Reference ranges for third-trimester maternal cardiovascular function parameters measured in normotensive pregnant women using a non-invasive cardiac output monitor: A study based on data from the prospective PEACH cohort study.

OBJECTIVE: We defined reference ranges for maternal cardiac output, systemic vascular resistance, and stroke volume measured in the third trimester of pregnancy using the Ultrasound Cardiac Output Monitor 1A. DESIGN: Based on data from the prospective PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension) cohort study. SETTING: Rigshospitalet and Hvidovre Hospital, Denmark. SAMPLE: Normotensive pregnant women aged 18-45 years with singleton pregnancies, enrolled in the PEACH study in 2016-2018. METHODS: We modelled cardiac output, systemic vascular resistance and stroke volume as a function of gestational age using multilevel linear models with fractional polynomials. MAIN OUTCOME MEASURES: Unconditional and conditional reference ranges for cardiovascular parameters measured in gestational weeks 28-40. RESULTS: Our study cohort included 405 healthy pregnant women who contributed 1210 cardiovascular function measurements for analysis. Maximum cardiac output and stroke volume values were measured in gestational weeks 30-32 and decreased over the third trimester, whereas systemic vascular resistance increased during the same period. We created reference ranges for eight combinations of maternal height, age and parity. We also created a simple calculator to allow for implementation of the reference ranges in clinical practice. CONCLUSIONS: Our reference ranges allow the use of a bedside ultrasound device to non-invasively assess cardiac function in pregnancy and identify women at risk of complications. The unconditional ranges allow clinicians to evaluate isolated measurements and identify women needing follow-up. The conditional ranges incorporate information from previous measurements and improve monitoring over time.

Cohort profile: The PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension (PEACH) Study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) remain a leading cause of maternal morbidity and mortality worldwide, with implications for maternal and neonatal well-being in the short term and for long-term maternal cardiovascular health. Although the mechanisms behind HDP remain incompletely understood, evidence suggests that preeclampsia in particular is a syndrome with more than one distinct subtype. OBJECTIVES: The PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction, Hypertension) Study was established to identify new HDP subtyping systems reflecting aetiology and prognosis and to find markers of later cardiovascular disease risk associated with preeclampsia. POPULATION: The PEACH Study recruited pregnant women referred to two Copenhagen-area hospitals with suspected preeclampsia (mean gestational age at enrolment: 36.7 weeks) and a group of frequency-matched pregnant women planning delivery at the same hospitals and healthy when enrolled mid-pregnancy. DESIGN: Prospective, longitudinal pregnancy cohort. METHODS: Participants underwent repeated third-trimester blood sample collection, longitudinal cardiac function assessments using the USCOM-1A during the third trimester and at 1 year postpartum and collection of placental samples immediately after delivery. Medical information was abstracted from medical records and hospital databases. PRELIMINARY RESULTS: During 2016-2018, we recruited 1149 pregnant women, of whom 1101 were followed to delivery. Among 691 women enrolled with suspected preeclampsia, 310 and 172 developed preeclampsia and gestational hypertension respectively. Among 410 women with healthy pregnancies when enrolled mid-pregnancy, 37 later developed hypertensive disorders of pregnancy. Of 1089 women still in the cohort 1 year postpartum, 578 (53.1%) participated in the follow-up assessment. CONCLUSIONS: The PEACH Study's rich data from women with and without HDP will enable us to identify new, clinically useful HDP subtypes to aid in decision-making regarding monitoring and treatment. Continued postpartum follow-up will help us develop algorithms to identify women at risk of persistent postpartum cardiac dysfunction and later cardiovascular disease after pregnancies complicated by HDP.

Challenging encounters in clinical dentistry: a qualitative study investigating online reviews of patient satisfaction with Norwegian dentists.

