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Abstract Denosumab is a monoclonal anti-RANKL antibody that inhibits bone resorption, increases bone mass, and reduces fracture risk. Denosumab discontinuation causes an extensive wave of rebound resorption, but the cellular mechanisms remain poorly characterized. We utilized in situ hybridization (ISH) as a direct approach to identify the cells that activate osteoclastogenesis through the RANKL/OPG pathway. ISH was performed across species, skeletal sites, and following recombinant OPG (OPG:Fc) and parathyroid hormone 1–34 (PTH) treatment of mice. OPG:Fc treatment in mice induced an increased expression of RANKL mRNA mainly in trabecular, but not endocortical bone surface cells. Additionally, a decreased expression of OPG mRNA was detected in bone surface cells and osteocytes of both compartments. A similar but more pronounced effect on RANKL and OPG expression was seen one hour after PTH treatment. These findings suggest that bone surface cells and osteocytes conjointly regulate the activation of osteoclastogenesis, and that OPG:Fc treatment induces a local accumulation of osteoclastogenic activation sites, ready to recruit and activate osteoclasts upon treatment discontinuation. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data from murine bone marrow stromal cells revealed that Tnfsf11 + cells expressed high levels of Mmp13, Limch1, and Wif1, confirming their osteoprogenitor status. ISH confirmed co-expression of Mmp13 and Tnfsf11 in bone surface cells of both vehicle- and OPG:Fc-treated mice. Under physiological conditions of human/mouse bone, RANKL is expressed mainly by osteoprogenitors proximate to the osteoclasts, while OPG is expressed mainly by osteocytes and bone-forming osteoblasts.

Objective To explore possible challenges to General Practitioners’ (GPs’) interpersonal contact with patients in video consultations (VCs), and learn how they change their communication strategies to carry out medical work in a setting with altered sensory conditions.Design, setting, subjects The study included 6 GPs from the Copenhagen area, with different levels of experience of VC. The data consist of 6 interviews with GPs, held in 2021-2022. The semi-structured interviews included playback of a recorded VC between each GP and a patient, inspired by the Video-Stimulated Interview technique. Interviews were transcribed and analyzed using Interpretative Phenomenological Analysis (IPA).Results GPs experienced alterations in the sensation of their patients in VCs, and worried about missing something important, including assessing the patient. Generally, GPs felt that interpersonal contact was good enough for the purpose. GPs compensated for altered sensory conditions on video by asking more questions, repeating their advice, and meta-communicating. They used their senses of sight and hearing relatively more in VCs. Compensation also took the form of triage, so that consultations on sensitive topics or with new patients were not selected to take place on video.Conclusion and implications By compensating for altered sensory conditions in VCs, GPs can carry out their medical work sufficiently well and sustain the best possible interpersonal contact. Our findings are useful for establishing ways to maintain good interpersonal contact between GPs and patients in VCs.

Abstract The potential of intraoral 3D photo scans in forensic odontology identification remains largely unexplored, even though the high degree of detail could allow automated comparison of ante mortem and post mortem dentitions. Differences in soft tissue conditions between ante- and post mortem intraoral 3D photo scans may cause ambiguous variation, burdening the potential automation of the matching process and underlining the need for limiting inclusion of soft tissue in dental comparison. The soft tissue removal must be able to handle dental arches with missing teeth, and intraoral 3D photo scans not originating from plaster models. To address these challenges, we have developed the grid-cutting method. The method is customisable, allowing fine-grained analysis using a small grid size and adaptation of how much of the soft tissues are excluded from the cropped dental scan. When tested on 66 dental scans, the grid-cutting method was able to limit the amount of soft tissue without removing any teeth in 63/66 dental scans. The remaining 3 dental scans had partly erupted third molars (wisdom teeth) which were removed by the grid-cutting method. Overall, the grid-cutting method represents an important step towards automating the matching process in forensic odontology identification using intraoral 3D photo scans.

AbstractObjective To analyse the mechanisms at play in the adjudications made by professionals and socially vulnerable patients with type 2 diabetes about their eligibility for care.Design, setting and subjects The study included 14 patients and 10 health professionals in seven general practice surgeries in deprived areas in Greater Copenhagen. The study data consist of 17 semi-structured interviews with patients and 22 with health professionals immediately after observation of 23 consultations. Our analytical approach was inspired by Systematic Text Condensation and the concept of ‘candidacy’ for access to health care.Results Adjudications of patients not being candidates for services were common, but we also found that both patients and health professionals worked to align the services to the needs of the patients. This could include using services differently than was intended by the providers or by changing routines to make it easier for patients to use the services. We discuss these processes as ‘tinkering’. This usually implies that the best individual solution for the patient is aimed for, and in this study, the best solution sometimes meant not focusing on diabetes.Conclusion The study adds to existing knowledge about access to services for socially vulnerable patients by demonstrating that both patients and professionals in general practice engage in tinkering processes to make services work.

