Investigating non-inferiority of internet-delivered versus face-to-face cognitive behavioural therapy for insomnia (CBT-I): a randomised controlled trial (iSleep well).

BACKGROUND: Insomnia is a highly prevalent disorder associated with numerous adverse health outcomes. Cognitive behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment by clinical guidelines but is accessible to only a minority of patients suffering from insomnia. Internet-delivered CBT-I (iCBT-I) could contribute to the widespread dissemination of this first-line treatment. As there is insufficient evidence regarding non-inferiority, this study directly aims to compare therapist-guided internet-delivered versus face-to-face CBT-I in terms of insomnia severity post-treatment. Furthermore, a health-economic evaluation will be conducted, and potential benefits and disadvantages of therapist-guided iCBT-I will be examined. METHODS: This study protocol describes a randomised controlled two-arm parallel-group non-inferiority trial comparing therapist-guided iCBT-I with face-to-face CBT-I in routine clinical care. A total of 422 patients with insomnia disorder will be randomised and treated at 16 study centres throughout Germany. Outcomes will be assessed at baseline, 10 weeks after randomisation (post), and 6 months after randomisation (follow-up). The primary outcome is insomnia severity measured using the Insomnia Severity Index. Secondary outcomes include depression-related symptoms, quality of life, fatigue, physical activity, daylight exposure, adverse events related to treatment, and a health-economic evaluation. Finally, potential moderator variables and several descriptive and exploratory outcomes will be assessed (e.g. benefits and disadvantages of internet-delivered treatment). DISCUSSION: The widespread implementation of CBT-I is a significant healthcare challenge. The non-inferiority of therapist-guided iCBT-I versus face-to-face CBT-I will be investigated in an adequately powered sample in routine clinical care, with the same therapeutic content and same level of therapist qualifications provided with both interventions. If this trial demonstrates the non-inferiority of therapist-guided iCBT-I, healthcare providers may be more confident recommending this treatment to their patients, contributing to the wider dissemination of CBT-I. TRIAL REGISTRATION: Trial registration number in the German Clinical Trials Register: DRKS00028153 ( https://drks.de/search/de/trial/DRKS00028153 ). Registered on 16th May 2023.

Complex Daphnia interactions with parasites and competitors.

Species interactions can strongly influence the size and dynamics of epidemics in populations of focal hosts. The "dilution effect" provides a particularly interesting type of interaction from a biological standpoint. Diluters - other host species which resist infection but remove environmentally-distributed propagules of parasites (spores) - should reduce disease prevalence in focal hosts. However, diluters and focal hosts may compete for shared resources. This combination of positive (dilution) and negative (competition) effects could greatly complicate, even undermine, the benefits of dilution and diluter species from the perspective of the focal host. Motivated by an example from the plankton (i.e., zooplankton hosts, a fungal parasite, and algal resources), we study a model of dilution and competition. Our model reveals a suite of five results: • A diluter that is a superior competitor wipes out the host, regardless of parasitism. Although expected, this outcome is an ever-present danger in strategies that might use diluters to control disease. • If the diluter is an inferior competitor, it can reduce disease prevalence, despite the competition, as parameterized in our model. However, competition may also reduce density of susceptible hosts to levels below that seen in focal host-parasite systems alone. • As they decrease disease prevalence, diluters destabilize dynamics of the focal host and their resources. Thus, diluters undermine the stabilizing effects of disease. • The four species combination can generate very complex dynamics, including period-doubling bifurcations and torus (Neimark-Sacker) bifurcations. • At lower resource carrying capacity, the diluter's dilution of spores is 'helpful' to the focal host, i.e., dilution can elevate host density by reducing disease. But, as the resource carrying capacity increases further, the equilibrium density of the diluter increases while the density of the focal host decreases, despite competition. Namely, the negative effects of competition start to outweigh the positive effects of dilution from the perspective of equilibrium density of the focal host.