OBJECTIVE: Mapping key themes that characterize challenging and positive encounters in dental practice using online reviews of patient satisfaction. MATERIALS AND METHODS: 11,764 online patient reviews of dental encounters, consisting of an overall satisfaction rating (1-5 stars) and a free-text response, were collected from the web-site Legelisten.no. The reviews were split into two sets: reviews from patients with low satisfaction (1-2 stars) representing challenging encounters vs. patients with high satisfaction (4-5 stars) representing positive encounters. A qualitative thematic analysis was used to analyse the text materials in the datasets. RESULTS: Five key themes to both challenging and positive patient encounters were identified: (1) Interpersonal factors, (2) Patient factors, (3) Dentist factors, (4) Situational factors, and (5) Consequences. These themes are discussed in light of their role in challenging and positive patient encounters, as well as previous studies of online reviews and patient satisfaction. CONCLUSIONS: Based on the patients' experiences with dental encounters, challenging encounters seem to arise when dentists' personality traits and communication skills fail to match the patients' expectations or preferences. It appears central to patient satisfaction that dentists are able to shift between different communication styles in order to adapt to the personality and preferences of the patients.

Annual incidence of cannabis-induced psychosis, other substance-induced psychoses and dually diagnosed schizophrenia and cannabis use disorder in Denmark from 1994 to 2016.

BACKGROUND: Worldwide, cannabis is the most used illegal substance, and the use of cannabis has increased over the years. An increase in the level of tetrahydrocannabinol (THC) in cannabis has also been seen. It is currently unclear whether this has led to an increase in the incidence of cannabis-induced psychosis. We aimed to investigate (1) the development of incidence of cannabis-induced psychosis over time compared with other substance-induced psychoses and (2) the development of incident cases of cannabis-induced psychosis over time compared with dual diagnosis defined as schizophrenia and a cannabis use disorder. METHOD: Data on psychiatric diagnoses were extracted from the Danish Psychiatric Central Research Register and summarized per year as both absolute incidence (number of cases) and incidence rates per 100 000 person years. RESULTS: The incidence rate of cannabis-induced psychosis increased steadily from 2.8 per 100 000 person years in 2006 to 6.1 per 100 000 person years in 2016. There was a corresponding increase in dual diagnosis with schizophrenia and cannabis use disorder, but a decrease in alcohol-induced psychosis. The data showed no trend in the other substance-induced psychosis investigated in this thesis. CONCLUSION: The increase in cannabis-induced psychosis follows both the increase in the level of THC in cannabis, and the increase in cannabis use. The change in diagnostic practice does not appear to explain the increase in incidence of cannabis-induced psychosis.

Apheresis principles in a patient with chronic myeloid leukemia during pregnancy: challenges in cell separation and assessing transcript levels.

BACKGROUND: Chronic myeloid leukemia (CML) is rarely diagnosed in pregnant women. CASE REPORT: We report a case of a pregnant woman who presented with a leukocyte count of 250 × 109 cells/L at gestational age (GA) 26 weeks and was diagnosed with CML in the chronic phase. Because the patient deliberately opted out of interferon α and tyrosine kinase inhibitor treatment, the main goal was to reduce the leukocyte count to postpone delivery beyond the number of weeks considered severely premature and avoid thromboembolic complications while continuously evaluating the clinical safety of the mother and fetus. Hence therapeutic leukapheresis was initiated, and we report the first application of an apheresis approach for this procedure using the Spectra Optia instrument without sedimentation agents. Leukapheresis was conducted 2 to 4 times per week for 9 weeks. RESULTS: During treatment the leukocyte count decreased remarkably, and the patient developed lymphopenia together with a paradoxical increase in her blood platelet count. Premature labor was induced at GA 35 weeks, and a healthy boy was delivered. Thereafter, the patient initiated imatinib treatment and was in major molecular and complete cytogenetic remission after 1 year. Despite the remarkable reduction of the leukocyte count, we observed a pronounced increase in expression of BCR-ABL1 transcripts, implying the need for close monitoring of patients with CML during pregnancy. CONCLUSIONS: We report a pregnant woman who was diagnosed with CML and treated solely with apheresis procedures using the Spectra Optia instrument for 9 weeks, ensuring the safe delivery of her child.

miRNA-130a regulates C/EBP-ε expression during granulopoiesis.

