Search

Background: The coronavirus disease 2019 seems to change antibiotic resistance pattern. Certain conditions in the Covid-19 era may be contributing to the rise of antimicrobial resistance (AMR). Due to the limited information on the impact of Covid-19 on antimicrobial resistance (AMR), the purpose of this research was to investigate the trend in antimicrobial resistance changes of E. coli, P. aeruginosa, K. pneumoniae, and A. baumannii in Hasheminezhad hospital. This hospital was a Corona center in Mashhad at the onset of this epidemic. Methods: 1672 clinical samples were collected between January 21, 2020 and January 30, 2022from patients hospitalized at Hasheminezhad Hospital in Mashhad, Conventional microbiological procedures for identifying gram-negative bacteria and antibiotic susceptibility testing were used, according to the clinical and laboratory standards institute (CLSI) 2021. The two years of the pandemic, from the initial stage of the outbreak until the 6th peak, (January 2020 to and January 2022) were divided into 9 periods according to the seasons. Results: Highest resistance rates were seen in E. coli (615 samples), K. pneumoniae (351 samples), P. aeruginosa (362 samples) and A. baumannii (344 samples) to Ampicillin (89.6%), Ampicillin (98%), Imipenem (91.8%), and Ceftazidime (94.6%), respectively. The largest change in antibiotic resistance was seen between Summer 2020 and Summer 2021 for K. pneumoniae with about a 30% rise in antibiotic resistance to Ceftriaxone. Conclusions: All 4 species evaluated in this study, have shown rising AMR rates during the first year of the pandemic in the northeast of Iran. This study revealed that E. coli, P. aeruginosa, K. pneumoniae, and A. baumannii strains in Northern Iran have a higher level of antibiotic resistance than what was measured in similar studies conducted before the pandemic. This will further restrict treatment choices and jeopardize global public health. [ABSTRACT FROM AUTHOR]

Background: The aim of the study is two-fold. It explores how managers and key employees at the Emergency Department (ED) and specialist departments in a university hospital in the Capital Region of Denmark respond to the planned change to a new ED, and how they perceive the change involved in the implementation of the new ED. The study investigates what happens when health professionals are confronted with implementation of policy that changes their organization and everyday work lives. Few studies provide in-depth investigations of health professionals' reactions to the implementation of new EDs, and particularly how they influence the implementation of a nationwide organizational change framed within a political strategy. Methods: The study used semi-structured individual interviews with 51 health professionals involved in implementation activities related to an organizational change of establishing a new ED with new patient pathways for acutely ill patients. The data was deductively analyzed using Leon Coetsee's theoretical framework of change responses, but the analysis also allowed for a more inductive reading of the material. Results: Fourteen types of responses to establishing a new ED were identified and mapped onto six of the seven overall change responses in Coetsee's framework. The participants perceived the change as particularly three changes. Firstly, they wished to create the best possible acute patient pathway in relation to their specialty. Whether the planned new ED would redeem this was disputed. Secondly, participants perceived the change as relocation to a new building, which both posed potentials and worries. Thirdly, both hopeful and frustrated statements were given about the newly established medical specialty of emergency medicine (EM), which was connected to the success of the new ED. Conclusions: The study showcases how implementation processes within health care are not straightforward and that it is not only the content of the implementation that determines the success of the implementation and its outcomes but also how these are perceived by managers and employees responsible for the process and their context. In this way, managers must recognize that it cannot be pre-determined how implementation will proceed, which necessitates fluid implementation plans and demands implementation managements skills. [ABSTRACT FROM AUTHOR]

