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1.
Opt Lett ; 49(15): 4242-4245, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090904

RESUMEN

The quantum theory of the electromagnetic field uncovered that classical forms of light were indeed produced by distinct superpositions of nonclassical multiphoton wave packets. This situation prevails for partially coherent light, the most common kind of classical light. Here, for the first time, to our knowledge, we demonstrate the extraction of the constituent multiphoton quantum systems of a partially coherent light field. We shift from the realm of classical optics to the domain of quantum optics via a quantum representation of partially coherent light using its complex-Gaussian statistical properties. Our formulation of the quantum Gaussian-Schell model (GSM) unveils the possibility of performing photon-number-resolving (PNR) detection to isolate the constituent quantum multiphoton wave packets of a classical light field. We experimentally verified the coherence properties of isolated vacuum systems and wave packets with up to 16 photons. Our findings not only demonstrate the possibility of observing quantum properties of classical macroscopic objects but also establish a fundamental bridge between the classical and quantum worlds.

2.
PLOS Glob Public Health ; 4(8): e0002224, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39093879

RESUMEN

Species distribution models (SDMs) are increasingly popular tools for profiling disease risk in ecology, particularly for infectious diseases of public health importance that include an obligate non-human host in their transmission cycle. SDMs can create high-resolution maps of host distribution across geographical scales, reflecting baseline risk of disease. However, as SDM computational methods have rapidly expanded, there are many outstanding methodological questions. Here we address key questions about SDM application, using schistosomiasis risk in Brazil as a case study. Schistosomiasis is transmitted to humans through contact with the free-living infectious stage of Schistosoma spp. parasites released from freshwater snails, the parasite's obligate intermediate hosts. In this study, we compared snail SDM performance across machine learning (ML) approaches (MaxEnt, Random Forest, and Boosted Regression Trees), geographic extents (national, regional, and state), types of presence data (expert-collected and publicly-available), and snail species (Biomphalaria glabrata, B. straminea, and B. tenagophila). We used high-resolution (1km) climate, hydrology, land-use/land-cover (LULC), and soil property data to describe the snails' ecological niche and evaluated models on multiple criteria. Although all ML approaches produced comparable spatially cross-validated performance metrics, their suitability maps showed major qualitative differences that required validation based on local expert knowledge. Additionally, our findings revealed varying importance of LULC and bioclimatic variables for different snail species at different spatial scales. Finally, we found that models using publicly-available data predicted snail distribution with comparable AUC values to models using expert-collected data. This work serves as an instructional guide to SDM methods that can be applied to a range of vector-borne and zoonotic diseases. In addition, it advances our understanding of the relevant environment and bioclimatic determinants of schistosomiasis risk in Brazil.

3.
South Afr J Crit Care ; 40(1): e1435, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38989476

RESUMEN

Background: Future pandemic planning involves analysing past experiences. We compared intensive care unit (ICU) admissions during the SARS-CoV-2 pandemic (2020) with the preceding year. Objectives: To assess the SARS-CoV-2 pandemic's effect on ICU admissions in a tertiary hospital, examining differences in patient characteristics, organ support requirements, reason for admission, mortality rates and length of ICU stay. Methods: This retrospective cohort study compared ICU patient data at a tertiary hospital during the SARS-CoV-2 pandemic (26 March 2020 to 20 September 2020) with the same period in 2019. Results: Patient admissions (p=0.39) and severity of illness (p=0.27 adults; p=0.92 paediatrics) showed no differences across the study period. Similarly, no differences were observed for underlying chronic conditions between the two years. Adult trauma admissions significantly declined, specifically those related to road traffic accidents (RR 0.63). Admissions for acute infectious conditions, including respiratory infections, sepsis, urosepsis, septic arthritis and gastroenteritis significantly declined in both adults (RR 0.50) and paediatric admissions (RR 0.25). During the lockdown period, the length of stay (LOS) decreased for adults, but mortality rates remained unchanged across the study period. The paediatric mortality rate decreased during the lockdown period (p=0.004). Conclusion: There was no reduction in SARS-CoV-2-negative ICU admissions during the 2020 lockdown period compared with the preceding year, likely due to chronic resource limitations. We found a decrease in acute trauma and acute infectious illness admissions, while acute surgical emergency admissions increased. These findings suggest that lockdown orders may have affected admission patterns, aiding in future pandemic planning. Contribution of the study: The study highlights the chronic shortage of critical care resources in South Africa and aids with future pandemic preparedness and planning in a resource limited setting.

