Parents' quality of life and health after treatment decision for a fetus with severe congenital heart defect.

PURPOSE: This exploratory study examines differences in parents' quality of life by treatment decision and the child's survival outcome in the context of life-threatening congenital heart disease (CHD). DESIGN AND METHODS: Parents of a fetus or neonate diagnosed with severe CHD enrolled in the observational control group of a clinical trial (NCT04437069) and completed quality of life (i.e., contact with clinicians, social support, partner relationship, state of mind), mental and physical health survey measures. Comparisons were made between parents who chose comfort-directed care or surgery and between those whose child did and did not survive. RESULTS: Parents who chose surgery and their child did not survive reported the most contact with their clinicians. Parents who chose comfort-directed care reported lower social support than parents who chose surgery and their child did not survive as well as poorer state of mind compared to parents who chose surgery. CONCLUSIONS: Some aspects of parents' quality of life differed based on their treatment decision. Parents who choose comfort-directed care are vulnerable to some negative outcomes. PRACTICE IMPLICATIONS: Decision support tools and bereavement resources to assist parents with making and coping with a complex treatment decision is important for clinical care.

Measles outbreak in Dubrovnik-Neretva County, Croatia, May to June 2018.

In May 2018, measles was introduced in the Dubrovnik region by an adult who recently travelled to Kosovo*. Control measures and an outbreak investigation were implemented: 15 epidemiologically-linked cases met the outbreak case definition of a visitor/resident of Dubrovnik-Neretva County with laboratory-confirmed measles and symptom onset beginning on May 19. New cases were identified through hospitals and primary care physicians. Throat swabs, urine and/or serum samples were collected from outbreak cases. RT-PCR detection of viral RNA and IgM/IgG was used to confirm infection. The median age of cases was 33 years, with one 8 month-old infant. Vaccination status was unknown for 9 cases, three were unvaccinated, one case had history of one dose and two cases reported receiving two doses of measles-containing vaccine. There were 11 hospitalisations and one person developed pneumonia. Control teams undertook an extensive search of contacts and implemented a range of control measures. Despite the outbreak occurring at the beginning of the summer tourism season, it was contained and did not spread to neighbouring regions. With continuing measles transmission in Europe, even small outbreaks create a burden on the health system in countries which have eliminated measles, and illustrate the importance of maintaining high immunisation coverage.

Salivary fluoride concentration and retention after rinsing with 0.05 and 0.2% sodium fluoride (NaF) compared with a new high F rinse containing 0.32% NaF.

OBJECTIVE: To compare salivary fluoride (F) concentration and F retention after rinsing with a new 0.32% sodium fluoride (NaF) rinse and conventional 0.05 and 0.2% NaF rinses. METHODS: Seventeen subjects (aged 22-26 years), with normal salivary secretion rates, participated in a double blind, cross-over study. In three separate sessions with a minimum washout period of 48 h, they rinsed for 1 min with 10 ml of 0.05, 0.2 or 0.32% NaF mouthrinse. Unstimulated whole saliva was collected before (baseline: 0 min) and after 1, 3, 5, 10, 20, 30, 45 and 60 min. The F concentration was plotted against time, and the area under the curve (AUC) calculated. Salivary F concentration and F retention for the three mouthrinses were compared by a randomized block test, followed by Tukey's test and a paired 2-tailed test. RESULTS: There was a clear dose-response for AUC 3-60 min; 0.32% > 0.2% > 0.05% (p < .05). The mean F retention was 0.25 mg for 0.05% NaF, 0.86 mg F for 0.2% Na and 1.31 mg F for 0.32% NaF, (p < .05). CONCLUSIONS: The higher salivary F concentration over time and the higher F retention after rinsing with an 0.32% NaF solution suggests a potential application in prevention of caries and dental erosion.

Measles seroprevalence after reactive vaccination campaigns during the 2015 measles outbreak in four health zones of the former Katanga Province, Democratic Republic of Congo.

