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1.
Fam Cancer ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733421

RESUMEN

Pancreatic cancer has a dismal prognosis in the general population. However, early detection and treatment of disease in high-risk individuals can improve survival, as patients with localized disease and especially patients with lesions smaller than 10 mm show greatly improved 5-year survival rates. To achieve early detection through MRI surveillance programs, optimization of imaging is required. Advances in MRI technologies in both hardware and software over the years have enabled reliable detection of pancreatic cancer at a small size and early stage. Standardization of dedicated imaging protocols for the pancreas are still lacking. In this review we discuss state of the art scan techniques, sequences, reduction of artifacts and imaging strategies that enable early detection of lesions. Furthermore, we present the imaging features of small pancreatic cancers from a large cohort of high-risk individuals. Refinement of MRI techniques, increased scan quality and the use of artificial intelligence may further improve early detection and the prognosis of pancreatic cancer in a screening setting.

2.
medRxiv ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38699297

RESUMEN

Mental health responses to the COVID-19 pandemic have been widely studied, but less is known about the potentially protective role of physical activity (PA) and the impact of low-grade inflammation. Using a sample of older adults from England, this study tested (1) if pre-pandemic PA and its changes during the pandemic were associated with mental health responses; (2) if older adults with low-grade inflammation experienced greater increases in depression and anxiety, compared to pre-pandemic levels; (3) if PA attenuated the association between inflammation and depression/anxiety. The study used data from the English Longitudinal Study of Ageing, a cohort study following a national sample aged 50+. Information on mental health and PA were collected before the pandemic (2016/17 and 2018/19) and during November and December 2020. Inflammation was ascertained using pre-pandemic C-reactive protein (CRP). Analyses were adjusted for sociodemographic and health-related factors and pre-pandemic mental health. Increasing PA from before to during the pandemic was linked to reduced odds of depression (OR = 0.955, 95%CI [0.937, 0.974]) and anxiety (OR = 0.954, 95%CI [0.927; 0.982]). Higher pre-pandemic PA was associated with reduced odds of depression (OR = 0.964, 95%CI [0.948, 0.981]) and anxiety (OR = 0.976, 95%CI [0.953, 1.000]), whereas elevated CRP was associated with 1.343 times higher odds of depression (95%CI [1.100, 1.641]). PA did not attenuate the inflammation-depression association. The findings suggest that PA may contribute to psychological resilience among older adults, independently of inflammation. Further research is needed to explore the psychobiological pathways underlying this protective mechanism.

3.
Microb Cell Fact ; 23(1): 110, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609906

RESUMEN

BACKGROUND: The wasabi receptor, also known as the Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel, is a potential target for development of repellents for insects, like the pine weevil (Hylobius abietis) feeding on conifer seedlings and causing damage in forestry. Heterologous expression of TRPA1 from pine weevil in the yeast Pichia pastoris can potentially provide protein for structural and functional studies. Here we take advantage of the Green Fluorescent Protein (GFP) tag to examine the various steps of heterologous expression, to get more insight in clone selection, expression and isolation of the intact purified protein. RESULTS: The sequence of HaTRPA1 is reported and GFP-tagged constructs were made of the full-length protein and a truncated version (Δ1-708 HaTRPA1), lacking the N-terminal ankyrin repeat domain. Clones were screened on GFP expression plates, induced in small liquid cultures and in fed-batch cultures, and evaluated by flow cytometry and fluorescence microscopy. The screening on plates successfully identifies low-expression clones, but fails to predict the ranking of the best performing clones in small-scale liquid cultures. The two constructs differ in their cellular localization. Δ1-708 HaTRPA1 is found in a ring at the perimeter of cell, whereas HaTRPA1 is forming highly fluorescent speckles in interior regions of the cell. The pattern is consistent in different clones of the same construct and persists in fed-batch culture. The expression of Δ1-708 HaTRPA1 decreases the viability more than HaTRPA1, and in fed-batch culture it is clear that intact cells first express Δ1-708 HaTRPA1 and then become damaged. Purifications show that both constructs suffer from degradation of the expressed protein, but especially the HaTRPA1 construct. CONCLUSIONS: The GFP tag makes it possible to follow expression by flow cytometry and fluorescence microscopy. Analyses of localization, cell viability and expression show that the former two parameters are specific for each of the two evaluated constructs, whereas the relative expression of the constructs varies with the cultivation method. High expression is not all that matters, so taking damaged cells into account, something that may be linked to protein degradation, is important when picking the most suitable construct, clone, and expression scheme.


