Pre-biologic disease trajectories are associated with morbidity burden and biologic treatment response in severe asthma.

Background: Biologics can induce remission in some patients with severe asthma, however, little is known about pre-biologic disease trajectories and their association with outcomes from biological treatment. We aimed to identify long-term trajectories of disease progression in patients initiating biologics and investigate trajectory associations with disease burden and impact on biologic therapy efficacy.

Methods: Patients in the Danish Severe Asthma Registry initiating biologic therapy between 2016-2022 were included and followed retrospectively in prescription databases starting 1995.

Early Reduction of FeNO on Anti-IL5 Biologics Is Associated With Clinical Remission of Severe Asthma.

Background: In patients with severe asthma, treatment with anti-interleukin-5 (IL-5) biologics can lead to a reduction in fractional exhaled nitric oxide (FeNO) in some patients. The clinical implications of varying FeNO responses to anti-IL-5 biologics remain unclear. This study aims to categorise patients based on their FeNO response to anti-IL-5 biologics and evaluate the association of these categories with clinical outcomes.

SSR4-CDG, an ultra-rare X-linked congenital disorder of glycosylation affecting the TRAP complex: Review of 22 affected individuals including the first adult patient.

Congenital disorders of glycosylation (CDG) are a group of rare, often multi-systemic genetic disorders that result from disturbed protein and lipid glycosylation. SSR4-CDG is an ultra-rare, comparably mild subtype of CDG, presenting mostly in males. It is caused by pathogenic variants in the SSR4 gene, which is located on the X chromosome.

Palliative psychiatry for a patient with treatment-refractory schizophrenia and severe chronic malignant catatonia: case report.

Background: Palliative psychiatry is an emerging field that suggests a role for palliative interventions in the management of severe and persistent mental illness (SPMI). Current literature describes using a palliative approach for patients with severe anorexia nervosa. To our knowledge, this is the first case report describing end-of-life care in a patient with treatment-refractory catatonic schizophrenia.

Neurological manifestations in PMM2-congenital disorders of glycosylation (PMM2-CDG): Insights into clinico-radiological characteristics, recommendations for follow-up, and future directions.

Purpose: In the absence of prospective data on neurological symptoms, disease outcome, or guidelines for system specific management in phosphomannomutase 2-congenital disorders of glycosylation (PMM2-CDG), we aimed to collect and review natural history data.

Methods: Fifty-one molecularly confirmed individuals with PMM2-CDG enrolled in the Frontiers of Congenital Disorders of Glycosylation natural history study were reviewed. In addition, we prospectively reviewed a smaller cohort of these individuals with PMM2-CDG on off-label acetazolamide treatment.

Clinical Response and Remission in Patients With Severe Asthma Treated With Biologic Therapies.

Background: The development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal.

Research Question: How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment?

Study Design And Methods: The Danish Severe Asthma Register is a nationwide cohort including all adult patients receiving biologic therapy for severe asthma in Denmark. This observational cohort study defined "clinical response" to treatment following 12 months as a ≥ 50% reduction in exacerbations and/or a ≥ 50% reduction in maintenance oral corticosteroid dose, if required.

Coagulation abnormalities in a prospective cohort of 50 patients with PMM2-congenital disorder of glycosylation.

Background: Given the lack of reliable data on the prevalence of bleeding abnormalities and thrombotic episodes in PMM2-CDG patients, and whether coagulation abnormalities change over time, we prospectively collected and reviewed natural history data. Patients with PMM2-CDG often have abnormal coagulation studies due to glycosylation abnormalities but the frequency of complications resulting from these has not been prospectively studied.

Methods: We studied fifty individuals enrolled in the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) natural history study with molecularly confirmed diagnosis of PMM2-CDG.

Long-term outcomes in ALG13-Congenital Disorder of Glycosylation.

ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported.

Complete response to anti-interleukin-5 biologics in a real-life setting: results from the nationwide Danish Severe Asthma Register.

Background: Phase III regulatory trials show that anti-interleukin (IL)-5 biologics efficiently reduce exacerbations and the use of maintenance oral corticosteroids (mOCS) in patients with severe eosinophilic asthma. However, patients eligible for these trials differ significantly compared with real-life severe asthma populations. Therefore, our aim was to explore efficacy in a real-life setting.

TRIT1 defect leads to a recognizable phenotype of myoclonic epilepsy, speech delay, strabismus, progressive spasticity, and normal lactate levels.

TRIT1 defect is a rare, autosomal-recessive disorder of transcription, initially described as a condition with developmental delay, myoclonic seizures, and abnormal mitochondrial function. Currently, only 13 patients have been reported. We reviewed the genetic, clinical, and metabolic aspects of the disease in all known patients, including two novel, unrelated TRIT1 cases with abnormalities in oxidative phosphorylation complexes I and IV in fibroblasts.

