Proc Natl Acad Sci U S A
July 2023
To ensure their survival in the human bloodstream, malaria parasites degrade up to 80% of the host erythrocyte hemoglobin in an acidified digestive vacuole. Here, we combine conditional reverse genetics and quantitative imaging approaches to demonstrate that the human malaria pathogen employs a heteromultimeric V-ATPase complex to acidify the digestive vacuole matrix, which is essential for intravacuolar hemoglobin release, heme detoxification, and parasite survival. We reveal an additional function of the membrane-embedded V-ATPase subunits in regulating morphogenesis of the digestive vacuole independent of proton translocation.
View Article and Find Full Text PDFThe chloroquine resistance transporter, PfCRT, of the human malaria parasite Plasmodium falciparum is sensitive to acidic pH. Consequently, PfCRT operates at 60% of its maximal drug transport activity at the pH of 5.2 of the digestive vacuole, a proteolytic organelle from which PfCRT expels drugs interfering with heme detoxification.
View Article and Find Full Text PDFThis is a study on indicators related to marital dissatisfaction. The research was conducted by the psychology department of a reproductive health institution in Mexico City. The objective was to know the relation between marital satisfaction/dissatisfaction and gender roles, self-esteem, the types of coping strategies and the types of violence perceived from the partner.
View Article and Find Full Text PDFTenecteplase (TNK) is a fibrinolytic drug that is administrated in a single bolus, recommended in eligible patients with acute ischemic stroke prior to mechanical thrombectomy. This study explores its usefulness in adverse situations, such as the SARS-CoV-2 pandemic. We conducted a retrospective study involving consecutive patients with suspected acute ischemic stroke treated either with intravenous fibrinolysis with alteplase during 2019 or with TNK (.
View Article and Find Full Text PDFBackground: The Andean condor () is the largest scavenger in South America. This predatory bird plays a crucial role in their ecological niche by removing carcasses. We report the first metagenomic analysis of the Andean condor gut microbiome.
View Article and Find Full Text PDFProposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)-based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti- effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes (AgTP13) and (AcTP13).
View Article and Find Full Text PDFGenetic surveillance of mosquito populations is becoming increasingly relevant as genetics-based mosquito control strategies advance from laboratory to field testing. Especially applicable are mosquito gene drive projects, the potential scale of which leads monitoring to be a significant cost driver. For these projects, monitoring will be required to detect unintended spread of gene drive mosquitoes beyond field sites, and the emergence of alternative alleles, such as drive-resistant alleles or non-functional effector genes, within intervention sites.
View Article and Find Full Text PDFEur J Surg Oncol
October 2023
Background: Pathologic complete response (pCR) after multimodal treatment for locally advanced rectal cancer (LARC) is used as surrogate marker of success as it is assumed to correlate with improved oncologic outcome. However, long-term oncologic data are scarce.
Methods: This retrospective, multicentre study updated the oncologic follow-up of prospectively collected data from the Spanish Rectal Cancer Project database.
Rev Esp Cir Ortop Traumatol
July 2023
Objective: A meta-analysis was carried out to evaluate the clinical-functional results of anterior cruciate ligament surgery in military population, as well as the complications associated with it.
Material And Method: Three major database sources up to December 2022 (PubMed, Google Scholar, and ScienceDirect) were searched for outcomes after anterior cruciate ligament surgery in military personnel. The systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses -PRISMA- standards, and the inclusion criteria following the PICO strategy.
Malaria is among the world's deadliest diseases, predominantly affecting Sub-Saharan Africa and killing over half a million people annually. Controlling the principal vector, the mosquito , as well as other anophelines, is among the most effective methods to control disease spread. Here, we develop a genetic population suppression system termed Ifegenia (inherited female elimination by genetically encoded nucleases to interrupt alleles) in this deadly vector.
View Article and Find Full Text PDFLarge sample datasets of evapotranspiration (ET) measurements with well documented data provenance and quality assurance are critical for water management and many fields of earth science research. We present a post-processed ET oriented dataset at daily and monthly timesteps, from 161 stations, including 148 eddy covariance flux towers, that were chosen based on their data quality from nearly 350 stations across the contiguous United States. In addition to ET, the data includes energy and heat fluxes, meteorological measurements, and reference ET downloaded from gridMET for each flux station.
View Article and Find Full Text PDFThe IGRA (Interferon Gamma Release Assays) test is currently the standard specific test for infection status. However, a positive test cannot distinguish between active tuberculosis disease (ATBD) and latent tuberculosis infection (LTBI). Developing a test with this characteristic is needed.
View Article and Find Full Text PDFBackground: There has been substantial controversy in the neuroethics literature regarding the extent to which deep brain stimulation (DBS) impacts dimensions of personality, mood, and behavior.