BACKGROUND: Measles continues to circulate in the Democratic Republic of Congo, and the country suffered from several important outbreaks over the last 5 years. Despite a large outbreak starting in the former province of Katanga in 2010 and the resulting immunization activities, another outbreak occurred in 2015 in this same region. We conducted measles seroprevalence surveys in four health zones (HZ) in the former Katanga Province in order to assess the immunity against measles in children 6 months to 14 years after the 2015 outbreak. METHODS: We conducted multi-stage cluster surveys stratified by age group in four HZs, Kayamba, Malemba-Nkulu, Fungurume, and Manono. The age groups were 6-11 months, 12-59 months, and 5-14 years in Kayamba and Malemba-Nkulu, 6-59 months and 5-14 years in Manono and Fungurume. The serological status was measured on dried capillary blood spots collected systematically along with vaccination status (including routine Extended Program of Immunization (EPI), and supplementary immunization activities (SIAs)) and previous self-reported history of suspected measles. RESULTS: Overall seroprevalence against measles was 82.7% in Kayamba, 97.6% in Malemba-Nkulu, 83.2% in Manono, and 74.4% in Fungurume, and it increased with age in all HZs. It was 70.7 and 93.8% in children 12-59 months in Kayamba and Malemba-Nkulu, and 49.8 and 64.7% in children 6-59 months in Fungurume and Manono. The EPI coverage was low but varied across HZ. The accumulation of any type of vaccination against measles resulted in an overall vaccine coverage (VC) of at least 85% in children 12-59 months in Kayamba and Malemba-Nkulu, 86.1 and 74.8% in children 6-59 months in Fungurume and Manono. Previous measles infection in 2015-early 2016 was more frequently reported in children aged 12-59 months or 6-59 months (depending on the HZ). CONCLUSION: The measured seroprevalence was consistent with the events that occurred in these HZs over the past few years. Measles seroprevalence might prove a valuable source of information to help adjust the timing of future SIAs and prioritizing support to the EPI in this region as long as the VC does not reach a level high enough to efficiently prevent epidemic flare-ups.

Mycoplasma ovipneumoniae in Wildlife Species beyond Subfamily Caprinae.

Elucidating the emergence of Mycoplasma ovipneumoniae-associated respiratory disease in ruminants requires identification of the pathogen host range. This bacterium was thought to be host restricted to subfamily Caprinae, but we describe its identification in healthy moose, caribou, and mule deer and diseased mule and white-tailed deer, all species in subfamily Capreolinae.

Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model.

BACKGROUND: Cathodic voltage-controlled electrical stimulation (CVCES) of titanium implants, either alone or combined with a short course of vancomycin, has previously been shown to reduce the bone and implant bacterial burden in a rodent model of methicillin-resistant Staphylococcus aureus (MRSA) implant-associated infection (IAI). Clinically, the goal is to achieve complete eradication of the IAI; therefore, the rationale for the present study was to evaluate the antimicrobial effects of combining CVCES with prolonged antibiotic therapy with the goal of decreasing the colony-forming units (CFUs) to undetectable levels. QUESTIONS/PURPOSES: (1) In an animal MRSA IAI model, does combining CVCES with prolonged vancomycin therapy decrease bacteria burden on the implant and surrounding bone to undetectable levels? (2) When used with prolonged vancomycin therapy, are two CVCES treatments more effective than one? (3) What are the longer term histologic effects (inflammation and granulation tissue) of CVCES on the surrounding tissue? METHODS: Twenty adult male Long-Evans rats with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, the rats were randomly divided into four groups of five: (1) VANCO: only vancomycin treatment (150 mg/kg, subcutaneous, twice daily for 5 weeks); (2) VANCO + 1STIM: vancomycin treatment (same as the VANCO group) coupled with one CVCES treatment (-1.8 V for 1 hour on postoperative day [POD] 7); (3) VANCO + 2STIM: vancomycin treatment (same as the VANCO group) coupled with two CVCES treatments (-1.8 V for 1 hour on POD 7 and POD 21); or (4) CONT: no treatment. On POD 42, the implant, bone, and peripheral blood were collected for CFU enumeration and histological analysis, where we compared CFU/mL on the implants and bone among the groups. A pathologist, blinded to the experimental conditions, performed a semiquantitative analysis of inflammation and granulation tissue present in serial sections of the humeral head for animals in each experimental group. RESULTS: The VANCO + 1STIM decreased the implant bacterial burden (median = 0, range = 0-10 CFU/mL) when compared with CONT (median = 5.7 × 10(4), range = 4.0 × 10(3)-8.0 × 10(5) CFU/mL; difference of medians = -5.6 × 10(4); p < 0.001) and VANCO (median = 4.9 × 10(3), range = 9.0 × 10(2)-2.1 × 10(4) CFU/mL; difference of medians = -4.9 × 10(3); p < 0.001). The VANCO + 1STIM decreased the bone bacterial burden (median = 0, range = 0-0 CFU/mL) when compared with CONT (median = 1.3 × 10(2), range = 0-9.4 × 10(2) CFU/mL; difference of medians = -1.3 × 10(2); p < 0.001) but was not different from VANCO (median = 0, range = 0-1.3 × 10(2) CFU/mL; difference of medians = 0; p = 0.210). The VANCO + 2STIM group had implant CFU (median = 0, range = 0-8.0 × 10(1) CFU/mL) and bone CFU (median = 0, range = 0-2.0 × 10(1) CFU/mL) that were not different from the VANCO + 1STIM treatment group implant CFU (median = 0, range = 0-10 CFU/mL; difference of medians = 0; p = 0.334) and bone CFU (median = 0, range = 0-0 CFU/mL; difference of medians = 0; p = 0.473). The histological analysis showed no deleterious effects on the surrounding tissue as a result of the treatments. CONCLUSIONS: Using CVCES in combination with prolonged vancomycin resulted in decreased MRSA bacterial burden, and it may be beneficial in treating biofilm-related implant infections. CLINICAL RELEVANCE: CVCES combined with clinically relevant lengths of vancomycin therapy may be a treatment option for IAI and allow for component retention in certain clinical scenarios. However, more animal research and human trials confirming the efficacy of this approach are needed before such a clinical recommendation could be made.

