The effectiveness of hand hygiene interventions for preventing community transmission or acquisition of novel coronavirus or influenza infections: a systematic review.

BACKGROUND: Novel coronaviruses and influenza can cause infection, epidemics, and pandemics. Improving hand hygiene (HH) of the general public is recommended for preventing these infections. This systematic review examined the effectiveness of HH interventions for preventing transmission or acquisition of such infections in the community. METHODS: PubMed, MEDLINE, CINAHL and Web of Science databases were searched (January 2002-February 2022) for empirical studies related to HH in the general public and to the acquisition or transmission of novel coronavirus infections or influenza. Studies on healthcare staff, and with outcomes of compliance or absenteeism were excluded. Study selection, data extraction and quality assessment, using the Cochrane Effective Practice and Organization of Care risk of bias criteria or Joanna Briggs Institute Critical Appraisal checklists, were conducted by one reviewer, and double-checked by another. For intervention studies, effect estimates were calculated while the remaining studies were synthesised narratively. The protocol was pre-registered (PROSPERO 2020: CRD42020196525). RESULTS: Twenty-two studies were included. Six were intervention studies evaluating the effectiveness of HH education and provision of products, or hand washing against influenza. Only two school-based interventions showed a significant protective effect (OR: 0.64; 95% CI 0.51, 0.80 and OR: 0.40; 95% CI 0.22, 0.71), with risk of bias being high (n = 1) and unclear (n = 1). Of the 16 non-intervention studies, 13 reported the protective effect of HH against influenza, SARS or COVID-19 (P < 0.05), but risk of bias was high (n = 7), unclear (n = 5) or low (n = 1). However, evidence in relation to when, and how frequently HH should be performed was inconsistent. CONCLUSIONS: To our knowledge, this is the first systematic review of effectiveness of HH for prevention of community transmission or acquisition of respiratory viruses that have caused epidemics or pandemics, including SARS-CoV-1, SARS-CoV-2 and influenza viruses. The evidence supporting the protective effect of HH was heterogeneous and limited by methodological quality; thus, insufficient to recommend changes to current HH guidelines. Future work is required to identify in what circumstances, how frequently and what product should be used when performing HH in the community and to develop effective interventions for promoting these specific behaviours in communities during epidemics.

Alopecia areata: A multifactorial autoimmune condition.

Alopecia areata is an autoimmune disease that results in non-scarring hair loss, and it is clinically characterised by small patches of baldness on the scalp and/or around the body. It can later progress to total loss of scalp hair (Alopecia totalis) and/or total loss of all body hair (Alopecia universalis). The rapid rate of hair loss and disfiguration caused by the condition causes anxiety on patients and increases the risks of developing psychological and psychiatric complications. Hair loss in alopecia areata is caused by lymphocytic infiltrations around the hair follicles and IFN-γ. IgG antibodies against the hair follicle cells are also found in alopecia areata sufferers. In addition, the disease coexists with other autoimmune disorders and can come secondary to infections or inflammation. However, despite the growing knowledge about alopecia areata, the aetiology and pathophysiology of disease are not well defined. In this review we discuss various genetic and environmental factors that cause autoimmunity and describe the immune mechanisms that lead to hair loss in alopecia areata patients.

Dietary nitrate supplementation alters the oral microbiome but does not improve the vascular responses to an acute nitrate dose.

