In vitro effects of wound-dressings on key wound healing properties of dermal fibroblasts.

Healing of complex wounds requires dressings that must, at least, not hinder and should ideally promote the activity of key healing cells, in particular fibroblasts. This in vitro study assessed the effects of three wound-dressings (a pure Ca2+ alginate: Algostéril®, a Ca2+ alginate + carboxymethylcellulose: Biatain alginate® and a polyacrylate impregnated with lipido-colloid matrix: UrgoClean®) on dermal fibroblast activity. The results showed the pure calcium alginate to be non-cytotoxic, whereas the other wound-dressings showed moderate to strong cytotoxicity. The two alginates stimulated fibroblast migration and proliferation, whereas the polyacrylate altered migration and had no effect on proliferation. The pure Ca2+ alginate significantly increased the TGF-ß-induced fibroblast activation, which is essential to healing. This activation was confirmed by a significant increase in Vascular endothelial growth factor (VEGF) secretion and a higher collagen production. The other dressings reduced these fibroblast activities. The pure Ca2+ alginate was also able to counteract the inhibitory effect of NK cell supernatants on fibroblast migration. These in vitro results demonstrate that tested wound-dressings are not equivalent for fibroblast activation. Only Algostéril was found to promote all the fibroblast activities tested, which could contribute to its healing efficacy demonstrated in the clinic.

The Pandemic Paranoia Scale (PPS): factor structure and measurement invariance across languages.

BACKGROUND: Globally, the corona virus disease 2019 (COVID-19) pandemic has created an interpersonally threatening context within which other people have become a source of possible threat. This study reports on the development and validation of a self-report measure of pandemic paranoia; that is, heightened levels of suspicion and mistrust towards others due to the COVID-19 pandemic. METHODS: An international consortium developed an initial set of 28 items for the Pandemic Paranoia Scale (PPS), which were completed by participants from the UK (n = 512), USA (n = 535), Germany (n = 516), Hong Kong (n = 454) and Australia (n = 502) using stratified quota sampling (for age, sex and educational attainment) through Qualtrics and translated for Germany and Hong Kong. RESULTS: Exploratory factor analysis in the UK sample suggested a 25-item, three-factor solution (persecutory threat; paranoid conspiracy and interpersonal mistrust). Confirmatory factor analysis (CFA) on the remaining combined sample showed sufficient model fit in this independent set of data. Measurement invariance analyses suggested configural and metric invariance, but no scalar invariance across cultures/languages. A second-order factor CFA on the whole sample indicated that the three factors showed large loadings on a common second-order pandemic paranoia factor. Analyses also supported the test-retest reliability and internal and convergent validity. CONCLUSION: The PPS offers an internationally validated and reliable method for assessing paranoia in the context of a pandemic. The PPS has the potential to enhance our understanding of the impact of the pandemic, the nature of paranoia and to assist in identifying and supporting people affected by pandemic-specific paranoia.

Production, physiological response, and calcium and magnesium balance of lactating Holstein cows fed different sources of supplemental magnesium with or without ruminal buffer.

The objective of this study was to evaluate the effects of dietary replacement of magnesium oxide (MgO) with calcium-magnesium hydroxide [CaMg(OH)2] and its interaction with ruminal buffer (sodium sesquicarbonate) supplementation on production, Ca and Mg balance, and overall physiological response of mid-lactation Holstein dairy cows. Sixty cows averaging 40.5 ± 7.0 kg of milk/d were used. Treatments were assigned following a 2 × 2 factorial arrangement: (1) MgO, (2) MgO + buffer, (3) CaMg(OH)2, or (4) CaMg(OH)2 + buffer. Diets were formulated to have 16.5% of crude protein, 1.82 Mcal/kg of net energy for lactation, 0.67% Ca, 0.39% P, and 0.25% Mg, all on a dry matter (DM) basis. Treatments were individually top dressed. Milk production, composition, and DM intake were evaluated. A subsample of 20 cows were randomly selected for the evaluation of Ca and Mg balance, blood gases, and electrolytes. Ruminal fluid was also collected for evaluation of pH and Ca and Mg solubility. Effects of Mg source, buffer, and the interaction Mg source × buffer were analyzed through orthogonal contrasts. An interaction of Mg source × buffer was found for DM intake and feed efficiency, in which cows fed CaMg(OH)2 had a similar feed efficiency regardless of ruminal buffer inclusion; however, when cows were fed MgO, the inclusion of buffer reduced feed efficiency. No effects on body weight and milk yield were observed. Buffer addition tended to increase the concentrations of fat, protein, and solids-not-fat, without affecting the yields of these milk components. Magnesium source and buffer did not affect ruminal fluid, blood, urine, or fecal pH; however, buffer supplementation increased urinary pH. Treatment with CaMg(OH)2 increased blood concentration of HCO3-, total CO2, and base excess compared with cows fed MgO. No differences were observed in the ruminal solubility of Ca and Mg or on milk or urinary Ca and Mg excretion. Greater plasma Mg concentration was observed for animals fed MgO compared with cows fed CaMg(OH)2; however, both sources were above the threshold recommended in the literature for dairy cows. Also, a reduction in fecal Mg excretion was observed in animals fed CaMg(OH)2. In summary, we provide evidence that CaMg(OH)2 could replace MgO without affecting performance, overall physiological response, or Ca and Mg balance of mid-lactating dairy Holstein cows.

