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Brain Sciences Jun 2024Cerebral amyloid angiopathy is characterized by a weakening of the small- and medium-sized cerebral arteries, as their smooth muscle cells are progressively replaced...
Cerebral amyloid angiopathy is characterized by a weakening of the small- and medium-sized cerebral arteries, as their smooth muscle cells are progressively replaced with acellular amyloid β, increasing vessel fragility and vulnerability to microhemorrhage. In this context, an aberrant overactivation of the complement system would further aggravate this process. The surface protein CD59 protects most cells from complement-induced cytotoxicity, but expression levels can fluctuate due to disease and varying cell types. The degree to which CD59 protects human cerebral vascular smooth muscle (HCSM) cells from complement-induced cytotoxicity has not yet been determined. To address this shortcoming, we selectively blocked the activity of HCSM-expressed CD59 with an antibody, and challenged the cells with complement, then measured cellular viability. Unblocked HCSM cells proved resistant to all tested concentrations of complement, and this resistance decreased progressively with increasing concentrations of anti-CD59 antibody. Complete CD59 blockage, however, did not result in a total loss of cellular viability, suggesting that additional factors may have some protective functions. Taken together, this implies that CD59 plays a predominant role in HCSM cellular protection against complement-induced cytotoxicity. The overexpression of CD59 could be an effective means of protecting these cells from excessive complement system activity, with consequent reductions in the incidence of microhemorrhage. The precise extent to which cellular repair mechanisms and other complement repair proteins contribute to this resistance has yet to be fully elucidated.
PubMed: 38928601
DOI: 10.3390/brainsci14060601 -
International Journal of Molecular... Jun 2024Breast cancer is the type of cancer with the highest prevalence in women worldwide. Skeletal muscle atrophy is an important prognostic factor in women diagnosed with... (Review)
Review
Breast cancer is the type of cancer with the highest prevalence in women worldwide. Skeletal muscle atrophy is an important prognostic factor in women diagnosed with breast cancer. This atrophy stems from disrupted skeletal muscle homeostasis, triggered by diminished anabolic signalling and heightened inflammatory conditions, culminating in an upregulation of skeletal muscle proteolysis gene expression. The importance of delving into research on modulators of skeletal muscle atrophy, such as microRNAs (miRNAs), which play a crucial role in regulating cellular signalling pathways involved in skeletal muscle protein synthesis and degradation, has been recognised. This holds true for conditions of homeostasis as well as pathologies like cancer. However, the determination of specific miRNAs that modulate skeletal muscle atrophy in breast cancer conditions has not yet been explored. In this narrative review, we aim to identify miRNAs that could directly or indirectly influence skeletal muscle atrophy in breast cancer models to gain an updated perspective on potential therapeutic targets that could be modulated through resistance exercise training, aiming to mitigate the loss of skeletal muscle mass in breast cancer patients.
Topics: Humans; MicroRNAs; Breast Neoplasms; Female; Muscular Atrophy; Muscle, Skeletal; Animals; Muscle Development
PubMed: 38928418
DOI: 10.3390/ijms25126714 -
International Journal of Molecular... Jun 2024The review discusses the potential relationship between hypoxia resistance and longevity, the influence of carbon dioxide on the mechanisms of aging of the mammalian... (Review)
Review
The review discusses the potential relationship between hypoxia resistance and longevity, the influence of carbon dioxide on the mechanisms of aging of the mammalian organism, and intermittent hypercapnic-hypoxic effects on the signaling pathways of aging mechanisms. In the article, we focused on the potential mechanisms of the gero-protective efficacy of carbon dioxide when combined with hypoxia. The review summarizes the possible influence of intermittent hypoxia and hypercapnia on aging processes in the nervous system. We considered the perspective variants of the application of hypercapnic-hypoxic influences for achieving active longevity and the prospects for the possibilities of developing hypercapnic-hypoxic training methods.
Topics: Hypercapnia; Humans; Hypoxia; Animals; Carbon Dioxide; Life Expectancy; Aging; Longevity; Signal Transduction
PubMed: 38928217
DOI: 10.3390/ijms25126512 -
Antibiotics (Basel, Switzerland) Jun 2024Antimicrobial resistance (AMR) is a major public health threat linked to increased morbidity and mortality. It has the potential to return us to the pre-antibiotic era....
Antimicrobial resistance (AMR) is a major public health threat linked to increased morbidity and mortality. It has the potential to return us to the pre-antibiotic era. Antimicrobial stewardship (AMS) programs are recognized as a key intervention to improve antimicrobial use and combat AMR. However, implementation of AMS remains limited in Africa, particularly in Rwanda. This study aimed to assess prescription practices, identify areas for improvement, and promote adherence to AMS principles. Conducted at King Faisal Hospital in Rwanda, this qualitative study used semi-structured interviews with eight participants until saturation was reached. The interviews were recorded, transcribed, and thematically analyzed, revealing four emerging themes. The first theme was on AMS activities that were working well based on availability of microbiology laboratory results and prescription guidelines as factors influencing antibiotic prescription adjustments. The second theme was related to challenges during the implementation of the AMS program, including the prescription of broad-spectrum antibiotics, limited local data on AMR patterns, and stock-outs of essential antibiotics. The third theme was on the importance of adhering to AMR management guidelines at KFH. The last emerged on recommendations from participants centered on regular training for healthcare workers, widespread dissemination of AMR findings across departments, and the enforcement of antibiotic restriction policies. These actions can improve prescription behaviors, upholding the highest standards of patient care, and strengthening the nascent AMS program.