Nitrate (NO3-) contained in food and beverages can transiently increase nitric oxide (NO) availability following a stepwise reduction to nitrite (NO2-) by commensal bacteria in the oral cavity. We tested the hypothesis that regular ingestion of dietary NO3- would influence the oral microbiome, the capacity to reduce NO3- to NO2- in saliva, and the vascular responses to an acute dose of NO3-. The abundance of bacterial species on the tongue, the availability of NO markers, and vascular function were assessed in 11 healthy males before and after 7 days of supplementation with NO3--rich beetroot juice and a NO3--depleted placebo. As expected, saliva and plasma NO2- and NO3- were significantly elevated after NO3- supplementation (all P < 0.05) but not placebo. We found that NO3- supplementation increased salivary pH (7.13 ±â€¯0.54 to 7.39 ±â€¯0.68, P = 0.043) and altered the abundance of some bacteria previously implicated in NO3- reduction: Neisseria (from 2% ±â€¯3%-9% ±â€¯5%, P < 0.001), Prevotella (from 34% ±â€¯17%-23% ±â€¯11%, P = 0.001) and Actinomyces (from 1% ±â€¯1%-0.5% ±â€¯0.4%). Despite these alterations to the oral microbiota, an acute dose of NO3- increased salivary and plasma NO2-, reduced systolic blood pressure and increased the response to flow mediated dilation to a similar extent before and after 7 days of supplementation (P > 0.05). Our study establishes that supplementing the diet with NO3- for a sustained period can alter the oral environment in favour of health but does not impact the response to an acute NO3- dose. Acute ingestion of NO3- results in transient improvements in vascular function but the dietary induced adaptations to the oral bacteria did not enhance these effects.

Variability in nitrate-reducing oral bacteria and nitric oxide metabolites in biological fluids following dietary nitrate administration: An assessment of the critical difference.

There is conflicting evidence on whether dietary nitrate supplementation can improve exercise performance. This may arise from the complex nature of nitric oxide (NO) metabolism which causes substantial inter-individual variability, within-person biological variation (CVB), and analytical imprecision (CVA) in experimental endpoints. However, no study has quantified the CVA and CVB of NO metabolites or the factors that influence their production. These data are important to calculate the critical difference (CD), defined as the smallest difference between sequential measurements required to signify a true change. The main aim of the study was to evaluate the CVB, CVA, and CD for markers of NO availability (nitrate and nitrite) in plasma and saliva before and after the ingestion of nitrate-rich beetroot juice (BR). We also assessed the CVB of nitrate-reducing bacteria from the dorsal surface of the tongue. It was hypothesised that there would be substantial CVB in markers of NO availability and the abundance of nitrate-reducing bacteria. Ten healthy male participants (age 25 ±â€¯5 years) completed three identical trials at least 6 days apart. Blood and saliva were collected before and after (2, 2.5 and 3 h) ingestion of 140 ml of BR (∼12.4 mmol nitrate) and analysed for [nitrate] and [nitrite]. The tongue was scraped and the abundance of nitrate-reducing bacterial species were analysed using 16S rRNA next generation sequencing. There was substantial CVB for baseline concentrations of plasma (nitrate 11.9%, nitrite 9.0%) and salivary (nitrate 15.3%, nitrite 32.5%) NO markers. Following BR ingestion, the CVB for nitrate (plasma 3.8%, saliva 12.0%) and salivary nitrite (24.5%) were lower than baseline, but higher for plasma nitrite (18.6%). The CD thresholds that need to be exceeded to ensure a meaningful change from baseline are 25, 19, 37, and 87% for plasma nitrate, plasma nitrite, salivary nitrate, and salivary nitrite, respectively. The CVB for selected nitrate-reducing bacteria detected were: Prevotella melaninogenica (37%), Veillonella dispar (35%), Haemophilus parainfluenzae (79%), Neisseria subflava (70%), Veillonella parvula (43%), Rothia mucilaginosa (60%), and Rothia dentocariosa (132%). There is profound CVB in the abundance of nitrate-reducing bacteria on the tongue and the concentration of NO markers in human saliva and plasma. Where these parameters are of interest following experimental intervention, the CD values presented in this study will allow researchers to interpret the meaningfulness of the magnitude of the change from baseline.

Implications of Antimicrobial Combinations in Complex Wound Biofilms Containing Fungi.

Diabetic foot ulcer treatment currently focuses on targeting bacterial biofilms, while dismissing fungi. To investigate this, we used an in vitro biofilm model containing bacteria and fungi, reflective of the wound environment, to test the impact of antimicrobials. Here we showed that while monotreatment approaches influenced biofilm composition, this had no discernible effect on overall quantity. Only by combining bacterium- and fungus-specific antibiotics were we able to decrease the biofilm bioburden, irrespective of composition.

Locally Excited State-Charge Transfer State Coupled Dyes as Optically Responsive Neuron Firing Probes.

