Biochemical and histological effects of the subchronic treatment with a beer containing Baccharis dracunculifolia in an experimental model of diabetes.

This article reports the development of a beer made with Baccharis dracunculifolia and its application in an experimental model of diabetes. Initially, the production of the beverage was standardized in order to incorporate the plant extract properly. Next, the beer was analyzed by the UHPLC-MS to identify the substances present.

Strengths use and emotional disorder symptom reduction during a transdiagnostic cognitive behavioral therapy: A random-intercept cross-lagged panel model study.

Strengths use, the engagement of positive character traits in everyday contexts, is associated with both positive functioning and symptom reduction. The present study examined longitudinal relationships between strengths use and emotional disorder symptoms (anxiety, stress, and depression) during a randomized clinical trial of the Digital Unified Protocol, a transdiagnostic cognitive behavioral therapy. Participants (N = 120) completed assessments at four major time points during treatment and at 3-month follow-up.

The use of recovery animals in nonclinical safety assessment studies with monoclonal antibodies: further 3Rs opportunities remain.

Assessment of reversibility from nonclinical toxicity findings in animals with potential adverse clinical impact is required during pharmaceutical development, but there is flexibility around how and when this is performed and if recovery animals are necessary. For monoclonal antibodies (mAbs) and in accordance with ICH S6(R1) if inclusion of recovery animals is warranted, this need only occur in one study. Data on study designs for first-in-human (FIH)-enabling and later-development toxicity studies were shared from a recent collaboration between the NC3Rs, EPAA, Netherlands Medicines Evaluation Board (MEB) and 14 pharmaceutical companies.

Re-evaluating the need for chronic toxicity studies with therapeutic monoclonal antibodies, using a weight of evidence approach.

To support registration of monoclonal antibodies (mAbs) for chronic indications, 6-month toxicity studies have historically been conducted. Experience with mAb development has shown a relatively benign and well-understood safety profile for this class, with most toxicity findings anticipated based on pharmacology. We evaluated whether a 6-month toxicity study is necessary to assess the long-term safety of mAbs.

Challenges of non-clinical safety testing for biologics: A Report of the 9th BioSafe European Annual General Membership Meeting.

New challenges and other topics in non-clinical safety testing of biotherapeutics were presented and discussed at the nineth European BioSafe Annual General Membership meeting in November 2019. The session topics were selected by European BioSafe organization committee members based on recent company achievements, agency interactions and new data obtained in the non-clinical safety testing of biotherapeutics, for which data sharing would be of interest and considered as valuable information. The presented session topics ranged from strategies of testing, immunogenicity prediction, bioimaging, and developmental and reproductive toxicology (DART) assessments to first-in-human (FIH) dose prediction and bioanalytical challenges, reflecting the entire space of different areas of expertise and different molecular modalities.

Magnetic Resonance Imaging in Patients With Hearing Implants - Follow-up on Prevalence and Complications.

Objective: To examine the number of magnetic resonance imaging (MRI) examinations performed in patients with hearing implants and to quantify side effects or complications related to this procedure.

Study Design: Questionnaire.

Setting: Tertiary referral center, academic hospital.

Nonclinical Development of Biologics: Integrating Safety, Pharmacokinetics, and Pharmacodynamics to Create Smarter and More Flexible Nonclinical Safety Programs Optimizing Animal Use.

Safety assessment of biological drugs has its challenges due to the multiple new different modalities, for example, antibody-drug conjugates, bispecifics, nanobodies, fusion proteins and advanced therapy medicinal products (ATMPs), their different pharmacokinetic and pharmacodynamic properties, and their ability to trigger immunogenicity and toxicity. In the public and in the pharmaceutical industry, there is a strong and general desire to reduce the number of animals used in research and development of drugs and in particular reducing the use of nonhuman primates. Important discussions and activities are ongoing investigating the smarter designs of early research and dose range finding studies, reuse of animals, and replacing animal experiments with in vitro studies.

