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1.
Front Psychol ; 15: 1340010, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562235

RESUMO

Health alterations and school refusal behavior may significantly affect student evolution in all areas of student lives. The objective of this study was to use latent profile analysis to identify school refusal profiles sustained by negative reinforcement and to determine their relationship with distinct self-perceived health variables (Satisfaction, Well-being, Resilience, Performance, and Risk-Taking). The School Refusal Assessment Scale-Revised (SRAS-R) and the Child Health and Illness Profile (CHIP-CE/CRF) were administered to 737 students (60.9% male) aged between 8 and 10 (M = 8.76, SD = 0.74). Three profiles of school refusal maintained by negative reinforcement were obtained: no risk, moderate risk, and high risk. It was confirmed that school refusal through negative reinforcement correlates negatively with health dimensions, also finding that a higher risk profile for school refusal is associated with lower levels of self-perceived health. Similarly, it was determined that the high-risk profile is the most maladaptive, with significantly lower data in four of the five self-perceived health dimensions that were evaluated. In conclusion, remaining in situations with no or moderate risk of school refusal due to negative reinforcement encourages higher levels of self-perceived health, while being at high risk of school refusal due to negative reinforcement is associated with worse self-perceived health.

2.
Reumatol Clin (Engl Ed) ; 20(4): 193-198, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38644030

RESUMO

BACKGROUND: The characteristics of synovial fluid (SF) in geriatric patients differ from those in younger patients. In Mexico, epidemiologic data on the incidence of different rheumatic diseases in geriatric patients are scarce. OBJECTIVE: To describe the physical characteristics of geriatric SF and the prevalence of crystals in knee and other joint aspirates from patients with previously diagnosed joint disease. MATERIALS AND METHODS: A retrospective study was performed with a baseline of 517 SF samples between 2011 and 2023. White blood cell count was performed by Neubauer chamber and crystals were identified by polarized light microscopy. Descriptive statistical analysis was performed and prevalence was reported as a percentage. RESULTS: The mean age of the adults was 73.5±5.0 years, 54.4% were women and 45.6% were men. The mean SF volume was 6.3±9.5mL in older adults and 15.3±24.9mL in those younger than 65 years. The mean viscosity in older adults was 9.5±4.5mm and the mean leukocyte count was 7352±16,402leukocytes/mm3. Seventy percent of the older adults' SFs were referred to the laboratory for osteoarthritis (OA), with lower proportions for rheumatoid arthritis (RA) (14.6%) and gout (5.1%). Of the crystals observed in the geriatric population, 14.6% corresponded to monosodium urate crystals (CUM) and 18.9% to calcium pyrophosphate crystals (CPP). CONCLUSIONS: The characteristics of LS in older adults were smaller volume, increased viscosity, and non-inflammatory. The main diagnoses were OA, RA, and gout. The crystal content of the SF of the geriatric population corresponded mainly to CPP.


Assuntos
Líquido Sinovial , Humanos , Líquido Sinovial/química , Idoso , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Gota/epidemiologia , Idoso de 80 Anos ou mais , Artrite Reumatoide , México/epidemiologia , Contagem de Leucócitos , Fatores Etários
3.
Reumatol. clín. (Barc.) ; 20(4): 193-198, Abr. 2024. graf, tab
Artigo em Inglês | IBECS | ID: ibc-232372

RESUMO

Background: The characteristics of synovial fluid (SF) in geriatric patients differ from those in younger patients. In Mexico, epidemiologic data on the incidence of different rheumatic diseases in geriatric patients are scarce. Objective: To describe the physical characteristics of geriatric SF and the prevalence of crystals in knee and other joint aspirates from patients with previously diagnosed joint disease. Materials and methods: A retrospective study was performed with a baseline of 517 SF samples between 2011 and 2023. White blood cell count was performed by Neubauer chamber and crystals were identified by polarized light microscopy. Descriptive statistical analysis was performed and prevalence was reported as a percentage. Results: The mean age of the adults was 73.5±5.0 years, 54.4% were women and 45.6% were men. The mean SF volume was 6.3±9.5mL in older adults and 15.3±24.9mL in those younger than 65 years. The mean viscosity in older adults was 9.5±4.5mm and the mean leukocyte count was 7352±16,402leukocytes/mm3. Seventy percent of the older adults’ SFs were referred to the laboratory for osteoarthritis (OA), with lower proportions for rheumatoid arthritis (RA) (14.6%) and gout (5.1%). Of the crystals observed in the geriatric population, 14.6% corresponded to monosodium urate crystals (CUM) and 18.9% to calcium pyrophosphate crystals (CPP). Conclusions: The characteristics of LS in older adults were smaller volume, increased viscosity, and non-inflammatory. The main diagnoses were OA, RA, and gout. The crystal content of the SF of the geriatric population corresponded mainly to CPP.(AU)