The value of five blood markers in differentiating mycosis fungoides and Sézary syndrome: a validation cohort.

BACKGROUND: Clinical and histological diagnosis of Sézary syndrome (SS) and mycosis fungoides (MF) is challenging in clinical routine. OBJECTIVES: We investigated five blood markers previously described for SS (T-plastin, Twist, KIR3DL2, NKp46 and Tox) in a prospective validation cohort of patients. METHODS: We included 447 patients in this study and 107 patients were followed up for prognosis. The markers were analysed by reverse transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) on peripheral blood leucocytes and CD4+ T cells in a cohort of consecutive patients with early MF, erythrodermic MF and SS and compared with patients presenting with benign inflammatory dermatoses (BID) and erythrodermic BID. The markers were assessed in parallel to gold standard values such as CD4/CD8 ratio, loss of CD7 and CD26 membrane expression and CD4 absolute values. Sensitivity and specificity were analysed by receiver operator characteristic curves. The prognostic value of selected markers was analysed on a subset of patients. This study was conducted in one centre. RESULTS: We defined cut-off values for each marker. T-plastin, Twist and KIR3DL2 had the best validity. SS may be overrepresented. The combination of T-plastin and Twist was able to differentiate between erythrodermic MF or BID and SS. The additional analysis of KIR3DL2 may be useful to predict the prognosis. CONCLUSIONS: We propose T-plastin, Twist and KIR3DL2 measured by RT-qPCR as new diagnostic markers for Sézary syndrome.

Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways.

BACKGROUND: Male androgenetic alopecia (AGA) is the most common form of hair loss in men. It is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined. OBJECTIVES: To identify biomarkers associated with AGA. METHODS: Molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless or bald men with premature AGA, and healthy volunteers. RESULTS: This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory mediators and immunoglobulin-associated immune mediators were significantly overexpressed in AGA. In contrast, underexpressed genes appear to be associated with the Wnt/ß-catenin and bone morphogenic protein/transforming growth factor-ß signalling pathways. Although involvement of these pathways in hair follicle regeneration is well described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin, as confirmed by polymerase chain reaction and immunohistochemistry. In addition, lower expression of CYP27B1 in patients with AGA supports the notion that changes in vitamin D metabolism contributes to hair loss. CONCLUSIONS: This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches.

Use of fluoroquinolones is the single most important risk factor for the high bacterial load in patients with nasal and gastrointestinal colonization by multidrug-resistant Acinetobacter baumannii.

Gastrointestinal colonization by carbapenem-resistant Acinetobacter baumannii (CRAB) and multidrug-resistant Acinetobacter baumannii (MRAB) provides an important reservoir for clinical infections and hospital outbreaks. We conducted a 7-month study in a 3200-bed healthcare network to investigate the prevalence of gastrointestinal colonization of CRAB and MRAB in Hong Kong. Between 1 June and 31 December 2014, a total of 17,760 fecal specimens from 9469 patients were screened. Testing showed that 340 (1.9%) specimens from 224 (2.6%) patients were CRAB-positive, which included 70 (0.39%) MRAB-positive specimens from 54 (0.57%) patients. The presence of wound or ulcer, use of broad-spectrum antibiotics in the preceding 6 months, and residence in elderly homes are independent risk factors for gastrointestinal colonization of CRAB. Quantitative bacterial counts in various body sites (rectal, nasal, axilla, wound, catheterized urine, if available) were performed in 33 (61.1%) of 54 MRAB patients. Ten (30.3%) and 8 (24.2%) patients had high bacterial load (defined as over 3 log10) in rectal and nasal swabs, with a median of 5.04 log10 cfu/ml of rectal swab and 4.89 log10 cfu/ml of nasal swab in saline diluent, respectively. Nine (81.8%) of 11 patients with wounds had high bacterial load in wound swabs, with a median of 5.62 log10 cfu/ml. Use of fluoroquinolones 6 months before admission was the only significant factor associated with high bacterial load in nasal and rectal swabs. With the implementation of directly observed hand hygiene before meals and medications to all conscious hospitalized patients, no hospital outbreaks were observed during our study period.

