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Aim: To describe the use of invasive mechanical ventilation core strategies, adjuvant treatments and the occurrence of barotrauma and prolonged ventilation in ICU patients with COVID-19 in Denmark, retrospectively., Methods: All ICUs admitting COVID-19 patients in Denmark from 10 March 2020 to 2 April 2021 were invited to participate. All patients with COVID-19 who received invasive mechanical ventilation were included and data was retrospectively collected from electronic patient records., Results: A total of 774 patients were invasively ventilated during the first two waves and included; 70% were males and the median age was 69 years. 340 (51.5%) of patients never exceeded tidal volumes of 8 mL/kg. For all patients, tidal volumes under 8 mL/kg were applied in 77.6% (IQR 54.5%-96.2%) of the time on ventilator in the ICU; plateau pressure was below 30 cm H 2 O in 125 (80.6%) patients; prone positioning was used in 44.7% of patients. In ICU, 169 of 774 (21.8%) patients experienced barotrauma and 220 (28.4%) prolonged ventilation. At 90 days, 306 (39.5%) had died., Conclusions: Lung protective ventilation and prone positioning were used in many of the Danish ICU patients with COVID-19, but barotrauma, prolonged ventilation and death occurred frequently., (© 2025 Acta Anaesthesiologica Scandinavica Foundation.)

Introduction: Giggle incontinence (GI) is a rare form of urinary incontinence that occurs during or immediately after laughing due to involuntary and complete bladder emptying. Few studies in the literature report that methylphenidate can be effective in treatment of this condition., Objective: The aim of this study is to characterize children with GI and evaluate their response to methylphenidate, as well as describe treatment duration, dosage of methylphenidate, relapse rates after discontinuation of medication, and side effects., Methods: Medical records and 48-h frequency-volume charts from children treated with methylphenidate for GI in the period January 2011-July 2021 were retrospectively analyzed., Results: Eighteen children were diagnosed with GI and fulfilled inclusion criteria. Fifteen patients were included in analysis, as 3 out of 18 children decided not to take the methylphenidate that was prescribed. In total, 14 out of the 15 GI patients treated with methylphenidate experienced clinical effect. All patients included in the study had methylphenidate prescribed in a dose range of 5-20 mg daily. Treatment duration ranged from 30 to 1001 days, with a median of 152 days (IQR 114, 243.5). Ten children experienced complete response and two of those reported symptom relapse after discontinuation of the methylphenidate. Only mild and short-lasting side effects were reported by two patients., Discussion: Our study demonstrates that methylphenidate is an effective treatment in children diagnosed with GI. Side effects are mild and uncommon., (© 2023 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

The mechanisms whereby insulin analogues may cause enhanced mitogenicity through activation of either the IR (insulin receptor) or the IGF-IR (insulin-like growth factor 1 receptor) are incompletely understood. We demonstrate that in L6 myoblasts expressing only IGF-IRs as well as in the same cells overexpressing the IR, IGF-I (insulin-like growth factor 1), insulin and X10 (AspB10 insulin) down-regulate the mRNA expression level of the cell cycle inhibitor cyclin G2, as measured by qRT-PCR (quantitative reverse transcription-PCR), and induce cell growth measured by [6-(3)H]thymidine incorporation into DNA. Western blotting showed a marked down-regulation of cyclin G2 at the protein level in both cell lines. Overexpression of cyclin G2 in the two cell lines diminished the mitogenic effect of all three ligands. The use of specific inhibitors indicated that both the MAPK (mitogen-activated protein kinase) and the PI3K (phosphoinositide 3-kinase) pathways mediate the down-regulation of Ccng2. The down-regulation of CCNG2 by the three ligands was also observed in other cell lines: MCF-7, HMEC, Saos-2, R(-)/IR and INS-1. These results indicate that regulation of cyclin G2 is a key mechanism whereby insulin, insulin analogues and IGF-I stimulate cell proliferation.