Antecedentes: Las características del líquido sinovial (LS) en pacientes geriátricos varían en comparación con pacientes más jóvenes. En México, los datos epidemiológicos sobre la incidencia de diversas enfermedades reumáticas en el paciente geriátrico son escasos. Objetivo: Describir las características físicas del LS geriátrico y la prevalencia de cristales en aspirados de rodilla y otras articulaciones de pacientes con enfermedades articulares previamente diagnosticadas.Materiales y métodos: Se realizó un estudio retrospectivo con una base de 517 muestras de LS entre 2011 y 2023. El recuento de glóbulos blancos se realizó con cámara de Neubauer, y los cristales se identificaron por microscopia de luz polarizada. Se realizó un análisis estadístico descriptivo y la prevalencia se reportó como porcentaje. Resultados: La edad promedio en los adultos fue de 73,5±5,0 años; el 54,4% fueron mujeres y el 45,6%, hombres. El volumen promedio del LS en adultos mayores fue de 6,3±9,5ml, mientras que en menores de 65 años fue de 15,3±24,9ml. La viscosidad promedio fue de 9,5±4,5mm en los adultos mayores, y una cuenta de 7.352±16.402 leucocitos/mm3. El 70% de los LS de los adultos mayores fueron remitidos a laboratorio por osteoartritis (OA), u una proporción más baja, por artritis reumatoide (AR) (14,6%) y gota (5,1%). En cuanto a los cristales observados en los LS de la población geriátrica, el 14,6% correspondieron a cristales de urato monosódico (CUM) y el 18,9%, a cristales de pirofosfato de calcio (CPP). Conclusiones: Las características del LS en los adultos mayores fueron menor volumen, viscosidad incrementada y no inflamatorios. Los principales diagnósticos fueron OA, AR y gota. El contenido de los cristales en los LS de la población geriátrica correspondió principalmente a CPP.(AU)


Assuntos
Humanos , Masculino , Feminino , Idoso , Geriatria , Líquido Sinovial/microbiologia , Osteoartrite , Saúde do Idoso , Reumatologia , Doenças Reumáticas , Estudos Retrospectivos , México
4.
J Trace Elem Med Biol ; 84: 127435, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38547726

RESUMO

STATEMENT OF PROBLEM: Contamination with heavy metals (HM) has great environmental consequences in the environment due to lack of biodegradation, in addition, accumulation in living beings causes defects in tissues and organs, deteriorating their function and inducing a wide spectrum of diseases. Human biomonitoring consists of the periodic measurement of a certain chemical substance or metabolite in a particular population, using matrices that can be acute or chronic. Teeth are chronic matrices that have great characteristics of resistance and chronological storage of information. This review aims to identify the mechanisms, spatial location, and affinity of HM within teeth, along with understanding its applicability as a chronological record matrix in the face of HM contamination. MATERIAL AND METHODS: A systematic search review was performed using the PubMed/Medline, Web of Science, and Scopus metasearch engines, and the terms "teeth" OR "dental" OR "tooth" AND "heavy metals" were intersected. Complete articles are included in Spanish, English and Portuguese without time restrictions, involving studies in humans or in vitro; Letters to the editor, editorials and those that did not refer to information on the incorporation and relationship of HM with the teeth were excluded. RESULTS: 837 published articles were detected, 91 were adjusted to the search objective, and 6 were manually included. Teeth are structures with a great capacity for information retention in the face of HM contamination due to low physiological turnover and their long processes of marked formations by developmental biorhythm milestones such as the neonatal line (temporal reference indicator). The contamination mechanisms inside the tooth are linked to the affinity of hydroxyapatite for HM; this incorporation can be in the soft matrix during the apposition phase or as part of the chemical exchanges between hydroxyapatite and the elements of the environment. CONCLUSION: The teeth present unique characteristics of great resistance and affinity for HM, as well as a chronological biomarker for human biomonitoring, so they can be used as means of expertise or evidence to confirm or rule out a fact of environmental characteristics in the legal field.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38441244

RESUMO

OBJECTIVE: To identify new parameters predicting fetal acidemia. METHODS: A retrospective case-control study in a cohort of deliveries from a tertiary referral hospital-based cohort deliveries in Zaragoza, Spain between 2018 and 2021 was performed. To predict fetal acidemia, the NICHD categorizations and non-NICHD parameters were analyzed in the electronic fetal monitoring (EFM). Those included total reperfusion time, total deceleration area and the slope of the descending limb of the fetal heart rate of the last deceleration curve. The accuracy of the parameters was evaluated using the specificity for (80%, 85%, 90%, 95%) sensitivity and the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 10 362 deliveries were reviewed, with 224 cases and 278 controls included in the study. The NICHD categorizations showed reasonable discriminatory ability (AUC = 0.727). The non-NICHD parameters measured during the 30-min fetal monitoring, total deceleration area (AUC = 0.807, 95% CI: 0.770, 0.845) and total reperfusion time (AUC = 0.750, 95% CI: 0.707, 0.792), exhibited higher discriminatory ability. The slope of the descending limb of the fetal heart rate of the last deceleration curve had the best AUC value (0.853, 95% CI: 0.816, 0.889). The combination of total deceleration area or total reperfusion time with the slope demonstrated high discriminatory ability (AUC = 0.908, 95% CI: 0.882, 0.933; specificities of 71.6% and 72.7% for a sensitivity of 90%). CONCLUSIONS: The slope of the descending limb of the fetal heart rate of the last deceleration curve is the strongest predictor of fetal acidosis, but its combination with the total reperfusion time shows better clinical utility.

