Managing arthralgia in a postmenopausal woman taking an aromatase inhibitor for hormonesensitive early breast cancer: a case study

Jane Bryce1, Martina Bauer2, Peyman Hadji21National Cancer Institute, Naples, Italy; 2Philipps University of Marburg, Marburg, GermanyBackground: In order to reduce the risk of recurrence, adjuvant treatment with an aromatase inhibitor (AI) is recommended for postmenopausal women following surgery for hormone receptor-positive breast cancer. AIs are associated with improved disease-free survival compared with tamoxifen. The adverse events associated with AIs resemble those of menopause, such as bone density loss and musculoskeletal symptoms.Purpose: We examine the case of a postmenopausal woman who was prescribed anastrozole, a nonsteroidal AI, as adjuvant therapy following surgery for estrogen and progesterone receptor-positive (ER and PgR+) breast cancer.Methods and sample: A 58-year-old postmenopausal woman diagnosed with ER and PgR+ breast cancer was prescribed anastrozole as adjuvant therapy following a right-inferior quadrantectomy. After experiencing joint pain and stiffness, she was prescribed paracetamol and a topical nonsteroidal anti-inflammatory drug. She was also counseled on nonpharmacological interventions. However, she continued to experience symptoms, and reported that she was not taking anastrozole regularly.Results: The case study patient ultimately found relief by switching to letrozole, another aromatase inhibitor. This approach is supported by recent studies examining the benefits of switching strategies between aromatase inhibitors in order to relieve symptoms of arthralgia/myalgia.Conclusions: Both adherence and strategies for managing aromatase inhibitor-associated arthralgia are key to deriving maximal clinical benefit from AI therapy. Switching from one aromatase inhibitor to another may provide a viable option in managing adverse events and enhancing adherence to medication.Keywords: adherence, anastrozole, aromatase inhibitor, arthralgia, breast cancer, letrozol

Pollen allergens do not come alone: pollen associated lipid mediators (PALMS) shift the human immue systems towards a TH2-dominated response

Pollen allergy is characterized by a TH2-biased immune response to pollen-derived allergens. However, pollen-exposed epithelia do not encounter pure allergen but rather a plethora of protein and non-protein substances. We demonstrated that pollen liberate lipids with chemical and functional similarities to leukotriens and prostaglandins - the pollen associated lipid mediators (PALMs). To date, two main groups of PALMs have been characterized: The immunostimulatory PALMs activating innate immune cells such as neutrophils and eosinophils, and the immunomodulatory E1-phytoprostanes blocking IL-12 production of dendritic cells, resulting in the preferential induction of TH2 responses. This article reviews our work in the field of PALMs and their effects on cells of the innate and adoptive immune system. From recent results a general picture starts to emerge in which PALMs (and possibly other pollen-associated substances) may - independently from protein allergens - propagate an overall TH2 favoring micromilieu in pollen exposed tissue of predisposed individuals

Wie beeinflussen Umwelterfahrungen unser Genom? Regulation auf molekularer Ebene durch epigenetische Prozesse

Differenzierte Zelllinien, Organismen in verschiedenen Metamorphose-Stadien, Bienenköniginnen und -Arbeiterinnen – bei all diesen Beispielen ist die Basenabfolge der DNA jeweils (größtenteils) identisch, die Phänotypen zeigen jedoch extreme Abweichungen untereinander. Im letzten Beispiel ist der Effekt sogar von Umwelteinflüssen induziert. Versucht man diese Phänomene zu erklären, stößt man schnell an die Grenzen klassischer molekulargenetischer Konzepte. Denn die Organisation des Genoms, die Regulation der Transkription, die variable Anpassung auf Umweltreize bis hin zur Vererbung solcher Anpassungen werden epigenetisch vermittelt. Aufgrund der rasanten Entwicklung dieses Forschungsgebiets ist es meist schwer die Übersicht über “die Epigenetik” zu wahren. Dieser Beitrag stellt die wichtigsten fachlichen Grundlagen der molekularen Mechanismen zusammen, skizziert einen Unterrichtsvorschlag im Flipped-Classroom-Format und stellt eine Vielzahl von Arbeitsmaterial zur Verfügung