Asunto(s)
Saccharomycetales , Gorgojos , Animales , Proteínas Fluorescentes Verdes/genética , Citometría de Flujo
4.
Brain Spine ; 4: 102816, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38666069

RESUMEN

Introduction: Imposter syndrome (IS), characterized by persistent doubts about one's abilities and fear of exposure as a fraud, is a prevalent psychological condition, particularly impacting physicians. In neurosurgery, known for its competitiveness and demands, the prevalence of IS remains high. Research question: Recognizing the limited literature on IS within the neurosurgical community, this European survey aimed to determine its prevalence among young neurosurgeons and identify associated factors. Material and methods: The survey, conducted by the Young Neurosurgeon Committee of the European Association of Neurosurgical Societies, gathered responses from 232 participants. The survey included demographics, the Clance Imposter Phenomenon Survey (CIPS), and an analysis of potential compensatory mechanisms. Results: Nearly 94% of respondents exhibited signs of IS, with the majority experiencing moderate (36.21%) or frequent (40.52%) symptoms. Analyses revealed associations between IS and factors such as level of experience, sex, and board-certification. Discussion and conclusion: The findings suggest a significant prevalence of IS among young neurosurgeons, with notable associations with sex and level of experience. Compensatory mechanisms, such as working hours, article reading, and participation in events, did not show significant correlations with IS. Notably, male sex emerged as an independent protective factor against frequent/intense IS, while reading more than five articles per week was identified as a risk factor. The identification of protective and risk factors, particularly the influence of gender and reading habits, contributes valuable insights for developing targeted interventions to mitigate IS and improve the well-being of neurosurgeons.

5.
J Neurosurg Sci ; 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38619188

RESUMEN

BACKGROUND: Robotic assistance in spine surgery is emerging as an accurate, effective and enabling technology utilized in the treatment of patients with surgical spinal pathology. The safety and reproducibility of robotic assistance in the placement of pedicle screw instrumentation is still being investigated. The objective of this study was to present our experience of instrumented spinal fusion utilizing an intraoperative robotic guidance system. METHODS: We retrospectively reviewed all cases of spinal instrumentation of the thoracic and lumbo-sacral spine using the Mazor X robotic system (Medtronic Inc, Minneapolis, MN, USA), performed at our institution by one surgeon between July 2017 and June 2020. Wilcoxon Rank test was used to compare time taken to place each screw during the first 20 cases and the cases thereafter. RESULTS: A total of 28 patients were included. A total of 159 screws were placed using the Mazor X robotic system. The overall mean time for screw placement was 7.8±2.3 minutes and there was a significant reduction in the mean time for screw placement after the 20th case or 120 screws (8.70 vs. 5.42 min, P=0.008). No postoperative neurologic deficit or new radiculopathy was noted to occur secondary to hardware placement. No revision surgery was required for replacement or removal of a mispositioned screw. CONCLUSIONS: From this single-center, single-surgeon series we conclude that robot-assisted spine surgery can be safely and efficiently integrated into the operating room workflow, which improves after a learning curve of approximately 20 operative interventions. We found robot-assisted spinal instrumentation to be reliable, safe, effective and highly precise.

