Freemanvendelbo9728
Bacterial resistance is considered one of the most important public health problems of the century, due to the rapid ability of bacteria to develop resistance mechanisms, which makes it difficult to treat infections, leading to a high rate of morbidity and mortality. Based on this, several options are being sought as an alternative to currently available treatments, with a particular focus on nanotechnology. Nanomaterials have important potential for use in medical interventions aimed at preventing, diagnosing and treating numerous diseases by directing the delivery of drugs. This review presents data on the use of polymeric nanoparticles related to in vitro and in vivo activity against bacteria belonging to the Enterobacteriaceae family.Cyclophilin A (CypA) is a ubiquitous and highly conserved protein. CypA, the intracellular target protein for the immunosuppressant cyclosporine A (CsA), plays important cellular roles through peptidyl-prolyl cis-trans isomerase (PPIase). Increasing evidence shows that CypA is up-regulated in a variety of human cancers. In addition to being involved in the occurrence and development of multiple tumors, overexpression of CypA also has been shown to be strongly associated with malignant transformation. Surgery, chemotherapy and radiotherapy are the three main treatments for cancer. Chemotherapy and radiotherapy are often used as direct or adjuvant treatments for cancer. However, various side effects and resistance to both chemotherapy and radiotherapy bring great challenges to these two forms of treatment. According recent reports, CypA can improve the chemosensitivity and/or radiosensitivity of cancers, possibly by affecting the expression of drug-resistant related proteins, cell cycle arrest and activation of the mitogen-activated protein kinase (MAPK) signaling pathways. In this review, we focus on the role of CypA in cancer, the impact on cancer chemotherapeutic and radiotherapy sensitivity, and the mechanism of action. It is suggested that CypA may be a novel potential therapeutic target for cancer chemotherapy and/or radiotherapy.
To identify and characterize peptide binders to truncated recombinant chikungunya virus envelope protein 2.
Despite extensive research on the chikungunya virus (CHIKV), the specific antiviral treatment's unavailability has stressed the need for the urgent development of therapeutics. The Envelope protein 2 (E2) of CHIKV that displays putative receptor binding sites and specific epitopes for virus neutralizing antibodies is a critical target for the therapeutic intervention.
The study aims to identify the unique peptides that can bind to truncated E2 protein of CHIKV and further explore their properties as potential therapeutic candidate.
A stretch of CHIKV-E2 (rE2), which is prominently exposed on the surface of virion, was used as bait protein to identify peptide binders to the CHIKV-rE2 using a 12-mer phage display peptide library. Three rounds of biopanning yielded several peptide binders to CHIKV-rE2 and their binding affinities were compared by phage ELISA. Additionally, a fully flexible-blind docking simulation investigated the possible binding modes of the selected peptides. Furthermore, the selected peptides were characterized and their ADMET properties were explored in silico.
Five peptides were identified as potential binders based on their robust reactivity to the bait protein. The selected peptides appeared to interact with the crucial residues that were notably exposed on the surface of E1-E2 trimeric structure. The explored in silico studies suggested their non-allergenicity, non-toxicity and likeliness to be antiviral.
The potential binding peptides of CHIKV-rE2 protein were identified using phage display technology and characterized in silico. The selected peptides could be further used for the development of therapeutics against the CHIKV infection.
The potential binding peptides of CHIKV-rE2 protein were identified using phage display technology and characterized in silico. The selected peptides could be further used for the development of therapeutics against the CHIKV infection.In Jordan, almost any medication can be bought from pharmacies. This ready availability is linked with abuse. Previous literature describes medicine abuse from pharmacists' and general public perspectives. Here we investigate experiences of 17 men in addiction treatment in Amman (21-39 years) of obtaining psychoactive medicines. Alprazolam, clonazepam, bromazepam and tramadol were most commonly abused. Psychoactive medicines were obtained from street dealers, but pharmacies were preferred. Regulations appears ineffective; lack of understanding of pharmacists of the abuse potential of some medicines was perceived; 'softening rules' on supply was attributed to cultural and social norms around familiarity.
Studies of mechanically ventilated patients with a low risk of reintubation have suggested that the use of high-flow nasal cannula (HFNC) oxygen therapy reduces the risk of reintubation compared with conventional oxygen therapy (COT). However, the effect of HFNC following extubation in elderly patients with a high risk of reintubation remains unclear.
All consecutive medical intensive care unit (ICU) patients aged >65 years who were mechanically ventilated for >24 h were prospectively registered between July 2017 and June 2018. Control was obtained from a historical database of patients attending the same ICU from January 2012 to December 2013. A total of 152 patients who underwent HFNC after planned extubation according to institutional protocols (HFNC group) were compared with a propensity-matched historical control group who underwent COT (
= 175, COT group). The primary outcome was the proportion of reintubated patients within 48 h after planned extubation.
One hundred patients from the HFNC reviews of this paper are available via the supplemental material section.
