New substances intended for human consumption must undergo extensive preclinical safety pharmacology testing prior to approval. These tests encompass the evaluation of effects on the central nervous system, which is highly sensitive to chemical substances. With the growing understanding of the species-specific characteristics of human neural cells and advancements in machine learning technology, the development of effective and efficient methods for the initial screening of chemical effects on human neural function using machine learning platforms is anticipated.
View Article and Find Full Text PDFtree canker is a major disease of in Japan. The pathogen was described as in 1916 by Hemmi and Miyabe. However, its current taxonomic status and phylogenetic position are uncertain.
View Article and Find Full Text PDFPhotosynthetic electron transport is carried out by the electron carrier, plastoquinone (PQ). Recently, another form of PQ, acylplastoquinol (APQ), was discovered in Synechocystis sp. PCC 6803 (Synechocystis), but its physiological function in photosynthesis is unclear.
View Article and Find Full Text PDFDuplicate testes lined in series were observed in the right scrotum of a 6-week-old Sprague-Dawley rat in a single-dose toxicity study. Of the two right testicles, one was spherical and less than half the size of a normal testis. The other was oval-shaped, slightly smaller than a normal testis, and possessed clear, tortuous blood vessels similar to those of a normal testis.
View Article and Find Full Text PDFA hallmark of fetal alcohol spectrum disorders (FASD) is neurobehavioral deficits that still do not have effective treatment. Here, we present that reduction of Apolipoprotein E (APOE) is critically involved in neurobehavioral deficits in FASD. We show that prenatal alcohol exposure (PAE) changes chromatin accessibility of Apoe locus, and causes reduction of APOE levels in both the brain and peripheral blood in postnatal mice.
View Article and Find Full Text PDFReducing Plasmodium parasite transmission via the mosquito vector is a promising strategy for malaria control and elimination in endemic regions. In the mosquito midgut after the ingestion of an infected blood meal, malaria parasite gametes egress from erythrocytes and fertilize to develop into motile ookinetes that traverse midgut epithelial cells and transform into oocysts adjacent the basal lamina. Plasmodium ookinetes and young oocysts possess a unique organelle called the crystalloid; which has a honeycomb-like matrix structure and is indicated to be involved in sporozoite formation and maturation.
View Article and Find Full Text PDFPlasmodium falciparum accounts for the majority of malaria deaths, due to pathology provoked by the ability of infected erythrocytes to adhere to vascular endothelium within deep tissues. The parasite recognizes endothelium by trafficking and displaying protein ligands on the surface of asexual stage infected erythrocytes, such as members of the large family of pathogenic proteins, P. falciparum erythrocyte membrane protein 1 (PfEMP1).
View Article and Find Full Text PDFSeverity of neurobehavioral deficits in children born from adverse pregnancies, such as maternal alcohol consumption and diabetes, does not always correlate with the adversity's duration and intensity. Therefore, biological signatures for accurate prediction of the severity of neurobehavioral deficits, and robust tools for reliable identification of such biomarkers, have an urgent clinical need. Here, we demonstrate that significant changes in the alternative splicing (AS) pattern of offspring lymphocyte RNA can function as accurate peripheral biomarkers for motor learning deficits in mouse models of prenatal alcohol exposure (PAE) and offspring of mother with diabetes (OMD).
View Article and Find Full Text PDFJ Neurosurg Case Lessons
October 2023
Background: Carotid endarterectomy (CEA) and carotid artery stenting are common surgical interventions for internal carotid artery stenosis. Cerebral hyperperfusion syndrome (CHS) is a well-known complication of both procedures that can lead to intracranial hemorrhage and worsen clinical outcomes. Here, the authors report a rare case of non-aneurysmal subarachnoid hemorrhage (SAH) following CEA and review the relevant literature.
View Article and Find Full Text PDFspecies cause malaria, and in the instance of is responsible for a societal burden of over 600,000 deaths annually. The symptoms and pathology of malaria are due to intraerythocytic parasites. Erythrocyte invasion is mediated by the parasite merozoite stage, and is accompanied by the formation of a parasitophorous vacuolar membrane (PVM), within which the parasite develops.
View Article and Find Full Text PDFObjective: To compare the diagnostic performance of dedicated breast positron emission tomography (dbPET) in breast cancer screening with digital mammography plus digital breast tomosynthesis (DM-DBT) and breast ultrasound (US).