A selection of NIR-optically responsive neuron probes was produced comprising of a donor julolidyl group connected to a BODIPY core and several different styryl and vinylpyridinyl derived acceptor moieties. The strength of the donor-acceptor interaction was systematically modulated by altering the electron withdrawing nature of the aryl unit. The fluorescence quantum yield was observed to decrease as the electron withdrawing effect of the aryl subunit increased in line with changes of the Hammett parameter. The effectiveness of these fluorophores as optically responsive dyes for neuronal imaging was assessed by measuring the toxicity and signal-to-noise ratio (SNR) of each dye. A great improvement of SNR was obtained when compared to the first-generation BODIPY-based voltage sensitive dyes with concomitant toxicity decrease. The mechanism for the optical response is disparate from conventional cyanine-based dyes, opening up a new way to produce effective voltage sensitive dyes that respond well into the NIR region.

One step closer to understanding the role of bacteria in diabetic foot ulcers: characterising the microbiome of ulcers.

BACKGROUND: The aim of this study was to characterise the microbiome of new and recurrent diabetic foot ulcers using 16S amplicon sequencing (16S AS), allowing the identification of a wider range of bacterial species that may be important in the development of chronicity in these debilitating wounds. Twenty patients not receiving antibiotics for the past three months were selected, with swabs taken from each individual for culture and 16S AS. DNA was isolated using a combination of bead beating and kit extraction. Samples were sequenced on the Illumina Hiseq 2500 platform. RESULTS: Conventional laboratory culture showed positive growth from only 55 % of the patients, whereas 16S AS was positive for 75 % of the patients (41 unique genera, representing 82 different operational taxonomic units (OTU's). S. aureus was isolated in 72 % of culture-positive samples, whereas the most commonly detected bacteria in all ulcers were Peptoniphilus spp., Anaerococcus spp. and Corynebacterium spp., with the addition of Staphylococcus spp. in new ulcers. The majority of OTU's residing in both new and recurrent ulcers (over 67 %) were identified as facultative or strict anaerobic Gram-positive organisms. Principal component analysis (PCA) showed no difference in clustering between the two groups (new and recurrent ulcers). CONCLUSIONS: The abundance of anaerobic bacteria has important implications for treatment as it suggests that the microbiome of each ulcer "starts afresh" and that, although diverse, are not distinctly different from one another with respect to new or recurrent ulcers. Therefore, when considering antibiotic therapy the duration of current ulceration may be a more important consideration than a history of healed ulcer.

Development and characterisation of a novel three-dimensional inter-kingdom wound biofilm model.

Chronic diabetic foot ulcers are frequently colonised and infected by polymicrobial biofilms that ultimately prevent healing. This study aimed to create a novel in vitro inter-kingdom wound biofilm model on complex hydrogel-based cellulose substrata to test commonly used topical wound treatments. Inter-kingdom triadic biofilms composed of Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus were shown to be quantitatively greater in this model compared to a simple substratum when assessed by conventional culture, metabolic dye and live dead qPCR. These biofilms were both structurally complex and compositionally dynamic in response to topical therapy, so when treated with either chlorhexidine or povidone iodine, principal component analysis revealed that the 3-D cellulose model was minimally impacted compared to the simple substratum model. This study highlights the importance of biofilm substratum and inclusion of relevant polymicrobial and inter-kingdom components, as these impact penetration and efficacy of topical antiseptics.

Data integrity of the Pediatric Cardiac Critical Care Consortium (PC4) clinical registry.