Control of hospital endemicity of multiple-drug-resistant Acinetobacter baumannii ST457 with directly observed hand hygiene.

An increasing endemicity of multiple-drug-resistant Acinetobacter baumannii (MRAB) ST457 was noted in Hong Kong. The epidemiology, risk factors, and infection control measures to prevent nosocomial transmission of this epidemic clone were analyzed. A total of 5,058 patients cultured positive with A. baumannii between 1 January 2004 and 30 June 2014 were included, of which 297 (5.9 %) had bacteremia. The first case of MRAB bacteremia emerged in 2009, with an incidence that increased from 0.27 (one case) in 2009 to 1.86 (14 cases) per 100,000 patient-days in 2013 (p < 0.001). With the implementation of strict contact precautions and directly observed hand hygiene in conscious patients immediately before receiving meals and medications in July 2013, the incidence of MRAB bacteremia reduced from its peak to 0.77 (one case) per 100,000 patient-days in the first 6 months of 2014 (p < 0.001). Patients from long-term care facilities for the elderly [odds ratio (OR) 18.6, confidence interval (CI) 2.1-162.4, p = 0.008] and history of carbapenem (OR 7.0, CI 1.7-28.0, p = 0.006) and beta-lactam/beta-lactamase use (OR 5.6, CI 1.1-28.7, p = 0.038) 90 days prior to admission were independent risk factors for MRAB bacteremia by logistic regression when compared with carbapenem-susceptible A. baumannii bacteremia.

Containment of Clostridium difficile infection without reduction in antimicrobial use in Hong Kong.

Clostridium difficile ribotype 002 with hypersporulating capacity has been increasingly identified in Hong Kong. Proactive infection control measures are important to prevent the establishment of endemicity of C. difficile ribotype 002. A total of 329 patients with healthcare-associated C. difficile infection (CDI) were recruited in our healthcare network between 1 January 2008 and 30 June 2012 in this study. The incidence rates of healthcare-associated CDI per 10,000 admissions and 10,000 patient-days increased significantly by 15.3 and 17.0%, respectively, per quarter (p < 0.001) from 2008 1Q to 2010 1Q by segmented Poisson regression. With the full implementation of enhanced infection control interventions, there was an immediate significant reduction in both healthcare-associated CDI rates per 10,000 admissions and per 10,000 patient-days by 47% (p < 0.001) in 2010 2Q, followed by a further decline of CDI per 10,000 admissions and CDI per 10,000 patient-days by -19.4 and -19.8% from 2010 2Q to 2012 2Q, respectively (p < 0.001), despite a replacement of hand washing with soap and water by alcohol-based hand rub in the healthcare network. The proportion of C. difficile ribotype 002 was not statistically different (34/177, 19.2% vs. 25/152, 16.4%, p = 0.515), and the consumption of broad-spectrum antibiotics presented as divided daily dose per 1,000 acute bed-day occupancy per quarter remained unchanged (140.9 vs. 152.3) before and after infection control interventions. Our results suggested that the reduction of healthcare-associated CDI was attributable to infection control interventions instead of replacement of ribotypes or reduction in antimicrobial selective pressure.

Air dispersal of multi-drug-resistant organisms including meticillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii and carbapenemase-producing Enterobacterales in general wards: surveillance culture of air grilles.