This case study describes a patient who had a unipolar depression and experienced long-lasting cognitive problems after electroconvulsive therapy (ECT). Neuropsychological testing revealed lower scores on measures of learning, memory and sustained attention. These results stress the importance of informing patients who have ECT of the potential cognitive consequences of this treatment as it may influence the patients' functional capabilities. Prospective studies are needed since we do not have sufficient knowledge regarding the 3-5% of these patients who experience sustained cognitive problems.

Background: Patients with affective disorders experience cognitive dysfunction in addition to their affective symptoms. The relationship between subjectively experienced and objectively measured cognitive function is controversial with several studies reporting no correlation between subjective and objective deficits., Aims: To investigate whether there is a correlation between subjectively reported and objectively measured cognitive function in patients with affective disorders, and whether subjective complaints predict objectively measured dysfunction., Methods: The study included 45 participants; 15 with bipolar disorder (BD), 15 with unipolar disorder (UD) and 15 healthy individuals. Participants' subjectively experienced cognitive function and objective cognitive function were assessed with the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) and the Screen for Cognitive Impairment in Psychiatry (SCIP), respectively. Patients were rated for affective symptoms with Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS)., Results: Patients demonstrated subjective and objective cognitive dysfunction relative to controls (P-values ≤ 0.01) but there were no differences between patient groups (P > 0.1). We found no correlation between subjectively experienced and objectively measured cognitive dysfunction in BD (P = 0.7), and a non-significant trend towards a correlation in UD (P = 0.06), which disappeared when controlling for gender (P = 0.1)., Conclusion: Our results suggest that it is not necessarily patients who have cognitive complaints that are most impaired. If confirmed in a larger sample, our findings suggest that neuropsychological assessment is warranted to elucidate the potential role of cognitive dysfunction in patients' everyday lives and to inform treatment strategies targeting these difficulties.

Recent evidence suggests that type II diabetes is associated with increased risk and/or aggressive behavior of several cancers, including those arising from the colon. Concerns have been raised that endogenous hyperinsulinemia and/or exogenous insulin and insulin analogs might stimulate proliferation of neoplastic cells. However, the mechanisms underlying possible growth-promoting effects of insulin and insulin analogs in cancer cells in vivo, such as changes in gene expression, are incompletely described. We observed that administration of the insulin analog X10 significantly increased tumor growth and proliferation in a murine colon cancer model (MC38 cell allografts). Insulin and X10 altered gene expression in MC38 tumors in a similar fashion, but X10 was more potent in terms of the number of genes influenced and the magnitude of changes in gene expression. Many of the affected genes were annotated to metabolism, nutrient uptake, and protein synthesis. Strikingly, expression of genes encoding enzymes in the serine synthesis pathway, recently shown to be critical for neoplastic proliferation, was increased following treatment with insulin and X10. Using stable isotopic tracers and mass spectrometry, we confirmed that insulin and X10 increased glucose contribution to serine synthesis in MC38 cells. The data demonstrate that the tumor growth-promoting effects of insulin and X10 are associated with changes in expression of genes involved in cellular energy metabolism and reveal previously unrecognized effects of insulin and X10 on serine synthesis.

We report the crystal structure of two variants of Drosophila melanogaster insulin-like peptide 5 (DILP5) at a resolution of 1.85 Å. DILP5 shares the basic fold of the insulin peptide family (T conformation) but with a disordered B-chain C terminus. DILP5 dimerizes in the crystal and in solution. The dimer interface is not similar to that observed in vertebrates, i.e. through an anti-parallel β-sheet involving the B-chain C termini but, in contrast, is formed through an anti-parallel β-sheet involving the B-chain N termini. DILP5 binds to and activates the human insulin receptor and lowers blood glucose in rats. It also lowers trehalose levels in Drosophila. Reciprocally, human insulin binds to the Drosophila insulin receptor and induces negative cooperativity as in the human receptor. DILP5 also binds to insect insulin-binding proteins. These results show high evolutionary conservation of the insulin receptor binding properties despite divergent insulin dimerization mechanisms.