PubMed: 38927214
DOI: 10.3390/antibiotics13060548 -
Antibiotics (Basel, Switzerland) Jun 2024is an indicator micro-organism in One Health antibiotic resistance surveillance programs. The purpose of the study was to describe and compare isolates obtained from...
is an indicator micro-organism in One Health antibiotic resistance surveillance programs. The purpose of the study was to describe and compare isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole-genome sequencing (WGS). Porcine isolates were proportionally more resistant phenotypically and harbored a richer diversity of antibiotic resistance genes as compared to human isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%, 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169), were detected at low frequencies. Sequence type complex (STc) 10 was the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human-livestock interface according to multilocus sequence typing (MLST). Core-genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2-HC200 was observed. In conclusion, even though the isolates shared a spatiotemporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles and cgMLST and HC according to the source of isolation.
PubMed: 38927209
DOI: 10.3390/antibiotics13060543 -
Antibiotics (Basel, Switzerland) Jun 2024While multiple studies have focused on the motivations surrounding antibiotic prescription among veterinarians, little is known about companion animal owners' knowledge,...
While multiple studies have focused on the motivations surrounding antibiotic prescription among veterinarians, little is known about companion animal owners' knowledge, attitude and perception (KAP) regarding the topic. A nationwide survey directed toward Portuguese dog and cat owners was conducted online and at veterinary practices to characterize their KAP regarding antibiotics. After database curation, a total of 423 valid submissions were considered. Although 97.9% of respondents stated that they knew what an antibiotic was, 23.5% and 19.2% answered that they were used to treat viral and fungal infections, respectively. Antimicrobial effectiveness was favored over cost when 87.7% of owners agreed they would prefer to spend more money to identify the appropriate antibiotic. Around 87% of respondents recognized antibiotic resistance as a significant health problem and 74.6% strongly agreed/somewhat agreed that antibiotic use in pets may contribute to resistance development. However, only 25.3% recognized that this could promote resistance dissemination, showing little awareness of the interconnection between human and animal health. Moreover, 55.6% of respondents were neutral when asked whether antibiotics used in veterinary medicine were also important for humans. These findings suggest that communication between veterinarians and pet owners can still be improved to further clarify the impact that antibiotic use has in pets from a One-Health perspective, also enabling antimicrobial stewardship interventions.
PubMed: 38927199
DOI: 10.3390/antibiotics13060533 -
Antibiotics (Basel, Switzerland) May 2024Antibiotic resistance poses a significant threat to public health, that can lead to reduced effectiveness of many therapies, increased morbidity, longer hospitalization...
INTRODUCTION
Antibiotic resistance poses a significant threat to public health, that can lead to reduced effectiveness of many therapies, increased morbidity, longer hospitalization times, increased deaths, and additional costs for health care systems. Unreasonable use of antibiotics may result from a lack of adequate knowledge about antibiotic therapy and a lack of knowledge of the risks associated with antibiotic resistance, both among medical personnel and patients.
AIM
The primary objective of the study was to verify the opinion of medical personnel on the risks associated with antibiotic resistance.
MATERIAL AND METHODS
The study was conducted in 2023 among 605 Polish sanitary workers. An anonymous survey designed specifically for the purpose of the study was used. The survey was made available on the Internet through the Trade Unions of Pharmacy Workers and directly to hospitals with the support of local authorities.
RESULTS
The majority of respondents were women (77.36%). The largest group consisted of individuals over 40 years of age (55.04%). More than half of the respondents were nurses (56.20%), and every fourth of the respondents was a physician (23.64%). Most respondents consider antibiotic resistance to be a very serious (24.13%) or extremely serious (30.75%) problem. The problem of antibiotic resistance on a global scale was mentioned, especially in the opinions of physicians and nurses ( < 0.01), people working in the profession for over a year ( < 0.01), and people with a specialization or undergoing specialist training ( = 0.00). Similarly, these groups most often indicated that antibiotic resistance poses a problem in their workplace. The main problems of antibiotic resistance were the use of antibiotics in farm animals (36.69%), the pressure on patients to take antibiotics (38.84%), and the prophylactic use of antibiotics (43.15%).
CONCLUSIONS
Medical personnel consider antibiotic resistance a somewhat serious problem, although not all agree in this regard. The risk of antibiotic resistance is much more seriously assessed by physicians and nurses, as well as by people with specializations or undergoing specialization training. Knowledge about antibiotic resistance should be further spread among all groups of medical personnel.