Cathodic Electrical Stimulation Combined With Vancomycin Enhances Treatment of Methicillin-resistant Staphylococcus aureus Implant-associated Infections.

BACKGROUND: Effective treatments for implant-associated infections are often lacking. Cathodic voltage-controlled electrical stimulation has shown potential as a treatment of implant-associated infections of methicillin-resistant Staphylococcus aureus (MRSA). QUESTIONS/PURPOSES: The primary purpose of this study was to (1) determine if cathodic voltage-controlled electrical stimulation combined with vancomycin therapy is more effective at reducing the MRSA bacterial burden on the implant, bone, and synovial fluid in comparison to either treatment alone or no treatment controls. We also sought to (2) evaluate the histologic effects of the various treatments on the surrounding bone; and to (3) determine if the cathodic voltage-controlled electrical stimulation treatment had an effect on the mechanical properties of the titanium implant as a result of possible hydrogen embrittlement. METHODS: Thirty-two adult male Long-Evans rats (Harlan Laboratories, Indianapolis, IN, USA) with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, eight animals received a treatment of cathodic voltage-controlled electrical stimulation at -1.8 V versus Ag/AgCl for 1 hour (STIM), eight received vancomycin twice daily for 1 week (VANCO), eight received the cathodic voltage-controlled electrical stimulation and vancomycin therapy combined (STIM + VANCO), and eight served as controls with no treatment (CONT). Two weeks after initial infection, the implant, bone, and synovial fluid were collected for colony-forming unit (CFU) enumeration, qualitative histological analysis by a pathologist blinded to the treatments each animal received, and implant three-point bend testing. RESULTS: The implant-associated CFU enumerated from the STIM + VANCO (mean, 3.7 × 10(3); SD, 6.3 × 10(3)) group were less than those from the CONT (mean, 1.3 × 10(6); SD, 2.8 × 10(6); 95% confidence interval [CI] of difference, -4.3 × 10(5) to -9.9 × 10(3); p < 0.001), STIM (mean, 1.4 × 10(6); SD, 2.0 × 10(6); 95% CI of difference, -2.1 × 10(6) to -1.8 × 10(3); p = 0.002), and VANCO (mean, 5.8 x 10(4); SD, 5.7 × 10(4); 95% CI of difference, -6.4 × 10(4) to -1.7 × 10(4); p < 0.001) group. The bone-associated CFU enumerated from the STIM + VANCO group (6.3 × 10(1); SD, 1.1 × 10(2)) were less than those from the CONT (mean, 2.8 × 10(5); SD, 4.8 × 10(5); 95% CI of difference, -9.4 × 10(4) to -5.0 × 10(3); p < 0.001) and STIM (mean, 2.6 × 10(4); SD, 2.5 × 10(4); 95% CI of difference, -4.1 × 10(4) to -1.6 × 10(3); p < 0.001) groups. The VANCO group (4.3 × 10(5); SD, 6.3 × 10(2)) also had lower bone-associated CFU as compared with the CONT (mean 95% CI of difference, -9.3 × 10(4) to -4.5 × 10(3); p < 0.001) and STIM (95% CI of difference, -4.0 × 10(4) to -1.5 × 10(3); p < 0.001) groups. In comparison to the synovial fluid CFU enumerated from the CONT group (mean, 3.3 × 10(4); SD, 6.0 × 10(4)), lower synovial CFU were reported for both the STIM + VANCO group (mean, 4.6 × 10(1); SD, 1.2 × 10(2); 95% CI of difference, -4.9 × 10(3) to -3.0 × 10(2); p < 0.001) and the VANCO group (mean, 6.8 × 10(1); SD, 9.2 × 10(1); 95% CI of difference, -4.9 × 10(3) to -2.8 × 10(2); p = 0.007). The histological analysis showed no discernable deleterious effects on the surrounding tissue as a result of the treatments. No brittle fracture occurred during mechanical testing and with the numbers available, no differences in implant flexural yield strength were detected between the groups. CONCLUSIONS: In this rodent model, cathodic voltage-controlled electrical stimulation combined with vancomycin is an effective treatment for titanium implant-associated infections showing greater than 99.8% reduction in bacterial burden on the implant, surrounding bone, and synovial fluid as compared with the controls and the stimulation alone groups. CLINICAL RELEVANCE: Cathodic voltage-controlled electrical stimulation combined with vancomycin may enable successful treatment of titanium orthopaedic implant-associated infections with implant retention. Future studies will focus on optimization of the stimulation parameters for complete eradication of infection and the ability to promote beneficial host tissue responses.