Peptides of the relaxin family bind to the relaxin family peptide receptors or RXFPs, members of the G-protein-coupled receptor (GPCR) superfamily. For many years, ligand binding to GPCRs was thought to take place as monomeric complexes, ignoring early evidence of negative cooperativity. However, recent research has shown that most GPCRs form constitutive dimers or larger oligomers. The connection between dimerization and negative cooperativity has now been shown for several GPCRs, including the thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone receptors, which like RXFP1 and -2 belong to the leucine-rich repeat-containing subgroup of class A GPCRs. We recently demonstrated homodimerization and negative cooperativity for RXFP1 and RXFP2 as well as their heterodimerization. Another study showed that RXFP1 has to homodimerize in order to be transported from the endoplasmic reticulum to the cell membrane.

The insulin/relaxin superfamily of peptide hormones comprises 10 members in humans. The three members of the insulin-related subgroup bind to receptor tyrosine kinases (RTKs), while four of the seven members of the relaxin-like subgroup are now known to bind to G-protein-coupled receptors (GPCRs), the so-called relaxin family peptide receptors (RXFPs). Both systems have a long evolutionary history and play a critical role in fundamental biological processes, such as metabolism, growth, survival and longevity, and reproduction. The structural biology and ligand-binding kinetics of the insulin and insulin-like growth factor I receptors have been studied in great detail, culminating in the recent crystal structure of the insulin receptor extracellular domain. Some of the fundamental properties of these receptors, including constitutive dimerization and negative cooperativity, have recently been shown to extend to other RTKs and GPCRs, including RXFPs, confirming kinetic observations made over 30 years ago.

H2 relaxin, a member of the insulin superfamily, binds to the G-protein-coupled receptor RXFP1 (relaxin family peptide 1), a receptor that belongs to the leucine-rich repeat (LRR)-containing subgroup (LGRs) of class A GPCRs. We recently demonstrated negative cooperativity in INSL3 binding to RXFP2 and showed that this subgroup of GPCRs functions as constitutive dimers. In this work, we investigated whether the binding of H2 relaxin to RXFP1 also shows negative cooperativity, and whether this receptor functions as a dimer using BRET(2). Both binding and dissociation were temperature dependent, and the pH optimum for binding was pH 7.0. Our results showed that RXFP1 is a constitutive dimer with negative cooperativity in ligand binding, that dimerization occurs through the 7TM domain, and that the ectodomain has a stabilizing effect on this interaction. Dimerization and negative cooperativity appear to be general properties of LGRs involved in reproduction as well as other GPCRs.

Insulin-like peptide 3 (INSL3) binds to a G protein-coupled receptor (GPCR) called relaxin family peptide receptor 2 (RXFP2). RXFP2 belongs to the leucine-rich repeat-containing subgroup (LGR) of class A GPCRs. Negative cooperativity has recently been demonstrated in other members of the LGR subgroup. In this work, the kinetics of INSL3 binding to HEK293 cells stably transfected with RXFP2 (HEK293-RXFP2) have been investigated in detail to study whether negative cooperativity occurs and whether this receptor functions as a dimer. Our results show that negative cooperativity is present and that INSL3-RXFP2 binding shows both similarities and differences with insulin binding to the insulin receptor. A dose-response curve for the negative cooperativity of INSL3 binding had a reverse bell shape reminiscent of that seen for the negative cooperativity of insulin binding to its receptor. This suggests that binding of INSL3 may happen in a trans rather than in a cis way in a receptor dimer. Bioluminescence resonance energy transfer (BRET(2)) experiments confirmed that RXFP2 forms constitutive homodimers. Heterodimerization between RXFP2 and RXFP1 was also observed.