4.
Environ Health (Wash) ; 2(7): 441-452, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39049895

RESUMEN

Although human health impacts of microplastics are not well understood, concern regarding chemical contaminants retained on or within them is growing. Drinking water providers are increasingly asked about these risks, but strategies for evaluating them and the extent of treatment needed to manage them are currently lacking. Microplastics can potentially induce health effects if the concentration of contaminants adsorbed to them exceeds predetermined drinking water guidelines (e.g., Maximum Contaminant Levels). The risk posed by microplastics due to adsorbed contaminants is difficult to determine, but a worst-case scenario can be evaluated by using adsorption capacity. Here, a "Threshold Microplastics Concentration" (TMC) framework is developed to evaluate whether waterborne microplastic concentrations can potentially result in the intake of regulated contaminants on/in microplastics at levels of human health concern and identify treatment targets for managing associated health risk. Exceeding the TMC does not indicate an immediate health risk; it informs the need for detailed risk assessment or further treatment evaluation to ensure particle removal targets are achieved. Thus, the TMC concept and framework provide an updateable, science-based screening tool to determine if there is a need for detailed risk assessment or treatment modification due to waterborne microplastics in supplies used for potable water production.

5.
Am Surg ; : 31348241265142, 2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39033341

RESUMEN

Introduction: Whole blood (WB) is associated with improved mortality while lowering blood product utilization. Furthermore, statin medications are associated with favorable outcomes in traumatic brain injury and risk reduction of venous thromboembolism. However, the use of statin medications has not been evaluated in those receiving WB. The objective of this study is to determine the effects of pre-injury statin exposure on patients receiving WB.Methods: Patients that underwent WB first resuscitation and received pre-injury statins were compared to those that did not receive pre-injury statins. Demographics as well as complication rates, blood product transfusion volumes, and mortality were evaluated. Univariate and multivariable analyses were used to determine independent predictors of mortality.Results: In the study period, 785 patients received WB as part of their resuscitation. One hundred and thirty five patients (17.3%) took statin medications prior to injury. Patients that were exposed to a pre-injury statin had a lower mortality rate than those that were not exposed (21.5% vs 32.5%, P = .01). After adjusting for imbalances, age, ISS, Glasgow Coma Scale, admission systolic blood pressures, and pre-injury statin use were independent predictors of mortality following multiple logistic regression. When evaluating outcomes based on statin intensity, the use of high-intensity statins was associated with lower mortality (OR: .37, 95% CI: .13-.93), whereas moderate and low-intensity statins were not.Conclusion: In patients resuscitated with WB, pre-injury statins use was associated with improved outcomes. Specifically, patients that received high-intensity pre-injury statins appeared to be the population that benefited.

6.
S Afr Med J ; 114(7): e1779, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39041520

RESUMEN

Drug-resistant tuberculosis (TB) has poor outcomes unless resistance is detected early, ideally by commercially available molecular tests. We present a case of occult multidrug-resistant TB where both rifampicin and isoniazid resistance were missed by molecular testing and were only identified by phenotypic testing.