6.
Astrobiology ; 24(3): 230-274, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38507695

RESUMO

As focus for exploration of Mars transitions from current robotic explorers to development of crewed missions, it remains important to protect the integrity of scientific investigations at Mars, as well as protect the Earth's biosphere from any potential harmful effects from returned martian material. This is the discipline of planetary protection, and the Committee on Space Research (COSPAR) maintains the consensus international policy and guidelines on how this is implemented. Based on National Aeronautics and Space Administration (NASA) and European Space Agency (ESA) studies that began in 2001, COSPAR adopted principles and guidelines for human missions to Mars in 2008. At that point, it was clear that to move from those qualitative provisions, a great deal of work and interaction with spacecraft designers would be necessary to generate meaningful quantitative recommendations that could embody the intent of the Outer Space Treaty (Article IX) in the design of such missions. Beginning in 2016, COSPAR then sponsored a multiyear interdisciplinary meeting series to address planetary protection "knowledge gaps" (KGs) with the intent of adapting and extending the current robotic mission-focused Planetary Protection Policy to support the design and implementation of crewed and hybrid exploration missions. This article describes the outcome of the interdisciplinary COSPAR meeting series, to describe and address these KGs, as well as identify potential paths to gap closure. It includes the background scientific basis for each topic area and knowledge updates since the meeting series ended. In particular, credible solutions for KG closure are described for the three topic areas of (1) microbial monitoring of spacecraft and crew health; (2) natural transport (and survival) of terrestrial microbial contamination at Mars, and (3) the technology and operation of spacecraft systems for contamination control. The article includes a KG data table on these topic areas, which is intended to be a point of departure for making future progress in developing an end-to-end planetary protection requirements implementation solution for a crewed mission to Mars. Overall, the workshop series has provided evidence of the feasibility of planetary protection implementation for a crewed Mars mission, given (1) the establishment of needed zoning, emission, transport, and survival parameters for terrestrial biological contamination and (2) the creation of an accepted risk-based compliance approach for adoption by spacefaring actors including national space agencies and commercial/nongovernment organizations.


Assuntos
Marte , Voo Espacial , Humanos , Meio Ambiente Extraterreno , Exobiologia , Contenção de Riscos Biológicos , Astronave
7.
Anticancer Res ; 44(3): 1201-1208, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38423672

RESUMO

BACKGROUND/AIM: Enzyme-mediated grafting of poly (gallic acid) (PGAL) and L-arginine and a-L-lysine onto PGAL produces reactive oxygen species (ROS)-suppressor multiradical molecules with low cytotoxicity, high thermostability and water solubility with cancer treatment potential. This study examined the anticancer effects of these molecules in hepatic (HepG2, ATCC HB-8065), breast (MCF7, ATCC HTB-22), and prostate (PC-3, ATCC CRL-1435 and DU 145, ATCC HTB-81) cancer cell lines, as well as in fibroblasts from healthy human skin as control cells. MATERIALS AND METHODS: PGAL was synthesized by the oxidative polymerization of the naturally abundant GA using laccase from Trametes versicolor. Insertions of amino acids L-arginine and α-L-lysine on the PGAL chain were carried out by microwave. The cells of dermal fibroblast (Fb) were obtained from primary skin cultures and isolated from skin biopsies. The cancer cells lines of hepatic (HepG2), breast (MCF7), and prostate (PC-3, DU 145) were obtained from ATCC. The viability of the cancer cells and the primary culture was obtained by the MTT assay. Proliferation was demonstrated by crystal violet assay. Cell migration was determined by Wound healing assay. Finally, cell cycle analysis was carried out with cells. RESULTS: The results show that 200 µg/ml of PGAL cultured in vitro with prostate cancer cells decreased viability, proliferation, and migration, as well as arrested cells in the G1 and S phases of the cell cycle. In contrast, the dermal fibroblasts and the hepatic line remained unaffected. The random grafting of L-Arg and a-L-Lys onto the PGAL chain also decreased the viability of prostate cancer cells. CONCLUSION: PGAL and PGAL-grafted amino acids are potential adjuvants for prostate cancer treatment, with improved physicochemical characteristics compared to GA.


