , Plasmodium falciparum
11.
Phys Rev Lett ; 132(6): 065102, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38394591

RESUMO

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

12.
ACS Chem Biol ; 19(2): 471-482, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38270591

RESUMO

Altered metabolism is a hallmark of cancer; however, it has been difficult to specifically target metabolism in cancer for therapeutic benefit. Cancers with genetically defined defects in metabolic enzymes constitute a subset of cancers where targeting metabolism is potentially accessible. Hürthle cell carcinoma of the thyroid (HTC) tumors frequently harbor deleterious mitochondrial DNA (mtDNA) mutations in subunits of complex I of the mitochondrial electron transport chain (ETC). Previous work has shown that HTC models with deleterious mtDNA mutations exhibit mitochondrial ETC defects that expose lactate dehydrogenase (LDH) as a therapeutic vulnerability. Here, we performed forward genetic screens to identify mechanisms of resistance to small-molecule LDH inhibitors. We identified two distinct mechanisms of resistance: upregulation of an LDH isoform and a compound-specific resistance mutation. Using these tools, we demonstrate that the anticancer activity of LDH inhibitors in cell line and xenograft models of complex I mutant HTC is through on-target LDH inhibition.


Assuntos
Adenoma Oxífilo , L-Lactato Desidrogenase , Neoplasias da Glândula Tireoide , Humanos , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Mutação , Mitocôndrias/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , DNA Mitocondrial/genética
13.
J Invest Dermatol ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38237729

RESUMO

Wound research has typically been performed without regard for where the wounds are located on the body, despite well-known heterogeneities in physical and biological properties between different skin areas. The skin covering the palms and soles is highly specialized, and plantar ulcers are one of the most challenging and costly wound types to manage. Using primarily the porcine model, we show that plantar skin is molecularly and functionally more distinct from nonplantar skin than previously recognized, with unique gene and protein expression profiles, broad alterations in cellular functions, constitutive activation of many wound-associated phenotypes, and inherently delayed healing. This unusual physiology is likely to play a significant but underappreciated role in the pathogenesis of plantar ulcers as well as the last 25+ years of futility in therapy development efforts. By revealing this critical yet unrecognized pitfall, we hope to contribute to the development of more effective therapies for these devastating nonhealing wounds.

14.
J Am Acad Dermatol ; 90(4): 767-774, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38086517

RESUMO

BACKGROUND: People with Neurofibromatosis Type 1 (NF1) suffer disfigurement and pain when hundreds to thousands of cutaneous neurofibromas (cNFs) appear and grow throughout life. Surgical removal of cNFs under anesthesia is the only standard therapy, leaving surgical scars. OBJECTIVE: Effective, minimally-invasive, safe, rapid, tolerable treatment(s) of small cNFs that may prevent tumor progression. METHODS: Safety, tolerability, and efficacy of 4 different treatments were compared in 309, 2-4 mm cNFs across 19 adults with Fitzpatrick skin types (FST) I-IV: radiofrequency (RF) needle coagulation, 755 nm alexandrite laser with suction, 980 nm diode laser, and intratumoral injection of 10 mg/mL deoxycholate. Regional pain, clinical responses, tumor height and volume (by 3D photography) were assessed before, 3 and 6 months post-treatment. Biopsies were obtained electively at 3 months. RESULTS: There was no scarring or adverse events > grade 2. Each modality significantly (P < .05) reduced or cleared cNFs, with large variation between tumors and participants. Alexandrite laser and deoxycholate were fast and least painful; 980 nm laser was most painful. Growth of cNFs was not stimulated by treatment(s) based on height and volume values at 3 and 6 months compared to baseline. LIMITATIONS: Intervention was a single treatment session; dosimetry has not been optimized. CONCLUSIONS: Small cNFs can be rapidly and safely treated without surgery.


Assuntos
Neurofibroma , Neurofibromatose 1 , Neuroma , Neoplasias Cutâneas , Adulto , Humanos , Estudos Prospectivos , Neurofibroma/cirurgia , Resultado do Tratamento , Neoplasias Cutâneas/cirurgia , Neurofibromatose 1/complicações , Neurofibromatose 1/terapia , Cicatriz , Dor , Ácido Desoxicólico
16.
Diabetes Care ; 47(1): 81-88, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37713477

RESUMO

OBJECTIVE: Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. RESEARCH DESIGN AND METHODS: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this prespecified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome. RESULTS: Of 15,076 patients, 5,676 (39%) had DM of whom 2,820 (49.7%) were assigned to 81 mg aspirin and 2,856 (50.3%) to 325 mg aspirin. Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% vs. 0.50%; P < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs. 10.0%; hazard ratio [HR] 0.98 [95% CI 0.83-1.16]; P = 0.265) or safety outcome (0.87% vs. 0.69%; subdistribution HR 1.25 [95% CI 0.72-2.16]; P = 0.772). CONCLUSIONS: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest that a higher dose of aspirin yields no added clinical benefit, even in a more vulnerable population.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Aspirina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/induzido quimicamente , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/induzido quimicamente , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Acidente Vascular Cerebral/epidemiologia
17.
Sex Abuse ; 36(4): 486-506, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37455145