PubMed: 38927161
DOI: 10.3390/antibiotics13060493 -
Antibiotics (Basel, Switzerland) May 2024The ultimate goal of antimicrobial stewardship (AMS) programmes is to decrease the occurrence and spread of antimicrobial resistance (AMR). In response to this, a...
The ultimate goal of antimicrobial stewardship (AMS) programmes is to decrease the occurrence and spread of antimicrobial resistance (AMR). In response to this, a pharmacist partnership was established between Malawi and Wales (UK) with the aim of strengthening antimicrobial stewardship (AMS) activities in Malawi, with the initial project focusing on two tertiary referral hospitals. The Global Point Prevalence Survey (GPPS) was undertaken for the first time in Malawi at these sites and demonstrated a prescribing rate slightly lower than the African average, with ceftriaxone indicated for almost every bacterial infection. An educational intervention was also delivered, with a train-the-trainer approach upskilling pharmacists at the two sites, who then cascaded co-produced training sessions to an additional 120 multidisciplinary health professionals. A toolkit to support AMS at an individual patient level was also developed and disseminated to provide an ongoing reference to refer to. Both the trainings and toolkit were well received. Over the course of this project, significant progress has been made with the AMS programmes at the two sites, with local staff empowered to implement AMS activities. These interventions could be easily replicated and scaled and support the delivery of some of the AMS elements of the Malawi Ministry of Health National Action Plan for Antimicrobial Resistance.
PubMed: 38927147
DOI: 10.3390/antibiotics13060480 -
Evolution of STAT2 resistance to flavivirus NS5 occurred multiple times despite genetic constraints.Nature Communications Jun 2024Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host interferon response is...
Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host interferon response is required for viremia and pathogenesis in a vertebrate host. This affects viral species tropism, as mouse STAT2 resistance renders only immunocompromised or humanized STAT2 mice infectable. Here, we explore how STAT2 evolution impacts antagonism. By measuring the susceptibility of 38 diverse STAT2 proteins, we demonstrate that resistance arose numerous times in mammalian evolution. In four species, resistance requires distinct sets of multiple amino acid changes that often individually disrupt STAT2 signaling. This reflects an evolutionary ridge where progressive resistance is balanced by the need to maintain STAT2 function. Furthermore, resistance may come with a fitness cost, as resistance that arose early in lemur evolution was subsequently lost in some lemur lineages. These findings underscore that while it is possible to evolve resistance to antagonism, complex evolutionary trajectories are required to avoid detrimental host fitness consequences.
Topics: STAT2 Transcription Factor; Animals; Viral Nonstructural Proteins; Evolution, Molecular; Humans; Mice; Dengue Virus; Zika Virus; Flavivirus; Phylogeny; Host-Pathogen Interactions
PubMed: 38926343
DOI: 10.1038/s41467-024-49758-0 -
BMJ Open Jun 2024Patients with cirrhosis awaiting liver transplantation (LT) are often frail, and malnourished. The period of time on the waitlist provides an opportunity to improve...
INTRODUCTION
Patients with cirrhosis awaiting liver transplantation (LT) are often frail, and malnourished. The period of time on the waitlist provides an opportunity to improve their physical fitness. Prehabilitation appears to improve the physical fitness of patients before major surgery. Little is known about prehabilitation in patients with cirrhosis. The aim of this feasibility study will be to investigate the feasibility, safety, and effectiveness of a multimodal prehabilitation programme in this patient population.
METHODS AND ANALYSIS
This is an open-label single-arm feasibility trial recruiting 25 consecutive adult patients with cirrhosis active on the LT waiting list of the McGill University Health Centre (MUHC). Individuals will be excluded based on criteria developed for the safe exercise training in patients with cirrhosis. Enrolled individuals will participate in a multimodal prehabilitation programme conducted at the PeriOperative Programme complex of the MUHC. It includes exercise training with a certified kinesiologist (aerobic and resistance training), nutritional optimisation with a registered dietician and psychological support with a nurse specialist. The exercise training programme is divided into an induction phase with three sessions per week for 4 weeks followed by a maintenance phase with one session every other week for 20 weeks. Aerobic training will be individualised based on result from cardiopulmonary exercise testing (CPET) and will include a high-intensity interval training on a cycle ergometer. Feasibility, adherence and acceptability of the intervention will be assessed. Adverse events will be reviewed before each visit. Changes in exercise capacity (6-minute walk test, CPET, liver frailty index), nutritional status and health-related quality of life will be assessed during the study. Post-transplantation outcomes will be recorded.
ETHICS AND DISSEMINATION
The research ethics board of the MUHC has approved this study (2021-7646). Our findings will be submitted for presentation at national and international conferences, and for peer-reviewed publication.
TRIAL REGISTRATION NUMBER
NCT05237583.
Topics: Humans; Liver Transplantation; Feasibility Studies; Liver Cirrhosis; Preoperative Exercise; Waiting Lists; Quality of Life; Physical Fitness; Adult; Exercise Therapy; Male; Female
PubMed: 38925705
DOI: 10.1136/bmjopen-2023-081362