BACKGROUND: The environmental surveillance of air grilles in clinical areas has not been systematically analysed. METHODS: Samples were collected from frequently touched items (N = 529), air supply (N = 295) and exhaust (N = 184) grilles in six medical and 11 surgical wards for the cultures of multi-drug-resistant organisms (MDROs): meticillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenemase-producing Enterobacterales (CPE), and isolates were selected for whole-genome sequencing (WGS). The contamination rates were correlated with the colonization pressures of the respective MDROs. RESULTS: From 3rd October to 21st November 2023, 9.8% (99/1008) of the samples tested positive, with MRSA (24.2%, 24/99), CRAB (59.6%, 59/99) and CPE (2.0%, 2/99), being the only detected MDROs. The contamination rate in air exhaust grilles (26.6%, 49/184) was significantly higher than in air supply grilles (5.8%, 17/295; P<0.001). The contamination rate of air exhaust grilles with any MDRO in acute medical wards (73.7%, 14/19) was significantly higher than in surgical wards (12.5%, 4/32; P<0.001). However, there was no difference in the contamination rate of air exhaust grilles between those located inside and outside the cohort cubicles for MDROs (27.1%, 13/48 vs 28.8%, 30/104; P=0.823). Nevertheless, the weekly CRAB colonization pressure showed a significant correlation with the overall environmental contamination rate (r = 0.878; 95% confidence interval (CI): 0.136-0.986; P=0.004), as well as with the contamination rate in air supply grilles (r = 0.960; 95% CI: 0.375-0.999; P<0.001) and air exhaust grilles (r = 0.850; 95% CI: 0.401-0.980; P=0.008). WGS demonstrated clonal relatedness of isolates collected from patients and air exhaust grilles. CONCLUSIONS: Air grilles may serve as MDRO reservoirs. Cohort nursing in open cubicles may not completely prevent MDRO transmission through air dispersal, prompting the consideration of future hospital design.

Gut microbiome and symptoms in females with irritable bowel syndrome: a cross-sectional analysis.

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is associated with abdominal pain and stool frequency/character alterations that are linked to changes in microbiome composition. We tested whether taxa differentially abundant between females with IBS vs healthy control females (HC) are associated with daily gastrointestinal and psychological symptom severity. Participants (age 18-50 year) completed a 3-day food record and collected a stool sample during the follicular phase. They also completed a 28-day diary rating symptom intensity; analysis focused on the three days after the stool sample collection. 16S rRNA gene sequencing was used for bacterial identification. Taxon abundance was compared between IBS and HC using zero-inflated quantile analysis (ZINQ). We found that females with IBS (n = 67) had greater Bacteroides abundance (q = 0.003) and lower odds of Bifidobacterium presence (q = 0.036) compared to HC (n = 46) after adjusting for age, race, body mass index, fibre intake, and hormonal contraception use. Intestimonas, Oscillibacter, and Phascolarctobacterium were more often present and Christensenellaceae R-7 group, Collinsella, Coprococcus 2, Moryella, Prevotella 9, Ruminococcaceae UCG-002, Ruminococcaceae UCG-005, and Ruminococcaceae UCG-014 were less commonly present in IBS compared to HC. Despite multiple taxon differences in IBS vs HC, we found no significant associations between taxon presence or abundance and average daily symptom severity within the IBS group. This may indicate the need to account for interactions between microbiome, dietary intake, metabolites, and host factors.

Paranoid Thinking as a Function of Minority Group Status and Intersectionality: An International Examination of the Role of Negative Beliefs.

BACKGROUND: Paranoia is higher in minority group individuals, especially those reporting intersecting aspects of difference. High negative and low positive self and other beliefs, and low social rank, are predictive of paranoia overtime; however, data are typically from majority group participants. This study examined whether social defeat or healthy cultural mistrust best characterizes paranoia in minority groups. STUDY DESIGN: Using cross-sectional, survey design, with a large (n = 2510) international sample, moderation analyses (PROCESS) examined whether self and other beliefs, and perceived social rank, operate similarly or differently in minority vs majority group participants. Specifically, we tested whether beliefs moderated the influence of minority group, and intersecting aspects of difference, on paranoia. STUDY RESULTS: Paranoia was consistently higher in participants from minority vs majority groups and level of paranoid thinking was significantly higher at each level of the intersectionality index. Negative self/other beliefs were associated with elevated paranoia in all participants. However, in support of the notion of healthy cultural mistrust, low social rank, and low positive self/other beliefs were significantly associated with paranoia in majority group participants but unrelated to paranoia in respective minority group members. CONCLUSIONS: Although mixed, our findings signal the need to consider healthy cultural mistrust when examining paranoia in minority groups and bring into question whether "paranoia" accurately describes the experiences of marginalized individuals, at least at low levels of severity. Further research on paranoia in minority groups is crucial to developing culturally appropriate ways of understanding people's experiences in the context of victimization, discrimination, and difference.