Nonclinical Safety Assessment of an Inhaled Formulation of Serelaxin: A Recombinant Human Protein in Rats and Cynomolgus Monkeys ().

Serelaxin is a recombinant human relaxin-2 intended for cardiovascular indications. Inhalation was chosen as alternative route to intravenous to allow daily administration for chronic applications and home treatment. A total of 4 short-term studies were conducted in rats and cynomolgus monkeys with inhaled formulation of serelaxin at dose up to 10 mg/kg/d.

Baseline staging imaging for distant metastasis in women with stages I, II, and III breast cancer.

Background: In Ontario, there is no clearly defined standard of care for staging for distant metastasis in women with newly diagnosed and biopsy-confirmed breast cancer whose clinical presentation is suggestive of early-stage disease. This guideline addresses baseline imaging investigations for women with newly diagnosed primary breast cancer who are otherwise asymptomatic for distant metastasis.

Methods: The medline and embase databases were systematically searched for evidence from January 2000 to April 2019, and the best available evidence was used to draft recommendations relevant to the use of baseline imaging investigation in women with newly diagnosed primary breast cancer who are otherwise asymptomatic.

A Missense Mutation in RAB28 in a Family with Cone-Rod Dystrophy and Postaxial Polydactyly Prevents Localization of RAB28 to the Primary Cilium.

Purpose: Cone-rod dystrophy (CRD) is a rare hereditary eye disorder that causes progressive degeneration of cone and rod photoreceptors. More than 30 genes, including RAB28, have been associated with CRD; however, only a few RAB28 variants have been reported to be associated with CRD. In this study, we describe two brothers with CRD and a homozygous missense variant, c.

"Simulect" as a model compound for assessing placental transfer of monoclonal antibodies in minipigs.

The aim of this study was to directly test and measure in vivo, if placental transfer of monoclonal antibodies takes place in pregnant Göttingen Minipigs to assess their suitability for reproductive assessment of therapeutic monoclonal antibodies. Simulect®, an approved anti CD25 (anti IL-2 receptor alpha) chimeric monoclonal IgG1 antibody, was used as a model monoclonal antibody. Maternal systemic exposure and potential placental transfer of Simulect® to fetuses were investigated following 4 weekly bolus intravenous administration of 5.

Comparison of wait times across the breast cancer treatment pathway among screened women undergoing organized breast assessment versus usual care.

Objective: The benefit of organized breast assessment on wait times to treatment among asymptomatic women is unknown. The Ontario Breast Screening Program (OBSP) offers screening and organized assessment through Breast Assessment Centres (BAC). This study compares wait times across the treatment pathway among screened women diagnosed with breast cancer through BAC and usual care (UC).

The impact of organized breast assessment on survival by stage for screened women diagnosed with invasive breast cancer.

Purpose: Since 1998, the Ontario Breast Screening Program (OBSP) has offered organized assessment through Breast Assessment Centres (BAC). This study compares survival between screened women diagnosed with breast cancer who have undergone assessment through a BAC and usual care (UC).

Methods: A retrospective design identified two concurrent cohorts of women aged 50 to 69 within the OBSP diagnosed with screen-detected invasive breast cancer at a BAC (n = 2010) and UC (n = 1844) between 2002 and 2010 and followed until 2016.

Validity of Administrative Databases in Comparison to Medical Charts for Breast Cancer Treatment Data.

Objective: Medical chart abstraction is the gold standard for collecting breast cancer treatment data for monitoring and research. A less costly alternative is the use of administrative databases. This study will evaluate administrative data in comparison to medical charts for breast cancer treatment information.

Biotherapeutics in non-clinical development: Strengthening the interface between safety, pharmacokinetics-pharmacodynamics and manufacturing.

Biological drugs comprise a wide field of different modalities with respect to structure, pharmacokinetics and pharmacological function. Considerable non-clinical experience in the development of proteins (e.g.

Lessons learned implementing a province-wide smoking cessation initiative in Ontario's cancer centres.