Asunto(s)
Antituberculosos , Isoniazida , Mycobacterium tuberculosis , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Masculino , Adulto
7.
Cancers (Basel) ; 16(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39001443

RESUMEN

MM is a common type of cancer that unfortunately leads to a significant number of deaths each year. The majority of the reported MM cases are detected in the advanced stages, posing significant challenges for treatment. Additionally, all MM patients eventually develop resistance or experience relapse; therefore, advances in treatment are needed. However, developing new anti-cancer drugs, especially for MM, requires significant financial investment and a lengthy development process. The study of drug repurposing involves exploring the potential of existing drugs for new therapeutic uses. This can significantly reduce both time and costs, which are typically a major concern for MM patients. The utilization of pre-existing non-cancer drugs for various myeloma treatments presents a highly efficient and cost-effective strategy, considering their prior preclinical and clinical development. The drugs have shown promising potential in targeting key pathways associated with MM progression and resistance. Thalidomide exemplifies the success that can be achieved through this strategy. This review delves into the current trends, the challenges faced by conventional therapies for MM, and the importance of repurposing drugs for MM. This review highlights a noncomprehensive list of conventional therapies that have potentially significant anti-myeloma properties and anti-neoplastic effects. Additionally, we offer valuable insights into the resources that can help streamline and accelerate drug repurposing efforts in the field of MM.

9.
PNAS Nexus ; 3(7): pgae267, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39081786

RESUMEN

The skin microbiome plays a pivotal role in the production of attractive cues detected by mosquitoes. Here, we leveraged recent advances in genetic engineering to significantly reduce the production of L-(+)-lactic acid as a strategy to reduce mosquito attraction to the highly prominent skin commensals Staphylococcus epidermidis and Corynebacterium amycolatum. Engraftment of these engineered bacteria onto the skin of mice reduced mosquito attraction and feeding for up to 11 uninterrupted days, which is considerably longer than the several hours of protection conferred by the leading chemical repellent N,N-diethyl-meta-toluamide. Taken together, our findings demonstrate engineering the skin microbiome to reduce attractive volatiles represents an innovative untapped strategy to reduce vector attraction, preventing bites, and pathogen transmission. These findings set the stage for new classes of long-lasting microbiome-based repellent products.

10.
bioRxiv ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39071362

RESUMEN

Genetic biocontrol interventions targeting mosquito-borne diseases require the release of male mosquitoes exclusively, as only females consume blood and transmit human pathogens. This reduces the risk of spreading pathogens while enabling effective population control. Robust sex sorting methods to enable early larval sorting in mosquitoes need to be developed to allow for scalable sex sorting for genetic biocontrol interventions. This study applies the SEPARATOR (Sexing Element Produced by Alternative RNA-splicing of A Transgenic Observable Reporter) system, previously developed for Aedes aegypti, to the Asian malaria vector Anopheles stephensi. We hypothesized that the intron from the doublesex gene in Anopheles gambiae would function in An. stephensi due to evolutionary conservation. Our results confirm that the splicing module from An. gambiae operates effectively in An. stephensi, demonstrating evolutionary conservation in sex-specific splicing events between these species. This system enables reliable positive male selection from first instar larval to pupal stages. RT-PCR analysis demonstrates that male-specific EGFP expression is dependent on doublesex sex-specific splicing events. The SEPARATOR system's independence from sex-chromosome linkage confers resistance to meiotic recombination and chromosomal rearrangements. This approach may facilitate the mass release of males, and the cross-species portability of SEPARATOR establishes it as a valuable tool for genetic biocontrol interventions across various pest species.

11.
Heliyon ; 10(12): e33091, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39021902

RESUMEN

Multiple Myeloma (MM) is a malignant expansion of plasma cells in the bone marrow (BM), resulting in a disease characterized by symptoms of end organ damage from light chain secretion, crowding of the BM, and bone lesions. Although the past two decades have been characterized by numerous novel therapies emerging, the disease remains incurable due to intrinsic or acquired drug resistance. A major player in MM's drug resistance arises from its intimate relationship with the BM microenvironment (BMME). Through stress-inducing conditions, soluble messengers, and physical adhesion to BM elements, the BMME activates numerous pathways in the myeloma cell. This not only propagates myeloma progression through survival and growth signals, but also specific mechanisms to circumvent therapeutic actions. In this review, we provide an overview of the BMME, the role of individual components in MM survival, and various therapy-specific resistance mechanisms reported in the literature.