Gastrointestinal colonization of meticillin-resistant Staphylococcus aureus: an unrecognized burden upon hospital infection control.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) has become endemic in many healthcare settings. AIM: To analyse the incidence, risk factors, outcomes, and genomic relatedness of patients with newly diagnosed gastrointestinal colonization of MRSA. METHODS: Epidemiology and genetic analysis by whole-genome sequencing (WGS) in a hospital network in Hong Kong. FINDINGS: Between October 1st, 2015 and December 31st, 2018, a total of 919 (2.7%) of 34,667 patients had newly diagnosed gastrointestinal MRSA colonization by admission screening. The incidence was 0.67 ± 0.32 per 1000 patient-days per quarter. Including patients with gastrointestinal MRSA colonization, the overall burden of MRSA increased by 59.2%, with an addition of 4727 MRSA patient-days during the study period. Patients referred from residential care home for the elderly, with history of hospitalization in the past six months, and consumption of fluoroquinolones, cephalosporins, and proton-pump inhibitors in the preceding six months were found to be independent risk factors by multivariate analysis in the case-control analysis. The median survival of cases was significantly shorter than that of controls (860 vs 1507 days, P < 0.001). Of 919 patients, 127 (13.8%) developed symptomatic MRSA infection in a median of 112 days. Of 19 patients with paired MRSA faecal and blood culture isolates subjected to WGS, clonality was found in 16 (84.2%) pairs of MRSA isolates. MRSA ST45 constituted 44.7% (17/38) of MRSA isolates. CONCLUSION: Gastrointestinal MRSA colonization may contribute to adverse clinical outcomes and pose an unrecognized burden upon hospital infection control.

Air dispersal of meticillin-resistant Staphylococcus aureus in residential care homes for the elderly: implications for transmission during the COVID-19 pandemic.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) infections are rampant in hospitals and residential care homes for the elderly (RCHEs). AIM: To analyse the prevalence of MRSA colonization among residents and staff, and degree of environmental contamination and air dispersal of MRSA in RCHEs. METHODS: Epidemiological and genetic analysis by whole-genome sequencing (WGS) in 12 RCHEs in Hong Kong. FINDINGS: During the COVID-19 pandemic (from September to October 2021), 48.7% (380/781) of RCHE residents were found to harbour MRSA at any body site, and 8.5% (8/213) of staff were nasal MRSA carriers. Among 239 environmental samples, MRSA was found in 39.0% (16/41) of randomly selected resident rooms and 31.3% (62/198) of common areas. The common areas accessible by residents had significantly higher MRSA contamination rates than those that were not accessible by residents (37.2%, 46/121 vs. 22.1%, 17/177, P=0.028). Of 124 air samples, nine (7.3%) were MRSA-positive from four RCHEs. Air dispersal of MRSA was significantly associated with operating indoor fans in RCHEs (100%, 4/4 vs. 0%, 0/8, P=0.002). WGS of MRSA isolates collected from residents, staff and environmental and air samples showed that ST 1047 (CC1) lineage 1 constituted 43.1% (66/153) of all MRSA isolates. A distinctive predominant genetic lineage of MRSA in each RCHE was observed, suggestive of intra-RCHE transmission rather than clonal acquisition from the catchment hospital. CONCLUSION: MRSA control in RCHEs is no less important than in hospitals. Air dispersal of MRSA may be an important mechanism of dissemination in RCHEs with operating indoor fans.

Induction of bone formation by Escherichia coli-expressed recombinant human bone morphogenetic protein-2 using block-type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models.

BACKGROUND AND OBJECTIVE: The potential of the Escherichia coli-expressed recombinant human bone morphogenetic protein-2 (ErhBMP-2) to support new bone formation/maturation using a block-type of macroporous biphasic calcium phosphate (bMBCP) carrier was evaluated in an orthotopic and ectopic rat model. MATERIAL AND METHODS: Critical-size (Φ 8 mm) calvarial defects and subcutaneous pockets in 32 Sprague-Dawley rats received implants of rhBMP-2 (2.5 µg) in a bMBCP carrier or bMBCP alone (control). Implant sites were evaluated using histological and histometric analysis following 2- and 8-wk healing intervals (eight animals/group/interval). RESULTS: ErhBMP-2/bMBCP supported significantly greater bone formation at 2 and 8 wk (10.8% and 25.4%, respectively) than the control at 2 and 8 wk (5.3% and 14.0%, respectively) in calvarial defects (p < 0.01). Bone formation was only observed for the ErhBMP-2/bMBCP ectopic sites and was significantly greater at 8 wk (7.5%) than at 2 wk (4.5%) (p < 0.01). Appositional and endochondral bone formation was usually associated with a significant increase in fatty marrow at 8 wk. The bMBCP carrier showed no evidence of bioresorption. CONCLUSION: ErhBMP-2/bMBCP induced significant bone formation in both calvarial and ectopic sites. Further study appears to be required to evaluate the relevance of the bMBCP carrier.