Assuntos
Ácido Gálico , Neoplasias da Próstata , Salicilatos , Masculino , Humanos , Ácido Gálico/farmacologia , Lisina , Trametes , Neoplasias da Próstata/patologia , Células MCF-7 , Arginina/farmacologia , Proliferação de Células
8.
Med. U.P.B ; 43(1): 56-64, ene.-jun. 2024. tab
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1531501

RESUMO

Objetivo: la ferritina es importante en el almacenamiento de hierro intracelular, en una forma soluble no tóxica. Sus niveles en la gestación se la relacionan con la salud de la madre y con su descendencia. El objetivo es escribir los niveles séricos de ferritina y prevalencia de déficit de ferritina, así como los factores sociodemográficos asociados en gestantes de Colombia. Metodología: estudio transversal; análisis secundario de la Encuesta de Situación Nutricional de Colombia, 2015. Se evaluaron en 1.234 embarazadas con edades entre 12 y 48 años: sus características sociodemográficas y antropométricas, la distribución de los niveles séricos y la prevalencia de déficit de ferritina. Para estimar la asociación entre las diferentes variables sociodemográficas y los niveles séricos, o la prevalencia de déficit de ferritina, se utilizaron modelos de regresión multivariables. Resultados: la prevalencia de deficiencia de ferritina fue de 44.5 % (IC 95 % 40.1 % a 49.0 %), los niveles séricos de ferritina oscilaron entre 4 µg/L y 295,7 µg/L, con un promedio de 29.3 µg/L (IC 95 % 26,5 µg/L-32.2 µg/L). Las gestantes del segundo (OR (OR 2.19 IC 95 % 1.50 a 3.19) y tercer trimestre (OR 3.84 IC 95 % 2.68 a 5.50), aquellas que residen en la región Atlántica (OR 2.18 IC 95 % 1.25 a 3.82) y en la región Orinoquia (OR 2.41 IC 95 %1.19 a 4.88), mostraron asociación con el déficit de ferritina. Conclusión: se halló alta prevalencia en el déficit de ferritina en gestantes colombianas.


Introduction: Ferritin is important in the storage of intracellular iron, in a non-toxic soluble form. Its levels during pregnancy are related to the health of the mother and her offspring. Objective: To describe the serum ferritin levels and the prevalence of ferritin deficiency, and the associated sociodemographic factors in pregnant women in Colombia. Methodology: Cross-sectional study; secondary analysis of the Nutritional Situation Survey of Colombia, 2015. The following were evaluated in 1,234 pregnant women aged between 12 and 48 years: their sociodemographic and anthropometric characteristics, the distribution of serum levels, and the prevalence of ferritin deficiency. To estimate the association between the different sociodemographic variables and serum levels, or the prevalence of ferritin deficiency, multivariate regression models were used. Results: The prevalence of ferritin deficiency was 44.5% (95% CI 40.1% to 49.0%), serum ferritin levels ranged from 4 µg/L to 295.7 µg/L, with a average of 29.3 µg/L (95% CI 26.5 µg/L - 32.2 µg/L). Pregnant women in the second (OR (OR 2.19 95% CI 1.50 to 3.19) and third trimester (OR 3.84 95% CI 2.68 to 5.50), those residing in the Atlantic region ( OR 2.18 95% CI 1.25 to 3.82) and in the Orinoquia region (OR 2.41 95% CI 1.19 to 4.88), showed an association with ferritin deficiency. Conclusion: A high prevalence of ferritin deficiency was found in Colombian pregnant women.


Assuntos
Humanos , Feminino , Gravidez
9.
Mol Biol Rep ; 51(1): 237, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38285273

RESUMO

BACKGROUND: The purpose of this study was to investigate the relationship between biofilm-forming microorganisms (BFM) and DEFB1 gene variants on ß-defensin levels in patients with periprosthetic joint infection (PJI) of Mexican origin. METHODS AND RESULTS: One hundred and five clinical aspirates were obtained from patients with suspected PJI. After microbiologic culture, samples were classified as non-septic and septic; of the latter, only those positive for Staphylococcus aureus and Pseudomonas aeruginosa were selected. ß-Defensin levels were quantified by ELISA, DNA was extracted from total leukocytes of the samples, and - 20G > A (rs11362) and - 44 C > G (rs1800972) variants were genotyped using TaqMan probes. Forty-one clinical aspirates were non-septic, 18 were positive for S. aureus and 18 were positive for P. aeruginosa. It was observed that ß-defensin levels were higher in the P. aeruginosa group compared to S. aureus group (2339.0 pg/mL IQR = 1809.2 vs. 1821.3 pg/mL IQR = 1536.4) and non-septic group (2339.0 pg/mL IQR = 1809.2 vs. 1099.7 pg/mL IQR = 1744.5, P < 0.001). The CG genotype of the rs1800972 variant was associated with higher ß-defensin levels compared to the CC genotype for both P. aeruginosa and S. aureus (1905.8 vs. 421.7 pg/mL, P = 0.004; and 1878.2 vs. 256.4 pg/mL, P = 0.006, respectively). CONCLUSIONS: Our results show that ß-defensin levels are significantly elevated in patients with BFM-associated PJI compared to those without infection. Furthermore, carriers of the CG genotype of the rs1800972 variant have an increased risk of PJI. Further research is needed to replicate these findings in a larger population.