BACKGROUND: Clinical databases in congenital and paediatric cardiac care provide a foundation for quality improvement, research, policy evaluations and public reporting. Structured audits verifying data integrity allow database users to be confident in these endeavours. We report on the initial audit of the Pediatric Cardiac Critical Care Consortium (PC4) clinical registry. Materials and methods Participants reviewed the entire registry to determine key fields for audit, and defined major and minor discrepancies for the audited variables. In-person audits at the eight initial participating centres were conducted during a 12-month period. The data coordinating centre randomly selected intensive care encounters for review at each site. The audit consisted of source data verification and blinded chart abstraction, comparing findings by the auditors with those entered in the database. We also assessed completeness and timeliness of case submission. Quantitative evaluation of completeness, accuracy, and timeliness of case submission is reported. RESULTS: We audited 434 encounters and 29,476 data fields. The aggregate overall accuracy was 99.1%, and the major discrepancy rate was 0.62%. Across hospitals, the overall accuracy ranged from 96.3 to 99.5%, and the major discrepancy rate ranged from 0.3 to 0.9%; seven of the eight hospitals submitted >90% of cases within 1 month of hospital discharge. There was no evidence for selective case omission. CONCLUSIONS: Based on a rigorous audit process, data submitted to the PC4 clinical registry appear complete, accurate, and timely. The collaborative will maintain ongoing efforts to verify the integrity of the data to promote science that advances quality improvement efforts.

The active metabolite of spleen tyrosine kinase inhibitor fostamatinib abrogates the CD4⁺ T cell-priming capacity of dendritic cells.

OBJECTIVES: Spleen tyrosine kinase (SYK) is a core signalling protein that drives inflammatory responses and is fundamental to the propagation of signals via numerous immune receptors, including the B cell receptor and Fc receptors (FcRs). Fostamatinib, a small molecule SYK inhibitor, has shown evidence of ameliorating inflammation in RA patients. We sought to understand how the active metabolite of fostamatinib, R406, affects the inflammatory response at the cellular level. METHODS: Antigen-specific in vivo systems and in vitro fluorescence microscopy were combined to investigate the effects of fostamatinib on antigen-specific interactions between dendritic cells (DCs) and CD4(+) T cells. RESULTS: Although it has previously been shown that R406 reduces the response of DCs to immune complexes (ICs), we found that fostamatinib failed to reduce specific CD4(+) T cell proliferation in mice after immunization with ICs. However, we observed in vitro that R406 reduces both the area and duration of cellular interactions between IC-activated DCs and specific CD4(+) T cells during the initial phase of cellular crosstalk. This led to diminished proliferation of antigen-specific CD4(+) T cells after R406 treatment compared with vehicle controls. This decreased proliferative capacity of CD4(+) T cells was accompanied by reduced expression of the co-stimulatory molecules, inducible T cell co-stimulator (ICOS) and PD-1, and abrogation of the production of inflammatory cytokines such as IFN-γ and IL-17. CONCLUSION: Our findings indicate a potential mechanism by which this compound may be effective in inhibiting FcR-driven CD4(+) T cell responses.

A Case-Control Study on the Impact of Ventilator-Associated Tracheobronchitis in the PICU.

OBJECTIVES: Hospital-acquired infections increase morbidity, mortality, and charges in the PICU. We implemented a quality improvement bundle directed at ventilator-associated pneumonia in our PICU in 2005. We observed an increase in ventilator-associated tracheobronchitis coincident with the near-elimination of ventilator-associated pneumonia. The impact of ventilator-associated tracheobronchitis on critically ill children has not been previously described. Accordingly, we hypothesized that ventilator-associated tracheobronchitisis associated with increased length of stay, mortality, and hospital charge. DESIGN: Retrospective case-control study. PATIENTS: Critically ill children admitted to a quaternary PICU at a free-standing academic children's hospital in the United States. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a retrospective case control study, with institutional review board approval, of 77 consecutive cases of ventilator-associated tracheobronchitis admitted to our PICU from 2004-2010. We matched each case with a control based on the following criteria (in rank order): age range (< 30 d, 30 d to 24 mo, 24 mo to 12 yr, > 12 yr), admission Pediatric Risk of Mortality III score ± 10, number of ventilator days of control group (> 75% of days until development of ventilator-associated tracheobronchitis), primary diagnosis, underlying organ system dysfunction, surgical procedure, and gender. The primary outcome measured was PICU length of stay. Secondary outcomes included ventilator days, hospital length of stay, mortality, and PICU and hospital charges. Data was analyzed using chi square analysis and p less than 0.05 was considered significant. We successfully matched 45 of 77 ventilator-associated tracheobronchitis patients with controls. There were no significant differences in age, gender, diagnosis, or Pediatric Risk of Mortality III score between groups. Ventilator-associated tracheobronchitis patients had a longer PICU length of stay (median, 21.5 d, interquartile range, 24 d) compared to controls (median, 18 d; interquartile range, 17 d), although not statistically significant (p = 0.13). Ventilator days were also longer in the ventilator-associated tracheobronchitis patients (median, 17 d; IQR, 22 d) versus control (median, 10.5 d; interquartile range, 13 d) (p = 0.01). There was no significant difference in total hospital length of stay (54 d vs 36 d; p = 0.69). PICU mortality was higher in the ventilator-associated tracheobronchitis group (15% vs 5%; p = 0.14), although not statistically significant. There was an increase in both median PICU charges ($197,393 vs $172,344; p < 0.05) and hospital charges ($421,576 vs $350,649; p < 0.05) for ventilator-associated tracheobronchitis patients compared with controls. CONCLUSIONS: Ventilator-associated tracheobronchitis is a clinically significant hospital-acquired infection in the PICU and is associated with longer duration of mechanical ventilation and healthcare costs, possibly through causing a longer PICU length of stay. Quality improvement efforts should be directed at reducing the incidence of ventilator-associated tracheobronchitis in the PICU.