[Poisoning with Jimson weed. Five cases treated with physostigmine]. / Forgiftning med piggeple. Fem tilfeller behandlet med fysostigmin.

During the autumn of 1995, the National Poisons Information Centre was contacted about several cases of poisoning with Jimson weed (Datura stramonium). Five cases are described here. Upon admission to hospital the patients had moderate to severe anticholinergic symptoms, such as mydriasis, sinus tachycardia, agitation, dry mouth, urine retention, fever, hypertension, hallucinations and seizures. Owing to their agitated behaviour, gastrointestinal decontamination was impossible. Repeated doses of physostigmine (2-3 mg) administered intravenously reversed the anticholinergic features without side-effects. In the most severe case, physostigmine was needed for 18 hours (total dose; 25.5 mg). The patients recovered in a day or two, but mydriasis persisted in many cases.

Granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor and interleukin 4 induce differentiation in the U-937 human monocytic leukemia cell line.

We studied the effect of TPA, G-CSF, GM-CSF, conditioned medium from 5637 cells (CM5637) and IL-4 on U-937 cell line proliferation and differentiation. Flow cytometry analysis showed that the expression of the CD14 cell surface antigen, initially detected in 90% of the cells, decreased when the cells were cultured with either G-CSF, GM-CSF, CM5637, or IL-4. The CD11c expression only decreased by exposure to GM-CSF and IL-4. The cells also showed a decrease in alpha-naphthylesterase (alpha-NAE) activity and an increase in peroxidase (Px) activity in the GM-CSF supplemented cultures. Remarkable changes in cell morphology were also observed. IL-4 induced morphologic features resembling histiocytic-like cells positive for the expression of alpha-NAE and negative for Px. GM-CSF induced cells with pseudopods, negative for alpha-NAE expression and positive for Px. TPA effect on U-937 cells was similar to that observed with GM-CSF. No proliferative response was detected with any of the factors assayed. These results suggest that GM-CSF and IL-4 can promote distinct changes in the differentiative pathway of U-937 cells, as evidenced by the marked morphological, immunological and cytochemical changes observed in the cell cultures.

Immunological characterization of blood group A epitopes expressed on cells and tissues with a monoclonal anti-CEA antibody.

BACKGROUND AND METHODS: Monoclonal antibodies (mAb) specific for the oligosaccharide epitopes of glycoproteins or glycolipids, such as blood group antigens, are powerful tools for studying the antigenic structure of normal and pathological cells and tissues. Anti-A human red blood cell monoclonal antibodies were produced by immunizing mice with normal cells, but only a few fulfilled the conditions necessary for revealing qualitative differences among A-antigens. Only those produced by hybridomas obtained from mice immunized with human tumor antigens specifically recognize A1 and A2 blood group antigens. We report here several immunological properties of the A-antigen defined by a mAb raised against the tumor-associated carcinoembryonic antigen. RESULTS AND CONCLUSIONS: The hybridoma B2C114, obtained as a result of the fusion of spleen cells from mice immunized with the carcinoembryonic antigen and a murine myeloma cell line, produces a mAb which reacts specifically against erythrocytes bearing the A blood-group antigen. The monoclonal antibody showed a high stability and a low dissociation rate from the antigen/antibody complex formed with adult A1, A2, A2B and cord blood samples. The antibody was able not only to discriminate between A1- and A2-RBC but also to detect kinetic differences among A-sites. On the one hand B2C114, reactive with the glycosidic moiety of the A-antigen, can discern at least two qualitatively different epitopes expressed on the A1-RBC surface, with a total number of A sites that is in close agreement with the figures already described for A1-RBC. On the other hand, A2-RBC shows a single phenotype that is kinetically similar to A1-low affinity binding sites. This antibody also labelled spontaneous and chemically-induced murine tumors as well as human tumors. Its reactivity with colon carcinoma frozen specimens obtained from O- and B-blood group patients indicated expression of an incompatible A-antigen. The immunochemical properties of B2C114 described here give support to our purpose of employing this mAb as a blood group reagent as well as a histopathological probe for in vitro and in vivo cancer diagnosis.