Abstract The cGAS-STING pathway plays a crucial role in anti-tumoral responses by activating inflammation and reprogramming the tumour microenvironment. Upon activation, STING traffics from the endoplasmic reticulum (ER) to Golgi, allowing signalling complex assembly and induction of interferon and inflammatory cytokines. Here we report that cGAMP stimulation leads to a transient decline in ER cholesterol levels, mediated by Sterol O-Acyltransferase 1-dependent cholesterol esterification. This facilitates ER membrane curvature and STING trafficking to Golgi. Notably, we identify two cholesterol-binding motifs in STING and confirm their contribution to ER-retention of STING. Consequently, depletion of intracellular cholesterol levels enhances STING pathway activation upon cGAMP stimulation. In a preclinical tumour model, intratumorally administered cholesterol depletion therapy potentiated STING-dependent anti-tumoral responses, which, in combination with anti-PD-1 antibodies, promoted tumour remission. Collectively, we demonstrate that ER cholesterol sets a threshold for STING signalling through cholesterol-binding motifs in STING and we propose that this could be exploited for cancer immunotherapy.

Introduction Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit.Methods and analysis The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0–3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient.Ethics and dissemination The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals.Trial registration numbers NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00.

Abstract Background Cardiovascular mortality and the impact of cardiac risk factors in advanced chronic kidney disease (CKD) remain poorly investigated. We examined the risk of cardiovascular mortality in patients with advanced CKD with and without diabetes as well as the impact of albuminuria, plasma hemoglobin, and plasma low-density lipoprotein (LDL) cholesterol levels. Methods In a Danish nationwide registry-based cohort study, we identified persons aged ≥ 18 years with an estimated glomerular filtration rate

Introduction Patients receiving haemodialysis are at increased risk of arrhythmias and sudden cardiac death, but data on arrhythmia burden and the pathophysiology remain limited. Among potential risk factors, hypoglycaemia is proposed as a possible trigger of lethal arrhythmias. The development of implantable loop recorders (ILR) and continuous glucose monitoring (CGM) enables long-term continuous ECG and glycaemic monitoring. The current article presents the protocol of a study aiming to increase the understanding of arrhythmias and risk factors in patients receiving haemodialysis. The findings will provide a detailed exploration of the burden and nature of arrhythmias in these patients including the potential association between hypoglycaemia and arrhythmias.Methods and analysis The study is an investigator-initiated, prospective, multicentre cohort study recruiting 70 patients receiving haemodialysis: 35 with diabetes and 35 without diabetes. Participants are monitored with ILRs and CGM for 18 months follow-up. Data collection further includes a monthly collection of predialysis blood samples and dialysis parameters. The primary outcome is the presence of clinically significant arrhythmias defined as a composite of bradycardia, ventricular tachycardia, or ventricular fibrillation. Secondary outcomes include the characterisation of clinically significant arrhythmias and other arrhythmias, glycaemic characteristics, and mortality. The data analyses include an assessment of the association between arrhythmias and hypoglycaemia and hyperglycaemia, baseline clinical variables, and parameters related to kidney failure and the haemodialysis procedure.Ethics and dissemination The study has been approved by the Ethics Committee of the Capital Region of Denmark (H-20069767). The findings will be presented at national and international congresses as well as in international peer-reviewed scientific journals.Trial registration number NCT04841304.

Abstract Objectives Oral rehabilitation can be a challenge in patients on high‐dose antiresorptive medication (HDAR), especially if the alveolar anatomy has changed due to previous medication‐related osteonecrosis of the jaw (MRONJ) resection. In healthy patients, dental implant treatment has found wide acceptance in prosthetic rehabilitation as it increases the patient's oral health‐related quality of life. However, it is considered contraindicated in patients on HDAR due to the risk of MRONJ, although a recent feasibility study indicates that implant treatment may indeed be an option in these patients. The aim of the present case report is to illustrate the risk of MRONJ in a patient with cancer on HDAR and to discuss the reasons behind the outcomes of the implant treatment. Materials and Methods A patient with prostate cancer with bone metastases on high‐dose denosumab therapy with previous MRONJ had four implants inserted bilaterally in the maxilla (14, 13, 23, 24). Two identical implant‐supported screw‐retained cantilever bridges were fabricated. The patient was followed for more than 1 year. Results and Conclusion Peri‐implantitis, and/or MRONJ, was diagnosed around two of the implants (23, 24), probably induced by crestal bone trauma from a healing abutment and/or a misfitting prosthetic reconstruction. A peri‐implantitis operation was performed, but without the desired response, and the two implants (23, 24) were later removed in an MRONJ resection. The implants on the other side of the maxilla (14, 13) remained without complications. Dental implant treatment is feasible in patients on HDAR, but comorbidities (e.g., diabetes mellitus) and polypharmacy (e.g., chemotherapy and steroids) may add to the risk of implant failure. Minimal trauma surgery and prosthodontics are crucial to increase the chance of successful healing in an HDAR patient.