Assuntos
Infecções Relacionadas à Prótese , Infecções por Pseudomonas , Infecções Estafilocócicas , beta-Defensinas , Humanos , beta-Defensinas/genética , Biofilmes , Infecções Relacionadas à Prótese/genética , Pseudomonas aeruginosa , Infecções por Pseudomonas/genética , Infecções Estafilocócicas/genética , Staphylococcus aureus
10.
Immunol Res ; 72(1): 119-127, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37665559

RESUMO

Ankylosing spondylitis (AS) is an autoinflammatory disease that affects the sacroiliac joints, causing stiffness and pain in the back. MICA is a ligand of the NKG2D receptor, and an increase in its expression affects the immune response in various diseases. NLRP3 is a multiprotein complex that promotes the release of IL-1ß, but its role in AS has been minimally explored. The objective of this study was to analyze the association and interaction of polymorphic variants of the MICA and NLRP3 genes in patients with AS. In this case-control study, patients with AS were included and compared with healthy controls of Mexican origin. The polymorphisms rs4349859 and rs116488202 of MICA and rs3806268 and rs10754558 of NLRP3 were genotyped using TaqMan probes. Associations were determined using logistic regression models, while interactions were analyzed by the multifactorial dimensionality reduction (MDR) method. A P value < 0.05 was considered statistically significant. The minor allele of rs4349859 (A) and rs116488202 (T) of MICA polymorphisms showed risk associations with AS (OR = 9.22, 95% CI = 4.26-20.0, P < 0.001; OR = 9.36, 95% CI = 4.17-21.0, P < 0.001), while the minor allele of the rs3806268 (A) polymorphism of NLRP3 was associated with protection (OR = 0.55, 95% CI = 0.33-0.91, P = 0.019). MDR analysis revealed synergistic interactions between the MICA and NLRP3 polymorphisms (P = 0.012). In addition, high- and low-risk genotypes were identified among these variants. The study findings suggest that the MICA rs4349859 A allele and rs116488202 T allele are associated with AS risk. An interaction between MICA and NLRP3 was observed which could increase the genetic risk in AS.


Assuntos
Espondilite Anquilosante , Humanos , Espondilite Anquilosante/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Genótipo
11.
Ortop Traumatol Rehabil ; 25(3): 143-147, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38078350

RESUMO

BACKGROUND: We aim to compare the preoperative planning radiographs of 50 patients in whom both a short stem and its homonymous standard version were programmed, focusing on the preservation of the neck and the invasion of the femoral shaft. The secondary objective was to evaluate the 50 preoperative radiographs with the 50 postoperative radiographs in which the short stem was implanted, measuring the real invasion of the diaphysis and the real preservation of the femoral neck. MATERIAL AND METHODS: We measured cut level at the femoral neck and diaphyseal invasion in 50 preoperative x-rays where an Alteon Neck Preserving Stem (ANPS) was templated and we compared it with 50 preoperative x-rays where an Alteon Taper Wedge Stem (ATWS) was templated. After surgery, we compared both parameters previously measured in the preoperative x-rays with the 50 postoperative radiographs where the short stem was implanted obtaining the real bone preservation at the femoral neck and the real diaphyseal invasion length. RESULTS: For templating comparison, mean bone preservation at the femoral neck was 14.87mm (SD 3.64) for the ANPS group and 9.94mm (SD 8.39) for the ATWS group (p <0.001). The mean diaphyseal bone invasion was 47.21mm (SD 5.89) and 76.77mm (SD 8.39) for ANPS and ATWS respectively (p <0.001). After surgery, the mean postoperative bone preservation at the femoral neck was 15.08mm (SD 3.1) with a mean of 0.17mm (SD 0.51) more preservation in the preoperative group. CONCLUSION: 1. ANPS allow bone preservation with limited diaphyseal invasion when compared with his homonymous ATWS in the preoperative templates. 2. ANPS showed a good correlation between preoperative radiographs and real bone preservation of the femoral neck and invasion of the femoral shaft.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/cirurgia , Diáfises/diagnóstico por imagem , Diáfises/cirurgia , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Estudos Retrospectivos
12.
Int J Mol Sci ; 24(23)2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38069104

RESUMO

CagY is the largest and most complex protein from Helicobacter pylori's (Hp) type IV secretion system (T4SS), playing a critical role in the modulation of gastric inflammation and risk for gastric cancer. CagY spans from the inner to the outer membrane, forming a channel through which Hp molecules are injected into human gastric cells. Yet, a tridimensional structure has been reported for only short segments of the protein. This intricate protein was modeled using different approaches, including homology modeling, ab initio, and deep learning techniques. The challengingly long middle repeat region (MRR) was modeled using deep learning and optimized using equilibrium molecular dynamics. The previously modeled segments were assembled into a 1595 aa chain and a 14-chain CagY multimer structure was assembled by structural alignment. The final structure correlated with published structures and allowed to show how the multimer may form the T4SS channel through which CagA and other molecules are translocated to gastric cells. The model confirmed that MRR, the most polymorphic and complex region of CagY, presents numerous cysteine residues forming disulfide bonds that stabilize the protein and suggest this domain may function as a contractile region playing an essential role in the modulating activity of CagY on tissue inflammation.