Specific biodetection of a murine spontaneous mammary carcinoma with labelled anti-human blood group-A monoclonal antibody.

The expression of cell surface antigens of the spontaneous transplantable M3-murine tumour was studied by means of the monoclonal antibody (MAb) B2C114 which recognizes the human blood group-A carbohydrate antigen. Following radioiodination the MAb retained their immunoreactivity and demonstrated a significantly higher in vitro binding with isolated M3-tumour cells as compared with a control antibody. B2C114 revealed 10(6) antigenic sites per cell, with a constant affinity of 5.1 x 10(9)/M. Biodistribution studies showed that B2C114 discriminated between malignant tumour and mouse normal tissues. Radioimmunodetection of Balb/c mice bearing s.c. M3-tumour showed that tumour was specifically defined without subtraction 1 day after injection of the radiolabelled antibody.

Diseño y evaluación de un modelo para la radioinmunolocalización e inmunoterapia del cáncer / Design and evolution of a model for the radioimmunotargetting and immunotherapy of cancer

El anticuerpo mionoclonal B2C114 producido contra el antígeno carcinoembrionario reconoce un carbohidrato del antígeno A de grupo sanguineo humano. La expresión de este determinante antigénico se investigó en estirpes celulares del adenocarcinoma mamario espontáneo M3 y su derivada experimental MM3 de mayor capacidad metastatizante. La reactividad específica in vitro de B2C114 marcado con I a la 125 permitió determinar el número de epitopes antigénicos por celula M3 y la constante de asociación. La biodistribución del anticuerpo monoclonal mostró que I a la 125-B2C114 discriminó, con alta sensibilidad, entre el tumor M3, la variante MM3 y tejidos normales, confirmado por la obtención de imágenes positivas de M3 en cámara gamma. Estos estudios han permitido la obtención de un modelo que facilita el desarrollo de diferentes tecnologías aplicadas al diagnóstico y a la terapéutica del cáncer (AU)

Diseño y evaluación de un modelo para la radioinmunolocalización e inmunoterapia del cáncer / Design and evolution of a model for the radioimmunotargetting and immunotherapy of cancer

El anticuerpo mionoclonal B2C114 producido contra el antígeno carcinoembrionario reconoce un carbohidrato del antígeno A de grupo sanguineo humano. La expresión de este determinante antigénico se investigó en estirpes celulares del adenocarcinoma mamario espontáneo M3 y su derivada experimental MM3 de mayor capacidad metastatizante. La reactividad específica in vitro de B2C114 marcado con I a la 125 permitió determinar el número de epitopes antigénicos por celula M3 y la constante de asociación. La biodistribución del anticuerpo monoclonal mostró que I a la 125-B2C114 discriminó, con alta sensibilidad, entre el tumor M3, la variante MM3 y tejidos normales, confirmado por la obtención de imágenes positivas de M3 en cámara gamma. Estos estudios han permitido la obtención de un modelo que facilita el desarrollo de diferentes tecnologías aplicadas al diagnóstico y a la terapéutica del cáncer

Rapid and correct diagnosis of myocardial infarction: standardized case history and clinical examination provide important information for correct referral to monitored beds.

The value of thorough examination of the case history as a diagnostic tool on hospitalization of patients with suspected myocardial infarction was investigated in three independent prospective studies. Use of a limited number of pain-related elements (= 'criteria'), that had already been obtained in the emergency room, could improve the decision on whether or not to admit patients to the coronary-care unit. As an example, in one of the studies, use of such criteria would have reduced the number of 'unnecessary' coronary-care-unit admissions from 298 to 162, a 46% reduction (P less than 0.001). In the same patient sample, use of the criteria could have reduced the number of patients with definite acute myocardial infarction, admitted to the general wards, from 47 to 22, a 53% reduction (P less than 0.01). These favourable results were confirmed in the two independent, smaller-scale studies.

