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Traditional beta-lactam dosing results in low target attainment in the majority of critically ill patients. Male gender, high BMI, and high eGFR were significant risk factors for target non-attainment. These predictors, together with therapeutic drug monitoring, may help ICU clinicians in optimizing beta-lactam dosing in critically ill patients.
Netherlands Trial Registry (EXPAT trial), NTR 5632 . Registered on 7 December 2015.
Netherlands Trial Registry (EXPAT trial), NTR 5632 . Registered on 7 December 2015.This letter comments on the article "The treatment of sarcoptic mange in wildlife a systematic review" published in Parasites & Vectors 2019, 1299, and discusses the limitations in the use of endectocides for scabies control in free-ranging wildlife. The ecological impact and drug resistance to ivermectin are also discussed. In our view, scabies control in free-ranging wildlife should be based preferably on population management measures, and whether to apply individual treatments to free-ranging populations should be considered very carefully and avoided where not absolutely warranted.
Microsporidians are opportunistic pathogens with a wide range of hosts, including invertebrates, vertebrates and even humans. Microsporidians possess a highly specialized invasion structure, the polar tube. When spores encounter an appropriate environmental stimulation, the polar tube rapidly everts out of the spore, forming a 50-500 µm hollow tube that serves as a conduit for sporoplasm passage into host cells. The polar tube is mainly composed of polar tube proteins (PTPs). So far, five major polar tube proteins have been isolated from microsporidians. Nosema bombycis, the first identified microsporidian, infects the economically important insect silkworm and causes heavy financial loss to the sericulture industry annually.
A novel polar tube protein of N. bombycis (NbPTP6) was identified. NbPTP6 was rich in histidine (H) and serine (S), which contained a signal peptide of 16 amino acids at the N-terminus. NbPTP6 also had 6 potential O-glycosylation sites and 1 potential N-glycosylation site. The sequenn.
Patients with chronic low back pain undergoing lumbar spinal fusion (LSF) are physically inactive and thereby at risk of poor health. Barriers to being physically active need to be acknowledged in post-surgical rehabilitation. The primary objective of this randomized controlled trial (RCT) is to examine the effect of an early active intervention consisting of graded activity and pain education (GAPE) on sedentary behaviour in a population of patients undergoing LSF. The secondary objective is to examine the effect of GAPE on disability, pain, fear of movement, self-efficacy for exercise, and health-related quality of life.
The study is an RCT planned to include 144 patients undergoing LSF at 1-2 levels for low back pain caused by degeneration of the lumbar spine. ML349 The patients will be randomly assigned to receive either usual care or usual care plus GAPE. GAPE consists of nine individual physiotherapist-guided sessions over a 10-week period. The overall purpose is to reduce sedentary behaviour, by educatin's self-efficacy for exercise and quality of life.
www.clinicaltrials.gov NCT04103970 , Registered on 24 September 2019.
www.clinicaltrials.gov NCT04103970 , Registered on 24 September 2019.Recently, the focus of enhancing tumor radiosensitivity has shifted from chemotherapeutics to targeted therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a novel class of selective cell cycle therapeutics that target the cyclin D-CDK4/6 complex and induce G1 phase arrest. These agents have demonstrated favorable effects when used as monotherapy or combined with endocrine therapy and targeted inhibitors, stimulating further explorations of other combination strategies. Multiple preclinical studies have indicated that CDK4/6 inhibitors exhibit a synergistic effect with radiotherapy both in vitro and in vivo. The principal mechanisms of radiosensitization effects include inhibition of DNA damage repair, enhancement of apoptosis, and blockade of cell cycle progression, which provide the rationale for clinical use. CDK4/6 inhibitors also induce cellular senescence and promote anti-tumor immunity, which might represent potential mechanisms for radiosensitization. Several small sample clinical studies have preliminarily indicated that the combination of CDK4/6 inhibitors and radiotherapy exhibited well-tolerated toxicity and promising efficacy. However, most clinical trials in combined therapy remain in the recruitment stage. Further work is required to seek optimal radiotherapy-drug combinations. In this review, we describe the effects and underlying mechanisms of CDK4/6 inhibitors as a radiosensitizer and discuss previous clinical studies to evaluate the prospects and challenges of this combination.Contamination from present-day DNA is a fundamental issue when studying ancient DNA from historical or archaeological material, and quantifying the amount of contamination is essential for downstream analyses. We present AuthentiCT, a command-line tool to estimate the proportion of present-day DNA contamination in ancient DNA datasets generated from single-stranded DNA libraries. The prediction is based solely on the patterns of post-mortem damage observed on ancient DNA sequences. link2 The method has the power to quantify contamination from as few as 10,000 mapped sequences, making it particularly useful for analysing specimens that are poorly preserved or for which little data is available.