Astrocyte and Neuronal Plasticity in the Somatosensory System.

Changing the whisker complement on a rodent's snout can lead to two forms of experience-dependent plasticity (EDP) in the neurons of the barrel cortex, where whiskers are somatotopically represented. One form, termed coding plasticity, concerns changes in synaptic transmission and connectivity between neurons. This is thought to underlie learning and memory processes and so adaptation to a changing environment. The second, called homeostatic plasticity, serves to maintain a restricted dynamic range of neuronal activity thus preventing its saturation or total downregulation. Current explanatory models of cortical EDP are almost exclusively neurocentric. However, in recent years, increasing evidence has emerged on the role of astrocytes in brain function, including plasticity. Indeed, astrocytes appear as necessary partners of neurons at the core of the mechanisms of coding and homeostatic plasticity recorded in neurons. In addition to neuronal plasticity, several different forms of astrocytic plasticity have recently been discovered. They extend from changes in receptor expression and dynamic changes in morphology to alteration in gliotransmitter release. It is however unclear how astrocytic plasticity contributes to the neuronal EDP. Here, we review the known and possible roles for astrocytes in the barrel cortex, including its plasticity.

Interventions for preventing or controlling health care-associated infection among health care workers or patients within primary care facilities: A scoping review.

BACKGROUND: This review aimed to synthesize the evidence on infection prevention and control interventions for the prevention of health care-associated infection among health care workers or patients within primary care facilities. METHODS: PubMed, CINAHL, EMBASE, and CENTRAL databases were searched for quantitative studies published between 2011 and 2022. Study selection, data extraction, and quality assessment using Cochrane and Joanna Briggs tools, were conducted by independent review with additional sensitivity checking performed on study selection. RESULTS: Four studies were included. A randomized trial and a cross-sectional survey, respectively, found no statistical difference in laboratory-confirmed influenza in health care workers wearing N95 versus medical masks (P = .18) and a significant inverse association between the implementation of tuberculosis control measures and tuberculosis incidence (P = .02). For the prevention of surgical site infections following minor surgery, randomized trials found nonsterile gloves (8.7%; 95% confidence interval, 4.9%-12.6%) to be noninferior to sterile gloves (9.3%; 95% confidence interval, 7.4%-11.1%) and no significant difference between prophylactic antibiotics compared to placebo (P = .064). All studies had a high risk of bias. CONCLUSIONS: Evidence for infection prevention and control interventions for the prevention of health care-associated infection in primary care is very limited and insufficient to make practice recommendations. Nevertheless, the findings highlight the need for future research.

Prevalence of reactive attachment disorder in a deprived population.