ABSTRACT Purpose: Sperm DNA fragmentation (SDF) and seminal oxidative stress are emerging measurable factors in male factor infertility, which interventions could potentially reduce. We evaluated (i) the impact of lifestyle changes combined with oral antioxidant intake on sperm DNA fragmentation index (DFI) and static oxidation-reduction potential (sORP), and (ii) the correlation between DFI and sORP. Materials and Methods: We conducted a prospective study involving 93 infertile males with a history of failed IVF/ICSI. Ten healthy male volunteers served as controls. Semen analysis was carried out according to 2010 WHO manual, whereas seminal sORP was measured using the MiOXSYS platform. SDF was assessed by sperm chromatin structure assay. Participants with DFI >15% underwent a three-month lifestyle intervention program, primarily based on diet and exercise, combined with oral antioxidant therapy using multivitamins, coenzyme Q10, omega-3, and oligo-elements. We assessed changes in semen parameters, DFI, and sORP, and compared DFI results to those of volunteers obtained two weeks apart. Spearman rank correlation tests were computed for sORP and DFI results. Results: Thirty-eight (40.8%) patients had DFI >15%, of whom 31 participated in the intervention program. A significant decrease in median DFI from 25.8% to 18.0% was seen after the intervention (P

Although many suffering from congenital heart defects (CHDs) have seen their conditions become chronic in Denmark today, the risk of complications, deteriorations, and further surgical interventions often lurk in the future. Building on fieldwork in outpatient clinics in Denmark and the homes of families living with CHDs, I explore the role outpatient encounters play in families’ efforts to understand and navigate the prognoses of CHDs by examining how they become routine punctuations and images of uncertainty, and how they play into families’ efforts to prepare for futures where CHDs might develop negatively while also trying to keep such scenarios at bay. I argue that these encounters exemplify, generate, and tentatively curb the particular uncertainties of living with CHDs. Hence, I suggest that they can be thought of as prognostic calibrations—a conceptual oxymoron that encapsulates the anxiety and uncertainty that I show persist around CHD prognoses despite many efforts by families and healthcare staff to establish routine, a sense of security, and certainty.

Abstract Background Childhood maltreatment is an established risk factor for incident unipolar disorder and bipolar disorder. It is separately observed that affective disorders (AD) are also associated with higher nucleoside damage by oxidation. Childhood maltreatment may induce higher levels of nucleoside damage by oxidation and thus contribute to the development of AD; however, this relation is only sparsely investigated. Methods In total, 860 participants (468 patients with AD, 151 unaffected first-degree relatives, and 241 healthy control persons) completed the Childhood Trauma Questionnaire (CTQ). The association between CTQ scores and markers of systemic DNA and RNA damage by oxidation as measured by urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) levels, respectively, was investigated. Results In multiple regression models adjusted for sex- and age, 8-oxodG and 8-oxoGuo levels were found to be higher in individuals who had experienced more childhood maltreatment. These associations persisted in models additionally adjusted for body mass index, alcohol, and current smoking status. Emotional abuse, sexual abuse, and emotional neglect were principally responsible for the foregoing associations. Conclusions Our findings of an association between childhood maltreatment and oxidative stress markers suggest that childhood maltreatment overall, notably emotional abuse and emotional neglect, is associated with enhanced systemic damage to DNA and RNA in adulthood. Further, individuals with AD reported a higher prevalence of childhood maltreatment, which may induce higher levels of nucleoside damage by oxidation in adulthood, possibly leading to increased risk of developing AD. Longitudinal studies are needed to clarify this relationship further.

Abstract Introduction This study examined the prevalence of microvascular and macrovascular complications in people receiving dialysis with and without diabetes and investigated independent risk factors for foot ulcers and lower‐extremity amputations. Methods We performed a cross‐sectional study of 119 individuals with diabetes and 219 individuals without diabetes receiving chronic dialysis during June 2019 at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Effects of diabetes and other risk factors were assessed by log‐binomial regression. Prevalence data were compared with a historical control group of 38 individuals with diabetes receiving dialysis examined in 2004 in the same department. Results We found that persons with diabetes had a twofold higher risk ratio of current (unadjusted risk ratio 2.2 [95% CI 1.1, 4.7]) and previous foot ulcer (2.5 [1.7, 3.7]) and a fourfold higher risk ratio of lower‐extremity amputation (4.2 [2.1, 8.6]) in comparison with persons without diabetes (all p