Plasmodium knowlesi is a significant cause of human malaria in Sarawak, Malaysian Borneo. Only one study has been previously undertaken in Sarawak to identify vectors of P. knowlesi, where Anopheles latens was incriminated as the vector in Kapit, central Sarawak. A study was therefore undertaken to identify malaria vectors in a different location in Sarawak.
Mosquitoes found landing on humans and resting on leaves over a 5-day period at two sites in the Lawas District of northern Sarawak were collected and identified. DNA samples extracted from salivary glands of Anopheles mosquitoes were subjected to nested PCR malaria-detection assays. The small subunit ribosomal RNA (SSU rRNA) gene of Plasmodium was sequenced, and the internal transcribed spacer 2 (ITS2) and mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of the mosquitoes were sequenced from the Plasmodium-positive samples for phylogenetic analysis.
Totals of 65 anophelines and 127 culicines were collected. By PCR, 6 An. link3 balabacensis and 5 vector for P. knowlesi in Kapit, central Sarawak, Malaysian Borneo, and now An. balabacensis and An. donaldi have been incriminated as vectors for zoonotic malaria in Lawas, northern Sarawak.
Atypical femoral fracture is one of the many complications after the long-term use of bisphosphonates. The American Society for Bone and Mineral Research has officially excluded periprosthetic femoral fractures (PFFs) from the definition of atypical femoral fractures (AFFs). Several case reports found that PFFs can occur with characteristics similar to those of AFFs. The purpose of our study was to evaluate the proportion of atypical fractures among Vancouver type B1 fractures, and to determine the association between the long-term use of bisphosphonates and the occurrence of atypical periprosthetic femoral fractures (APFFs).
In this retrospective study, we reviewed 41 patients with Vancouver type B1 periprosthetic fractures between January 1, 2011 and December 31, 2018. We classified them into two groups, namely atypical and typical PFFs, based on the fracture morphology. We noted the proportion of atypical periprosthetic fractures among B1 fractures and identified risk factors.
Among the 41 PFFs, 5 (1hu/hu/kutatasetika/jovahagyott-vizsgalatok-koezerdeku-adatai/category/25-jovahagyott-vizsgalatok-kozerdeku-adatai-rkeb-2019.html?download=98522-2019 .Exploitation of the protein degradation machinery as a therapeutic strategy to degrade oncogenic proteins is experiencing revolutionary advances with the development of proteolysis targeting chimeras (PROTACs). PROTACs are heterobifunctional structures consisting of a ligand that binds a protein to be degraded and a ligand for an E3 ubiquitin ligase. The bridging between the protein of interest and the E3 ligase mediated by the PROTAC facilitates ubiquitination of the protein and its proteasomal degradation. In this review we discuss the molecular medicine behind PROTAC mechanism of action, with special emphasis on recent developments and their potential translation to the clinical setting.
The goals of this retrospective study were to estimate parasite positivity in samples from cats using zinc sulfate fecal flotation by centrifugation ("centrifugation") and coproantigen and examine trends with age, geographical region and reason for visit to veterinarian. Common methods of parasite detection, such as centrifugal flotation, passive flotation, or direct smear, may underrepresent the true prevalence of intestinal parasites in cats. Coproantigen testing detects more positive samples than traditional methods alone.
Feline fecal test results from the continental USA containing results for fecal exams performed using centrifugation paired with coproantigen results for ascarid, hookworm, whipworm and Giardia were obtained from the database of a national commercial reference laboratory comprised of multiple regional sites.
Parasite positivity was highest in samples from young cats and decreased with cat age. The western region of the USA had lower total parasite positivity than other regions for all parasites except Giardia. Cats receiving fecal tests during veterinary wellness visits had only slightly lower parasite positivity than samples from cats during sick clinical visits.
This study showed a larger population of cats are at increased risk of parasitism than commonly believed and coproantigen testing produces more positive test results for the four parasites that antigen can detect than centrifugation of feline fecal samples.
This study showed a larger population of cats are at increased risk of parasitism than commonly believed and coproantigen testing produces more positive test results for the four parasites that antigen can detect than centrifugation of feline fecal samples.
Multi-agent chemotherapy is an important pillar in treatment of high-grade osteosarcoma. In an effort to improve patient survival, it is imperative to determine the effectiveness of new substances. The objective of this study was to investigate whether the chick chorioallantoic membrane (CAM) model can be used to analyze drug sensitivity in high-grade osteosarcoma.
Spare biopsy tissue from five patients diagnosed with high-grade osteosarcoma was transferred into non-immortalized primary cell culture. After a pre-incubation period of 10days, fertilized chick eggs were inoculated with primary tumor cells suspended in extracellular matrix gel. On day 16, treatment with 20µmol/l doxorubicin (n = 4) or 25µl of culture medium (n = 6) was performed for 24h. CAM membranes were documented macroscopically, harvested and examined histologically. Transfer of biopsy specimens into primary cell culture was successful in all cases. 50% (n = 10) of eggs died after inoculation with tumor cells and before application of doxorubicin.
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