BACKGROUND: Reactive attachment disorder (RAD) is associated with early childhood maltreatment and has unknown population prevalence beyond infancy. AIMS: To estimate RAD prevalence in a deprived population of children. METHOD: All 1646 children aged 6-8 years old in a deprived sector of an urban UK centre were screened for RAD symptoms. Parents of high and low scorers were interviewed using semi-structured interviews probing for psychopathology and individuals likely to have RAD were offered face-to-face assessment. RESULTS: Questionnaire data were available from 92.8% of teachers and 65.8% of parents. Assessments were conducted with 50% of those invited and missing data were imputed--based on the baseline data--for the rest. We calculated that there would be 23 children with definite RAD diagnoses, suggesting that the prevalence of RAD in this population was 1.40% (95% CI 0.94-2.10). CONCLUSIONS: In this deprived general population, RAD was not rare.

Influence of periodontal disease, Porphyromonas gingivalis and cigarette smoking on systemic anti-citrullinated peptide antibody titres.

BACKGROUND: Anti-citrullinated protein antibody (ACPA) responses may precede clinical onset of rheumatoid arthritis. Porphyromonas gingivalis peptidylarginine deiminase can citrullinate proteins possibly inducing autoimmunity in susceptible individuals. AIM: To determine whether periodontitis, carriage of P. gingivalis, smoking and periodontal therapy influence ACPA titres. METHODS: Serum and plaque samples were collected from 39 periodontitis patients before and after non-surgical periodontal treatment, and from 36 healthy subjects. Carriage of P. gingivalis was determined by PCR of plaque DNA. ACPA was determined by anti-cyclic citrullinated peptide (CCP) enzyme-linked immunosorbent assay (ELISA). Anti-P. gingivalis titres were determined by ELISA. RESULTS: Untreated periodontitis patients had higher anti-CCP antibody titres than healthy controls [three patients (8%) greater than manufacturer suggested assay diagnostic threshold (5 Assay Units/AU) versus none (0%); mean ± SEM: 1.37 ± 0.23 versus 0.40 ± 0.10 AU, p < 0.0001]. Periodontitis patients who smoked demonstrated lower anti-P. gingivalis (15956 ± 4385 versus 2512 ± 1290 Units/ml, p < 0.05), but similar anti-CCP than non-smoking periodontitis patients (smokers: 1.31 ± 0.35; non-smokers: 1.41 ± 0.32 AU). Healthy smokers demonstrated elevated anti-CCP titres (0.75 ± 0.19 AU), at levels between healthy non-smokers (0.15 ± 0.05 AU) and non-smoker periodontitis patients. Six months after periodontal treatment, there were significant reductions in anti-CCP (non-smokers p < 0.05) and anti-P. gingivalis (all participants p < 0.01). CONCLUSION: In subjects with periodontitis, P. gingivalis infection may be responsible for inducing autoimmune responses that characterize rheumatoid arthritis.

Development of macrocyclic inhibitors of HCV NS3/4A protease with cyclic constrained P2-P4 linkers.

A series of macrocyclic compounds containing a cyclic constraint in the P2-P4 linker region have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155K, A156T, A156V, and D168V mutant activity while maintaining high rat liver exposure. The effect of the constraint is most dramatic against gt 1b A156 mutants where ~20-fold improvements in potency are achieved by introduction of a variety of ring systems into the P2-P4 linker.

Development of potent macrocyclic inhibitors of genotype 3a HCV NS3/4A protease.

A series of macrocyclic compounds containing 2-substituted-quinoline moieties have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155K mutant activity while maintaining the high rat liver exposure. Cyclization of the 2-substituted quinoline substituent led to a series of tricyclic P2 compounds which also display superb gt3a potency.

Impaired dendritic cell proinflammatory cytokine production in psoriatic arthritis.