CCAAT/enhancer binding protein-ε (C/EBP-ε) is considered a master transcription factor regulating terminal neutrophil maturation. It is essential for expression of secondary granule proteins, but it also regulates proliferation, cell cycle, and maturation during granulopoiesis. Cebpe(-/-) mice have incomplete granulocytic differentiation and increased sensitivity toward bacterial infections. The amount of C/EBP-ε messenger RNA (mRNA) increases with maturation from myeloblasts with peak level in myelocytes (MC)/metamyelocytes (MM), when the cells stop proliferating followed by a decline in more mature cells. In contrast, C/EBP-ε protein is virtually detectable only in the MC/MM population, indicating that expression in more immature cells could be inhibited by microRNAs (miRNAs). We found that miRNA-130a (miR-130a) regulates C/EBP-ε protein expression in both murine and human granulocytic precursors. Overexpression of miR-130a in a murine cell line downregulated C/EBP-ε protein and lactoferrin (Ltf), cathelicidin antimicrobial protein (Camp), and lipocalin-2 (Lcn2) mRNA expression giving rise to cells with a more immature phenotype, as seen in the Cebpe(-/-) mouse. Introduction of a C/EBP-ε mRNA without target site for miR-130a restored both C/EBP-ε production, expression of Camp and Lcn2, and resulted in the cells having a more mature phenotype. We conclude that miR-130a is important for the regulation of the timed expression of C/EBP-ε during granulopoiesis.

Positive allosteric modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action.

Drugs that increase monoamine neurotransmission are effective in both anxiety and depression. The therapeutic effects of monoamine-based antidepressant drugs may involve indirect effects on neurotransmission through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPAR). Thus, chronic antidepressant treatment increases AMPAR-mediated neurotransmission and AMPAR-positive allosteric modulators have shown antidepressant-like efficacy in rodents. Here, the effect of enhanced AMPAR neurotransmission on the antidepressant-like and anxiolytic-like actions of the selective serotonin reuptake inhibitor citalopram (0-10 mg/kg) was investigated in mice using the AMPAR-positive allosteric modulator LY451646 (0-3 mg/kg). Antidepressant-like effects were assessed using the forced-swim test (FST), whereas anxiolytic-like effects were tested using the elevated zero maze (EZM) and the marble burying test. LY451646 (3 mg/kg) increased swim distance in the FST and a subactive dose of LY451646 (1 mg/kg) enhanced the effect of citalopram in the FST. In the EZM, LY451646 (3 mg/kg) did not show anxiogenic effects alone, but blocked the anxiolytic-like action of citalopram in the EZM, as reflected by an increase in the latency to enter the open areas and a decrease in the number of entries and time spent in the open areas in citalopram-treated mice. In the marble burying test, LY451646 (3 mg/kg) showed no effect alone, but significantly attenuated the anxiolytic-like effect of citalopram (1.25-2.5 mg/kg) by increasing the number of marbles buried in citalopram-treated mice. These results suggest that AMPAR neurotransmission plays opposite roles in anxiety and depression as AMPAR potentiation facilitated the antidepressant-like effects of citalopram while attenuating its anxiolytic-like effect. These findings have ramifications in the search for AMPAR-based novel anxiolytic and antidepressant treatments.

NSP4 is stored in azurophil granules and released by activated neutrophils as active endoprotease with restricted specificity.

Whereas neutrophil elastase, cathepsin G, and proteinase 3 have been known as granule-associated serine proteases of neutrophils for decades, a fourth member, called neutrophil serine protease 4 (NSP4), was just recently described and provisionally characterized. In this study, we identified NSP4 as a novel azurophil granule protein of neutrophils by Western blot analyses of subcellular fractions as well as by RT-PCR analyses of neutrophil precursors from human bone marrow. The highest mRNA levels were observed in myeloblasts and promyelocytes, similar to myeloperoxidase, a marker of azurophil granules. To determine the extended sequence specificity of recombinant NSP4, we used an iterative fluorescence resonance energy transfer-based optimization strategy. In total, 142 different peptide substrates with arginine in P1 and variations at the P1', P2', P3, P4, and P2 positions were tested. This enabled us to construct an α1-proteinase inhibitor variant (Ile-Lys-Pro-Arg-/-Ser-Ile-Pro) with high specificity for NSP4. This tailor-made serpin was shown to form covalent complexes with all NSP4 of neutrophil lysates and supernatants of activated neutrophils, indicating that NSP4 is fully processed and stored as an already activated enzyme in azurophil granules. Moreover, cathepsin C was identified as the activator of NSP4 in vivo, as cathepsin C deficiency resulted in a complete absence of NSP4 in a Papillon-Lefèvre patient. Our in-depth analysis of NSP4 establishes this arginine-specific protease as a genuine member of preactivated serine proteases stored in azurophil granules of human neutrophils.