Integrated Solutions for Intertwined Challenges: A Statewide Collaboration in Supportive Housing for Child Welfare-Involved Families.

This paper describes Connecticut's Supportive Housing for Families (SHF) program, which is one of five national sites comprising a federally- funded demonstration of housing and child welfare. Evaluations of supportive housing (SH) interventions are complicated by contextual factors that make it difficult to isolate their effects. 'Ihese and other challenges complicate efforts to conduct rigorous research and establish external validity, and to date, few studies examine the impact of SH interventions for child- welfare involved families. We describe retrospectively the development of SHF using. six stages of imple- mentation articulated within an implementation science framework, noting both the core components of the program and its expansion from a small pilot exploration, to a statewide initiative, and now to the center of a systems change effort with potential to influence national policy and implementation.

Moraxella catarrhalis is susceptible to antimicrobial photodynamic therapy with Photofrin.

BACKGROUND AND OBJECTIVE: Moraxella catarrhalis is a significant cause of pediatric otitis media (OM), which is the most prevalent bacterial infection in children and primary reason for antibiotic administration in this population. Moreover, biofilm formation has been implicated as a primary mechanism of chronic or recurrent OM disease. As bacterial biofilms are inherently resistant to most antibiotics and these complex structures also present a significant challenge to the immune system, there is a clear need to identify novel antimicrobial approaches to treat OM infections. In this study, we evaluated the potential efficacy of antibacterial photodynamic therapy (aPDT) with porfimer sodium (Photofrin (PF)) against planktonic as well as biofilm-associated M. catarrhalis. MATERIALS AND METHODS: The bactericidal activity of aPDT with PF was assessed against multiple recent clinical isolates of M. catarrhalis grown planktonically as well as in biofilms. The bactericidal activity of PF-aPDT was quantified by enumeration of colony forming units post-treatment. The effect of aPDT on M. catarrhalis biofilms was further investigated with scanning electron microscopy (SEM) imaging. RESULTS: aPDT with PF significantly reduced M. catarrhalis viability. Although PF-aPDT caused higher killing in planktonic grown organisms (5-6 log kill), biofilm grown bacteria also demonstrated a statistically significant reduction in viable organisms (3-4 log decrease in recoverable bacteria) following treatment as compared to saline only controls (P < 0.01). SEM studies indicated the PF-aPDT treated bacteria exhibited prominent morphological changes with visibly distorted cell membranes. CONCLUSIONS: aPDT with PF elicits significant bactericidal activity against both planktonic and biofilm-associated M. catarrhalis, suggesting this technology warrants further analysis as a potential novel antimicrobial treatment for acute or recurrent OM.

Spread of Puumala Hantavirus to New Areas in a Large Croatian Outbreak of Hemorrhagic Fever with Renal Syndrome, 2021.

Background: The largest documented outbreak of hemorrhagic fever with renal syndrome occurred in Primorje-Gorski Kotar County, Croatia, in 2021, marking the first-time cases of hantavirus infection recorded outside of the known endemic region in the north of the county. Aim: To identify the factors contributing to the spread of the outbreak and to compare risk factors for acquiring hantavirus infection in the endemic and newly affected regions. Methods and Results: A total of 189 cases were confirmed by positive Puumala IgM/IgG antibodies (93.6%), and 13 probable cases were identified by clinical and epidemiological data (6.4%) using a structured questionnaire. Of the 179 cases with available clinical data, 59 (33.0%) were hospitalized. Three cases received hemodialysis, and no deaths were reported. Among 170 cases with information on exposures, 66 (38.8%) reported occupational risk. Cases in the northern part of county were more likely to have been infected in early spring (OR 27.1, 95% CI 2.93-250.7), to report seeing a rodent (OR 6.5; 95%CI 2.3-18.4), and to know someone with hemorrhagic fever with renal syndrome (HFRS) (OR 3.0; 95%CI 1.2-8.0) than cases from the southern part of the county. Data from Croatian Forests Ltd. suggested that an unusually good production of beech seeds in 2020 may have contributed to an increased rodent population in 2021. However, average temperature, rainfall, and humidity data from 2021 did not illustrate a significant difference from previous years (Kruskal-Wallis p = 0.837, p = 0.999, p = 0.108). Conclusion: The 2021 HFRS outbreak was likely fueled by an abundant rodent population and virus transmission in rodent hosts. Human activity, environmental factors, and the ensuing animal-human interactions have spread hantavirus infection from Croatia's mountainous region to a previously nonendemic coastal area with a Mediterranean climate.