OBJECTIVE: The pathogenesis of psoriatic arthritis (PsA) remains poorly understood. The underlying chronic inflammatory immune response is thought to be triggered by unknown environmental factors potentially arising from a defective immune function. We undertook this study to determine whether an impaired acute inflammatory response by dendritic cells (DCs) might compromise the clearance of bacteria and predispose to chronic inflammation. METHODS: We determined cytokine production by DCs from healthy controls and from patients with rheumatoid arthritis, PsA, and psoriasis in response to Mycobacterium tuberculosis, Mycobacterium avium paratuberculosis, and a range of other bacteria and Toll-like receptor (TLR) ligands. Phenotypic differences involved in cellular responses against (myco)bacteria were determined by quantitative polymerase chain reaction and flow cytometry. RESULTS: The secretion of proinflammatory cytokines by PsA DCs was impaired upon in vitro challenge with mycobacteria and TLR-2 ligands. This impairment was associated with elevated serum levels of C-reactive protein. The expression of TLR-2 and other receptors known to mediate mycobacterial recognition was unaltered. In contrast, the intracellular TLR inhibitors suppressor of cytokine signaling 3 and A20 were more highly expressed in DCs from PsA patients. PsA DCs further demonstrated up-regulated levels of ATG16L1, NADPH oxidase 2, and LL37, which are molecules implicated in the immune response against intracellular bacteria. CONCLUSION: Our findings indicate that DCs from PsA patients have a disordered immune response toward some species of (myco)bacteria. This might predispose to impaired immune responses to, and in turn impaired clearance of, these bacteria, setting the stage for the chronic inflammation of joints, entheses, skin, and the gut.

A requirement for astrocyte IP3R2 signaling for whisker experience-dependent depression and homeostatic upregulation in the mouse barrel cortex.

Changes to sensory experience result in plasticity of synapses in the cortex. This experience-dependent plasticity (EDP) is a fundamental property of the brain. Yet, while much is known about neuronal roles in EDP, very little is known about the role of astrocytes. To address this issue, we used the well-described mouse whiskers-to-barrel cortex system, which expresses a number of forms of EDP. We found that all-whisker deprivation induced characteristic experience-dependent Hebbian depression (EDHD) followed by homeostatic upregulation in L2/3 barrel cortex of wild type mice. However, these changes were not seen in mutant animals (IP3R2-/-) that lack the astrocyte-expressed IP3 receptor subtype. A separate paradigm, the single-whisker experience, induced potentiation of whisker-induced response in both wild-type (WT) mice and IP3R2-/- mice. Recordings in ex vivo barrel cortex slices reflected the in vivo results so that long-term depression (LTD) could not be elicited in slices from IP3R2-/- mice, but long-term potentiation (LTP) could. Interestingly, 1 Hz stimulation inducing LTD in WT paradoxically resulted in NMDAR-dependent LTP in slices from IP3R2-/- animals. The LTD to LTP switch was mimicked by acute buffering astrocytic [Ca2+] i in WT slices. Both WT LTD and IP3R2-/- 1 Hz LTP were mediated by non-ionotropic NMDAR signaling, but only WT LTD was P38 MAPK dependent, indicating an underlying mechanistic switch. These results demonstrate a critical role for astrocytic [Ca2+] i in several EDP mechanisms in neocortex.

Reducing catheter-associated bloodstream infections in the pediatric intensive care unit: Business case for quality improvement.

OBJECTIVE: To determine whether catheter-associated bloodstream infections were associated with increased lengths of stay in pediatric intensive care units and hospitals and increased healthcare costs in critically ill children. Previous studies have shown that hospital-acquired bloodstream infections are associated with longer stays in pediatric intensive care units, increased hospital costs, and increased hospital mortality. Catheter-associated bloodstream infections comprise the vast majority of hospital-acquired bloodstream infections. DESIGN: Retrospective, case-matched, cohort study and financial analysis. SETTING: University-affiliated children's medical center. PATIENTS: Twenty-two critically ill children with catheter-associated bloodstream infections and their matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared the length of stay, mortality, and hospital costs in critically ill children with catheter-associated bloodstream infections and matched controls. The presence of catheter-associated bloodstream infections extended the entire hospital length of stay by 9 days (6.5 days while in the pediatric intensive care unit) and increased hospital costs by $33,039, primarily driven by the increase in length of stay days. Quality improvement efforts directed at reducing the prevalence of catheter-associated bloodstream infections during the period of study decreased total hospital days by 354, reduced total hospital costs by $1,298,271, and reduced total costs to payers by $1,415,676. CONCLUSION: The potential cost savings from reducing or eliminating catheter-associated bloodstream infections in the pediatric intensive care unit are significant. Elimination of catheter-associated bloodstream infections will directly reduce hospital costs, improve asset utilization, and most importantly, improve clinical care.