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Photochemistry and Photobiology Jul 2024The thermodynamic characteristics, antioxidant potential, and photoprotective benefits of full-spectrum cannabidiol (FS-CBD) against UVB-induced cellular death were...
The thermodynamic characteristics, antioxidant potential, and photoprotective benefits of full-spectrum cannabidiol (FS-CBD) against UVB-induced cellular death were examined in this study. In silico analysis of CBD showed antioxidant capacity via proton donation and UV absorption at 209.09, 254.73, and 276.95 nm, according to the HAT and SPLET methodologies. FS-CBD protected against UVB-induced bacterial death for 30 min. FS-CBD protected against UVB-induced cell death by 42% (1.5 μg/mL) and 35% (3.5 μg/mL) in an in vitro keratinocyte cell model. An in vivo acute irradiated CD-1 mouse model (UVB-irradiated for 5 min) presented very low photoprotection when FS-CBD was applied cutaneously, as determined by histological analyses. In vivo skin samples showed that FS-CBD regulated inflammatory responses by inhibiting the inflammatory markers TGF-β1 and NLRP3. The docking analysis showed that the CBD molecule had a high affinity for TGF-β1 and NLRP3, indicating that protection against inflammation might be mediated by blocking these proinflammatory molecules. This result was corroborated by the docking interactions between CBD and TGF-β1 and NLRP3, which resulted in a high affinity and inhibition of both proteins The present work suggested a FS-CBD moderate photoprotective agent against UVB light-induced skin damage and that this effect is partially mediated by its anti-inflammatory activity.
PubMed: 38958000
DOI: 10.1111/php.13993 -
Ghana Medical Journal Dec 2023The study aimed to determine the prevalence of self-medication with antibiotics among attendants of the Out-patient Department (OPD) at Madina Polyclinic before seeking...
OBJECTIVES
The study aimed to determine the prevalence of self-medication with antibiotics among attendants of the Out-patient Department (OPD) at Madina Polyclinic before seeking medical consultation and associated factors.
DESIGN
Cross-sectional study.
SETTING
The study was conducted at Madina Polyclinic.
PARTICIPANTS
The study involved 319 general OPD attendants aged 18 years and above accessing healthcare services at the Madina Polyclinic between May and June 2019.
MAIN OUTCOME MEASURES
The prevalence of antibiotic self-medication and the factors associated with this practice.
RESULTS
From the study, 46.4% (95% CI 40.8%- 52.0%) had self-medicated with antibiotics before presenting for medical consultation at the hospital. Less than half of the respondents (44.5%) had adequate knowledge about the use of antibiotics. Having a tertiary level of education was significantly associated with self-medication (aOR= 8.09, 95% CI 2.31-28.4, p = 0.001), whilst adequate knowledge on the use of antibiotics reduced the odds of self-medication by 53% (aOR= 0.47, 95% CI 0.23- 0.66, p<0.001). The level of education modified the relationship between knowledge and self-medication with antibiotics.
CONCLUSION
The practice of antibiotic self-medication is rife among OPD attendants. Therefore, adequate public education on the use of antibiotics and the effects of using them inappropriately must be done. The Antimicrobial Resistance (AMR) policy ought to be reinforced and made known to all, especially among the pharmacies that dispense antibiotics indiscriminately.
FUNDING
None declared.
Topics: Humans; Self Medication; Male; Female; Adult; Cross-Sectional Studies; Anti-Bacterial Agents; Middle Aged; Health Knowledge, Attitudes, Practice; Young Adult; Outpatients; Adolescent; Aged; Educational Status
PubMed: 38957850
DOI: 10.4314/gmj.v57i4.8 -
Ethiopian Journal of Health Sciences Jan 2024Visual Inspection with Acetic acid (VIA) is the best feasible method of screening and early detecting for cervical dysplasia for resource limited settings like Africa.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Visual Inspection with Acetic acid (VIA) is the best feasible method of screening and early detecting for cervical dysplasia for resource limited settings like Africa. There is no study that can represent Africa on VIA positivity. Therefore, this metaanalysis was planned to verify the best available articles to pool the visual inspection with acetic acid positivity in screening and early detection of cervical dysplasia in Africa.
METHODS
The Cochrane Library, Web of Science, PubMed, Scopus, free Google database search engines, Google Scholar, and Science Direct databases were used to conduct a true search of this research article. STATA version 14.0 was used to do the metaanalysis. This meta-analysis was registered in PROSPERO database under the identity pf CRD42023392197.