6.
Fam Cancer ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38619782

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths and is associated with a poor prognosis. The majority of these cancers are detected at a late stage, contributing to the bad prognosis. This underscores the need for novel, enhanced early detection strategies to improve the outcomes. While population-based screening is not recommended due to the relatively low incidence of PDAC, surveillance is recommended for individuals at high risk for PDAC due to their increased incidence of the disease. However, the outcomes of pancreatic cancer surveillance in high-risk individuals are not sorted out yet. In this review, we will address the identification of individuals at high risk for PDAC, discuss the objectives and targets of surveillance, outline how surveillance programs are organized, summarize the outcomes of high-risk individuals undergoing pancreatic cancer surveillance, and conclude with a future perspective on pancreatic cancer surveillance and novel developments.

7.
LGBT Health ; 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38557157

RESUMEN

Fertility preservation is the process of collecting and storing oocytes, sperm, or reproductive tissue so that a person may retain their ability to have biologically related children. In instances of infertility caused by medical intervention or an underlying medical condition, this procedure is often sought by affected patient populations. U.S. Title 21 regulations have produced disparities in access, disproportionately restricting services for sexually and gender diverse subpopulations capable of producing sperm. This article examines policies contributing to these disparities, explores how these policies may translate to real-world health care delivery, and proposes policy changes that would increase equitable access to care.

8.
Pancreas ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38598368

RESUMEN

OBJECTIVES: The study aimed to investigate the added value of blood glucose monitoring in high-risk individuals (HRIs) participating in pancreatic cancer surveillance. METHODS: HRIs with a CDKN2A/p16 germline pathogenic variant (PV) participating in pancreatic cancer surveillance were included in this study. Multivariable logistic regression was performed to assess the relationship between new-onset diabetes (NOD) and pancreatic ductal adenocarcinoma (PDAC). To quantify the diagnostic performance of NOD as a marker for PDAC, receiver operating characteristic curve with area under the curve (AUC) was computed. RESULTS: In total, 220 HRIs were included between 2000-2019. Median age was 61 (IQR 53-71) years and 62.7% of participants were female. During the study period, 26 (11.8%) HRIs developed NOD, of whom 5 (19.2%) later developed PDAC. The other 23 (82.1%) PDAC cases remained NOD-free. Multivariable analysis showed no statistically significant relationship between NOD and PDAC (OR 1.21; 95% CI, 0.39-3.78) and four out of five PDAC cases appeared to have NOD within three months before diagnosis. Furthermore, NOD did not differentiate between HRIs with- and without PDAC (AUC 0.54; 95% CI, 0.46-0.61). CONCLUSIONS: In this study we found no added value for longitudinal glucose monitoring in CDKN2A PV carriers participating in an imaging-based pancreatic cancer surveillance program.

9.
Brain Spine ; 4: 102765, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38510593

RESUMEN

Introduction: Artificial intelligence (AI) based large language models (LLM) contain enormous potential in education and training. Recent publications demonstrated that they are able to outperform participants in written medical exams. Research question: We aimed to explore the accuracy of AI in the written part of the EANS board exam. Material and methods: Eighty-six representative single best answer (SBA) questions, included at least ten times in prior EANS board exams, were selected by the current EANS board exam committee. The questions' content was classified as 75 text-based (TB) and 11 image-based (IB) and their structure as 50 interpretation-weighted, 30 theory-based and 6 true-or-false. Questions were tested with Chat GPT 3.5, Bing and Bard. The AI and participant results were statistically analyzed through ANOVA tests with Stata SE 15 (StataCorp, College Station, TX). P-values of <0.05 were considered as statistically significant. Results: The Bard LLM achieved the highest accuracy with 62% correct questions overall and 69% excluding IB, outperforming human exam participants 59% (p = 0.67) and 59% (p = 0.42), respectively. All LLMs scored highest in theory-based questions, excluding IB questions (Chat-GPT: 79%; Bing: 83%; Bard: 86%) and significantly better than the human exam participants (60%; p = 0.03). AI could not answer any IB question correctly. Discussion and conclusion: AI passed the written EANS board exam based on representative SBA questions and achieved results close to or even better than the human exam participants. Our results raise several ethical and practical implications, which may impact the current concept for the written EANS board exam.