Assuntos
Gastrite , Infecções por Helicobacter , Helicobacter pylori , Humanos , Proteínas de Bactérias/metabolismo , Helicobacter pylori/metabolismo , Antígenos de Bactérias/metabolismo , Inflamação
13.
Intern Med J ; 53(12): 2346-2349, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38130050

RESUMO

This cost analysis, from a societal perspective, compared the cost difference of a networked teletrial model (NTTM) with four regional hubs versus conventional trial operation at a single metropolitan specialist centre. The Australian phase 3 cancer interventional randomised controlled trial included 152 of 328 regional participants (patient enrolment 2018-2021; 6-month primary end point). The NTTM significantly reduced (AU$2155 per patient) patient travel cost and time and lost productivity.


Assuntos
Neoplasias , Telemedicina , Humanos , Austrália/epidemiologia , Análise Custo-Benefício , Custos e Análise de Custo , Oncologia , Neoplasias/epidemiologia , Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase III como Assunto
14.
Exp Biol Med (Maywood) ; 248(20): 1754-1767, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37916410

RESUMO

Even though smoking has been scarcely studied in osteoarthritis (OA) etiology, it is considered a controversial risk factor for the disease. Exposure to tobacco smoke has been reported to promote oxidative stress (OS) as part of the damage mechanism. The aim of this study was to assess whether smoking increases cartilage damage through the generation of OS. Peripheral blood (PB) and synovial fluid (SF) samples from patients with OA were analyzed. The samples were stratified according to smoking habit, Kellgren-Lawrence score, pain, and cotinine concentrations in PB. Malondialdehyde (MDA), methylglyoxal (MGO), advanced protein oxidation products (APOPs), and myeloperoxidase (MPO) were assessed; the activity of antioxidant enzymes such as gamma-glutamyl transferase (GGT), glutathione S-transferase (GST) and catalase (CAT), as well as the activity of arginase, which favors the destruction of cartilage, was determined. When stratified by age, for individuals <60 years, the levels of MDA and APOPs and the activity of MPO and GST were higher, as well as antioxidant system activity in the smoking group (OA-S). A greater degree of pain in the OA-S group increased the concentrations of APOPs and arginase activity (P < 0.01 and P < 0.05, respectively). Arginase activity increased significantly with a higher degree of pain (P < 0.01). Active smoking can be an important risk factor for the development of OA by inducing systemic OS in young adults, in addition to reducing antioxidant enzymes in older adults and enhancing the degree of pain and loss of cartilage.


Assuntos
Osteoartrite do Joelho , Adulto Jovem , Humanos , Idoso , Pessoa de Meia-Idade , Osteoartrite do Joelho/metabolismo , Antioxidantes/metabolismo , Fumar/efeitos adversos , Arginase/metabolismo , Oxirredução , Dor
15.
J Pers Med ; 13(11)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38003920

RESUMO

Compared with conventional colposcopy, colposcopy assisted by DSI-map increases the detection of HSIL/CIN2+ and might help to identify the lesions more likely to regress. INTRODUCTION: Comparison of the performance of colposcopy assisted by dynamic spectral imaging (C-DSI) with that of conventional colposcopy (CC) in the diagnosis of cervical intraepithelial neoplasia (HSIL/CIN2 or CIN3). MATERIALS AND METHODS: A total of 1655 women were referred for colposcopy between 2012 and 2020 and included in the study. Of that total, 973 were examined by the same colposcopist with C-DSI, and 682 with CC. Comparisons between CC and C-DSI were made by using the histological diagnosis performed with a punch biopsy or loop electrosurgical excision procedure (LEEP) as the gold standard. A follow-up study was conducted until 2021 to detect progression to HSIL/CIN2 at 6, 12 and 24 months after first examination. RESULTS: C-DSI provided higher sensitivity for the diagnosis of HSIL/CIN2 or CIN 3 than CC (sensitivity of 76.8% and 86.6% vs. 54.2% and 72.2%, respectively). In negative or ASCUS/LSIL Pap smear results, C-DSI showed higher sensitivity than CC (sensitivity of 66.7% and 61.5% vs. 21.4% and 33.3%, respectively). In contrast, these differences were not observed in high-grade Pap smears. The sensitivity of C-DSI in cases with HPV16/18 infection was stronger than that of CC (73.53% vs. 56.67%). The sensitivity of C-DSI to detect the progression to HSIL/CIN2+ during follow-up was 30, 17.6 and 35.7% at 6, 12 and 24 months, respectively. CONCLUSIONS: The present study shows that C-DSI in women referred for colposcopy increases the HSIL/CIN 2-3 detection rate compared to conventional colposcopy. Nevertheless, C-DSI does not seem to be an important tool to predict the evolution of the lesions during follow-up.