Background: Elements are the basis of life on Earth, whereby organisms are essentially evolved chemical substances that dynamically interact with each other and their environment. Determining species elemental quotas (their elementome) is a key indicator for their success across environments with different resource availabilities. Elementomes remain undescribed for functionally diverse dinoflagellates within the family Symbiodiniaceae that includes coral endosymbionts. We used dry combustion and ICP-MS to assess whether Symbiodiniaceae (ten isolates spanning five genera Breviolum, Cladocopium, Durusdinium, Effrenium, Symbiodinium) maintained under long-term nutrient replete conditions have unique elementomes (six key macronutrients and nine micronutrients) that would reflect evolutionarily conserved preferential elemental acquisition. For three isolates we assessed how elevated temperature impacted their elementomes. Further, we tested whether Symbiodiniaceae conform to common stoichiometric hypotheses (e.g., the growth rate hypothesis) documented in other marine algae. This study considers whether Symbiodiniaceae isolates possess unique elementomes reflective of their natural ecologies, evolutionary histories, and resistance to environmental change. Results: Symbiodiniaceae isolates maintained under long-term luxury uptake conditions, all exhibited highly divergent elementomes from one another, driven primarily by differential content of micronutrients. All N:P and C:P ratios were below the Redfield ratio values, whereas C:N was close to the Redfield value. Elevated temperature resulted in a more homogenised elementome across isolates. The Family-level elementome was (C19.8N2.6 P1.0S18.8K0.7Ca0.1) · 1000 (Fe55.7Mn5.6Sr2.3Zn0.8Ni0.5Se0.3Cu0.2Mo0.1V0.04) mmol Phosphorous-1 versus (C25.4N3.1P1.0S23.1K0.9Ca0.4) · 1000 (Fe66.7Mn6.3Sr7.2Zn0.8Ni0.4Se0.2Cu0.2Mo0.2V0.05) mmol Phosphorous -1 at 27.4 ± 0.4 °C and 30.7 ± 0.01 °C, respectively. Symbiodiniaceae isolates tested here conformed to some, but not all, stoichiometric principles. Conclusions: Elementomes for Symbiodiniaceae diverge from those reported for other marine algae, primarily via lower C:N:P and different micronutrient expressions. Long-term maintenance of Symbiodiniaceae isolates in culture under common nutrient replete conditions suggests isolates have evolutionary conserved preferential uptake for certain elements that allows these unique elementomes to be identified. Micronutrient content (normalised to phosphorous) commonly increased in the Symbiodiniaceae isolates in response to elevated temperature, potentially indicating a common elemental signature to warming. [ABSTRACT FROM AUTHOR]

Background: The aim of the study is two-fold. It explores how managers and key employees at the Emergency Department (ED) and specialist departments in a university hospital in the Capital Region of Denmark respond to the planned change to a new ED, and how they perceive the change involved in the implementation of the new ED. The study investigates what happens when health professionals are confronted with implementation of policy that changes their organization and everyday work lives. Few studies provide in-depth investigations of health professionals' reactions to the implementation of new EDs, and particularly how they influence the implementation of a nationwide organizational change framed within a political strategy.Methods: The study used semi-structured individual interviews with 51 health professionals involved in implementation activities related to an organizational change of establishing a new ED with new patient pathways for acutely ill patients. The data was deductively analyzed using Leon Coetsee's theoretical framework of change responses, but the analysis also allowed for a more inductive reading of the material.Results: Fourteen types of responses to establishing a new ED were identified and mapped onto six of the seven overall change responses in Coetsee's framework. The participants perceived the change as particularly three changes. Firstly, they wished to create the best possible acute patient pathway in relation to their specialty. Whether the planned new ED would redeem this was disputed. Secondly, participants perceived the change as relocation to a new building, which both posed potentials and worries. Thirdly, both hopeful and frustrated statements were given about the newly established medical specialty of emergency medicine (EM), which was connected to the success of the new ED.Conclusions: The study showcases how implementation processes within health care are not straightforward and that it is not only the content of the implementation that determines the success of the implementation and its outcomes but also how these are perceived by managers and employees responsible for the process and their context. In this way, managers must recognize that it cannot be pre-determined how implementation will proceed, which necessitates fluid implementation plans and demands implementation managements skills. [ABSTRACT FROM AUTHOR]