Purpose: A large body of evidence clearly shows that cancer patients experience significant health benefits with smoking cessation. Cancer Care Ontario, the provincial agency responsible for the quality of cancer services in Ontario, has undertaken a province-wide smoking cessation initiative. The strategies used, the results achieved, and the lessons learned are the subject of the present article.

Evaluation of Sensitivity and Specificity Performance of Elecsys HTLV-I/II Assay in a Multicenter Study in Europe and Japan.

Screening of blood for human T-cell lymphotropic virus type 1 and type 2 (HTLV-1 and -2, respectively) is important to diagnose and prevent infection and ensure the safety of blood supplies. The Elecsys HTLV-I/II assay is a newly developed, electrochemiluminescence screening assay for the detection of HTLV-1/2 infection. The sensitivity and specificity of the Elecsys HTLV-I/II assay were determined using well-characterized HTLV-1/2-positive serum and plasma samples and routine diagnostic and blood donor samples expected to be HTLV negative, respectively.

Safety and General Considerations for the Use of Antibodies in Infectious Diseases.

Monocolonal antibodies are valuable potential new tools for meeting unmet needs in treating infectious dieseases and to provide alternatives and supplements to antibiotics in these times of growing resistance. Especially when considering the ability to screen for antibodies reacting to very diverse target antigens and the ability to design and engineer them to work specifically to hit and overcome their strategies, like toxins and their hiding in specific cells to evade the immuneresponse and their special features enabling killing of the infectious agents and or the cells harbouring them. Antibodies are generally very safe and adverse effects of treatments with therapeutic antibodies are usually related to exaggeration of the intended pharmacology.

Colorectal Cancer Screening in Average Risk Populations: Evidence Summary.

Introduction. The objectives of this systematic review were to evaluate the evidence for different CRC screening tests and to determine the most appropriate ages of initiation and cessation for CRC screening and the most appropriate screening intervals for selected CRC screening tests in people at average risk for CRC. Methods.

Assessment of the risk of pressure ulcer development among hospitalized HIV/Aids patients.

Objective: to assess the risk of pressure ulcer development among hospitalized HIV/Aids. Metod: study quantitative descriptive with 35 patients admitted to an infectious diseases hospital in Curitiba-PR-BR. Characterized clinical and epidemiological of patients using a data collection instrument and the Braden Scale.

FcRn Expression on Placenta and Fetal Jejunum during Early, Mid-, and Late Gestation in Minipigs.

Developmental toxicity testing of therapeutic antibodies is most often conducted in nonhuman primates owing to lack of cross-reactivity in other species. Minipigs may show cross-reactivity for some humanized antibodies but have not been used for developmental toxicity testing due to an assumed lack of embryo-fetal exposure. Unlike in humans, maternal IgGs do not cross the porcine placenta to reach the fetus.

Age, Sex, and Ethnic Variations in Inner and Outer Retinal and Choroidal Thickness on Spectral-Domain Optical Coherence Tomography.

Purpose: To evaluate age, sex, and ethnic variations in inner and outer retinal and choroidal thickness and foveal pit, using spectral-domain optical coherence tomography (SD OCT).

Design: Single-center observational cross-sectional study.

Methods: Ninety randomly selected, healthy individuals of white, black, and South Asian origin underwent SD OCT raster and enhanced depth imaging scan.

History and Practice: Antibodies in Infectious Diseases.

Antibodies and passive antibody therapy in the treatment of infectious diseases is the story of a treatment concept which dates back more than 120 years, to the 1890s, when the use of serum from immunized animals provided the first effective treatment options against infections with Clostridium tetani and Corynebacterium diphtheriae. However, after the discovery of penicillin by Fleming in 1928, and the subsequent introduction of the much cheaper and safer antibiotics in the 1930s, serum therapy was largely abandoned. However, the broad and general use of antibiotics in human and veterinary medicine has resulted in the development of multi-resistant strains of bacteria with limited to no response to existing treatments and the need for alternative treatment options.