Commensal-derived short-chain fatty acids disrupt lipid membrane homeostasis in Staphylococcus aureus.

The role of commensal anaerobic bacteria in chronic respiratory infections is unclear, yet they can exist in abundances comparable to canonical pathogens in vivo. Their contributions to the metabolic landscape of the host environment may influence pathogen behavior by competing for nutrients and creating inhospitable conditions via toxic metabolites. Here, we reveal a mechanism by which the anaerobe-derived short chain fatty acids (SCFAs) propionate and butyrate negatively affect Staphylococcus aureus physiology by disrupting branched chain fatty acid (BCFA) metabolism. In turn, BCFA impairment results in impaired growth, diminished expression of the agr quorum sensing system, as well as increased sensitivity to membrane-targeting antimicrobials. Altered BCFA metabolism also reduces S. aureus fitness in competition with Pseudomonas aeruginosa, suggesting that airway microbiome composition and the metabolites they produce and exchange directly impact pathogen succession over time. The pleiotropic effects of these SCFAs on S. aureus fitness and their ubiquity as metabolites in animals also suggests that they may be effective as sensitizers to traditional antimicrobial agents when used in combination.

Context-dependence of T-loop Mediated Long-range RNA Tertiary Interactions.

The architecture and folding of complex RNAs is governed by a limited set of highly recurrent structural motifs that form long-range tertiary interactions. One of these motifs is the T-loop, which was first identified in tRNA but is broadly distributed across biological RNAs. While the T-loop has been examined in detail in different biological contexts, the various receptors that it interacts with are not as well defined. In this study, we use a cell-based genetic screen in concert with bioinformatic analysis to examine three different, but related, T-loop receptor motifs found in the flavin mononucleotide (FMN) and cobalamin (Cbl) riboswitches. As a host for different T-loop receptors, we employed the env8 class-II Cbl riboswitch, an RNA that uses two T-loop motifs for both folding and supporting the ligand binding pocket. A set of libraries was created in which select nucleotides that participate in the T-loop/T-loop receptor (TL/TLR) interaction were fully randomized. Library members were screened for their ability to support Cbl-dependent expression of a reporter gene. While T-loops appear to be variable in sequence, we find that the functional sequence space is more restricted in the Cbl riboswitch, suggesting that TL/TLR interactions are context dependent. Our data reveal clear sequence signatures for the different types of receptor motifs that align with phylogenic analysis of these motifs in the FMN and Cbl riboswitches. Finally, our data suggest the functional contribution of various nucleobase-mediated long-range interactions within the riboswitch subclass of TL/TLR interactions that are distinct from those found in other RNAs.

Parents' Psychological and Decision-Making Outcomes following Prenatal Diagnosis with Complex Congenital Heart Defect: An Exploratory Study.

Background. Parents with a fetus diagnosed with a complex congenital heart defect (CHD) are at high risk of negative psychological outcomes. Purpose. To explore whether parents' psychological and decision-making outcomes differed based on their treatment decision and fetus/neonate survival status. Methods. We prospectively enrolled parents with a fetus diagnosed with a complex, life-threatening CHD from September 2018 to December 2020. We tested whether parents' psychological and decision-making outcomes 3 months posttreatment differed by treatment choice and survival status. Results. Our sample included 23 parents (average Age[years]: 27 ± 4, range = 21-37). Most were women (n = 18), non-Hispanic White (n = 20), and married (n = 21). Most parents chose surgery (n = 16), with 11 children surviving to the time of the survey; remaining parents (n = 7) chose comfort-directed care. Parents who chose comfort-directed care reported higher distress (x¯ = 1.51, s = 0.75 v. x¯ = 0.74, s = 0.55; Mdifference = 0.77, 95% confidence interval [CI], 0.05-1.48) and perinatal grief (x¯ = 91.86, s = 22.96 v. x¯ = 63.38, s = 20.15; Mdifference = 27.18, 95% CI, 6.20-48.16) than parents who chose surgery, regardless of survival status. Parents who chose comfort-directed care reported higher depression (x¯ = 1.64, s = 0.95 v. x¯ = 0.65, s = 0.49; Mdifference = 0.99, 95% CI, 0.10-1.88) than parents whose child survived following surgery. Parents choosing comfort-directed care reported higher regret (x¯ = 26.43, s = 8.02 v. x¯ = 5.00, s = 7.07; Mdifference = 21.43, 95% CI, 11.59-31.27) and decisional conflict (x¯ = 20.98, s = 10.00 v. x¯ = 3.44, s = 4.74; Mdifference = 17.54, 95% CI; 7.75-27.34) than parents whose child had not survived following surgery. Parents whose child survived following surgery reported lower grief (Mdifference = -19.71; 95% CI, -39.41 to -0.01) than parents whose child had not. Conclusions. The results highlight the potential for interventions and care tailored to parents' treatment decisions and outcomes to support parental coping and well-being. Highlights: Question: Do the psychological and decision-making outcomes of parents differ based on their treatment decision and survival outcome following prenatal diagnosis with complex CHD?Findings: In this exploratory study, parents who decided to pursue comfort-directed care after a prenatal diagnosis reported higher levels of psychological distress and grief as well as higher decisional conflict and regret than parents who decided to pursue surgery.Meaning: The findings from this exploratory study highlight potential differences in parents' psychological and decision-making outcomes following a diagnosis of complex CHD for their fetus, which appear to relate to the treatment approach and the treatment outcome and may require tailoring of psychological and decision support.