Investigating Patient Satisfaction Through Web-Based Reviews of Norwegian Dentists: Quantitative Study Using the Meaning Extraction Method.

BACKGROUND: Challenging encounters in health care professions, including in dentistry, are relatively common. Challenging encounters can be defined as stressful or emotional situations involving patients that could impact both treatment outcomes and patients' experiences. Through written web-based reviews, patients can share their experiences with health care providers, and these posts can be a useful source for investigating patient satisfaction and their experiences of challenging encounters. OBJECTIVE: This study aims to identify dominant themes from patient-written, web-based reviews of dentists and investigate how these themes are related to patient satisfaction with dental treatment. METHODS: The study data consisted of 11,764 reviews written by dental patients, which included 1- to 5-star ratings on overall satisfaction and free-text comments. The free-text comments were analyzed using Linguistic Inquiry and Word Count software, and the meaning extraction method was used to group words into thematic categories. These themes were used as variables in a multilevel logistic regression analysis to predict patient satisfaction. RESULTS: Eight themes emerged from the analyses, of which 6 (75%)-explanation (odds ratio [OR] 2.56, 95% CI 2.16-3.04; P<.001), assurance (OR 3.61, 95% CI 2.57-5.06; P<.001), performance assessment (OR 2.17, 95% CI 1.84-2.55; P<.001), professional advice (OR 1.81, 95% CI 1.55-2.13; P<.001), facilities (OR 1.78, 95% CI 1.08-2.91; P=.02), and recommendation (OR 1.31, 95% CI 1.12-1.53; P<.001)-increased the odds of high patient satisfaction. The remaining themes (2/8, 25%)-consequences of treatment need (OR 0.24, 95% CI 0.20-0.29; P<.001) and patient-centered care (OR 0.62, 95% CI 0.52-0.74; P<.001)-reduced the odds of high patient satisfaction. CONCLUSIONS: The meaning extraction method is an interesting approach to explore patients' written accounts of encounters with dental health professionals. The experiences described by patients provide insight into key elements related to patient satisfaction that can be used in the education of dental health professionals and to improve the provision of dental health services.

Pregnancy As Window of Opportunity? A Danish RCT on Physical Activity During Pregnancy.

Pregnancy is seen as a window of opportunity for health interventions, with the potential to produce long-term health changes for mother and child. The RCT FitMum investigates the effects of different regimes of physical activity during pregnancy. We suggest that rather than hitting a window of opportunity, the trial works in choreography with different timescapes through the processes of management of time. These timescapes are characterized by linear progression and futurity, alongside composite, complex time. We reconceptualize the intervention as a navigation of flows and passages in collective efforts, providing a situated and sustainable approach to interventions.

Effect of non-pharmacological interventions on symptoms and quality of life in patients with hematological malignancies - A systematic review.

BACKGROUND: Non-pharmacological interventions have the potential to enhance health-related quality of life (HRQoL) through symptom management. This systematic review aims to identify, collate, and assess randomized controlled trials investigating the effect of non-pharmacological interventions on symptoms and HRQoL within hematology. METHODS: MEDLINE/PUBMED, EMBASE, CINAHL, PSYCINFO and COCHRANE were searched up to April 2021. Outcomes were changes in symptoms and HRQoL. RESULTS: Sixty-five studies were categorized into five intervention types: Mind/body (n=9), Web-based (n=9), Music/art (n=6), Consultation-based (n=4), and Physical activity (n=37). We found significantly reduced fatigue (n=12 studies), anxiety (n=8) and depression (n=7), with 11 studies showing significant improvements in HRQoL. CONCLUSIONS: The evidence for non-pharmacological interventions shows substantial variation in efficacy and methodological quality. While specific symptoms and HRQoL outcomes significantly favored the intervention, no particular intervention can be emphasized as more favorable, given the inability to conduct a meta-analysis.

Transforming health care: Investigating Influenzer, a novel telemedicine-supported early discharge program for patients with lower respiratory tract infection: A non-randomized feasibility study.