16.
Biochem Biophys Rep ; 36: 101556, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37854941

RESUMO

The membrane flickering of human fetal red blood cells (RBCs) affected by gestational diabetes mellitus (GDM) was studied with dual time resolved membrane fluctuation spectroscopy (D-TRMFS). This new technique is a modified version of the dual optical tweezers method that has been adapted to measure the mechanical properties of RBCs at two distant membrane points simultaneously. The micro-rheological parameters were obtained from direct membrane flickering measurements, followed by Fourier decomposition and cell membrane model adjustment. Our results show a significant decrease of 6.01 ± 1.19 nm in membrane fluctuations amplitude in healthy fetal, compared with healthy adult RBCs, meanwhile the amplitude in GDM cells increased 3.22 ± 1.10 nm compared with healthy fetal RBCs. Between GDM and healthy fetal RBCs, there are significant differences, especially in the bending modulus. Considering the mean of the two membrane points measured, the tension for GDM RBCs increased by 6.431 ± 3.57 (10-7 [N/m]) compared with healthy fetal RBCs, meanwhile, the bending was increased by 2.483 ± 0.58 (10-19 [J]) in GDM compared with healthy fetal RBCs. These results showed significant increment of 1.23 ± 0.07-fold and 3.29 ± 0.36-fold in tension and bending modulus in GDM, respectively. The strong impact of GDM on bending modulus could be associated with oxidative stress and lipid peroxidation, previously reported in fetal plasma of GDM cases.

17.
J Geriatr Oncol ; 14(8): 101621, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37683368

RESUMO

INTRODUCTION: Prostate cancer (PC) is the second commonest malignancy and fifth leading cause of cancer death in men worldwide. Older men are more likely to develop PC but are underrepresented in pivotal clinical trials, leading to challenges in treatment selection in the real-world setting. We aimed to examine treatment patterns and outcomes in older Australians with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: We identified 753 men with mCRPC within the electronic CRPC Australian Database (ePAD). Clinical data were analysed retrospectively to assess outcomes including time to treatment failure (TTF), overall survival (OS), PSA doubling time (PSADT), PSA50 response rate, and pre-defined adverse events of special interest (AESIs). Descriptive statistics were used to report baseline characteristics, stratified by age groups (<75y, 75-85y and >85y). Groups were compared using Kruskal-Wallis and Chi-square analyses. Time-to-event analyses were performed using Kaplan-Meier methods and compared through log-rank tests. Cox proportional hazards univariate and multivariate analyses were performed to evaluate the influence of variables on OS. RESULTS: Fifty-seven percent of men were aged <75y, 31% 75-85y, and 12% >85y. Patients ≥75y more frequently received only one line of systemic therapy (40% of <75y vs 66% 75-85y vs 68% >85y; P < 0.01). With increasing age, patients were more likely to receive androgen receptor signalling inhibitors (ARSIs) as initial therapy (42% of <75y vs 70% of 75-85y vs 84% of >85y; p < 0.01). PSA50 response rates or TTF did not significantly differ between age groups for chemotherapy or ARSIs. Patients >85y receiving enzalutamide had poorer OS but this was not an independent prognostic variable on multivariate analysis (hazard ratio [HR] 0.93(0.09-9.35); p = 0.95). PSADT >3 months was an independent positive prognostic factor for patients receiving any systemic therapy. Older patients who received docetaxel were more likely to experience AESIs (18% in <75y vs 37% 75-85y vs 33% >85y, p = 0.038) and to stop treatment as a result (21% in <75y vs 39% in 75-85y; p = 0.011). DISCUSSION: In our mCRPC cohort, older men received fewer lines of systemic therapy and were more likely to cease docetaxel due to adverse events. However, treatment outcomes were similar in most subgroups, highlighting the importance of individualised assessment regardless of age.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Idoso , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Docetaxel/uso terapêutico , Estudos Retrospectivos , Antígeno Prostático Específico , Austrália/epidemiologia , Resultado do Tratamento
18.
Sensors (Basel) ; 23(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37687799

RESUMO

All-sky cameras capture a panoramic view of the full sky from horizon to horizon to generate a wide-angle image of the observable sky. State-of-the-art all-sky imagers are limited to imaging in the visible and infrared spectrum and cannot image in the UV spectrum. This article describes the development of an all-sky imaging system capable of capturing 130° wide-angle sky images from horizon to horizon in the UV-AB spectrum. The design of the UV all-sky imaging system is based on low-cost, accessible, and scalable components to develop multiple images that can be deployed over a wider geographical area. The spectral response of the camera system has been validated in the UV spectrum (280-420 nm) using a monochromatic UV beam with an average power output of 22 nW. UV all-sky imaging systems complement existing infrared and visible all-sky cameras. They have wide applications in astronomy, meteorology, atmospheric science, vulcanology, meteors and auroral monitoring, and the defence sector.