10.
J Fungi (Basel) ; 10(3)2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38535207

RESUMEN

Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to Pneumocystis and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for Pneumocystis pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a CARMIL2 nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory Bordetella pneumonia (n = 1). CARMIL2 encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious CARMIL2 variants have recently been reported in human patients with PCP and other recurrent pneumonias. In addition to opportunistic respiratory infection, the affected dogs also exhibited other clinical manifestations of CARMIL2 deficiencies that have been reported in humans, including early-onset gastrointestinal disease, allergic skin disease, mucocutaneous lesions, abscesses, autoimmune disorders, and gastrointestinal parasitism. This discovery highlights the potential utility of a natural canine model in identifying and studying primary immunodeficiencies in patients affected by PCP.

11.
Artículo en Alemán | MEDLINE | ID: mdl-38519358

RESUMEN

BACKGROUND/AIM: Evidence-based practice (EBP) provides an important basis for improving both the quality of care and patient safety. Formulating a research question, searching the literature, and critical appraisal are crucial to developing evidence-based practice. The aim of this survey was to provide an overview of how these topics are integrated into bachelor's degree programs in nursing in Austria, Germany, and the German-speaking part of Switzerland. We also aimed to show how teachers implement these subjects and how they experience and assess the implementation. METHOD: We conducted an exploratory cross-sectional study using an online survey sent out to program directors and teaching staff of all 58 bachelor's degree programs in nursing in Austria, Germany and the German-speaking part of Switzerland. For data collection, a questionnaire was developed containing items on general teaching conditions, contents, and methods of evidence-based nursing practice, as well as on the estimated thematic interest of students. The data were analysed descriptively. RESULTS: The program directors returned 24 questionnaires (41%). Of 75 questionnaires forwarded to the faculty, 17 (23%) were received from nine programs. On average, 5.6 teaching units (SD 2.6) are used for formulating a research question, 10 teaching units (SD 4.1) for literature review, and 11.3 teaching units (SD 6.9) for critical appraisal. Half of the teaching staff indicated that linkages between education and nursing care practice have been established. The traditional teaching method of frontal teaching is used predominantly. Student interest in topics was rated as moderate by most teachers. CONCLUSIONS: Topics on evidence-based practice are an integral part of bachelor's degree programs in nursing in German-speaking countries. An increase in teaching units, active learning methods and the growing interconnection between education and practice could improve the acquisition of competencies and attitudes of students regarding EBP and further advance its implementation in practice.

12.
JDS Commun ; 5(2): 172-177, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38482119

RESUMEN

Bacterial endospores, or simply spores, are formed by a diverse group of members within the phylum Bacillota and include notable genera such as Bacillus, Paenibacillus, and Clostridium. Spores are distributed ubiquitously in natural environments, with soil being an important primary reservoir for these microbes. As such, spores are present throughout the dairy farm environment, and transmission into raw milk occurs through several pathways that coalesce at the point of milk harvest. Despite the very low spore concentrations typically found in bulk tank raw milk, the impact of spores on dairy product quality, safety, and product conformance is widely documented. Processed dairy products affected by the presence of sporeforming bacteria include milk, cheese, dairy powders, ice cream mix, and more. Although raw milk is a major source of spores leading to quality, safety, and conformance issues in dairy products, the impact of other sources should not be discounted and may include ingredients (e.g., cocoa powder), contamination originating from biofilms in processing equipment, and even cross-contamination from the processing environment itself. Addressing spore contamination in the dairy system is complicated by this widespread distribution and by the diversity of these organisms, and successful source tracking often requires discriminatory molecular subtyping tools. Here, we review the key sources of sporeforming bacteria in the dairy system, the factors leading to the transmission of this diverse group of microbes into processed dairy products, and methods employed to enumerate and track spore contaminants.