Resolving Pseudohyponatremia: Validation of Plasma Sodium on Radiometer ABL800 Blood Gas Analyzers for Immediate Reflex Testing.

OBJECTIVE: To perform validation of plasma sodium on blood gas analyzers to reflexively correct erroneous measurements by ion-selective electrodes (ISEs). METHODS: We compared remnant specimens of whole blood and plasma collected by lithium heparin vacutainer with normal protein concentrations and no lipemia. Whole-blood specimens were tested for sodium concentration on the ABL800 Flex blood gas analyzer, followed by centrifugation for plasma separation, and repeat sodium determination on an aliquot of the plasma only. Also, plasma specimens were analyzed by indirect ISE on the Cobas 8000 series and by direct ISE on the ABL800 Flex for instrument comparison. RESULTS: Plasma aliquots yielded comparable results to the parent whole-blood specimen, with an average change of -1.33 mmol/L (R2 = 0.9727). Comparison of indirect ISE to direct ISE similarly yielded comparable results, with an average change of + 0.8 mmol/L (R2 = 0.9016). CONCLUSION: Plasma is a valid specimen matrix for use on blood gas analyzers for sodium determination, eliminating the need for re-collection of whole-blood specimens from patients with pseudohyponatremia.

Targeting the MYC interaction network in B-cell lymphoma via histone deacetylase 6 inhibition.

Overexpression of MYC is a genuine cancer driver in lymphomas and related to poor prognosis. However, therapeutic targeting of the transcription factor MYC remains challenging. Here, we show that inhibition of the histone deacetylase 6 (HDAC6) using the HDAC6 inhibitor Marbostat-100 (M-100) reduces oncogenic MYC levels and prevents lymphomagenesis in a mouse model of MYC-induced aggressive B-cell lymphoma. M-100 specifically alters protein-protein interactions by switching the acetylation state of HDAC6 substrates, such as tubulin. Tubulin facilitates nuclear import of MYC, and MYC-dependent B-cell lymphoma cells rely on continuous import of MYC due to its high turn-over. Acetylation of tubulin impairs this mechanism and enables proteasomal degradation of MYC. M-100 targets almost exclusively B-cell lymphoma cells with high levels of MYC whereas non-tumor cells are not affected. M-100 induces massive apoptosis in human and murine MYC-overexpressing B-cell lymphoma cells. We identified the heat-shock protein DNAJA3 as an interactor of tubulin in an acetylation-dependent manner and overexpression of DNAJA3 resulted in a pronounced degradation of MYC. We propose a mechanism by which DNAJA3 associates with hyperacetylated tubulin in the cytoplasm to control MYC turnover. Taken together, our data demonstrate a beneficial role of HDAC6 inhibition in MYC-dependent B-cell lymphoma.

Vaccination attitudes, beliefs and behaviours among primary health care workers in northern Croatia.