BACKGROUND: The COVID-19 pandemic has posed unprecedented challenges to healthcare systems globally, necessitating innovative care models like hospital-at-home and virtual care programs. The Influenzer telemedicine program aims to deliver hospital-led monitoring and treatment to patients at home. Integrating telemedicine technology with domestic visits provides an alternative to traditional hospitalization, with the aim of easing the burden on healthcare facilities without compromising patient safety. To evaluate the effectiveness of the Influenzer program, a randomized controlled trial is proposed. This study aimed to assess the feasibility of the proposed clinical trial design. METHODS: A non-randomized feasibility study was conducted at the Department of Pulmonary and Infectious Diseases at Nordsjaellands Hospital offering a telemedicine-supported early discharge program to patients with lower respiratory tract infections, including COVID-19. The feasibility of trial procedures, including recruitment, adherence, and retention, was analyzed. Also, participants' characteristics and trajectory during the intervention, including telemedicine and domestic services, were assessed. RESULTS: Nineteen patients were enrolled from June 2022 to April 2023 and treated at home. Forty patients were not enrolled as 15 (25%) were non-eligible according to study protocol, 15 (25%) refused to participate and 10 (17%) had not been approached. Subjects treated at home had comparable clinical outcomes to those treated in the acute hospital, no major safety incidences occurred and patients were highly satisfied. Participants demonstrated 99% adherence to planned daily monitoring activities. In total, 63% completed all survey assessments at least partially including baseline, at discharge, and 3 months post-discharge, while 89% participated in a follow-up interview. No participants withdrew their consent. CONCLUSIONS: The feasibility study documented that the Influenzer home-hospital program was feasible and well accepted in a Scandinavian setting in terms of no withdrawals and excellent participant adherence to the planned daily monitoring activities. Challenges in the organizational structures including patient recruitment and data collection required resolution prior to our randomized clinical trial. Insights from this feasibility study have led to the improved design of the final Influenzer program evaluation trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05087082. Registered on 18 August 2021.

Serglycin participates in retention of α-defensin in granules during myelopoiesis.

The mechanism by which proteins are targeted to neutrophil granules is largely unknown. The intracellular proteoglycan serglycin has been shown to have important functions related to storage of proteins in several types of granules. The possible role of serglycin in the localization of the α-defensin, human neutrophil peptide 1 (HNP-1), a major azurophil granule protein in human neutrophils, was investigated. Murine myeloid cells, stably transfected to express HNP-1, were capable of processing HNP-1, and HNP-1 was found to associate with serglycin in murine and human myeloid cell lines as well as in human bone marow cells. A transgenic mouse expressing HNP-1 in the myeloid compartment was crossed with mice deficient in serglycin or neutrophil elastase to investigate HNP-1 sorting and processing. Neither deficiency affected processing of HNP-1, but the ability to retain fully processed HNP-1 intracellularly was reduced in mice that lack serglycin. Human granulocyte precursors transfected with siRNA against serglycin displayed similar reduced capability to retain fully processed HNP-1, demonstrating a role of serglycin in retaining mature HNP-1 intracellularly, thus preventing potential toxic effects of extracellular HNP-1.

MicroRNA-130a-mediated down-regulation of Smad4 contributes to reduced sensitivity to TGF-ß1 stimulation in granulocytic precursors.

Smad4 is important in the TGF-ß pathway and required for transcriptional activation and inhibition of cell growth after TGF-ß1 stimulation. We demonstrate that miR-130a is differentially expressed during granulopoiesis and targets Smad4 mRNA. The transcript for Smad4 is present throughout neutrophil maturation, but Smad4 protein is undetectable in the most immature cells, where miR-130a is highly expressed. Two miR-130a binding sites were identified in the 3'-untranslated region of the Smad4 mRNA. Overexpression of miR-130a in HEK293, A549, and 32Dcl3 cells repressed synthesis of Smad4 protein without affecting Smad4 mRNA level. Repression of Smad4 synthesis in a granulocytic cell line by miR-130a reduced its sensitivity to TGF-ß1-induced growth inhibition. This effect was reversed by inhibiting the activity of miR-130a with an antisense probe or by expressing a Smad4 mRNA lacking miR-130a binding sites. High endogenous miR-130a and Smad4 mRNA levels and low expression of Smad4 protein were found in the t(8;21)(q22;q22) acute myelogenous leukemia-derived cell line Kasumi-1. When miR-130a was inhibited by an antisense RNA, the amount of Smad4 protein increased in Kasumi-1 cells and rendered it susceptible for TGF-ß1-mediated cell growth inhibition. Our data indicate that miR-130a is involved in cell cycle regulation of granulocytic cells through engagement of Smad4 in the TGF-ß pathway.