12.
IJTLD Open ; 1(5): 215-222, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-39022776

RESUMEN

INTRODUCTION: In South Africa, Xpert® MTB/RIF Ultra (Ultra) is the recommended diagnostic assay for TB with line-probe assays for first- (LPAfl) and second-line drugs (LPAsl) providing additional drug susceptibility testing (DST) for samples that were rifampicin-resistant (RR-TB). To guide implementation of the recently launched Xpert® MTB/XDR (MTB/XDR) assay, a cost-outcomes analysis was conducted comparing total costs for genotypic DST (gDST) for persons diagnosed with RR-TB considering three strategies: replacing LPAfl/LPAsl (centralised level) with MTB/XDR vs. Ultra reflex testing (decentralised level). Further, DST was performed using residual specimen following RR-TB diagnosis. METHODS: The total cost of gDST was determined for three strategies, considering loss to follow-up (LTFU), unsuccessful test rates, and specimen volume. RESULTS: For 2019, 9,415 persons were diagnosed with RR-TB. A 35% LTFU rate between RR-TB diagnosis and LPAfl/LPAsl-DST was estimated. Unsuccessful test rates of 37% and 23.3% were reported for LPAfl and LPAsl, respectively. The estimated total costs were $191,472 for the conventional strategy, $122,352 for the centralised strategy, and $126,838 for the decentralised strategy. However, it was found that sufficient residual volume for reflex MTB/XDR testing is a limiting factor at the decentralised level. CONCLUSION: Centralising the implementation of XDR testing, as compared to LPAfl/LPAsl, leads to significant cost savings.


INTRODUCTION: En Afrique du Sud, Xpert® MTB/RIF Ultra (Ultra) est le test de diagnostic recommandé pour la TB avec des tests par sonde de ligne pour les médicaments de première (LPAfl) et de deuxième ligne (LPAsl) fournissant des tests de sensibilité aux médicaments (DST) supplémentaires pour les échantillons résistants à la rifampicine (RR-TB). Afin d'orienter la mise en œuvre du test Xpert® MTB/XDR (MTB/XDR) récemment lancé, une analyse coûts-résultats a été réalisée en comparant les coûts totaux de la DST génotypique (gDST) pour les personnes diagnostiquées avec une RR-TB en tenant compte de trois stratégies : remplacer le LPAfl/LPAsl (niveau centralisé) par le MTB/XDR par rapport au test Ultra reflex (niveau décentralisé). De plus, l'heure d'été a été réalisée à l'aide d'un échantillon résiduel après le diagnostic de RR-TB. MÉTHODES: Le coût total de la gDST a été déterminé pour trois stratégies, en tenant compte de la perte de suivi (LTFU), des taux d'échec des tests et du volume d'échantillons. RÉSULTATS: En 2019, 9 415 personnes ont reçu un diagnostic de RR-TB. Un taux de LTFU de 35% entre le diagnostic de RR-TB et le diagnostic de LPAfl/LPAsl-DST a été estimé. Des taux d'échec de 37% et de 23,3% ont été signalés pour LPAfl et LPAsl, respectivement. Les coûts totaux estimés étaient de 191 472 dollars pour la stratégie conventionnelle, de 122 352 dollars pour la stratégie centralisée et de 126 838 dollars pour la stratégie décentralisée. Cependant, il a été constaté qu'un volume résiduel suffisant pour les tests réflexes MTB/XDR est un facteur limitant au niveau décentralisé. CONCLUSION: La centralisation de la mise en œuvre des tests XDR, par rapport à LPAfl/LPAsl, permet de réaliser d'importantes économies.