RESULT
This meta-analysis analyzed data from 21,066 women who had VIA examination to estimate the pooled VIA positivity in Africa. The overall pooled effect estimate of VIA positivity in Africa was 11.93 (95%CI: 11.48-12.37). Age <16 year during first intercourse 2.58(95%CI: 1.53-3.62), lifetime sexual partner ≥2 3.92(95%CI: 2.05-5.78) and HIV positivity 2.92(95%CI: 1.72-4.12) were the significant variables which influence VIA positivity.
CONCLUSION
Overall pooled effect estimate of VIA positivity in Africa was high compared to other continents. The main factors that affect VIA positivity are age at first sexual contact being under 16 years old, the number of lifetime sexual partners being at least two, and HIV positivity. Therefore, the WHO's goal of creating Africa free of cervical cancer is still one that requires significant effort.
Topics: Humans; Female; Acetic Acid; Uterine Cervical Dysplasia; Early Detection of Cancer; Africa; Uterine Cervical Neoplasms; Mass Screening; Adult
PubMed: 38957338
DOI: 10.4314/ejhs.v34i1.2 -
Ghana Medical Journal Mar 2024This study aims to examine the frequency of Paratyphi found in blood cultures and evaluate the antibiotic susceptibility pattern of isolates to different antibiotics....
OBJECTIVE
This study aims to examine the frequency of Paratyphi found in blood cultures and evaluate the antibiotic susceptibility pattern of isolates to different antibiotics. Additionally, the study aims to assess the paradigm shift in the trend of enteric fever caused by Typhi (. Typhi) to Paratyphi(. Paratyphi) .
STUDY DESIGN
Retrospective study.
PARTICIPANT
The study enrolled patients aged 12 years and above diagnosed with enteric fever (positive blood culture) and admitted to Peelamedu Samanaidu Govindasamy Naidu (PSG) Hospital.
INTERVENTIONS
The study analyzed demographic and antibiotic susceptibility profiles of isolates collected from 106 enteric fever patients in the hospital between 2010 and 2022. The susceptibility profiles of isolates to multiple antibiotics were assessed.
RESULTS
There were 106 participants, and 95 (89.62%) of them had enteric fever linked to Typhi, while only 11 (10.38%) had enteric fever linked to Paratyphi A. From 2010 to 2022, the study discovered a general decline in the prevalence of enteric fever caused by species. But between 2014 and 2022, the incidence of enteric fever linked to rapidly increased. Azithromycin (100% , n = 106) and ceftriaxone (99% , n = 105) were highly effective against the isolates, whereas nalidixic acid was resisted by 3 isolates (4.72%, n = 3).
CONCLUSION
The study observed a higher incidence of Typhi in comparison to Paratyphi A and a greater susceptibility of males to enteric fever.
FUNDING
None declared.
Topics: Humans; Male; Female; Anti-Bacterial Agents; Typhoid Fever; Retrospective Studies; Salmonella typhi; Microbial Sensitivity Tests; Salmonella paratyphi A; Adult; Adolescent; Child; Middle Aged; Young Adult; Paratyphoid Fever; Incidence; Drug Resistance, Bacterial; Azithromycin; Ceftriaxone; Aged; Prevalence
PubMed: 38957275
DOI: 10.4314/gmj.v58i1.12 -
Critical Care Explorations Jul 2024Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of... (Randomized Controlled Trial)
Randomized Controlled Trial
Can Biomarkers Correctly Predict Ventilator-associated Pneumonia in Patients Treated With Targeted Temperature Management After Cardiac Arrest? An Exploratory Study of the Multicenter Randomized Antibiotic (ANTHARTIC) Study.
IMPORTANCE
Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated.
OBJECTIVES
To evaluate biomarkers' impact in helping VAP diagnosis after cardiac arrest.
DESIGN SETTING AND PARTICIPANTS
This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included.
MAIN OUTCOMES AND MEASURES
The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group.
RESULTS
Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP ( = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP ( = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C-C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C.
CONCLUSIONS AND RELEVANCE
Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.
Topics: Humans; Biomarkers; Pneumonia, Ventilator-Associated; Male; Female; Hypothermia, Induced; Middle Aged; Aged; Prospective Studies; Procalcitonin; Double-Blind Method; Anti-Bacterial Agents; C-Reactive Protein; Heart Arrest; Predictive Value of Tests
PubMed: 38957212
DOI: 10.1097/CCE.0000000000001104 -
Genome Medicine Jul 2024Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great...
BACKGROUND
Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan.
METHODS
Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture.
RESULTS
We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo.
CONCLUSIONS
Our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.
Topics: Humans; Animals; DNA Methylation; Longevity; Aging; Epigenesis, Genetic; Drug Discovery; Cellular Senescence; Drug Evaluation, Preclinical; Drosophila; Cells, Cultured; Sirolimus
PubMed: 38956711
DOI: 10.1186/s13073-024-01349-w -
BMC Medicine Jul 2024With the global challenge of antimicrobial resistance intensified during the COVID-19 pandemic, evaluating adverse events (AEs) post-antibiotic treatment for common...