RESUMO

OBJECTIVE: Prior research has rarely focused on sexual motives (e.g., motives for having sex) when studying sexual violence perpetration prevention. The current study examined the role of sexual motives alongside other risk factors like alcohol expectancies in predicting sexual violence. METHOD: We analyzed data from 205 male college students; 36% reported sexual perpetration of some type. Participants completed a series of questionnaires in a randomized order, including: measures of prior sexual perpetration, sexual motives, rape myth acceptance, alcohol expectancies, and a measure of social desirability. Data were analyzed using a series of T-tests and logistic regressions. RESULTS: With one exception (coping motives), all sexual motives (intimacy, enhancement, self-affirmation, peer approval, and partner approval) were endorsed at higher levels by individuals who perpetrated sexual violence than those who did not (p < .05, Cohen's d = .25-.56). The partner approval motive significantly predicted sexual violence perpetration on its own. The enhancement motive, both independently and in interaction with alcohol expectancies for aggression, predicted sexual violence perpetration. Two other motives, intimacy and self-affirmation, were only significant in interaction with alcohol expectancies for aggression. CONCLUSION: All sexual motives were endorsed more frequently by those who perpetrated sexual violence than those who did not. Sexual motives had a complex interaction with alcohol expectancies in predicting sexual violence perpetration. The results suggest that intervention programs should emphasize healthy, consensual sexual relationships that do not involve alcohol.


Assuntos
Estupro , Delitos Sexuais , Humanos , Masculino , Comportamento Sexual , Violência , Agressão , Etanol
18.
Photodiagnosis Photodyn Ther ; 45: 103952, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38145771

RESUMO

The rise of antibiotic-resistant bacteria calls for innovative approaches to combat multidrug-resistant strains. Here, the potential of the standard histological stain, Giemsa, to act as a photosensitizer (PS) for antimicrobial photodynamic inactivation (aPDI) against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) strains is reported. Bioassays were performed using various Giemsa concentrations (ranging from 0.0 to 20.0 µM) under 625 nm illumination at a light dose of 30 J cm-2. Remarkably, Giemsa completely inhibited the growth of MSSA and MRSA bacterial colonies for concentrations at 10 µM and higher but exhibited no inhibitory effect without light exposure. Partition coefficient analysis revealed Giemsa's affinity for membranes. Furthermore, we quantified the production of reactive oxygen species (ROS) and singlet oxygen (1O2) to elucidate the aPDI mechanisms underlying bacterial inactivation mediated by Giemsa. These findings highlight Giemsa stain's potential as a PS in aPDI for targeting multidrug-resistant bacteria.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Infecções Estafilocócicas , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Corantes Azur/farmacologia , Corantes Azur/uso terapêutico , Fotoquimioterapia/métodos , Staphylococcus aureus , Anti-Infecciosos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123773, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38142492

RESUMO

In this work, excitation-emission matrices (EEMs) were used in association with parallel factor analysis (PARAFAC) to assess biodiesel content in undiluted diesel-biodiesel blends (DBBs) without pre-sample preparation. EEMs were decomposed using the PARAFAC (EEMs-PARAFAC), and the loading values of the PARAFAC component as a function of biodiesel content in the blends were used to build an analytical model to quantify the biodiesel content in DBBs. The proposed model presenting a limit of detection (LOD) and a limit of quantification (LOQ) of 2.5% and 11% w/w, respectively, successfully predicted the biodiesel content in the validation samples. The robustness of the model was confirmed by a close analysis of the root mean square error of prediction, standard error of prediction, relative standard deviation of prediction, and Bias. Therefore, an accurate and robust analytical model based on EEMs-PARAFAC was developed to quantify the biodiesel content in undiluted DBBs without sample preparation.


Assuntos
Biocombustíveis , Biocombustíveis/análise , Espectrometria de Fluorescência/métodos , Análise Fatorial
20.
Sci Med Footb ; : 1-7, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38078467

RESUMO

The aim of this study was to assess and compare menstrual health literacy in professional women's football. A three-section questionnaire was completed by professional players (n = 25), development players (n = 22) and staff (n = 19). The mean total knowledge score (out of 19) was lower for development players (5.4 ± 2.9) than professional players (7.8 ± 3.2) and staff (9.1 ± 4.8) (p < 0.001). No group achieved >50% correct answers. For each group, knowledge of the menstrual cycle (MC) was greater than knowledge of hormonal contraceptives (HC) (p < 0.001). Previous MC and HC education did not correspond to higher knowledge scores in professional players (p = 0.823) or development players (p = 0.274). In professional and development players, comfort of communication was influenced by the sex of whom they were communicating with (p < 0.001), with a preference for females. In conclusion, results from the present study suggest refined education strategies and new approaches are required for both players and staff to improve menstrual health literacy in professional women's football.

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