13.
Cureus ; 16(6): e63001, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39050289

RESUMEN

BACKGROUND: Acute coronary syndrome (ACS) is the leading cause of mortality and morbidity worldwide. Recognition of its symptoms affects the time-sensitive benefits of reperfusion therapy. Furthermore, lowering the risk factors can prevent long-term complications. OBJECTIVES: To evaluate the public knowledge and perception of the symptoms and risk factors of ACS in the Saudi-Western region. METHOD: A cross-sectional study was conducted on a convenience sample of 733 among the general population in the western region of Saudi Arabia by using the Acute Coronary Syndrome Response Index, with additional questions about risk factors for heart attack and physical activities. The research information was acquired through a self-administered questionnaire without any identifying personal information. RESULT: Participants demonstrated awareness of certain ACS symptoms and risk factors. Chest pain was widely recognized (49.2%, n = 361), followed by shortness of breath (44.8%, n = 329), arm pain or shoulder pain (38.6%, n = 283), palpitation (37.3%, n = 274), and fatigue (22.2%, n = 163). A total of 544 (74.2%) and 474 (64.6%) respondents were aware that smoking and obesity are the most common risk factors for ACS, respectively. However, gaps persisted, particularly regarding the association between diabetes mellitus and ACS, with 31.6% (n = 232) reporting diabetes mellitus. A total of 331 (45.2%) and 322 (43.9%) study sample were unsure whether they could identify ACS in themselves or other people. However, 391 (53.3%) decided that they should go to the hospital as soon as possible when they have chest pain that does not stop after 15 minutes. Notably, female participants demonstrated substantially higher knowledge (OR = 2.40, p = 0.001). The study highlights the influence of gender, age, and education on ACS-related awareness. CONCLUSION: This study provides valuable insights into ACS awareness in the western region of Saudi Arabia. Relatively older respondents, female participants, and those with postgraduate education were more knowledgeable about ACS than the others. These findings emphasize the importance of tailored interventions for specific demographic groups in enhancing public health outcomes.

14.
J Surg Case Rep ; 2024(6): rjae257, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38832055

RESUMEN

Myiasis is infestation of live human tissue by larva. It usually involves immunocompromised people or people living in unsanitary conditions. The cutaneous myiasis is most common type and can enter the skin with a pre-existing wound. Herein we present a case of an 18-year-old girl known case of Dystrophic Epidermolysis Bullosa with cutaneous myiasis affecting the knee managed surgically with full recovery. Such case has not reported previously in the literature, and detailed management plan is described.

15.
Sci Rep ; 14(1): 13057, 2024 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844650

RESUMEN

Combined action observation and motor imagery (AOMI) facilitates corticospinal excitability (CSE) and may potentially induce plastic-like changes in the brain in a similar manner to physical practice. This study used transcranial magnetic stimulation (TMS) to explore changes in CSE for AOMI of coordinative lower-limb actions. Twenty-four healthy adults completed two baseline (BLH, BLNH) and three AOMI conditions, where they observed a knee extension while simultaneously imagining the same action (AOMICONG), plantarflexion (AOMICOOR-FUNC), or dorsiflexion (AOMICOOR-MOVE). Motor evoked potential (MEP) amplitudes were recorded as a marker of CSE for all conditions from two knee extensor, one dorsi flexor, and two plantar flexor muscles following TMS to the right leg representation of the left primary motor cortex. A main effect for experimental condition was reported for all three muscle groups. MEP amplitudes were significantly greater in the AOMICONG condition compared to the BLNH condition (p = .04) for the knee extensors, AOMICOOR-FUNC condition compared to the BLH condition (p = .03) for the plantar flexors, and AOMICOOR-MOVE condition compared to the two baseline conditions for the dorsi flexors (ps ≤ .01). The study findings support the notion that changes in CSE are driven by the imagined actions during coordinative AOMI.