Objectives: Cryotherapy is frequently used to diminish postoperative sequelae following mandibular third molar surgery. The objective of this single-blinded randomized controlled trial was to assess the therapeutic efficiency of 30 minutes continuous cryotherapy on postoperative sequelae following surgical removal of mandibular third molars compared with no cryotherapy. Material and Methods: Thirty patients (14 male and 16 female) including 60 mandibular third molars were randomly allocated to 30 minutes of immediately cryotherapy or no cryotherapy. Outcome measures included pain (visual analogue scale score), maximum mouth opening (trismus) and quality of life (oral health impact profile-14). Outcome measures were assessed preoperatively and one day, three days, seven days and one month following surgical removal of mandibular third molars. Descriptive and generalized estimating equation analyses were made. Level of significance was 0.05. Results: No cryotherapy following surgical removal of mandibular third molars revealed a statistically significant lower visual analogue scale score of pain compared to thirty minutes of continuous cryotherapy after one day (P < 0.05). However, no statistically significant difference in trismus or oral health-related quality of life were revealed at any time point compared with no cryotherapy. Conclusions: The therapeutic effect of 30 minutes continuous cryotherapy following surgical removal of mandibular third molars seem to be negligible. Thus, further randomized controlled trials assessing a prolonged application period of cryotherapy, alternative devices or use of intermittent cryotherapy are needed before definite conclusions and evidence-based clinical recommendations can be provided.

BackgroundThe COVID-19 pandemic has changed various spheres of health care. General practitioners (GPs) have widely replaced face-to-face consultations with telephone or video consultations (VCs) to reduce the risk of COVID-19 transmission. Using VCs for health service delivery is an entirely new way of practicing for many GPs. However, this transition process has largely been conducted with no formal guidelines, which may have caused implementation barriers. This study presents a rapid cycle coproduction approach for developing a guide to assist VC implementation in general practice. ObjectiveThe aim of this paper is to describe the developmental phases of the VC guide to assist general practices in implementing VCs and summarize the evaluation made by general practice users. MethodsThe development of a guide for VC in general practice was structured as a stepped process based on the coproduction and prototyping processes. We used an iterative framework based on rapid qualitative analyses and interdisciplinary collaborations. Thus, the guide was developed in small, repeated cycles of development, implementation, evaluation, and adaptation, with a continuous exchange between research and practice. The data collection process was structured in 3 main phases. First, we conducted a literature review, recorded observations, and held informal and semistructured interviews. Second, we facilitated coproduction with stakeholders through 4 workshops with GPs, a group interview with patient representatives, and individual revisions by GPs. Third, nationwide testing was conducted in 5 general practice clinics and was followed by an evaluation of the guide through interviews with GPs. ResultsA rapid cycle coproduction approach was used to explore the needs of general practice in connection with the implementation of VC and to develop useful, relevant, and easily understandable guiding materials. Our findings suggest that a guide for VCs should include advice and recommendations regarding the organization of VCs, the technical setup, the appropriate target groups, patients’ use of VCs, the performance of VCs, and the arrangements for booking a VC. ConclusionsThe combination of coproduction, prototyping, small iterations, and rapid data analysis is a suitable approach when contextually rich, hands-on guide materials are urgently needed. Moreover, this method could provide an efficient way of developing relevant guide materials for general practice to aid the implementation of new technology beyond the pandemic period.

To evaluate the effect of arthroplasty using interpositional cartilage allografts in patients with temporomandibular joint (TMJ) arthrosis. This retrospective study included patients treated consecutively between 2007 and 2013 using discectomy and interpositional grafting with lyophilized costal cartilage allograft (Tutoplast) sheets. TMJ pain based on the visual analogue scale (VAS), maximal interincisal opening (MIO), joint tenderness to palpation, crepitus from the affected joint, and postoperative complications were assessed. Arthroplasty was performed on 37 joints among 34 patients (28 women; mean age: 54 years); 24 joints underwent simultaneous condyle shaving. At final follow-up (3 [n = 37] or 5 [n = 21] years), we observed reduced mean VAS (from 7.6 to 0.9; P <.001) increased mean MIO (from 32.5 to 41.1 mm; P <.001), number of joints with capsule tenderness (from 30 to 3; P <.001), and percentage of joints with crepitus (from 97% to 75%; P =.008). One joint required reoperation because of interposed cartilage fragmentation. No permanent facial nerve injury or malocclusion occurred after treatment. Interpositional arthroplasty is a relatively simple, moderately invasive, and effective surgical treatment for TMJ arthrosis with few complications. However, long-term outcomes of this treatment, specifically beyond 3-5 years postoperatively, remain unknown. [ABSTRACT FROM AUTHOR]