Risk of emergency hospital admission related to adverse events after antibiotic treatment in adults with a common infection: impact of COVID-19 and derivation and validation of risk prediction models.
BACKGROUND
With the global challenge of antimicrobial resistance intensified during the COVID-19 pandemic, evaluating adverse events (AEs) post-antibiotic treatment for common infections is crucial. This study aims to examines the changes in incidence rates of AEs during the COVID-19 pandemic and predict AE risk following antibiotic prescriptions for common infections, considering their previous antibiotic exposure and other long-term clinical conditions.
METHODS
With the approval of NHS England, we used OpenSAFELY platform and analysed electronic health records from patients aged 18-110, prescribed antibiotics for urinary tract infection (UTI), lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), sinusitis, otitis externa, and otitis media between January 2019 and June 2023. We evaluated the temporal trends in the incidence rate of AEs for each infection, analysing monthly changes over time. The survival probability of emergency AE hospitalisation was estimated in each COVID-19 period (period 1: 1 January 2019 to 25 March 2020, period 2: 26 March 2020 to 8 March 2021, period 3: 9 March 2021 to 30 June 2023) using the Kaplan-Meier approach. Prognostic models, using Cox proportional hazards regression, were developed and validated to predict AE risk within 30 days post-prescription using the records in Period 1.
RESULTS
Out of 9.4 million patients who received antibiotics, 0.6% of UTI, 0.3% of URTI, and 0.5% of LRTI patients experienced AEs. UTI and LRTI patients demonstrated a higher risk of AEs, with a noted increase in AE incidence during the COVID-19 pandemic. Higher comorbidity and recent antibiotic use emerged as significant AE predictors. The developed models exhibited good calibration and discrimination, especially for UTIs and LRTIs, with a C-statistic above 0.70.
CONCLUSIONS
The study reveals a variable incidence of AEs post-antibiotic treatment for common infections, with UTI and LRTI patients facing higher risks. AE risks varied between infections and COVID-19 periods. These findings underscore the necessity for cautious antibiotic prescribing and call for further exploration into the intricate dynamics between antibiotic use, AEs, and the pandemic.
Topics: Humans; COVID-19; Anti-Bacterial Agents; Adult; Middle Aged; Female; Aged; Male; Aged, 80 and over; Young Adult; Adolescent; Risk Assessment; Hospitalization; England; SARS-CoV-2; Emergency Service, Hospital; Incidence
PubMed: 38956603
DOI: 10.1186/s12916-024-03480-2 -
BMC Pulmonary Medicine Jul 2024Myasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to...
BACKGROUND
Myasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to post-thymectomy myasthenia gravis (PTMG). Diffuse panbronchiolitis (DPB), is a rare form of bronchiolitis and is largely restricted to East Asia, has been reported in association with thymic neoplasms. Only three cases of combined MG and DPB have been reported in the literature.
CASE PRESENTATION
A 45-year-old Taiwanese woman presented to our hospital with productive cough, rhinorrhea, anosmia, ear fullness, shortness of breath, and weight loss. She had a history of thymoma, and she underwent thymectomy with adjuvant radiotherapy 7 years ago. Chest computed tomography scan revealed diffuse bronchitis and bronchiolitis. DPB was confirmed after video-assisted thoracoscopic surgery lung biopsy, and repeated sputum cultures grew Pseudomonas aeruginosa. She has been on long-term oral azithromycin therapy thereafter. Intravenous antipseudomonal antibiotics, inhaled amikacin, as well as oral levofloxacin were administered. Three months after DPB diagnosis, she developed ptosis, muscle weakness, and hypercapnia requiring the use of noninvasive positive pressure ventilation. MG was diagnosed based on the acetylcholine receptor antibody and repetitive stimulation test results. Her muscle weakness gradually improved after pyridostigmine and corticosteroid therapies. Oral corticosteroids could be tapered off ten months after the diagnosis of MG. She is currently maintained on azithromycin, pyridostigmine, and inhaled amikacin therapies, with intravenous antibiotics administered occasionally during hospitalizations for respiratory infections.
CONCLUSIONS
To our knowledge, this might be the first case report of sequential development of DPB followed by PTMG. The coexistence of these two disorders poses a therapeutic challenge for balancing infection control for DPB and immunosuppressant therapies for MG.