Respiratory viral infections, particularly influenza, are known to cause significant morbidity and mortality, often due to secondary infections. Our aim was to comparatively analyze the incidence, epidemiology, and outcomes of secondary pneumonia in adult patients hospitalized with influenza
noninfluenza viral infections and determine whether influenza particularly predisposes to secondary infections.
This was a retrospective analysis from a single tertiary medical center of adult patients admitted to the hospital between 2008 and 2010 with respiratory viral infections. Microbiological patterns and clinical outcomes were compared between those with influenza (VI,
= 57) and those with noninfluenza (NI,
= 77) respiratory viral infections.
The NI group was older (60.6 ± 14.0
53.3 ± 19.7 years,
= 0.019) with higher rates of lung transplantation (29%
9%,
= 0.009) than VI. Overall, 35% developed secondary pneumonia, higher among NI (44%) than VI (23%,
= 0.017).
was the most common cn among adults hospitalized with viral respiratory infections. Within our population, NI results in more frequent secondary pneumonia and longer hospital stays than those with VI. Given the high number of infections caused by Gram-negative rods, monitoring local epidemiology is critical for guiding initial antibiotic selection in empirical treatment of secondary infections.The reviews of this paper are available via the supplemental material section.
We reviewed the effect of a hybrid remediation model combining co-regulated learning and deliberate practice on future exam performance of pre-clerkship medical students who had been unsuccessful on a previous clinic skills exam. With this remediation model, we aimed to strengthen students' self-regulated learning to improve future exam performance and support sustained and improved learning.
Observing that some students who initially performed well post remediation with deliberate practice, still struggled on future exams, we looked to address a method that could improve both short-and long-term clinical skills learning success with sustained performance.
Comparing the remediated students' exam scores pre- and post-coaching to their cohort's performance, we observed the majority of students post remediation performed above their cohort's exam average.
Combining learning models resulted in improved learning outcomes.
We reviewed the effect of a hybrid remediation model combining co-regulated learning and deliberate practice on future exam performance of pre-clerkship medical students who had been unsuccessful on a previous clinic skills exam. With this remediation model, we aimed to strengthen students' self-regulated learning to improve future exam performance and support sustained and improved learning. Educational problem addressed Observing that some students who initially performed well post remediation with deliberate practice, still struggled on future exams, we looked to address a method that could improve both short-and long-term clinical skills learning success with sustained performance. Intervention outcome Comparing the remediated students' exam scores pre- and post-coaching to their cohort's performance, we observed the majority of students post remediation performed above their cohort's exam average. Lessons learned Combining learning models resulted in improved learning outcomes.Universal Health Coverage (UHC) forces governments to consider not only how services will be provided - but which services - and to whom, when, where, how and at what cost. This paper considers the implications for achieving UHC through the lens of abortion-related care for adolescents. Our comparative study design includes three countries purposively selected to represent varying levels of restriction on access to abortion Ethiopia (abortion is legal and services implemented); Zambia (legal, complex services with numerous barriers to implementations and provision of information); Malawi (legally highly restricted). Glycochenodeoxycholic acid chemical Our policy and legal analyses are supplemented by comparative vignettes based on interviews (n = 330) in 2018/2019 with adolescents aged 10-19 who have sought abortion-related care in each country. We focus on an under-considered but critical legal framing for adolescents - the age of consent. We compare legal and political commitments to advancing adolescent sexual and reproductive health and rights, including abortion-related care. Ethiopia appears to approach UHC for safe abortion care, and the legal provision for under 18-year-olds appears to be critical. In Malawi, the most restrictive legal environment for abortion, little progress appears to have been made towards UHC for adolescents. In Zambia, despite longstanding legal provision for safe abortion on a wide range of grounds, the limited services combined with low levels of knowledge of the law mean that the combined rights and technical agendas of UHC have not yet been realised. Our comparative analyses showing how policies and laws are framed have critical implications for equity and justice.
Chest high-resolution computed tomography (HRCT) is the central diagnostic tool in discerning idiopathic pulmonary fibrosis (IPF) from other interstitial lung disease (ILDs). In 2018, new guidelines were published and the nomenclature for HRCT interpretation was changed. We sought to evaluate how clinicians' interpretation would change based on reading HRCTs under the framework of the old
new categorization.
We collated HRCTs from 50 random cases evaluated in the Inova Fairfax ILD clinic. Six ILD experts were provided the deidentified HRCTs. They were all instructed to independently provide two reads of each HRCT, based on the old and the new guidelines.
The kappa statistic for concordance for HRCT reads under old guidelines was 0.5, while for the new guidelines it was 0.38. Under the framework of the old guidelines, there were 22 HRCTs with unanimous consensus reads, while only 15 with the new guidelines. There were 12 HRCTs read unanimously as usual interstitial pneumonia (UIP) pattern based on both the old and the new guidelines.