Objective: To investigate the validity of microscopy as a diagnostic tool for urinary tract infection in general practice. Methods: (Design/setting) A systematic review was conducted by searching Medline for clinical studies made in general practice, outpatient clinics or similar settings in which the accuracy/validity of microscopy was evaluated with urine culture as the reference standard. Results: Our search resulted in 108 titles. 28 potentially eligible studies were retrieved for full-text reading. We included eight studies involving 4582 patients in this review. The quality of the studies was moderate to high. Specificity ranged from 27% to 100%, sensitivity from 47% to 97%. The variation between studies did not allow for meta-analysis. Conclusion: We did not find substantial evidence to determine the clinical validity of microscopy performed in general practice on urine samples from patients with symptoms of UTI.Key points Urinary tract infection is common in general practice. Methods for precise diagnosis are needed in order to avoid inappropriate treatment. Currently no evidence-based consensus exists regarding the use of urinary microscopy in general practice. We did not find substantial evidence to determine the overall clinical validity of microscopy performed in general practice on urine samples from patients with symptoms of UTI. Light microscopy with oil immersion had high sensitivity and specificity but is time-consuming. Phase-contrast microscopy is quick and had high specificity but lower sensitivity.

Introduction Infection with SARS-CoV-2 may progress to severe pulmonary disease, COVID-19. Currently, patients admitted to hospital because of COVID-19 have better prognosis than during the first period of the pandemic due to improved treatment. However, the overall societal susceptibility of being infected makes it pivotal to prevent severe courses of disease to avoid high mortality rates and collapse of the healthcare systems. Positive expiratory pressure (PEP) self-care is used in chronic pulmonary disease and has been shown to prevent pneumonia in a high-risk cohort of patients with leukaemia. PEP flute self-care to prevent respiratory deterioration and hospitalisation in early COVID-19: a randomised trial (The PEP-CoV trial) examines the effectiveness on respiratory symptoms and need of hospital admission by regular PEP flute use among non-hospitalised individuals with confirmed SARS-CoV-2 infection and COVID-19 symptoms.Methods and analysis In this randomised controlled trial, we hypothesise that daily PEP flute usage as add-on to usual care is superior to usual care as regards symptom severity measured by the COPD Assessment Test (CAT) at 30-day follow-up (primary outcome) and hospital admission through register data (secondary outcome). We expect to recruit 400 individuals for the trial. Participants in the intervention group receive a kit of 2 PEP flutes and adequate resistances and access to instruction videos. A telephone hotline offers possible contact to a nurse. The eight-item CAT score measures cough, phlegm, chest tightness, dyspnoea, activities of daily living at home, feeling safe at home despite symptoms, sleep quality and vigour. The CAT score is measured daily in both intervention and control arms by surveys prompted through text messages.Ethics and dissemination The study was registered prospectively at www.clinicaltrials.gov on 27 August 2020 (NCT04530435). Ethical approval was granted by the local health research ethics committee (Journal number: H-20035929) on 23 July 2020. Enrolment of participants began on 6 October 2020. Results will be published in scientific journals.Trial registration number NCT04530435; Pre-results.

Introduction: Patients admitted with COVID-19 often have severe hypoxemic respiratory insufficiency and it can be difficult to maintain adequate oxygenation with oxygen supplementation alone. There is a physiological rationale for the use of Continuous Positive Airway Pressure (CPAP), and CPAP could keep some patients off mechanical ventilation. We aimed to examine the physiological response to CPAP and the outcome of this treatment. Methods: Data from all patients admitted with COVID-19 and treated with CPAP, from March to July 2020 were collected retrospectively. CPAP was initiated on a medical ward when oxygen supplementation exceeded 10 liters/min to maintain oxygen saturation (SpO2) ≥92%. CPAP was administered with full face masks on a continuous basis until stable improvement in oxygenation or until intubation or death. Results: CPAP was initiated in 53 patients (35 men, 18 women) with a median (IQR) age of 68 (57–78) years. Nine patients were not able to tolerate the CPAP treatment. Median duration for the 44 patients receiving CPAP was 3 (2–6) days. The PaO2/FiO2 ratio was severely reduced to an average of 101 mmHg at initiation of treatment. A positive response of CPAP was seen on respiratory rate (p = 0.002) and on oxygenation (p