Background: Clinical quality registries (CQRs) can likely improve quality in healthcare and research. However, studies indicate that effective use of CQRs is hindered by lack of engagement and interest among stakeholders, as well as factors related to organisational context, registry design and data quality. To fulfil the potential of CQRs, more knowledge on stakeholders' perceptions of the factors that will facilitate or hamper the development of CQRs is essential to the more appropriate targeting of registry implementation and the subsequent use of the data. The primary aim of this study was to examine factors that can potentially affect the development of a national CQR for interventional radiology in Norway from the perspective of stakeholders. Furthermore, we wanted to identify the intervention functions likely to enable CQR development. Only one such registry, located in Sweden, has been established. To provide a broader context for the Norwegian study, we also sought to investigate experiences with the development of this registry.Methods: A qualitative study of ten Norwegian radiologists and radiographers using focus groups was conducted, and an in-depth interview with the initiator of the Swedish registry was carried out. Questions were based on the Capability, Opportunity and Motivation for Behaviour Model and the Theoretical Domains Framework. The participants' responses were categorised into predefined themes using a deductive process of thematic analysis.Results: Knowledge of the rationale used in establishing a CQR, beliefs about the beneficial consequences of a registry for quality improvement and research and an opportunity to learn from a well-developed registry were perceived by the participants as factors facilitating CQR development. The study further identified a range of development barriers related to environmental and resource factors (e.g., a lack of organisational support, time) and individuallevel factors (e.g., role boundaries, resistance to change), as well as several intervention functions likely to be appropriate in targeting these barriers.Conclusion: This study provides a deeper understanding of factors that may be involved in the behaviour of stakeholders regarding the development of a CQR. The findings may assist in designing, implementing and evaluating a methodologically rigorous CQR intervention. [ABSTRACT FROM AUTHOR]

Background: Emotional and behavioural problems linked to changes to expectations – resistance to change – are linked to disability in neurodevelopmental disorders, including autism spectrum disorder (ASD), Prader-Willi (PWS) and fragile X syndromes (FXS). Structuring routines is best practice for minimising current resistance to change. But complete structure is impractical and flexibility in early life may actually reduce later resistance by supporting cognitive development. We aimed to examine the psycho-social context of families with children at risk of developing resistance to change so as to identify design requirements for an intervention that strikes a beneficial balance between structure and flexibility. Methods: Thirty-six caregivers of children aged 4–12 years (17 ASD, 15 PWS, and 4 FXS) took part in an interview designed collaboratively with 12 professional stakeholders. Results: Children need to feel like they are in control of flexibility but they also need support in choice making, understanding plans (using individually tailored visuals) and anxiety reduction. Caregivers need an accessible approach that they have full control over, and which they can tailor for their child. Caregivers also need clear guidance, education and support around structure and flexibility. Conclusions: We propose a digital approach which addresses the needs identified. It tackles the most perplexing challenge by presenting flexibility to children in the context of a game that children can feel they have full control over, whilst caregivers can maintain control in reality. Furthermore, individualised support for children and caregivers would be enabled. [ABSTRACT FROM AUTHOR]

Background: Resistance to change and organizational culture are essential factors to consider in change management in health care settings. Implementation of structural change remains a challenge. There is a lack of studies providing information on the impact of implementation processes on the organization. The aim of this study was to describe the impact of implementing a systematic change process concerning postoperative person-centred pain management on resistance to change and organizational culture in an orthopaedic spine surgery unit.Methods: The study was set in an orthopaedic spine surgery unit at a university hospital. Person-centred bundles of care for postoperative pain management of spine surgery patients were developed in co-creation by a multi-professional expert group and implemented throughout the care pathway. The intervention was underpinned by theories on organizational culture and inspired by principles of person-centred care. Quantitative data were collected using the Resistance to Change Scale and the Organizational Culture Assessment Instrument and analysed using descriptive statistics.Results: The findings showed a low resistance to change decreasing during the study. The organizational culture shifted from a result-oriented to a formalized and structured culture after the implementation. The culture preferred by the staff was team-oriented and participation-focused throughout the study. The discrepancy between the current and preferred cultures remained extensive over time.Conclusion: It is challenging to describe the influence of the development and implementation of a postoperative pain management program on organizational culture as well as in terms of resistance to change, in a complex health care setting. In the current study the unit was under organizational strain during the implementation. Albeit, the important discrepancy between the current and preferred organizational culture could imply that structural changes aren't enough when implementing person-centred pain management structures and needs to be combined with relational aspects of change. [ABSTRACT FROM AUTHOR]