Fangschreckenkrebse – Superlative in der Tierwelt: Präparation eines Gliederfüßers zur Erarbeitung von Struktur-Funktionszusammenhängen

Superlative begeistern Kinder und Jugendliche. Fangschreckenkrebse (Stomatopoden) zeigen einige Merkmale, die man als „Superlative“ bezeichnen könnte. Zunächst fallen dabei die Fangmechanismen der Stomatopoden auf. Man unterscheidet gemein gebräuchlich sogenannte “Speerer” und “Boxer”. Die “Speerer” erreichen mit ihrem großen Raubbein eine Geschwindigkeit von über 100 km/h beim Beutefang, eine der schnellsten muskelvermittelten Bewegungen in der Tierwelt. Die “Boxer“ erzeugen eine Krafteinwirkung ähnlich einem Wolfsbiss oder einer Kleinkaliberkugel mit darauffolgender Druckwelle zum Zertrümmern der Schalen von Beutetieren. Außerdem ist der Besitz eines der besonderen optischen Apparate mit den meisten Fotorezeptortypen im gesamten Tierreich beeindruckend (Cronin et al. 2017).  Doch nicht nur diese Superlative machen die Fangschreckenkrebse für den Unterricht interessant. Fangschreckenkrebse sind leicht und kostengünstig zu besorgen und  mit einer Verkaufsgröße von bis zu ca. 25 cm sind die Extremitäten gut und anschaulich zu präparieren.  Die Extremitäten weisen eine morphologische Vielfalt auf, die als Angepasstheiten an die unterschiedlichen Funktionen zu verstehen sind.   So lassen sich die vielfältigen Variationen einer grundlegenden Körperorganisation am Original zeigen

Novel associations in disorders of sex development: findings from the I-DSD registry

Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases.<p></p> Objective: To report the range of associated conditions identified in the international DSD (I-DSD) Registry.<p></p> Design, Setting, and Patients: Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician.<p></p> Results: Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations.<p></p> Conclusions: Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.<p></p&gt

Plasmodium malariae in Haitian Refugees, Jamaica

Since 1963, reported malaria transmission in Haiti has been restricted to Plasmodium falciparum. However, screening of Haitian refugees in Jamaica in 2004, by microscopic examination, identified P. falciparum, P. vivax, and P. malariae. PCR confirmed the P. malariae and P. falciparum but not P. vivax infections. DNA sequencing and rRNA gene sequences showed transmission of P. malariae. This report confirms that P. malariae is still being transmitted in Haiti

Novel associations in disorders of sex development: findings from the I-DSD registry

Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases.<p></p> Objective: To report the range of associated conditions identified in the international DSD (I-DSD) Registry.<p></p> Design, Setting, and Patients: Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician.<p></p> Results: Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations.<p></p> Conclusions: Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.<p></p&gt

A glossary for biometeorology

Here we present, for the first time, a glossary of biometeorological terms. The glossary aims to address the need for a reliable source of biometeorological definitions, thereby facilitating communication and mutual understanding in this rapidly expanding field. A total of 171 terms are defined, with reference to 234 citations. It is anticipated that the glossary will be revisited in coming years, updating terms and adding new terms, as appropriate. The glossary is intended to provide a useful resource to the biometeorology community, and to this end, readers are encouraged to contact the lead author to suggest additional terms for inclusion in later versions of the glossary as a result of new and emerging developments in the field

TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A

Variants of UNC13A, a critical gene for synapse function, increase the risk of amyotrophic lateral sclerosis and frontotemporal dementia1-3, two related neurodegenerative diseases defined by mislocalization of the RNA-binding protein TDP-434,5. Here we show that TDP-43 depletion induces robust inclusion of a cryptic exon in UNC13A, resulting in nonsense-mediated decay and loss of UNC13A protein. Two common intronic UNC13A polymorphisms strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia risk overlap with TDP-43 binding sites. These polymorphisms potentiate cryptic exon inclusion, both in cultured cells and in brains and spinal cords from patients with these conditions. Our findings, which demonstrate a genetic link between loss of nuclear TDP-43 function and disease, reveal the mechanism by which UNC13A variants exacerbate the effects of decreased TDP-43 function. They further provide a promising therapeutic target for TDP-43 proteinopathies