Takotsubo syndrome (TSS) is a reversible, acute cardiomyopathy with transient heart failure, often secondary to other disorders. A 64-year-old woman, with no history of ischemic heart disease, was admitted to the emergency department after developing sudden-onset dyspnea after a planned acupuncture treatment for back pain. Acute echocardiography showed decreased left ventricular function with basal hypercontraction and apical akinesia and was interpreted, and treated, as acute heart failure. When the attending cardiologist arrived, the patient still had dyspnea with a declining blood pressure (97/65 mmHg) and tachycardia (111/minute). The cardiologist suspected a tension pneumothorax induced by the penetration of an acupuncture needle to the apex of the lung, as well as secondary TSS cardiomyopathy. An acute chest X-ray was performed, which showed a large left-sided rim pneumothorax. The attending surgeon placed a chest tube in the left 6th intercostal space in the midaxillary line, and the patient reported immediate pain relief and improvement in her dyspnea. The patient’s clinical condition improved, and a control X-ray showed that the lung was fully expanded. The chest tube was removed, but after a few minutes, the patient developed a massive subcutaneous emphysema in the upper chest and in the face and her clinical condition deteriorated rapidly. A new chest tube was inserted, and the patient’s tachycardia diminished, with her clinical condition improving immediately. The patient remained hospitalized for the next seven days. After three continuous days without any escaped air in the chest tube, the tube was removed, and the patient was observed for another 48 hours. This time, the removal was without any complications and within two days, the patient was ready for discharge. The follow-up echocardiography showed complete recovery of left ventricular function.

Foliar fertilization is a potential tool to increase the use-efficiency of nitrogen (N) fertilizers. However, whilst leaf scorching has frequently been reported, the underlying physiological processes are not clear. In the present work, we investigate the intensity of leaf scorching as affected by the balance between ammonium assimilation and accumulation. Leaves were sprayed with urea–ammonium nitrate (UAN) solution without surfactant or applied liquid droplets of urea in different N concentrations with surfactant. UAN solutions without surfactant containing >10% N caused leaf scorching already after 24 h and the severity increased with the N concentration. The same pattern was observed 3 days after the application of urea solutions containing >4% N together with surfactant. The scorching was accompanied by a massive increase in foliar and apoplastic ammonium (NH4+) concentration. Moreover, the activity of glutamine synthetase (GS), most pronouncedly that of the chloroplastic isoform (GS2), decreased a few hours after the application of high N-concentrations. Along with this, the concentration of glutamate—the substrate for GS—decreased. We conclude that leaf scorching is promoted by NH4+ accumulation due to a limitation in N assimilation capacity.

Objectives: To evaluate the influence of a single intraoperative injection of methylprednisolone on short-term haematological parameters following surgical removal of mandibular third molars. Material and Methods: Fifty-two patients with indications for surgical removal of bilateral impacted mandibular third molars were included in a randomized, split-mouth and double-blinded study design. Each molar were randomly allocated into one of following four groups: 20 mg methylprednisolone, 30 mg methylprednisolone, 40 mg methylprednisolone and placebo. Peripheral blood samples were obtained before and three days after surgery. Haematological parameters involving haemoglobin, white blood cell count and C-reactive protein (CRP) were evaluated and expressed as mean changes. Level of significance was 0.05. Furthermore, outcomes were correlated for age, sex, smoking and time of surgery. Results: There were no significant differences in postoperative haematological parameters with different doses of methylprednisolone compared with placebo. Peripheral blood samples revealed decreased level of haemoglobin and increased level of leucocytes and CRP in each group. Smokers displayed a significant lower level of haemoglobin and CRP compared with non-smokers (P < 0.05) and level of eosinophils decreased significantly with increasing age (P < 0.05). Conclusions: This study indicates that a single intraoperative injection of methylprednisolone seems not to cause suppression of short-term haematological parameters compared with placebo following surgical removal of mandibular third molars.

Introduction Patients with coronavirus disease (COVID-19) and pneumonitis often have hypoxemic respiratory failure and a need of supplementary oxygen. Guidelines recommend controlled oxygen, for most patients with a recommended interval of SpO2 between 92 and 96%. We aimed to determine if closed-loop control of oxygen was feasible in patients with COVID-19 and could maintain SpO2 in the specified interval. Methods Patients were prospectively enrolled in an observational study on a medical ward dedicated to patients with COVID-19. Closed-loop controlled oxygen was delivered by O2matic® which can deliver 0–15 liters/min and adjusts flow every second based on 15 seconds averaging of SpO2 measured by pulse oximetry. Lung function parameters were measured at admission. Results Fifteen patients (six women, nine men) participated in the study. Average age was 72 years. Lung function was severely impaired with FEV1, FVC and PEF reduced to approximately 50%. The average stay on the ward was 3.2 days and O2matic was used on average for 66 hours, providing 987 hours of observation. O2matic maintained SpO2 in the desired interval for 82.9% of the time. Time with SpO2 > 2% below interval was 5.1% and time with SpO2 > 2% above interval was 0.6%. Conclusion Closed-loop control of oxygen to patients with COVID-19 is feasible and can maintain SpO2 in the specified interval in the majority of time. Closed-loop automated control could be of particular benefit for patients in isolation with decreased visibility, surveillance and monitoring. Further studies must examine the clinical benefits.