Hypoxia typically accompanies acute inflammatory responses in patients and animal models. However, a limited number of studies have examined the effect of hypoxia in combination with inflammation (Hypo-Inf) on neural function. We previously reported that neuronal excitability in hippocampal CA1 neurons decreased during hypoxia and greatly rebounded upon reoxygenation. We attributed this altered excitability mainly to the dynamic regulation of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels and input resistance. However, the molecular mechanisms underlying input resistance changes by Hypo-Inf and reperfusion remained unclear. In the present study, we found that a change in the density of the delayed rectifier potassium current (IDR) can explain the input resistance variability. Furthermore, voltage-dependent inactivation of A-type potassium (IA) channels shifted in the depolarizing direction during Hypo-Inf and reverted to normal upon reperfusion without a significant alteration in the maximum current density. Our results indicate that changes in the input resistance, and consequently excitability, caused by Hypo-Inf and reperfusion are at least partially regulated by the availability and voltage dependence of KV channels. Moreover, these results suggest that selective KV channel modulators can be used as potential neuroprotective drugs to minimize hypoxia- and reperfusion-induced neuronal damage. [ABSTRACT FROM AUTHOR]

Background: Safe, high-quality surgical care in many African countries is a critical need. Challenges include availability of surgical providers, improving quality of care, and building workforce capacity. Despite growing evidence that mentoring is effective in African healthcare settings, less is known about its role in surgery. We examined a multimodal approach to mentorship as part of a safe surgery intervention (Safe Surgery 2020) to improve surgical quality. Our goal was to distill lessons for policy makers, intervention designers, and practitioners on key elements of a successful surgical mentorship program.Methods: We used a convergent, mixed-methods design to examine the experiences of mentees, mentors, and facility leaders with mentorship at 10 health facilities in Tanzania's Lake Zone. A multidisciplinary team of mentors worked with surgical providers over 17 months using in-person mentorship, telementoring, and WhatsApp. We conducted surveys, in-depth interviews, and focus groups to capture data in four categories: (1) satisfaction with mentorship; (2) perceived impact; (3) elements of a successful mentoring program; and (4) challenges to implementing mentorship. We analyzed quantitative data using frequency analysis and qualitative data using the constant comparison method. Recurrent and unifying concepts were identified through merging the qualitative and quantitative data.Results: Overall, 96% of mentees experienced the intervention as positive, 88% were satisfied, and 100% supported continuing the intervention in the future. Mentees, mentors, and facility leaders perceived improvements in surgical practice, the surgical ecosystem, and in reducing postsurgical infections. Several themes related to the intervention's success emerged: (1) the intervention's design, including its multimodality, side-by-side mentorship, and standardization of practices; (2) the mentee-mentor relationship, including a friendly, safe, non-hierarchical, team relationship, as well as mentors' understanding of the local context; and (3) mentorship characteristics, including non-judgmental feedback, experience, and accessibility. Challenges included resistance to change, shortage of providers, mentorship dose, and logistics.Conclusions: Our study suggests a multimodal mentorship approach is promising in building the capacity of surgical providers. By distilling the experiences of the mentees, mentors, and facility leaders, our lessons provide a foundation for future efforts to establish effective surgical mentorship programs that build provider capacity and ultimately improve surgical quality. [ABSTRACT FROM AUTHOR]

Background: Electronic health record (EHR) systems often face user resistance in hospitals, which results in a failure to acquire their full benefits. To implement the EHR successfully, it is crucial to reduce nurses' resistance to use the system. This study aimed to investigate the factors associated with nurses' resistance to use the EHR system.Methods: A descriptive correlational study was conducted with nurses working at four university hospitals in Korea using self-administered questionnaires to measure user resistance behavior, resistance to change, perceived usefulness, perceived ease of use, perceived value, colleagues' opinions, self-efficacy for change, and organizational support for change. Path analysis was performed to examine direct and indirect association with user resistance behavior.Results: A total of 223 nurses completed the questionnaires. All seven factors were found to be significantly associated with user resistance, either directly or indirectly. The total effect on user resistance behavior was highest in resistance to change (0.65), followed by perceived usefulness (- 0.33); both had direct but no indirect effects. Conversely, self-efficacy for change (- 0.25), perceived value (- 0.21), colleagues' opinions (- 0.16), perceived ease of use (- 0.16), and organizational support for change (- 0.05) had indirect but no direct effects.Conclusions: The study examined the factors associated with nurses' user resistance behavior after the implementation of a new EHR system. These findings could help hospitals develop better EHR implementation strategies to reduce user resistance behavior among the nursing staff. [ABSTRACT FROM AUTHOR]