Asunto(s)
Potenciales Evocados Motores , Imaginación , Extremidad Inferior , Corteza Motora , Músculo Esquelético , Tractos Piramidales , Estimulación Magnética Transcraneal , Humanos , Masculino , Femenino , Potenciales Evocados Motores/fisiología , Adulto , Corteza Motora/fisiología , Imaginación/fisiología , Adulto Joven , Tractos Piramidales/fisiología , Extremidad Inferior/fisiología , Músculo Esquelético/fisiología , Electromiografía
16.
Heliyon ; 10(11): e32048, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38882352

RESUMEN

Gestational diabetes mellitus (GDM) has been linked with adverse pregnancy outcomes. Vitamin D receptor (VDR) gene variants have been associated with diabetes mellitus susceptibility and related complications. This study assessed the association between VDR gene polymorphism (rs2228570) and GDM risk among pregnant Arab women. A total of 368 pregnant Saudi women who were screened for GDM at 24-28 weeks of gestation and genotyped for the VDR gene variant (rs2228570) were included in this cross-sectional study. Circulatory insulin levels, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and vitamin D (25(OH)D) were measured. There were 108 women with GDM and 260 women without GDM. The genotype frequency of women with GDM was CC 60.2 %, CT 33.3 %, TT 6.9 %, and CT + TT 39.8 %; for non-GDM women, were CC 61.1 %, CT 31.5 %, TT 6.9 %, and CT + TT 38.4 %. No association was found between the VDR gene variant (rs2228570-FokI) and GDM susceptibility after adjustment for covariates. Serum 25(OH)D had a significant inverse association with FBG (r = -0.49, p = 0.01) and HbA1c (r = -0.45, p = 0.03) among carriers of the TT-genotype. Furthermore, a significant inverse correlation was observed between serum 25(OH)D and HOMA-ß (r = -0.20, p = 0.035) in individuals with the T-allele. Among pregnant Saudi women, glycemic indices appear to be influenced by vitamin D, suggesting a possible role it may play in mitigating the metabolic changes associated with GDM, particularly among individuals with specific genetic backgrounds. In our study population, rs2228570-FokI did not appear to be a significant contributor to GDM risk.

17.
Food Nutr Res ; 682024.
Artículo en Inglés | MEDLINE | ID: mdl-38863742

RESUMEN

This study aimed to evaluate the effect of a family-based lifestyle intervention on reducing body weight among Jordanian children with obesity aged 6-9 years old. The pretest-posttest control group design was conducted among 162 children (75 in the intervention group and 87 in the control group) with obesity aged 6-9 years old at four primary schools in Jordan during the period from March 2021 to July 2021. The results found that, after the intervention, there was a statistically significant change in the F scores in the control group vs. in the intervention group (M = 37.07, SD = 2.77; M = 33.48, SD = 2.73; t (160) = 8.29, P < 0.001), where the mean BMI percentile was reduced by 2.05 in the intervention group. A significant difference was demonstrated in the median BMI percentile in the intervention and control groups post-intervention (P < 0.001). A significant difference was also noticed between the average weekly reported dietary habits and the physical activities of both the control group and the intervention group post-intervention. The findings support the effect of family-based lifestyle interventions. Healthcare providers should adopt such interventions for children living with obesity. Future study is required to evaluate the long-term effectiveness of this intervention on weight reduction.

18.
Cureus ; 16(5): e59992, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38854258

RESUMEN

Carcinosarcoma or sarcomatoid carcinoma of the urinary bladder is a rare but aggressive bladder cancer characterized by malignant epithelial and mesenchymal components, with only a few cases reported in the literature so far. In this report, we discuss a case of a 74-year-old female nonsmoker who presented with intermittent hematuria and passage of clots in the last four months. Radiographic images showed an irregular mass lesion (6.2 x 6 cm) in the left lateral wall of the urinary bladder near to left vesicoureteral junction. The mass was completely removed with transurethral resection of the bladder tumor (TUR-BT). Histopathological study revealed high-grade carcinosarcoma, and immunohistochemistry showed diffuse positivity for vimentin, pan-cytokeratin (CK) and CK7, epithelial membrane antigen (EMA), and CK5/6. The patient declined radical cystectomy and only agreed to receive intravesical chemotherapy (gemcitabine), and she remains alive after more than four years of follow-up. Carcinosarcoma of the urinary bladder is a rare tumor primarily affecting older people, and it is most commonly treated with radical cystectomy and different combination treatments such as chemotherapy and radiation. However, tumor resection followed by intravesical chemotherapy may be an alternative option in the early stages of bladder carcinosarcoma for some patients, thereby avoiding the need for aggressive treatments, especially for elderly patients who decline to undergo radical surgery.