Primary health care workers (HCWs) provide almost all vaccine services in Croatia, so they play an essential role in vaccine recommendations and uptake. The aim of this study was to determine the level of vaccine hesitancy among primary HCWs, to identify differences between nurses and physicians in attitudes, beliefs and behaviours towards vaccination, and to determine predictors of vaccine hesitancy among HCWs. We conducted a cross-sectional study from July to December in 2018 among physicians and nurses employed in the services of epidemiology, public health, school medicine, pediatrics and general practice/family medicine in Primorje-Gorski Kotar County, a primarily urban region with a population around 300 000 in the northern part of Croatia. The list of primary HCWs offices was obtained from the Croatian Health Insurance Fond website. We used a self-administered questionnaire on their attitudes, beliefs and behaviours relative to vaccination. Obtained response rate was 65.5% (324/495) of eligible primary HCWs; 64.1% (143/223) of physicians and 66.5% (181/272) of nurses. Seventeen percent of HCWs were identified as vaccine hesitant, and in univariate analysis, we observed an association between HCWs occupation and their own vaccination against flu (p = 0.001), measles (p = 0.016) and HPV (p = 0.025). Nurses and physicians differed (p < 0.001) in their general attitude, beliefs and behaviours towards vaccination, with a higher level of hesitancy among nurses. In multiple logistic regression, those more likely to be vaccine-hesitant were nurses (AOR = 5.73, 95%CI = 2.48-13.24), those who were uncertain or would never receive a vaccine against measles (AOR=11.13; 95%CI=5.37-23.10) and HPV (AOR=5.02; 95%CI=2.60-9.74), as well as those who had encountered a serious adverse event following immunization (AOR=7.55; 95%CI=3.13-19.18). As personal hesitancy may have a negative impact on vaccination education and recommendations, and therefore vaccine coverage, it is necessary to implement interventions to increase vaccination knowledge and confidence among primary health care workers, especially nurses.

Study protocol for a randomised clinical trial of a decision aid and values clarification method for parents of a fetus or neonate diagnosed with a life-threatening congenital heart defect.

INTRODUCTION: Parents who receive the diagnosis of a life-threatening, complex heart defect in their fetus or neonate face a difficult choice between pursuing termination (for fetal diagnoses), palliative care or complex surgical interventions. Shared decision making (SDM) is recommended in clinical contexts where there is clinical equipoise. SDM can be facilitated by decision aids. The International Patient Decision Aids Standards collaboration recommends the inclusion of values clarification methods (VCMs), yet little evidence exists concerning the incremental impact of VCMs on patient or surrogate decision making. This protocol describes a randomised clinical trial to evaluate the effect of a decision aid (with and without a VCM) on parental mental health and decision making within a clinical encounter. METHODS AND ANALYSIS: Parents who have a fetus or neonate diagnosed with one of six complex congenital heart defects at a single tertiary centre will be recruited. Data collection for the prospective observational control group was conducted September 2018 to December 2020 (N=35) and data collection for two intervention groups is ongoing (began October 2020). At least 100 participants will be randomised 1:1 to two intervention groups (decision aid only vs decision aid with VCM). For the intervention groups, data will be collected at four time points: (1) at diagnosis, (2) postreceipt of decision aid, (3) postdecision and (4) 3 months postdecision. Data collection for the control group was the same, except they did not receive a survey at time 2. Linear mixed effects models will assess differences between study arms in distress (primary outcome), grief and decision quality (secondary outcomes) at 3-month post-treatment decision. ETHICS AND DISSEMINATION: This study was approved by the University of Utah Institutional Review Board. Study findings have and will continue to be presented at national conferences and within scientific research journals. TRIAL REGISTRATION NUMBER: NCT04437069 (Pre-results).

Association of Osteonecrosis of the Jaw With Zoledronic Acid Treatment for Bone Metastases in Patients With Cancer.

IMPORTANCE: Osteonecrosis of the jaw (ONJ) affects patients with cancer and metastatic bone disease (MBD) treated with bone-modifying agents (BMAs), yet the true incidence is unknown. OBJECTIVE: To define the cumulative incidence of ONJ at 3 years in patients receiving zoledronic acid for MBD from any malignant neoplasm. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective observational cohort study (SWOG Cancer Research Network S0702) included patients with MBD with either limited or no prior exposure to BMAs and a clinical care plan that included use of zoledronic acid within 30 days of registration. Medical, dental, and patient-reported outcome forms were submitted at baseline and every 6 months. Follow-up was 3 years. Osteonecrosis of the jaw was defined using established criteria. Data were collected from January 30, 2009, to December 13, 2013, and analyzed from August 24, 2018, to August 6, 2020. INTERVENTIONS/EXPOSURES: Cancer treatments, BMAs, and dental care were administered as clinically indicated. MAIN OUTCOMES AND MEASURES: Cumulative incidence of confirmed ONJ, defined as an area of exposed bone in the maxillofacial region present for more than 8 weeks with no concurrent radiotherapy to the craniofacial region. Risk factors for ONJ were also examined. RESULTS: The SWOG S0702 trial enrolled 3491 evaluable patients (1806 women [51.7%]; median age, 63.1 [range, 2.24-93.9] years), of whom 1120 had breast cancer; 580, myeloma; 702, prostate cancer; 666, lung cancer; and 423, other neoplasm. A baseline dental examination was performed in 2263 patients (64.8%). Overall, 90 patients developed confirmed ONJ, with cumulative incidence of 0.8% (95% CI, 0.5%-1.1%) at year 1, 2.0% (95% CI, 1.5%-2.5%) at year 2, and 2.8% (95% CI, 2.3%-3.5%) at year 3; 3-year cumulative incidence was highest in patients with myeloma (4.3%; 95% CI, 2.8%-6.4%). Patients with planned zoledronic acid dosing intervals of less than 5 weeks were more likely to experience ONJ than patients with planned dosing intervals of 5 weeks or more (hazard ratio [HR], 4.65; 95% CI, 1.46-14.81; P = .009). A higher rate of ONJ was associated with fewer total number of teeth (HR, 0.51; 95% CI, 0.31-0.83; P = .006), the presence of dentures (HR, 1.83; 95% CI, 1.10-3.03; P = .02), and current smoking (HR, 2.12; 95% CI, 1.12-4.02; P = .02). CONCLUSIONS AND RELEVANCE: As the findings show, the cumulative incidence of ONJ after 3 years was 2.8% in patients receiving zoledronic acid for MBD. Cancer type, oral health, and frequency of dosing were associated with the risk of ONJ. These data provide information to guide stratification of risk for developing ONJ in patients with MBD receiving zoledronic acid.