13.
Artículo en Inglés | MEDLINE | ID: mdl-38481365

RESUMEN

BACKGROUND: Intradermal testing (IDT) with iodinated contrast media (ICMs) is an established diagnostic tool in patients with ICM hypersensitivity. Currently, it is unclear which test concentration is the more useful one, up to pure or up to 1:10 diluted ICMs. METHODS: We searched the literature database PubMed for eligible papers dealing with ICM allergy and their IDT results. We analyzed the data presented by the papers and compared the pooled groups tested with diluted and undiluted ICMs. RESULTS: We identified 29 eligible original papers, and extracted data of 1137 patients that formed the study population. Although in the cohort tested with diluted ICMs the number of tested ICMs was greater, the percentage of positive tests was significantly less (9.0% vs. 24.7%; P < 0.0001; OR 0.30 [0.26-0.34]). The frequency of positive tested culprit ICMs was also lesser in the group tested with diluted ICMs (31.0% vs. 72.5%; P < 0.0001; OR 0.17 [0.12-0.23]). The number of drug provocation tests (DPTs) was greater in patients with diluted IDTs (374 vs. 89; P < 0.0001; OR 2.54 [1.93-3.36]). We detected an increased sensitivity in patients with undiluted tests (0.774 vs. 0.282) and a nearly identical specificity in both groups (1 vs. 0.983). CONCLUSIONS: For the first time, we show that IDT up to pure ICM concentrations is superior to using diluted ICMs only. Possibly, we can reduce the number of DPTs when performing IDTs with pure ICMs. In the undiluted group, there were no hints for skin irritations or unspecific test reactions.

14.
J Org Chem ; 89(7): 4261-4282, 2024 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-38508870

RESUMEN

Small molecule therapeutics represent the majority of the FDA-approved drugs. Yet, many attractive targets are poorly tractable by small molecules, generating a need for new therapeutic modalities. Due to their biocompatibility profile and structural versatility, peptide-based therapeutics are a possible solution. Additionally, in the past two decades, advances in peptide design, delivery, formulation, and devices have occurred, making therapeutic peptides an attractive modality. However, peptide manufacturing is often limited to solid-phase peptide synthesis (SPPS), liquid phase peptide synthesis (LPPS), and to a lesser extent hybrid SPPS/LPPS, with SPPS emerging as a predominant platform technology for peptide synthesis. SPPS involves the use of excess solvents and reagents which negatively impact the environment, thus highlighting the need for newer technologies to reduce the environmental footprint. Herein, fourteen American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable (ACS GCIPR) member companies with peptide-based therapeutics in their portfolio have compiled Process Mass Intensity (PMI) metrics to help inform the sustainability efforts in peptide synthesis. This includes PMI assessment on 40 synthetic peptide processes at various development stages in pharma, classified according to the development phase. This is the most comprehensive assessment of synthetic peptide environmental metrics to date. The synthetic peptide manufacturing process was divided into stages (synthesis, purification, isolation) to determine their respective PMI. On average, solid-phase peptide synthesis (SPPS) (PMI ≈ 13,000) does not compare favorably with other modalities such as small molecules (PMI median 168-308) and biopharmaceuticals (PMI ≈ 8300). Thus, the high PMI for peptide synthesis warrants more environmentally friendly processes in peptide manufacturing.


Asunto(s)
Péptidos , Técnicas de Síntesis en Fase Sólida , Péptidos/química , Técnicas de Química Sintética , Solventes
15.
Curr Biol ; 34(6): 1364-1369.e2, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38490201