19.
Sci Rep ; 13(1): 15277, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37714862

RESUMO

DNA is an incontrovertible biosignature whose sequencing aids in species identification, genome functionality, and evolutionary relationships. To study life within the rocks of Earth and Mars, we demonstrate, in an ISO5 clean room, a procedure based on nanopore technology that correctly identifies organisms at picogram levels of DNA without amplification. Our study with E. coli and S. cerevisiae DNA samples showed that MinION sequencer (Oxford Nanopore Technologies) can unequivocally detect and characterise microbes with as little as 2 pg of input with just 50 active nanopores. This result is an excellent advancement in sensitivity, immediately applicable to investigating low biomass samples. This value is also at the level of possible background contamination associated with the reagents and the environment. Cultivation of natural and heat-treated Martian analogue (MMS-2) regolith samples, exposed to atmospheric water vapour or in increasing water concentrations, led to the extraction of 600-1000 pg of DNA from 500 mg of soil. Applying the low detectability technology enabled through MinION sequencer for a natural low biomass setting, we characterised the dry MMS-2 and found few soil-related organisms and airborne contaminants. The picogram detection level and the procedure presented here, may be of interest for the future Mars sample Return program, and the life research and planetary protection studies that will be implemented through the sample safety assessment.


Assuntos
Marte , Escherichia coli/genética , Meio Ambiente Extraterreno , Saccharomyces cerevisiae/genética , Análise de Sequência de DNA , Solo
20.
JAMA Oncol ; 9(11): 1536-1545, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37733336

RESUMO

Importance: Thromboprophylaxis for individuals receiving systemic anticancer therapies has proven to be effective. Potential to maximize benefits relies on improved risk-directed strategies, but existing risk models underperform in cohorts with lung and gastrointestinal cancers. Objective: To assess clinical benefits and safety of biomarker-driven thromboprophylaxis and to externally validate a biomarker thrombosis risk assessment model for individuals with lung and gastrointestinal cancers. Design, Setting, and Participants: This open-label, phase 3 randomized clinical trial (Targeted Thromboprophylaxis in Ambulatory Patients Receiving Anticancer Therapies [TARGET-TP]) conducted from June 2018 to July 2021 (with 6-month primary follow-up) included adults aged 18 years or older commencing systemic anticancer therapies for lung or gastrointestinal cancers at 1 metropolitan and 4 regional hospitals in Australia. Thromboembolism risk assessment based on fibrinogen and d-dimer levels stratified individuals into low-risk (observation) and high-risk (randomized) cohorts. Interventions: High-risk patients were randomized 1:1 to receive enoxaparin, 40 mg, subcutaneously daily for 90 days (extending up to 180 days according to ongoing risk) or no thromboprophylaxis (control). Main Outcomes and Measures: The primary outcome was objectively confirmed thromboembolism at 180 days. Key secondary outcomes included bleeding, survival, and risk model validation. Results: Of 782 eligible adults, 328 (42%) were enrolled in the trial (median age, 65 years [range, 30-88 years]; 176 male [54%]). Of these participants, 201 (61%) had gastrointestinal cancer, 127 (39%) had lung cancer, and 132 (40%) had metastatic disease; 200 (61%) were high risk (100 in each group), and 128 (39%) were low risk. In the high-risk cohort, thromboembolism occurred in 8 individuals randomized to enoxaparin (8%) and 23 control individuals (23%) (hazard ratio [HR], 0.31; 95% CI, 0.15-0.70; P = .005; number needed to treat, 6.7). Thromboembolism occurred in 10 low-risk individuals (8%) (high-risk control vs low risk: HR, 3.33; 95% CI, 1.58-6.99; P = .002). Risk model sensitivity was 70%, and specificity was 61%. The rate of major bleeding was low, occurring in 1 participant randomized to enoxaparin (1%), 2 in the high-risk control group (2%), and 3 in the low-risk group (2%) (P = .88). Six-month mortality was 13% in the enoxaparin group vs 26% in the high-risk control group (HR, 0.48; 95% CI, 0.24-0.93; P = .03) and 7% in the low-risk group (vs high-risk control: HR, 4.71; 95% CI, 2.13-10.42; P < .001). Conclusions and Relevance: In this randomized clinical trial of individuals with lung and gastrointestinal cancers who were stratified by risk score according to thrombosis risk, risk-directed thromboprophylaxis reduced thromboembolism with a desirable number needed to treat, without safety concerns, and with reduced mortality. Individuals at low risk avoided unnecessary intervention. The findings suggest that biomarker-driven, risk-directed primary thromboprophylaxis is an appropriate approach in this population. Trial Registration: ANZCTR Identifier: ACTRN12618000811202.


Assuntos
Neoplasias Gastrointestinais , Trombose , Tromboembolia Venosa , Adulto , Humanos , Masculino , Idoso , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/induzido quimicamente , Hemorragia/induzido quimicamente , Trombose/tratamento farmacológico , Neoplasias Gastrointestinais/tratamento farmacológico , Pulmão , Biomarcadores
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