Purpose: It has been suggested that patients with inspiratory muscle weakness could benefit from specific inspiratory muscle training (IMT). We aimed to examine the frequency of patients with inspiratory muscle weakness in a Danish hospital-based outpatient pulmonary rehabilitation program, and to evaluate the association between inspiratory muscle strength and peripheral muscle strength and walking capacity. Methods: Maximal Inspiratory Pressure (MIP) was assessed in 97 patients with COPD (39 men, 58 women, mean age years 70 ± 9, forced expiratory volume in 1 s ((FEV1) = 35 ± 10% pred.). The impact of MIP on knee-extension strength, walking distance, and symptom burden was evaluated using multiple linear regression analyses. Results: The MIP of the patients with COPD was 63 (95% CI 59; 67) cmH2O and it was significantly reduced compared to gender and age-matched reference values 76 (95% CI 73; 79) cmH2O (p < 0.001). Seven patients (7.2%) were under the lower limit of normal. MIP was negatively correlated with increasing age, female gender, decreasing knee-extension strength and lower FEV1% pred. Walking distance was associated with knee-extension strength and it was not associated with MIP. Conclusion: Maximal inspiratory pressure was reduced in patients with COPD but only a few patients had a weak MIP. Whilst MIP was associated with leg muscle strength, it was not associated with walking distance or symptoms.

Abstract Background Pulmonary rehabilitation (PR), delivered as a supervised multidisciplinary program including exercise training, is one of the cornerstones in the chronic obstructive pulmonary disease (COPD) management. We performed a systematic review and meta-analysis to assess the effect on mortality of a supervised early PR program, initiated during or within 4 weeks after hospitalization with an acute exacerbation of COPD compared with usual post-exacerbation care or no PR program. Secondary outcomes were days in hospital, COPD related readmissions, health-related quality of life (HRQoL), exercise capacity (walking distance), activities of daily living (ADL), fall risk and drop-out rate. Methods We identified randomized trials through a systematic search using MEDLINE, EMBASE and Cocharne Library and other sources through October 2017. Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using the Cochrane Risk of Bias tool. Results We included 13 randomized trials (801 participants). Our meta-analyses showed a clinically relevant reduction in mortality after early PR (4 trials, 319 patients; RR = 0.58 (95% CI: [0.35 to 0.98])) and at the longest follow-up (3 trials, 127 patients; RR = 0.55 (95% CI: [0.12 to 2.57])). Early PR reduced number of days in hospital by 4.27 days (1 trial, 180 patients; 95% CI: [− 6.85 to − 1.69]) and hospital readmissions (6 trials, 319 patients; RR = 0.47 (95% CI: [0.29 to 0.75])). Moreover, early PR improved HRQoL and walking distance, and did not affect drop-out rate. Several of the trials had unclear risk of bias in regard to the randomization and blinding, for some outcome there was also a lack of power. Conclusion Moderate quality of evidence showed reductions in mortality, number of days in hospital and number of readmissions after early PR in patients hospitalized with a COPD exacerbation. Long-term effects on mortality were not statistically significant, but improvements in HRQoL and exercise capacity appeared to be maintained for at least 12 months. Therefore, we recommend early supervised PR to patients with COPD-related exacerbations. PR should be initiated during hospital admission or within 4 weeks after hospital discharge.

Abstract Background Plants and in particular grasses benefit from a high uptake of silicon (Si) which improves their growth and productivity by alleviating adverse effects of biotic and abiotic stress. However, the silicon present in plant tissues may have a negative impact on the processing and degradation of lignocellulosic biomass. Solutions to reduce the silicon content either by biomass engineering or development of downstream separation methods are therefore targeted. Different cell wall components have been proposed to interact with the silica pool in plant shoots, but the understanding of the underlying processes is still limited. Results In the present study, we have characterized silicon deposition and cell wall composition in Brachypodium distachyon wild-type and low-silicon 1 (Bdlsi1-1) mutant plants. Our analyses included different organs and plant developmental stages. In the mutant defective in silicon uptake, low silicon availability favoured deposition of this element in the amorphous form or bound to cell wall polymers rather than as silicified structures. Several alterations in non-cellulosic polysaccharides and lignin were recorded in the mutant plants, indicating differences in the types of linkages and in the three-dimensional organization of the cell wall network. Enzymatic saccharification assays showed that straw from mutant plants was marginally more degradable following a 190 °C hydrothermal pretreatment, while there were no differences without or after a 120 °C hydrothermal pretreatment. Conclusions We conclude that silicon affects the composition of plant cell walls, mostly by altering linkages of non-cellulosic polymers and lignin. The modifications of the cell wall network and the reduced silicon concentration appear to have little or no implications on biomass recalcitrance to enzymatic saccharification.