Background: Obesity leads to low-grade inflammation in the adipose tissue and liver and neuroinflammation in the brain. Obesity-induced insulin resistance (IR) and neuroinflammation seem to intensify neurodegeneration including Alzheimer's disease. In this study, the impact of high-fat (HF) diet-induced obesity on potential neuroinflammation and peripheral IR was tested separately in males and females of THY-Tau22 mice, a model of tau pathology expressing mutated human tau protein.Methods: Three-, 7-, and 11-month-old THY-Tau22 and wild-type males and females were tested for mobility, anxiety-like behavior, and short-term spatial memory in open-field and Y-maze tests. Plasma insulin, free fatty acid, cholesterol, and leptin were evaluated with commercial assays. Liver was stained with hematoxylin and eosin for histology. Brain sections were 3',3'-diaminobenzidine (DAB) and/or fluorescently detected for ionized calcium-binding adapter molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and tau phosphorylated at T231 (pTau (T231)), and analyzed. Insulin signaling cascade, pTau, extracellular signal-regulated kinase 1/2 (ERK1/2), and protein phosphatase 2A (PP2A) were quantified by western blotting of hippocampi of 11-month-old mice. Data are mean ± SEM and were subjected to Mann-Whitney t test within age and sex and mixed-effects analysis and Bonferroni's post hoc test for age comparison.Results: Increased age most potently decreased mobility and increased anxiety in all mice. THY-Tau22 males showed impaired short-term spatial memory. HF diet increased body, fat, and liver weights and peripheral IR. HF diet-fed THY-Tau22 males showed massive Iba1+ microgliosis and GFAP+ astrocytosis in the hippocampus and amygdala. Activated astrocytes colocalized with pTau (T231) in THY-Tau22, although no significant difference in hippocampal tau phosphorylation was observed between 11-month-old HF and standard diet-fed THY-Tau22 mice. Eleven-month-old THY-Tau22 females, but not males, on both diets showed decreased synaptic and postsynaptic plasticity.Conclusions: Significant sex differences in neurodegenerative signs were found in THY-Tau22. Impaired short-term spatial memory was observed in 11-month-old THY-tau22 males but not females, which corresponded to increased neuroinflammation colocalized with pTau(T231) in the hippocampi and amygdalae of THY-Tau22 males. A robust decrease in synaptic and postsynaptic plasticity was observed in 11-month-old females but not males. HF diet caused peripheral but not central IR in mice of both sexes. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus is one of the main causative agents of mastitis in small ruminants. Antimicrobial use is the major treatment, but there are many flaws linked to resistance, tolerance or persistence. This study aimed to verify changes in resistance, virulence and clonal profiles of S. aureus isolated from persistent mastitis goat milk before and after enrofloxacin treatment. Results: MIC increased to at least one antimicrobial in S. aureus isolates after enrofloxacin treatment compared to before. The most detected resistance genes before and after treatment were tetK, tetM, and blaZ, with more resistance genes detected after enrofloxacin treatment (p < 0.05). Occasional variations in efflux system gene detection were observed before and after treatment. Nine virulence genes (hla, fnbA, fnbB, eta, etb, sea, sec, seh, and sej) were detected at both times, and between these, the hla and eta genes were detected more in isolates after treatment. All isolates of S. aureus belonged to the same sequence type (ST) 133, except for two S. aureus isolates prior to enrofloxacin treatment which were classified as ST5 and the other as a new one, ST4966. Isolates of S. aureus 4, 8, and 100 from before and after treatment had identical pulse types, while others obtained from other animals before and after treatment were classified into distinct pulse types. Conclusion: There were occasional changes in the studied profiles of S. aureus isolated before and after treatment of animals with enrofloxacin, which may have contributed to the permanence of bacteria in the mammary gland, even when using traditional treatment, resulting in persistent mastitis. [ABSTRACT FROM AUTHOR]