Methods: Women who participated in opportunistic whole-body PET/computed tomography cancer screening programs with breast examinations using dbPET, DM-DBT, and US between 2016-2020, whose results were determined pathologically or by follow-up for at least 1 year, were included. DbPET, DM-DBT, and US assessments were classified into four diagnostic categories: A (no abnormality), B (mild abnormality), C (need for follow-up), and D (recommend further examination).
During invasion, parasites secrete proteins from rhoptry and microneme apical end organelles, which have crucial roles in attaching to and invading target cells. A sporozoite stage-specific gene silencing system revealed that rhoptry neck protein 2 (RON2), RON4, and RON5 are important for sporozoite invasion of mosquito salivary glands. Here, we further investigated the roles of RON4 during sporozoite infection of the liver .
View Article and Find Full Text PDFBackground: Patients with rheumatoid arthritis (RA) are prone to muscle atrophy due to inflammatory cytokines and corticosteroid use and immobility due to joint pain and deformity. Although resistance training is effective and safe in reversing muscle atrophy in RA, some patients are unable to perform a conventional high-load exercise program due to disease-related limitations. This study aims to examine the efficacy of individualized exercise therapy on physical function in elderly patients with RA who are at a high risk for sarcopenia.
View Article and Find Full Text PDFmalaria parasites use erythrocyte-binding-like (EBL) ligands to invade erythrocytes in their vertebrate host. EBLs are released from micronemes, which are secretory organelles located at the merozoite apical end and bind to erythrocyte surface receptors. Because of their essential nature, EBLs have been studied as vaccine candidates, such as the Duffy binding protein.
View Article and Find Full Text PDFThroughout our lives, we are exposed to a variety of hazards, such as environmental pollutants and chemical substances that affect our health, and viruses and bacteria that cause infectious diseases. These external factors that are undesirable to an organism are called environmental stress. During the perinatal period, when neural networks are drastically reorganized and refined, the tolerance of the developing brain to various environmental stresses is lower than in adulthood.
View Article and Find Full Text PDFRadiation therapy (RT) can enhance the abscopal effect of immune checkpoint blockade. This phase I/II study investigated the efficacy and safety of nivolumab plus RT in HER2-negative metastatic breast cancer requiring palliative RT for bone metastases. Cohort A included luminal-like disease, and cohort B included both luminal-like and triple-negative disease refractory to standard systemic therapy.
View Article and Find Full Text PDFWe read with great interest the article by Hein et al., which described the meta-analysis study on the impact of disease-modifying anti-rheumatic drugs (DMARDs) therapy on skeletal muscle mass in rheumatoid arthritis (RA) patients. While the data presented are impressive, we add some remarks about methodological issues that should be considered.
View Article and Find Full Text PDFThis review summarizes the evidence for the management of sarcopenia in patients with rheumatoid arthritis (RA) in terms of drugs, exercise, and nutrition. Sarcopenia is a decrease in skeletal muscle mass and muscle strength or physical function. The prevalence of sarcopenia in patients with RA is higher than that in the general population.
View Article and Find Full Text PDFEsophago-pulmonary fistula after esophagectomy is a fatal complication of severe respiratory distress. Minimally invasive treatments, such as esophageal stent placement, have been developed to treat esophago-pulmonary fistulae; however refractory fistulae may not be cured by this mode of treatment. We encountered a case in which the esophago-pulmonary fistula did not close even though sealing of polyglycolic acid sheets and fibrin glue was administered three times over 4 mo while the esophageal stent was in place.
View Article and Find Full Text PDFA vaccine targeting multiple stages of the Plasmodium falciparum parasite life cycle is desirable. The sporozoite surface Circumsporozoite Protein (CSP) is the target of leading anti-infective P. falciparum pre-erythrocytic vaccines.
View Article and Find Full Text PDFJ Antimicrob Chemother
October 2022
Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19) and a devastating worldwide health concern. Development of safe and effective treatments is not only important for interventions during the current pandemic, but also for providing general treatment options moving forward. We have developed ensitrelvir, an antiviral compound that targets the 3C-like protease of SARS-CoV-2.
View Article and Find Full Text PDFHybridization induced by human activities, such as crossbreeding between invasive and native species, can adversely affect the natural biodiversity of an ecosystem. In Japan, the endemic turtle species is known to hybridize with the alien species , and putative hybrids have been encountered in the wild. If × hybrids can readily crossbreed with , the hybridization with could lead to the extinction of pure populations.
View Article and Find Full Text PDFExisting control measures have significantly reduced malaria morbidity and mortality in the last two decades, although these reductions are now stalling. Significant efforts have been undertaken to develop malaria vaccines. Recently, extensive progress in malaria vaccine development has been made for Plasmodium falciparum.
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