Quality of life, mentalization, and perception of challenging patient encounters in dentistry: A cross-sectional study.

OBJECTIVE: This study investigated how exposure to challenging patient encounters influenced participants' self-reported quality of life, and how participants' mentalization capabilities affected the perceptions of challenging patients encounters among Norwegian dentists and dental students. MATERIALS AND METHODS: Data was collected with an online questionnaire, and a total of 165 dentists (n = 126) and dental students (n = 39) responded. RESULTS: Participants who reported higher total exposure of challenging encounters reported lower quality of life (QoL). Mentalization tendencies affected the perception of challenging encounters with specific types of patients; critical and anxious; as well as the estimation of the total exposure to challenging patient encounters. Participants that were overconfident with regards to the mental states of others found these patient types less challenging and they reported less overall exposure to challenging patients than underconfident participants. Also, overconfident participants reported higher QoL than underconfident participants. CONCLUSIONS: Mentalization capabilities of dental practitioners interact with the perception of challenging encounters in dental practice, and how practitioners respond to these challenges. Measures should be undertaken to increase the awareness of metacognitive skills in dentistry with the dual goal of improving patient care as well as the quality of life of dental practitioners.

Diabetic retinopathy is a predictor of chronic respiratory failure: A nationwide register-based cohort study.

Purpose: Diabetic retinopathy (DR) is a hypoxic retinal disease, but so far, the association with systemic hypoxia is poorly understood. Hence, the aim of this study was to evaluate cross-sectional and longitudinal associations between DR and chronic respiratory failure (CRF) in a national cohort. Design: Cross-sectional and 5-year longitudinal register-based cohort study. Methods: Between 2013 and 2018, we included patients with diabetes from the Danish Registry of Diabetic Retinopathy, who were each age and sex matched with five controls without diabetes. At index date, the prevalence of CRF was compared between cases and controls, and the longitudinal relationship between DR and CRF was assessed in a five-year follow-up. Results: At baseline, we identified 1,980 and 9,990 patients with CRF among 205,970 cases and 1,003,170 controls. The prevalence of CRF was higher among cases than controls (OR 1.75, 95% CI 1.65-1.86), but no difference between cases with and without DR was found.During follow-up, we identified 1,726 and 5,177 events of CRF among cases and controls, respectively. The incidence of CRF was higher among both cases with and without DR compared to controls (DR level 0: HR 1.24, 95% CI 1.16-1.33, DR level 1-4: HR 1.86, 95% CI 1.63-2.12), and higher among cases with DR compared to cases without DR (HR 1.54, 95% CI 1.38-1.72). Conclusion: In this study based on nationwide data, we found an increased risk of present and incident CRF in patients with diabetes with or without DR, and we identified DR as a predictor of future CRF.

A porcine model of subcutaneous Staphylococcus aureus infection: a pilot study.

In this descriptive pilot study, we aim to establish a porcine Staphylococcus aureus skin infection model by subcutaneous injection (s.c.) of the porcine S54F9 S. aureus strain in the groin area. Six pigs were used in the study: Five pigs were injected with S. aureus, inocula ranging from 7 × 103 to 5 × 107 colony-forming units per kg bodyweight; one pig was injected with saline exclusively. Lesions were recorded up to 6 days postinoculation using clinical evaluation, ultrasound evaluation, microbiology, flow cytometry, and pathology. Inoculation gave rise to lesions ranging from localized skin infection, that is, minute histological changes, intracellular infection, and macroscopic abscess formation with sequestration of soft tissue, to generalized infection and development of disseminated intravascular coagulation necessitating euthanasia only 10 h after inoculation. Ultrasound assessment of maximum width and characteristics was not able to disclose the progress of the local infection. Flow cytometry and immunohistochemistry revealed the participation of γδT cells in the immune response. In conclusion, we did see a graded inflammatory response associated with the dose of s.c. inoculated bacteria, which may be useful for studying, in particular, the interaction of bacteria and inflammatory mononuclear cell populations. It needs to be investigated if the model is discriminatory and robust.

Alpha-1-antitrypsin is produced by human neutrophil granulocytes and their precursors and liberated during granule exocytosis.