Antimicrobial Photodynamic Therapy with Chlorin e6 Is Bactericidal against Biofilms of the Primary Human Otopathogens.

Moraxella catarrhalis, Streptococcus pneumoniae, and nontypeable Haemophilus influenzae (NTHi) are ubiquitous upper respiratory opportunistic pathogens. Together, these three microbes are the most common causative bacterial agents of pediatric otitis media (OM) and have therefore been characterized as the primary human otopathogens. OM is the most prevalent bacterial infection in children and the primary reason for antibiotic administration in this population. Moreover, biofilm formation has been confirmed as a primary mechanism of chronic and recurrent OM disease. As bacterial biofilms are inherently metabolically recalcitrant to most antibiotics and these complex structures also present a significant challenge to the immune system, there is a clear need to identify novel antimicrobial approaches to treat OM infections. In this study, we evaluated the potential efficacy of antibacterial photodynamic therapy (aPDT) with the photosensitizer chlorin e6 (Ce6) against planktonic as well as biofilm-associated M. catarrhalis, S. pneumoniae, and NTHi. Our data indicate aPDT with Ce6 elicits significant bactericidal activity against both planktonic cultures and established biofilms formed by the three major otopathogens (with an efficacy of ≥99.9% loss of viability). Notably, the implementation of a novel, dual-treatment aPDT protocol resulted in this disinfectant effect on biofilm-associated bacteria and, importantly, inhibited bacterial regrowth 24 h posttreatment. Taken together, these data suggest this novel Ce6-aPDT treatment may be a powerful and innovative therapeutic strategy to effectively treat and eradicate bacterial OM infections and, significantly, prevent the development of recurrent disease.IMPORTANCE Otitis media (OM), or middle ear disease, is the most prevalent bacterial infection in children and the primary reason for antibiotic use and surgical intervention in the pediatric population. Biofilm formation by the major bacterial otopathogens, Moraxella catarrhalis, Streptococcus pneumoniae, and nontypeable Haemophilus influenzae, has been shown to occur within the middle ears of OM patients and is a key factor in the development of recurrent disease, which may result in hearing impairment and developmental delays. Bacterial biofilms are inherently impervious to most antibiotics and present a significant challenge to the immune system. In this study, we demonstrate that antimicrobial photodynamic therapy (aPDT) using the photosensitizer chlorin e6 elicits significant bactericidal activity versus planktonic and biofilm-associated otopathogens and supports further analyses of this novel, efficacious, and promising technology as an adjunctive treatment for acute and recurrent OM.

Tick-borne encephalitis outbreak following raw goat milk consumption in a new micro-location, Croatia, June 2019.

In June 2019, the Croatian Institute of Public Health was informed of a cluster of patients with laboratory confirmed tick-borne encephalitis (TBE) from the Gorski Kotar region. Five of the six patients with TBE reported consuming raw (unpasteurized) goat milk in the two week period before symptom onset, and one reported a recent tick bite. To assess risk factors for infection, we selected six control individuals from among healthy family and community members, and conducted a case-control analysis. None of the cases or controls were vaccinated against TBE. Individuals with TBE (cases) had 25 (95 % CI 0.8-1410.2, p = 0.021) times higher odds of raw goat milk consumption compared to healthy controls. Milk samples from 12 goats from the implicated farm were tested for the TBE virus (TBEV) using RT-PCR. TBEV RNA was not detected in the milk, but serological testing of goats and other farm animals yielded evidence of exposure to the virus: Six goats from the flock had TBEV neutralizing antibodies. Our findings suggest that the vehicle for the outbreak was raw goat milk from a single farm. Following public health advice to cease consumption of raw dairy products, no further cases have been reported.