Objective: Analyze the changes in antimicrobial drug resistance patterns due to hospital relocation. To this end, we conducted a retrospective analysis of microbiological results, especially minimum inhibitory concentrations (MIC) of all isolates from blood, urine and bronchial secretions, in our pediatric university hospital before and after moving to a new building. Results: While the number of tests done did not change, the fraction of those positive increased, more MICs were determined and certain microbes (A. baumannii, E. faecalis, Klebsiella spp. and P. mirabilis) were detected more frequently. Most changes in MICs occurred in E. faecium (increases in 8 antimicrobials, decreases only in linezolid and gentamicin). For imipenem and aminopenicillins the MICs commonly rose after relocation, the opposite is true for gentamicin and trimethoprim/sulfamethoxazole. The other factors that alter by moving a hospital such as changes in medical personnel or case severity cannot be corrected for, but using MICs we are able to provide insights into changes down to the individual antimicrobial drug and even small changes usually undetectable to the common categorical reporting of resistance. [ABSTRACT FROM AUTHOR]

Background: Information systems implementation projects have been historically plagued by failures for which user resistance has consistently been identified as a salient reason. Most prior studies investigated either the causes or the consequences of Resistance to Change (RTC) of medical related Information Systems. In this study, we simultaneously explore the causes and impacts of RTC of Disability Determination System (DDS).Methods: This study adopts the Status Quo Bias perspective and combines the information systems usage model and Technology Acceptance Model (TAM) as theoretical foundation to investigates the causes and impacts of users' RTC on their intention to use the DDS. Data were obtained through internet questionnaire survey. Totally, 326 respondents from 22 local governments and 142 hospitals were collected, of which 252 were valid samples and were analyzed using structure model analysis.Results: The research model is proved with eight out of 11 hypotheses being supported. The antecedents of RTC can explain 21.4% of the RTC variation, and the RTC impacts can explain 57.5% of the variation of intention to use DDS.Conclusions: Combining the Status Quo Bias perspective and key component of TAM provides an adequate explanation of adopting intention of changing systems and extend the existing knowledge of information systems adoption. The results provide as a reference for managing users' RTC and enhance the effects and efficiency of new systems adoption. [ABSTRACT FROM AUTHOR]

Background: Biomechanical remodeling of coronary resistance arteries in physiological left ventricular hypertrophy has not yet been analyzed, and the possible sex differences are unknown. Methods: Wistar rats were divided into four groups: male and female sedentary controls (MSe and FSe) and male and female animals undergoing a 12-week intensive swim training program (MEx and FEx). On the last day, the in vitro contractility, endothelium-dependent dilatation, and biomechanical properties of the intramural coronary resistance arteries were investigated by pressure microarteriography. Elastica and collagen remodeling were studied in histological sections. Results: A similar outer radius and reduced inner radius resulted in an elevated wall to lumen ratio in the MEx and FEx animals compared to that in the sedentary controls. The wall elastic moduli increased in the MEx and FEx rats. Spontaneous and TxA2 agonist-induced tone was increased in the FEx animals, whereas endothelium-dependent relaxation became more effective in MEx rats. Arteries of FEx rats had stronger contraction, while arteries of MEx animals had improved dilation. Conclusions: According to our results, the coronary arterioles adapted to an elevated load during long-term exercise, and this adaptation depended on sex. It is important to emphasize that in addition to differences, we also found many similarities between the sexes in the adaptive response to exercise. The observed sport adaptation in the coronary resistance arteries of rats may contribute to a better understanding of the physiological and pathological function of these arteries in active and retired athletes of different sexes. [ABSTRACT FROM AUTHOR]