19.
Proc Natl Acad Sci U S A ; 121(27): e2312456121, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38917000

RESUMEN

Controlling the principal African malaria vector, the mosquito Anopheles gambiae, is considered essential to curtail malaria transmission. However, existing vector control technologies rely on insecticides, which are becoming increasingly ineffective. Sterile insect technique (SIT) is a powerful suppression approach that has successfully eradicated a number of insect pests, yet the A. gambiae toolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass releases of nonbiting, nondriving, sterile males which seek out and mate with monandrous wild females. Once mated, females are permanently sterilized due to mating-induced refractoriness, which results in population suppression of the subsequent generation. However, sterilization by traditional methods renders males unfit, making the creation of precise genetic sterilization methods imperative. Here, we introduce a vector control technology termed precision-guided sterile insect technique (pgSIT), in A. gambiae for inducible, programmed male sterilization and female elimination for wide-scale use in SIT campaigns. Using a binary CRISPR strategy, we cross separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding >99.5% male sterility and >99.9% female lethality in hybrid progeny. We demonstrate that these genetically sterilized males have good longevity, are able to induce sustained population suppression in cage trials, and are predicted to eliminate wild A. gambiae populations using mathematical models, making them ideal candidates for release. This work provides a valuable addition to the malaria genetic biocontrol toolkit, enabling scalable SIT-like confinable, species-specific, and safe suppression in the species.


Asunto(s)
Anopheles , Malaria , Control de Mosquitos , Mosquitos Vectores , Animales , Masculino , Anopheles/genética , Anopheles/fisiología , Mosquitos Vectores/genética , Mosquitos Vectores/parasitología , Malaria/transmisión , Malaria/prevención & control , Femenino , Control de Mosquitos/métodos , Infertilidad Masculina/genética , Sistemas CRISPR-Cas
20.
Methods Mol Biol ; 2802: 573-586, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38819572

RESUMEN

The Eukaryotic Pathogen, Vector and Host Informatics Resources ( VEuPathDB.org ) provide free online access to omic data from eukaryotic protozoan and fungal pathogens, arthropod vectors of disease, and host responses to pathogen infection. The goal of VEuPathDB is to make data easily accessible, findable, and importantly, re-usable by laboratory scientists. All integrated data and analyses follow standard workflows and methods to ensure data accuracy and enable data interoperability. Integrated data include genomes and annotation, transcriptomic (e.g., single-cell/bulk RNA-sequence and microarray data), proteomic (e.g., mass spectrometry evidence and quantitative data), isolate sequencing data used for variant calling and copy number variation determination, epigenomics, whole-genome phenotyping data (e.g., CRISPR screens and large-scale imaging and subcellular localization data), etc. Standard analyses provide additional data such as InterPro domains, signal peptide and transmembrane domain predictions, and metabolic pathways. Comparative genomic analysis in VEuPathDB is facilitated by leveraging orthology to enable the transformation of results between organisms and identifying genes with specific phyletic patterns. In addition, synteny between genomes is facilitated by shading orthologs across species and strains. Accessibility to and re-usability of the data is made possible through specialized searches and a graphical search strategy system that enables scientists to build in silico experiments combining results from multiple experiments with diverse data types.


Asunto(s)
Biología Computacional , Biología Computacional/métodos , Genómica/métodos , Proteómica/métodos , Programas Informáticos , Animales , Bases de Datos Genéticas , Humanos , Interacciones Huésped-Patógeno/genética , Internet
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