Topics: Humans; Female; Myasthenia Gravis; Middle Aged; Bronchiolitis; Thymectomy; Thymus Neoplasms; Tomography, X-Ray Computed; Haemophilus Infections; Thymoma; Anti-Bacterial Agents; Taiwan
PubMed: 38956567
DOI: 10.1186/s12890-024-03134-2 -
BMC Infectious Diseases Jul 2024Infections due to Citrobacter species are increasingly observed in hospitalized patients and are often multidrug-resistant. Yet, the magnitude and burden of Citrobacter... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Infections due to Citrobacter species are increasingly observed in hospitalized patients and are often multidrug-resistant. Yet, the magnitude and burden of Citrobacter spp. resistance in the hospital setting have not been reported. We aimed to evaluate the epidemiology of Citrobacter spp. infections among hospitalized patients, their main resistance patterns and Citrobacter spp. involvement in hospital outbreaks.
METHODS
We conducted a systematic review and meta-analysis of published literature (PROSPERO registration Jan-2023, CRD42023390084). We searched Embase, Medline and grey literature for studies on hospitalized patients diagnosed with Citrobacter spp. infections, and nosocomial outbreaks due to Citrobacter spp. published during the years 2000-2022. We included observational, interventional, surveillance studies and outbreak reports. Outcomes of interest were the frequency of Citrobacter spp. infections among hospitalized patients and 3rd generation cephalosporin and/or carbapenem resistance percentages in these infections. We used random-effects models to generate pooled outcome estimates and evaluated risk of bias and quality of reporting of outbreaks.
RESULTS
We screened 1609 deduplicated publications, assessed 148 full-texts, and included 41 studies (15 observational, 13 surveillance and 13 outbreak studies). Citrobacter spp. urinary tract- and bloodstream infections were most frequently reported, with Citrobacter freundii being the main causative species. Hospital-acquired infection occurred in 85% (838/990) of hospitalized patients with Citrobacter infection. After 2010, an increasing number of patients with Citrobacter spp. infections was reported in observational studies. Pooled frequency estimates for Citrobacter spp. infections could not be generated due to lack of data. The pooled prevalence of ESBL and carbapenemase producers among Citrobacter isolates were 22% (95%CI 4-50%, 7 studies) and 18% (95%CI 0-63%, 4 studies), respectively. An increased frequency of reported Citrobacter outbreaks was observed after 2016, with an infection/colonization ratio of 1:3 and a case-fatality ratio of 7% (6/89 patients). Common outbreak sources were sinks, toilets, contaminated food and injection material. Implemented preventive measures included environmental cleaning, isolation of positive patients and reinforcement of hand hygiene. Only seven out of 13 outbreaks (54%) were definitively controlled.
CONCLUSION
This review highlights the clinical importance of endemic and epidemic Citrobacter spp. in healthcare settings. As an emerging, multidrug‑resistant nosocomial pathogen it requires heightened awareness and further dedicated surveillance efforts.
Topics: Humans; Enterobacteriaceae Infections; Citrobacter; Cross Infection; Hospitalization; Anti-Bacterial Agents; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Urinary Tract Infections
PubMed: 38956542
DOI: 10.1186/s12879-024-09575-8 -
BMC Infectious Diseases Jul 2024The outpatient parenteral antibiotic therapy (OPAT) program of Vancouver General Hospital (VGH) was supervised by emergency physicians (EPs) until 2017 when infectious...
INTRODUCTION
The outpatient parenteral antibiotic therapy (OPAT) program of Vancouver General Hospital (VGH) was supervised by emergency physicians (EPs) until 2017 when infectious disease (ID) physicians began assisting in management. We designed a retrospective study to determine whether ID involvement led to improved outcomes.
METHODS
This study analyzes the impact of ID involvement by comparing the mean days patients spent on OPAT with ID involvement versus EPs alone through a retrospective chart review. Secondary research objectives were to compare patient care decisions, e.g., antibiotic choice, tests ordered, and final diagnosis.
RESULTS
There was no difference between the mean number of days on OPAT between physician types. Compared to historic patterns, patients seen in OPAT after increased ID consultation spent an average of 0.5 fewer days in the program. However, when grouped by the first day of ID assessment, the average total days in OPAT was closely aligned with the day of first ID assessment, implying that ID frequently discharged patients close to initial assessment. Patients seen by ID were less likely to return within one month of discharge compared to those not seen by ID. Secondary findings include ID physicians prescribing a greater range of antibiotics, providing more varied final diagnoses, prescribing antibiotics less frequently, as well as ordering more cultures, diagnostic imaging and specialist consults.
DISCUSSION
The findings of this study support the hypothesis that ID involvement in OPAT programs leads to changes in care that may have beneficial outcomes for patients and the healthcare system.
Topics: Humans; Anti-Bacterial Agents; Retrospective Studies; Emergency Service, Hospital; Male; Female; Middle Aged; Aged; Physicians; Practice Patterns, Physicians'; Adult; Communicable Diseases
PubMed: 38956481
DOI: 10.1186/s12879-024-09305-0