Objective/hypothesis: Despite extensive debate in the theoretical literature, there remains a paucity of empirical data available to support or refute claims related to the psychosocial changes following DBS.
Methods: A mixed-methods approach was used to examine the perspectives of patients who underwent DBS regarding changes to their personality, authenticity, autonomy, risk-taking, and overall quality of life.
In the biopharmaceutical industry, the use of mammalian cells to produce therapeutic proteins is becoming increasingly widespread. Monitoring of these cultures via different analysis techniques is essential to ensure a good quality product while respecting good manufacturing practice (GMP) regulations. Process Analytical Technologies (PAT) tools provide real-time measurements of the physiological state of the culture and enable process automation.
View Article and Find Full Text PDFImmune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy.
View Article and Find Full Text PDFThe Ross-Macdonald model has exerted enormous influence over the study of malaria transmission dynamics and control, but it lacked features to describe parasite dispersal, travel, and other important aspects of heterogeneous transmission. Here, we present a patch-based differential equation modeling framework that extends the Ross-Macdonald model with sufficient skill and complexity to support planning, monitoring and evaluation for Plasmodium falciparum malaria control. We designed a generic interface for building structured, spatial models of malaria transmission based on a new algorithm for mosquito blood feeding.
View Article and Find Full Text PDFDiving can have significant cardiovascular effects on the human body and increase the risk of developing cardiac health issues. This study aimed to investigate the autonomic nervous system (ANS) responses of healthy individuals during simulated dives in hyperbaric chambers and explore the effects of the humid environment on these responses. Electrocardiographic- and heart-rate-variability (HRV)-derived indices were analyzed, and their statistical ranges were compared at different depths during simulated immersions under dry and humid conditions.
View Article and Find Full Text PDFThe chloroquine resistance transporter (PfCRT) confers resistance to a wide range of quinoline and quinoline-like antimalarial drugs in Plasmodium falciparum, with local drug histories driving its evolution and, hence, the drug transport specificities. For example, the change in prescription practice from chloroquine (CQ) to piperaquine (PPQ) in Southeast Asia has resulted in PfCRT variants that carry an additional mutation, leading to PPQ resistance and, concomitantly, to CQ re-sensitization. How this additional amino acid substitution guides such opposing changes in drug susceptibility is largely unclear.
View Article and Find Full Text PDFBackground: Adoptive T cell therapy (ATCT) has been successful in treating hematological malignancies and is currently under investigation for solid-tumor therapy. In contrast to existing chimeric antigen receptor (CAR) T cell and/or antigen-specific T cell approaches, which require known targets, and responsive to the need for targeting a broad repertoire of antigens in solid tumors, we describe the first use of immunostimulatory photothermal nanoparticles to generate tumor-specific T cells.
Methods: Specifically, we subject whole tumor cells to Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) before culturing with dendritic cells (DCs), and subsequent stimulation of T cells.
Introduction: Competing noise in the environment negatively affects speech intelligibility, particularly when listening at a distance. This is especially true for children with hearing loss in classroom environments where the signal-to-noise ratio is often poor. Remote microphone technology has been shown to be highly beneficial at improving the signal-to-noise ratio in hearing device users.
View Article and Find Full Text PDFClinical management of breast cancer (BC) metastasis remains an unmet need as it accounts for 90% of BC-associated mortality. Although the luminal subtype, which represents >70% of BC cases, is generally associated with a favorable outcome, it is susceptible to metastatic relapse as late as 15 years after treatment discontinuation. Seeking therapeutic approaches as well as screening tools to properly identify those patients with a higher risk of recurrence is therefore essential.
View Article and Find Full Text PDFHydrogels are 3D scaffolds used as alternatives to in vivo models for disease modeling and delivery of cells and drugs. Existing hydrogel classifications include synthetic, recombinant, chemically defined, plant- or animal-based, and tissue-derived matrices. There is a need for materials that can support both human tissue modeling and clinically relevant applications requiring stiffness tunability.
View Article and Find Full Text PDFA colonial ascidian of the genus caused a mass mortality of the pen shell (Sowerby, 1835) during June 2016 in the southwest of the Gulf of California (Mexico), with a significant socio-economic cost. Tentatively identified in previous works as Distapliacf.stylifera, a precise taxonomic determination was still lacking.
View Article and Find Full Text PDFBackground: The Functional Independence Measure + Functional Assessment Measure (FIM+FAM) Scale is one of the most widely used instruments to measure functional independence post-stroke, and features many cultural adaptations to various languages.
Aim: The aim of this study was to determine the psychometric properties of a Spanish cross-cultural adaptation of the FIM+FAM for use in the stroke population.
Design: Observational study.