Nutrition interventions in congenital disorders of glycosylation.

Congenital disorders of glycosylation (CDG) are a group of more than 160 inborn errors of metabolism affecting multiple pathways of protein and lipid glycosylation. Patients present with a wide range of symptoms and therapies are only available for very few subtypes. Specific nutritional treatment options for certain CDG types include oral supplementation of monosaccharide sugars, manganese, uridine, or pyridoxine.

Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications.

Objective: Epalrestat, an aldose reductase inhibitor increases phosphomannomutase (PMM) enzyme activity in a PMM2-congenital disorders of glycosylation (CDG) worm model. Epalrestat also decreases sorbitol level in diabetic neuropathy. We evaluated the genetic, biochemical, and clinical characteristics, including the Nijmegen Progression CDG Rating Scale (NPCRS), urine polyol levels and fibroblast glycoproteomics in patients with PMM2-CDG.

Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study.

A recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study's conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin.

Therapist self-disclosure: Let's tackle the elephant in the room.

Therapist Self-Disclosure (TSD), the revealing of a therapist's feelings, thoughts or personal information to a client, is an inevitable aspect of therapeutic relationships. However, despite its prevalence in clinical settings, we believe there is insufficient recognition and exploration of TSD in our work with children and adolescents. Because TSD is not often formally addressed during training, therapists across the spectrum of clinical child psychology and psychiatry are often left with the belief that disclosures are rare or inherently negative occurrences that should be avoided.

Left ventricular systolic ejection time is an independent predictor of all-cause mortality in heart failure with reduced ejection fraction.

Aims: Colour tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to obtain cardiac time intervals including isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT) and systolic ejection time (SET). The myocardial performance index (MPI) is defined as [(IVCT + IVRT)/SET]. Whether cardiac time intervals obtained by the TDI M-mode method can be used to predict outcome in patients with heart failure with reduced ejection fraction (HFrEF) remains unknown.

Canines (Canis lupus familiaris) as biodetectors for conservation work: Can they discriminate the rock ptarmigan (Lagopus muta) from the willow grouse (L. lagopus) in a yes/no task?

Alpine and arctic bird populations have shown an unmistakable decrease over the last three decades, and the need for conservation is highly necessary. We investigated the use of five privately-owned dogs (Canis lupus familiaris) as a non-invasive tool to determine the presence of rock ptarmigan (Lagopus muta), through sniffing out faecal pellets, using a yes/no training regime. We carried out 36 double-blind experimental trials per dog and hypothesised that dogs could discriminate the rock ptarmigan from similar species, such as black grouse (Tetrao tetrix), western capercaillie (T.

First do no harm: Preventing harm and optimizing care in psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) are challenging clinical occurrences consisting of any combination of altered movement, sensation, or awareness that resemble epileptic seizures (ES) but do not coincide with electrographic ictal discharges and are presumed to be neuropsychiatric-neurobehavioral in origin. Securing the PNES diagnosis is a crucial first step and is best confirmed by recording events on video-electroencephalogram (v-EEG) and finding an absence of ictal EEG changes and the presence of normal awake EEG rhythms before, during, and after the event. However, obstacles to timely diagnosis and referral to psychiatric treatment frequently occur, placing these patients at risk for harm from unnecessary medications and procedure as well as placing high burden on medical systems.

Improved Resistance Prediction in by Better Handling of Insertions and Deletions, Premature Stop Codons, and Filtering of Non-informative Sites.

Resistance in is a major obstacle for effective treatment of tuberculosis. Multiple studies have shown promising results for predicting drug resistance in based on whole genome sequencing (WGS) data, however, these tools are often limited to this single species. We have previously developed a common platform for resistance prediction in multiple species.

Scent-sniffing dogs can discriminate between native Eurasian and invasive North American beavers.

The invasion of a species can cause population reduction or extinction of a similar native species due to replacement competition. There is a potential risk that the native Eurasian beaver (Castor fiber) may eventually be competitively excluded by the invasive North American beaver (C. canadensis) from areas where they overlap in Eurasia.

Allergy Development in Adulthood: An Occupational Cohort Study of the Manufacturing of Industrial Enzymes.

Background: Occupational allergy may serve as a model of allergy development in adults.

Objective: We aimed at describing respiratory allergy and IgE sensitization across different exposure strata defined by time, technology, and exposure control.

Methods: In a retrospective (1970-2017) cohort of industrial enzyme production employees, monitored by an occupational medical center, 5024 individuals were surveyed.