RESUMEN

Though common among humans, social play by adults is an uncommon occurrence in most animals, even between parents and offspring.1,2,3 The most common explanation for why adult play is so rare is that its function and benefits are largely limited to development, so that social play has little value later in life.3,4,5,6 Here, we draw from 10 years of behavioral data collected by the Kibale Chimpanzee Project to consider an alternative hypothesis: that despite its benefits, adult play in non-humans is ecologically constrained by energy shortage or time limitations. We further hypothesized that, since they may be the only available partners for their young offspring, mother chimpanzees pay greater costs of play than other adults. Our analysis of nearly 4,000 adult play bouts revealed that adult chimpanzees played both among themselves and with immature partners. Social play was infrequent when diet quality was low but increased with the proportion of high-quality fruits in the diet. This suggests that adults engage in play facultatively when they have more energy and/or time to do so. However, when diet quality was low and most adult play fell to near zero, play persisted between mothers and offspring. Increased use of play by adult chimpanzees during periods of resource abundance suggests that play retains value as a social currency beyond development but that its costs constrain its use. At the same time, when ecological conditions constrain opportunities for young to play, play by mothers fills a critical role to promote healthy offspring development.


Asunto(s)
Hominidae , Pan troglodytes , Animales , Femenino , Humanos , Dieta , Conducta Animal , Madres , Conducta Social
16.
J Infect ; 88(5): 106145, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552719

RESUMEN

OBJECTIVES: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes. METHODS: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology. RESULTS: The cohort included 3002 children (median age 2·4 months); 1101/3002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <6 months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age 6 months to 9 years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis. CONCLUSIONS: Bacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis. FUNDING: This study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research.


Asunto(s)
Meningitis Bacterianas , Meningitis Viral , Vacunas Conjugadas , Humanos , Niño , Lactante , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Bacterianas/microbiología , Preescolar , Adolescente , Femenino , Masculino , Estudios Prospectivos , Meningitis Viral/diagnóstico , Meningitis Viral/líquido cefalorraquídeo , Reglas de Decisión Clínica , Reino Unido/epidemiología , Neisseria meningitidis/aislamiento & purificación , Streptococcus pneumoniae/aislamiento & purificación , Técnicas de Apoyo para la Decisión
17.
Eur J Clin Invest ; 54(6): e14185, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38426563

RESUMEN

BACKGROUND: Osteosarcoma (OS) is a primary bone malignancy that mostly affects young people, characterized by high metastatic potential, and a marked chemoresistance that is responsible for disease relapse in most patients. Therefore, it is necessary to identify novel molecules to setup targeted strategies to improve the clinical outcome. The enzyme nicotinamide N-methyltransferase (NNMT) catalyses the N-methylation of nicotinamide and other analogs, playing a crucial role in the biotransformation of drugs and xenobiotics. NNMT overexpression was reported in a wide variety of cancers, and several studies demonstrated that is able to promote cell proliferation, migration and resistance to chemotherapy. The aim of this study was to explore the potential involvement of NNMT in OS. METHODS: Immunohistochemical analyses have been performed to evaluate NNMT expression in selected OS and healthy bone tissue samples. Subsequently, OS cell lines have been transfected with vectors targeting NNMT mRNA (shRNAs) and the impact of this downregulation on migration, cell proliferation, and response to chemotherapeutic treatment was also analysed by wound healing, MTT, SRB and Trypan blue assays, respectively. RESULTS: Results showed that OS samples display a significantly higher NNMT expression compared with healthy tissue. Preliminary results suggest that NNMT silencing in OS cell lines is associated to a decrease of cell proliferation and migration, as well as to enhanced sensitivity to chemotherapy. Data obtained showed that NNMT may represent an interesting marker for OS detection and a promising target for effective anti-cancer therapy.


Asunto(s)
Neoplasias Óseas , Movimiento Celular , Proliferación Celular , Nicotinamida N-Metiltransferasa , Osteosarcoma , Nicotinamida N-Metiltransferasa/metabolismo , Nicotinamida N-Metiltransferasa/genética , Humanos , Osteosarcoma/genética , Osteosarcoma/patología , Osteosarcoma/metabolismo , Osteosarcoma/tratamiento farmacológico , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/tratamiento farmacológico , Línea Celular Tumoral , Masculino , Femenino , Adulto , Adolescente , ARN Interferente Pequeño/genética , Adulto Joven , Resistencia a Antineoplásicos/genética , Niño
18.
PLoS One ; 19(2): e0292765, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38408074