Producción de un anticuerpo monoclonal para la detección de antígeno A del sistema ABO de grupos sanguíneos / Production of a monoclonal antibodies for the detection of antibody A of the ABO blood group system

Se demuestra en el presente trabajo la utilidad de anticuerpos monoclonales anti-grupo sanguíneo. A obtenidos a partir de un híbrido generado por fusión entre linfocitos de bazo de ratón inmunizado y células de mieloma. El clon productor del anticuerpo monoclonal, denominado B2/C114, fue propagado como tumor ascítico en ratones, lo que permitió su conservación y producción en gran escala. El reactivo obtenido es útil para la evaluación rutinaria de grupos sanguíneos, presentando gran avidez, estabilidad superior a 12 meses y alto título, condiciones que satisfacen ampliamente los requerimientos de seguridad diagnóstica y costo efectivo (AU)

Producción de un anticuerpo monoclonal para la detección de antígeno A del sistema ABO de grupos sanguíneos / Production of a monoclonal antibodies for the detection of antibody A of the ABO blood group system

Se demuestra en el presente trabajo la utilidad de anticuerpos monoclonales anti-grupo sanguíneo. A obtenidos a partir de un híbrido generado por fusión entre linfocitos de bazo de ratón inmunizado y células de mieloma. El clon productor del anticuerpo monoclonal, denominado B2/C114, fue propagado como tumor ascítico en ratones, lo que permitió su conservación y producción en gran escala. El reactivo obtenido es útil para la evaluación rutinaria de grupos sanguíneos, presentando gran avidez, estabilidad superior a 12 meses y alto título, condiciones que satisfacen ampliamente los requerimientos de seguridad diagnóstica y costo efectivo

An improved selection procedure for the rescue of hybridomas. A comparative study of methotrexate versus aminopterin.

Several of aminopterin's drawbacks such as photosensitivity and high toxicity prompted us to compare the ability of methotrexate to select for hybridomas. Assessing the effect of both drugs on X63/Ag 8.653 myeloma cells and hybrid cells secreting monoclonal antibodies by tritiated thymidine incorporation and percentage of viable cells, we have shown that methotrexate could be used in place of aminopterin for the rescue of hybrid cells in selective medium. In addition, methotrexate hybrids develop more rapidly and can therefore be processed earlier. The stability and low toxicity of methotrexate also favor its use in the selection of hybridomas.

Hybridoma cell lines secreting monoclonal antibodies against equine infectious anemia virus.

A monoclonal anti-equine infectious anemia virus (anti-EIAV) antibody (1B15) has been generated by fusion of X63 Ag 8.653 myeloma cells and spleen cells from mice hypersensitized with viral antigen p29. Ouchterlony double-diffusion analysis indicated that antibody 1B15 is of the IgG class. The specificity of the immune reaction for p29 was confirmed by cross-over immunoelectrophoresis and disc-gel electrophoresis. MAb 1B15 was used to devise a solid-phase 'capture' RIA for EIAV-p29 antigen. The antigen, bound by 1B15 adsorbed onto wells of flexible microtitre plates, was detected using a rabbit anti-p29 serum followed by a 125I-labelled tracer. The assay was applied to detected using a of virus in horse serum and infected cell culture fluids.

Hemodynamic effects at rest and during exercise in long-term treatment with prazosin in chronic congestive heart failure.

The long-term effects of prazosin in chronic congestive heart failure were studied in 10 patients (New York Heart Association class III-IV) in a double-blind cross-over study. Patients with systolic blood pressure greater than 120 mmHg and left ventricular filling pressure greater than 15 mmHg were included. Prazosin lowered the arteriovenous oxygen difference both at rest and during exercise (p less than 0.05), increased cardiac index (p less than 0.01) and reduced right atrial pressure and systemic vascular resistance (p less than 0.05) during exercise. Left ventricular filling pressure was also reduced, but not significantly, during exercise. Our data show that prazosin has beneficial long-term effects during exercise in patients with chronic congestive heart failure.