Background: Altered lipid metabolism is an important characteristic of neoplastic cells, with androgens and growth factors being major regulatory agents of the lipid metabolism process. We investigated the effect of physical resistance training on lipid metabolism and apoptosis in the adult Wistar rat prostate. Methods: Two experimental groups represented sedentary and physical resistance training. Three days per week for 13 weeks, rats performed jumps in water carrying a weight load strapped to their chests as part of a physical resistance exercise protocol. Two days after the last training session, rats were anesthetized and sacrificed for blood and prostate analysis. Results: Physical exercise improved feeding efficiency, decreased weight gain, regulated the serum-lipid profile, and modulated insulin-like growth factor-1 (IGF-1) and free testosterone concentration. Furthermore, upregulation of cluster of differentiation 36 (CD36), sterol regulatory element binding protein-1 (SREBP-1), sterol regulatory element-binding protein cleavage-activating protein (SCAP), and reduced lysosome membrane protein (LIMPII) expression were also observed in the blood and prostates of trained rats. Consistent with these results, caspase-3 expression was upregulating and the BCL-2/Bax index ratio was decreased in trained rats relative to sedentary animals. Conclusions: In this work, physical resistance training can alter lipid metabolism and increase markers of apoptosis in the prostate, suggesting physical resistance training as a potential novel therapeutic strategy for treating prostate cancer. [ABSTRACT FROM AUTHOR]

Background: European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) antimicrobial resistance (AMR) data are used to inform gonorrhoea treatment guidelines; therefore the data need to be robust and representative. We assessed the extent to which Euro-GASP reflects national measures of the AMR situation for Neisseria gonorrhoeae across the European Union/European Economic Area (EU/EEA).Methods: We compared data from Euro-GASP with published national gonococcal AMR data from 15 countries for azithromycin, cefixime and ciprofloxacin for the period 2009 to 2013 and performed Poisson regression to identify differences (p < 0.05) between the proportions of resistant isolates. The 2014 Euro-GASP AMR data for each country (n = 19) were weighted to account for differences in the distribution of patient characteristics between Euro-GASP and EU/EEA epidemiological gonorrhoea surveillance data. Data were compared to determine whether estimates of resistance levels differed with regards to the 5% threshold used to assess the clinical utility of first-line gonorrhoea treatments. We assessed the quality of decentralised testing by comparing AMR data for isolates tested both centrally and in the participating laboratories, and by evaluating external quality assessment (EQA) performance.Results: There was no significant difference for azithromycin, cefixime and ciprofloxacin resistance when Euro-GASP country data were compared with data from national reports. Weighting slightly altered the Euro-GASP AMR estimates (by between - 4.7 and 4.7% from the unweighted estimates). Weighting resulted in greater changes in estimates of resistance to azithromycin (from - 9.5 to 2.7%) and ciprofloxacin (from - 14.8 to 17.9%) in countries with low isolate numbers and low completeness of reporting (n = 3). Weighting caused AMR levels to fall below or above the 5% threshold for cefixime or azithromycin, respectively in only two countries. Susceptibility category data submitted from the decentralised Euro-GASP laboratories were concordant with the Euro-GASP data (> 90%). EQA performance was also good; < 5% of the minimum inhibitory concentration (MIC) results differed by > 4-fold from the modal MIC of the EQA isolate.Conclusions: The overall prevalence of AMR reported by Euro-GASP reflects closely the AMR situation for N. gonorrhoeae in the EU/EEA. Euro-GASP data can be used to provide robust AMR estimates to inform the European guideline for the management of gonorrhoea. [ABSTRACT FROM AUTHOR]