RESUMEN

BACKGROUND: The home-based vaccination card is an important health record for determining vaccination status of children during surveys, particularly in low- and middle-income countries. However, there are limited evidence on the factors that influence its retention in Ghana. We assessed the predictors of vaccination card retention in Tamale Metropolis, Ghana. METHODS: We conducted a cross-sectional study from 21st December 2022 to 10th January 2023 among children aged 0-59 months in the Tamale Metropolis. Multi-stage sampling was used to select caregivers of children aged 0-59 months for enrolment in the study. Data were collected using validated questionnaire through face-to-face interviews of caregivers. A vaccination card was retained if it was presented for physical inspection by research assistants. The factors that influence vaccination card retention were determined in a multivariate logistic regression analysis at p<0.05. RESULTS: A total of 1,532 eligible children were enrolled in this study. Vaccination card retention was 91.5%. Negative predictors of card retention included: being resident in the Nyohini (AOR = 0.28; 95% CI = 0.15-0.50) and Tamale Central (AOR = 0.51; 95% CI = 0.29-0.90) sub-Metro areas and being caregivers of children aged 24-59 months (AOR = 0.39; 95% CI = 0.22-0.68). On the other hand, paying for the vaccination card (AOR = 5.14; 95% CI = 2.95-8.95) was a positive predictor of vaccination card retention. CONCLUSION: In this study, vaccination card retention among children aged 0-59 months was higher than national estimates. Vaccination card retention was mainly influenced by sub-Metro area, age of child and mode of acquisition of the card such as out-of-pocket payment. There is need to design and deliver tailored messages including the importance of vaccination card retention to caregivers of children based on geographic context. Additionally, the policy on sale of vaccination cards should be revised to allow for cost sharing to enhance its retention.


Asunto(s)
Madres , Vacunación , Femenino , Niño , Humanos , Lactante , Ghana , Estudios Transversales , Encuestas y Cuestionarios
20.
PLoS One ; 19(2): e0298660, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38412155

RESUMEN

Insulin dysregulation in horses is characterised by hyperinsulinaemia and/or tissue insulin resistance and is associated with increased risk of laminitis. There is growing evidence in other species that dopamine attenuates insulin release from the pancreas; however, this has yet to be examined in horses. The present study aimed to identify whether there are cells capable of producing or responding to dopamine within the equine gastrointestinal mucosa and pancreas. Tissue samples were collected from the stomach, small and large intestines, and pancreas of six mature horses following euthanasia. Samples of stomach contents and faeces were also collected. Immunohistochemistry was performed to identify tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine production, and dopamine D2 receptors in tissue sections. Additional immunostaining for glucagon, insulin and chromogranin A was performed to identify α cells, ß cells and enteroendocrine cells, respectively. Gastric parietal cells expressed both TH and D2 receptors, indicating that they are capable of both producing and responding to dopamine. Dopamine was quantified in stomach contents and faeces by high-performance liquid chromatography with electrochemical detection, with similar concentrations found at both sites. Dopamine D2 receptors were expressed in duodenal epithelial cells but not more distally. A subset of enteroendocrine cells, located sporadically along the gastrointestinal tract, were found to be immunopositive for the D2 receptor. In pancreatic islets, TH was present in α cells, while D2 receptors were strongly expressed in ß cells and variably expressed in α cells. These findings are consistent with studies of other species; however, dynamic studies are required to further elucidate the role of dopamine in the modulation of insulin and glucagon secretion in horses. This descriptive study provides preliminary evidence for a potential role of dopamine to act as a paracrine messenger in the gastrointestinal mucosa and endocrine pancreas of horses.


Asunto(s)
Dopamina , Células Secretoras de Glucagón , Animales , Caballos , Receptores de Dopamina D2 , Glucagón , Páncreas , Tracto Gastrointestinal/química , Insulina , Membrana Mucosa , Receptores de Dopamina D1
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