Background: It has been hypothesized that antibiotic usage in early life could contribute to development of overweight in childhood. Studies have seen association between antibiotic usage and overweight in childhood. We aimed to investigate the relationship between antibiotic exposure in infancy and development of body mass index (BMI) and body composition. Methods: A prospective mother–child cohort study of 738 pregnant women and their 700 children, Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010). Information on antibiotic exposure was collected by interviews. Height/length and weight measures were collected at age 1, 2, 3, 4, 5 and 6 years and body composition was determined by a dual-energy X-ray absorptiometry (DXA) scan at age 3.5 and 6 years. Findings: 306 (46%) of the 661 children were exposed to antibiotics before 1 year of age. There were no differences in BMI z-score development at age 1–6 years between children exposed to antibiotics compared to unexposed: z-score difference, –0.06 (95%CI: –0.17;0.06), p = 0.33, and no sex-differences (p-interaction = 0.48). Children exposed vs. not exposed to antibiotics had comparable fat percentage at 6 years of age: log(mean difference), 0.60% (95%CI: −0.212 to 1.41), p = 0.15. Interpretation: Children exposed to antibiotics had similar BMI, BMI z-score and body composition between 1 and 6 years of life compared to unexposed children. Our study does not support the hypothesis that antibiotic exposure in infancy leads to development of obesity in the first 6 years of life. Funding: The Lundbeck Foundation, The Ministry of Health, Danish Council for Strategic Research and The Capital Region Research Foundation. Keywords: Antibiotic, Childhood, BMI, Growth, DXA scan, Fat percentage

The relationship between developmental milestone achievement in infancy and later cognitive function and mental health is well established, but underlying biochemical mechanisms are poorly described. Our study aims to discover pathways connected to motor milestone achievement during infancy by using untargeted plasma metabolomic profiles from 571 six-month-old children in connection with age of motor milestones achievement (Denver Developmental Index) in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) mother–child cohort. We used univariate regression models and multivariate modelling (Partial Least Squares Discriminant Analysis: PLS-DA) to examine the associations and the VDAART (Vitamin D Antenatal Asthma Reduction Trial) cohort for validation. The univariate analyses showed 62 metabolites associated with gross-motor milestone achievement (p < 0.05) as well as the PLS-DA significantly differentiated between slow and fast milestone achievers (AUC = 0.87, p = 0.01). Higher levels of tyramine-O-sulfate in the tyrosine pathway were found in the late achievers in COPSAC (p = 0.0002) and in VDAART (p = 0.02). Furthermore, we observed that slow achievers were characterized by higher levels of fatty acids and products of fatty acids metabolism including acyl carnitines. Finally, we also observed changes in the lysine, histidine, glutamate, creatine and tryptophan pathways. Observing these metabolic changes in relation to gross-motor milestones in the first year of life, may be of importance for later cognitive function and mental health.

Contemporary research on prostitution tends to treat it either as a social problem that needs to be solved by criminalizing customers and supportive social programs (exit programs) or as a manifestation of female agency. This article analyzes Danish ethnographic interview and observations with the so-called dominatrices. The theoretical concepts, boundary markers and body schema, are applied to identify dominatrices’ perception of themselves as businesswomen not representing a social problem. The dominatrices are used to discuss tailoring of exit programs, and the article concludes that core elements in these programs need to change if the dominatrices should be provided relevant opportunities to pursue a different profession.

Objectives: The objective of the present systematic review was to test the hypothesis of no difference in facial swelling, pain and trismus after surgical removal of mandibular third molar with different dosages of corticosteroids and administration routes. Material and Methods: A MEDLINE (PubMed), Embase database and Cochrane Library search in combination with a hand-search of relevant journals was conducted by including randomized controlled trials published in English until 1st December 2017. Results: Seven studies fulfilled the inclusion criteria. Considerable variation in the included studies prevented meta-analysis from being performed. Preoperative submucosal injection of corticosteroids significantly diminishes facial swelling, pain and trismus compared with placebo. However, different dosages of corticosteroid and administration routes reveal contrary results indicating that administration of a higher dosage of corticosteroids do not necessarily cause a further decrease in facial swelling, pain and trismus. Conclusions: Consequently, the optimal dosage of corticosteroids and administration route for diminishing postsurgical morbidity and improve quality of life after surgical removal of mandibular third molar is presently unknown. Therefore, further well-designed randomized clinical trials including a standardised protocol, patient-reported outcome measures and three-dimensional analysis of facial swelling is needed.