Alpha-1-antitrypsin (A1AT) is an important inhibitor of neutrophil proteases including elastase, cathepsin G, and proteinase 3. Transcription profiling data suggest that A1AT is expressed by human neutrophil granulocytes during all developmental stages. A1AT has hitherto only been found associated with azurophile granules in neutrophils indicative of A1AT expression being restricted to the promyelocyte stage. We examined the localization and production of A1AT in healthy donor neutrophils and found A1AT to be a constituent of all granule subtypes and to be released from neutrophils following stimulation. A1AT is produced at all stages of myeloid maturation in the bone marrow. The production increases as neutrophils enter circulation and increases further upon migration to tissues as observed in skin windows and when blood neutrophils are incubated with granulocyte colony-stimulating factor. Neutrophils from patients with A1AT-deficiency carrying the (PI)ZZ mutation in the A1AT gene appeared structurally and functionally normal, but A1AT produced in leukocytes of these patients lacked the ability to bind proteases efficiently. We conclude that A1AT generation and release from neutrophils add significantly to the antiprotease levels in tissues during inflammation. Impaired binding of neutrophil A1AT to serine proteases in patients with (PI)ZZ mutations may enhance their susceptibility to the development of emphysema.

Pregnant womens views on the timing of prophylactic antibiotics during caesarean delivery: A qualitative semi-structured interview study.

OBJECTIVE: To gain insight into pregnant women's preferences if given a choice between getting antibiotic prophylaxis before or after cord clamping during caesarean delivery. STUDY DESIGN: A qualitative semi-structured interview-study. The interviews were conducted at a Danish Hospital, with about 4000 deliveries a year. Fourteen individual semi-structured interviews were conducted with pregnant women, either considering or having a planned caesarean section, or scheduled for induction due to post-term gestational age. A systematic text condensation approach was used to analyze the transcribed interviews. RESULTS: Ten of the fourteen women favored antibiotic administration after cord clamping. Despite any adverse effects to the infant's microbiota and increased risk of long-term health outcomes were only hypothetical and the risk reduction in postpartum infections being well documented, they did not want to expose their offspring to antibiotics. Those who preferred antibiotic prophylaxis before cord clamping were concerned, if they would be able to care for the infant in case of a maternal infection. Three of the women preferring antibiotics after cord clamping said they would potentially change preference, if the maternal risk was higher. Most women preferred to be informed of the use of prophylactic antibiotic and that the timing has consequences for trans-placental exposure to the infant. CONCLUSIONS: With most of the interviewed women preferring antibiotic administration after cord clamping, we suggest patients should be involved in the decision regarding timing of prophylactic antibiotics before caesarean section.

Diabetic retinopathy as a potential marker of Parkinson's disease: a register-based cohort study.

Neurodegeneration is an early event in the pathogenesis of diabetic retinopathy, and an association between diabetic retinopathy and Parkinson's disease has been proposed. In this nationwide register-based cohort study, we investigated the prevalence and incidence of Parkinson's disease among patients screened for diabetic retinopathy in a Danish population-based cohort. Cases (n = 173 568) above 50 years of age with diabetes included in the Danish Registry of Diabetic Retinopathy between 2013 and 2018 were matched 1:5 by gender and birth year with a control population without diabetes (n = 843 781). At index date, the prevalence of Parkinson's disease was compared between cases and controls. To assess the longitudinal relationship between diabetic retinopathy and Parkinson's disease, a multivariable Cox proportional hazard model was estimated. The prevalence of Parkinson's disease was 0.28% and 0.44% among cases and controls, respectively. While diabetic retinopathy was not associated with present (adjusted odds ratio 0.93, 95% confidence interval 0.72-1.21) or incident Parkinson's disease (adjusted hazard ratio 0.77, 95% confidence interval 0.56-1.05), cases with diabetes were in general less likely to have or to develop Parkinson's disease compared to controls without diabetes (adjusted odds ratio 0.79, 95% confidence interval 0.71-0.87 and adjusted hazard ratio 0.88, 95% confidence interval 0.78-1.00). In a national cohort of more than 1 million persons, patients with diabetes were 21% and 12% were less likely to have prevalent and develop incident Parkinson's disease, respectively, compared to an age- and gender-matched control population without diabetes. We found no indication for diabetic retinopathy as an independent risk factor for incident Parkinson's disease.