Heart failure is a clinical syndrome that normally requires health care to be provided by both specialists and nonspecialists. This is advantageous because patients benefit from complementary skill sets and experience, but can present challenges in the development of a common, shared treatment plan. The Canadian Cardiovascular Society published a comprehensive set of recommendations on the diagnosis and management of heart failure in January 2006, and on the prevention, management during intercurrent illness or acute decompensation, and use of biomarkers in January 2007. The present update builds on those core recommendations. Based on feedback obtained through a national program of heart failure workshops during 2006 and 2007, several topics were identified as priorities because of the challenges they pose to health care professionals. New evidence-based recommendations were developed using the structured approach for the review and assessment of evidence that was adopted and previously described by the Society. Specific recommendations and practical tips were written for best practices during the transition of care of heart failure patients, and the recognition, investigation and treatment of some specific cardiomyopathies. Specific clinical questions that are addressed include: What information should a referring physician provide for a specialist consultation? What instructions should a consultant provide to the referring physician? What processes should be in place to ensure that the expectations and needs of each physician are met? When a cardiomyopathy is suspected, how can it be recognized, how should it be investigated and diagnosed, how should it be treated, when should the patient be referred, and what special tests are available to assist in the diagnosis and treatment? The goals of the present update are to translate best evidence into practice, apply clinical wisdom where evidence for specific strategies is weaker, and aid physicians and other health care providers to optimally treat heart failure patients, resulting in a measurable impact on patient health and clinical outcomes in Canada.

Heart failure is common, yet it is difficult to treat. It presents in many different guises and circumstances in which therapy needs to be individualized. The Canadian Cardiovascular Society published a comprehensive set of recommendations in January 2006 on the diagnosis and management of heart failure, and the present update builds on those core recommendations. Based on feedback obtained through a national program of heart failure workshops during 2006, several topics were identified as priorities because of the challenges they pose to health care professionals. New evidence-based recommendations were developed using the structured approach for the review and assessment of evidence adopted and previously described by the Society. Specific recommendations and practical tips were written for the prevention of heart failure, the management of heart failure during intercurrent illness, the treatment of acute heart failure, and the current and future roles of biomarkers in heart failure care. Specific clinical questions that are addressed include: which patients should be identified as being at high risk of developing heart failure and which interventions should be used? What complications can occur in heart failure patients during an intercurrent illness, how should these patients be monitored and which medications may require a dose adjustment or discontinuation? What are the best therapeutic, both drug and nondrug, strategies for patients with acute heart failure? How can new biomarkers help in the treatment of heart failure, and when and how should BNP be measured in heart failure patients? The goals of the present update are to translate best evidence into practice, to apply clinical wisdom where evidence for specific strategies is weaker, and to aid physicians and other health care providers to optimally treat heart failure patients to result in a measurable impact on patient health and clinical outcomes in Canada.

Heart failure remains a common diagnosis, especially in older individuals. It continues to be associated with significant morbidity and mortality, but major advances in both diagnosis and management have occurred and will continue to improve symptoms and other outcomes in patients. The Canadian Cardiovascular Society published its first consensus conference recommendations on the diagnosis and management of heart failure in 1994, followed by two brief updates, and reconvened this consensus conference to provide a comprehensive review of current knowledge and management strategies. New clinical trial evidence and meta-analyses were critically reviewed by a multidisciplinary primary panel who developed both recommendations and practical tips, which were reviewed by a secondary panel. The resulting document is intended to provide practical advice for specialists, family physicians, nurses, pharmacists and others who are involved in the care of heart failure patients. Management of heart failure begins with an accurate diagnosis, and requires rational combination drug therapy, individualization of care for each patient (based on their symptoms, clinical presentation and disease severity), appropriate mechanical interventions including revascularization and devices, collaborative efforts among health care professionals, and education and cooperation of the patient and their immediate caregivers. The goal is to translate best evidence-based therapies into clinical practice with a measureable impact on the health of heart failure patients in Canada.

Introduction: The aim of this article is to present the qualitative focus group interview as a useful method of evaluating psycho- and milieu therapeutic treatment., Material and Methods: We conducted two focus group interviews with former inpatients of a psychiatric ward specialising in group therapy. To enhance the quality of the data by triangulation, the staff, representing both milieu- and psychotherapists, were also interviewed., Results: Analysis of the results revealed the following dominant themes: The continuation of the treatment was jeopardised by the existence of a welcome group. There was a need for further information as soon as the patient came into contact with the hospital. Moreover, an earlier and increased involvement of the family was required. After their own interview, the staff participated in deciding which results should lead to alterations in treatment procedures, thereby becoming involved in implementing the results., Discussion: The focus group interview is a valuable method of evaluating psycho- and milieu therapeutic treatment. Interviewing the staff served as triangulation and eased the implementation of the results remarkably.