Background: Acid treatment is commonly used for controlling or killing pathogenic microorganisms on medical devices and environments; however, inadequate acid treatment may cause acid tolerance response (ATR) and offer cross-protection against environmental stresses, including antimicrobials. This study aimed to characterise an Escherichia coli strain that can survive in the acidic gastrointestinal environment. Results: We developed an acid-tolerant E. coli O157:H7 ATCC 43889 (ATCC 43889) strain that can survive at pH 2.75 via cell adaptation in low pH conditions. We also performed RNA sequencing and qRT-PCR to compare differentially expressed transcripts between acid-adapted and non-adapted cells. Genes related to stress resistance, including kdpA and bshA were upregulated in the acid-adapted ATCC 43889 strain. Furthermore, the polymyxin resistance gene arnA was upregulated in the acid-adapted cells, and resistance against polymyxin B and colistin (polymyxin E) was observed. As polymyxins are important antibiotics, effective against multidrug-resistant gram-negative bacterial infections, the emergence of polymyxin resistance in acid-adapted E. coli is a serious public health concern. Conclusion: The transcriptomic and phenotypic changes analysed in this study during the adaptation of E. coli to acid environments can provide useful information for developing intervention technologies and mitigating the risk associated with the emergence and spread of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Background: The Kuwaiti drug regulatory authority (DRA) lack a structured classification system for the assessment of imported herbal medicines (HMs), which leads to ambiguity in the registration process. This study aimed to examine the policy development and implementation process in an established HM registration system (Bahrain) and harness lessons to inform recommendations for a suitable HM classification system and explore implementation readiness in Kuwait. Methods: A sequential study design was chosen, with data collected in Bahrain (case 1), recommendations formed and readiness for implementation explored subsequently in Kuwait (case 2). With ethics and DRA approval in place, data sources were documentary review of regulatory policies, direct observations of HMs registration processes, and semi-structured interviews with twenty three key officials involved in the HMs registration processes. Data from all three sources were analysed thematically and findings triangulated. Results: The classification policy in Bahrain was found to be based on evidence and extensive stakeholder engagement, resulting in a clear and organised HM registration process. The availability of HMs classification policies in other DRAs, officials' dedication and teamwork, and support by higher authority, were identified as the main facilitators in policy development and successful implementation. Barriers were the diversity of HM classifications worldwide, a lack of staff and resultant workload, and lack of training. Proposed recommendations for Kuwait were to adopt a clear definition of what constituted HMs, and to introduce a Traditional Herbal Registration based on this definition and the product's characteristics. Interviews in Kuwait showed that almost all participants were in favour of the proposed recommendations and were in support of timely implementation. Interviewees anticipated that consistency in the HM registration process would be the main benefit, increasing reviewer's confidence in making regulatory decisions. Interviewees also identified potential challenges which may impede successful implementation, including staff shortages, resistance to change by internal and external stakeholders, and the impact of cultural and traditional ways of working. Conclusions: Insights into the HM policy development and implementation process in Bahrain, and exploration of Kuwait's readiness to implement resultant recommendations informed an effective implementation process for a well-designed HMs policy for Kuwait and other Arab countries. [ABSTRACT FROM AUTHOR]

Background: Cathepsin L (CTSL) is a cysteine protease known to have important roles in regulating cancer cellular resistance to chemotherapy. However mechanism underlying which regulates CTSL-mediated drug resistance remain largely unknown. Methods: We used NSCLC cell lines: A549, A549/TAX (paclitaxel-resistant), A549/DDP (cisplatin-resistant), H460 and PC9 cells, to evaluate CTSL and drug resistance changes. Tumor specimens from 53 patients with NSCLC and Xenograft models was also utilized to explore the regulatory relationship of CTSL, TGF-β, Egr-1 and CREB. Results: TGF-β and smad3 were overexpressed only in A549/TAX cells, silencing TGF-β or smad3 in A549/TAX cells decreased the expression of CTSL and enhanced their sensitivity to paclitaxel. Smad3 binds to the Smad-binding-element(SBE) of the CTSL promoter, resulting in increased activity of the CTSL promoter and subsequent CTSL. Egr-1 and CREB were overexpressed only in A549/DDP cells, and silencing Egr-1 or CREB reduced the expression of CTSL and increased cisplatin cytotoxicity. CREB could affect the activity of the CTSL promoter by binding to it. And the potential regulatory factors of CTSL were consistent in vivo and in human lung cancer. These different regulatory mechanisms of CTSL-mediated drug resistance exist in two other NSCLC cell lines. Conclusion: CTSL-mediated drug resistance to paclitaxel and cisplatin may be modulated by different mechanisms. The results of our study identified different mechanisms regulating CTSL-mediated drug resistance and identified smad3 as a novel regulator of CTSL. [ABSTRACT FROM AUTHOR]