Pseudotumoral tracheobronchial amyloidosis mimicking asthma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tracheobronchial amyloidosis is an uncommon localized form of amyloidosis that can simulate a tracheal tumor. Clinical signs are not specific and the diagnosis is rarely given before performing a bronchoscopy with multiples biopsies.</p> <p>Case presentation</p> <p>We report the case of a 60-year-old Moroccan woman, complaining of dyspnea and wheezing for three years, who was treated at our institution for management of severe asthma. A bronchoscopy revealed a tumor formation of her trachea; multiples biopsies were performed and a diagnosis made of amyloid light-chain amyloidosis. She successfully received an endoscopic resection.</p> <p>Conclusion</p> <p>This case highlights the importance of routinely carrying out an endoscopy in any patient complaining of atypical bronchial symptoms or with uncontrolled asthma. Tracheal amyloidosis is a rare disease, confirmed by histological examination of bronchial biopsies, and the treatment of choice is based on the bronchoscopic resection.</p

Insulin-like signalling to the maternal germline controls progeny response to osmotic stress

In 1893 August Weismann proposed that information about the environment could not pass from somatic cells to germ cells, a hypothesis now known as the Weismann barrier. However, recent studies have indicated that parental exposure to environmental stress can modify progeny physiology and that parental stress can contribute to progeny disorders. The mechanisms regulating these phenomena are poorly understood. We report that the nematode Caenorhabditis elegans can protect itself from osmotic stress by entering a state of arrested development and can protect its progeny from osmotic stress by increasing the expression of the glycerol biosynthetic enzyme GPDH-2 in progeny. Both of these protective mechanisms are regulated by insulin-like signalling: insulin-like signalling to the intestine regulates developmental arrest, while insulin-like signalling to the maternal germline regulates glycerol metabolism in progeny. Thus, there is a heritable link between insulin-like signalling to the maternal germline and progeny metabolism and gene expression. We speculate that analogous modulation of insulin-like signalling to the germline is responsible for effects of the maternal environment on human diseases that involve insulin signalling, such as obesity and type-2 diabetes

Internet-based treatment for adults with depressive symptoms: the protocol of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Depression is a highly prevalent condition, affecting more than 15% of the adult population at least once in their lives. Guided self-help is effective in the treatment of depression. The purpose of this study is to investigate the effectiveness of two Internet-based guided self-help treatments with adults reporting elevated depressive symptoms. Other research questions concern the identification of potential mediators and the search for subgroups who respond differently to the interventions.</p> <p>Methods</p> <p>This study is a randomized controlled trial with three conditions: two treatment conditions and one waiting list control group. The two treatment conditions are Internet-based cognitive behavior therapy and Internet-based problem-solving therapy. They consist of 8 and 5 weekly lessons respectively. Both interventions are combined with support by e-mail. Participants in the waiting list control group receive the intervention three months later.</p> <p>The study population consists of adults from the general population. They are recruited through advertisements in local and national newspapers and through banners on the Internet. Subjects with symptoms of depression (≥ 16 on the Center for Epidemiological Studies Depression scale) are included. Other inclusion criteria are having sufficient knowledge of the Dutch language, access to the Internet and an e-mail address.</p> <p>Primary outcome is depressive symptoms. Secondary outcomes are anxiety, quality of life, dysfunctional cognitions, worrying, problem solving skills, mastery, absence at work and use of healthcare. We will examine the following variables as potential mediators: dysfunctional cognitions, problem solving skills, worrying, anxiety and mastery. Potential moderating variables are: socio-demographic characteristics and symptom severity. Data are collected at baseline and at 5 weeks, 8 weeks, 12 weeks and 9 months after baseline. Analyses will be conducted on the intention-to-treat sample.</p> <p>Discussion</p> <p>This study evaluates two Internet-based treatments for depression, namely cognitive behavioral therapy and problem-solving therapy. The effectiveness of Internet-based problem-solving therapy suggest that this may be a worthwhile alternative to other more intensive treatment options. Strengths and limitations of this study are discussed.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN16823487</p

Genetic insights into age-related macular degeneration: Controversies addressing risk, causality, and therapeutics

Age-related macular degeneration (AMD) is a common condition among the elderly population that leads to the progressive central vision loss and serious compromise of quality of life for its sufferers. It is also one of the few disorders for whom the investigation of its genetics has yielded rich insights into its diversity and causality and holds the promise of enabling clinicians to provide better risk assessments for individuals as well as to develop and selectively deploy new therapeutics to either prevent or slow the development of disease and lessen the threat of vision loss. The genetics of AMD began initially with the appreciation of familial aggregation and increase risk and expanded with the initial association of APOE variants with the disease. The first major breakthroughs came with family-based linkage studies of affected (and discordant) sibs, which identified a number of genetic loci and led to the targeted search of the 1q31 and 10q26 loci for associated variants. Three of the initial four reports for the CFH variant, Y402H, were based on regional candidate searches, as were the two initial reports of the ARMS2/HTRA1 locus variants. Case-control association studies initially also played a role in discovering the major genetic variants for AMD, and the success of those early studies have been used to fuel enthusiasm for the methodology for a number of diseases. Until 2010, all of the subsequent genetic variants associated with AMD came from candidate gene testing based on the complement factor pathway. In 2010, several large-scale genome-wide association studies (GWAS) identified genes that had not been previously identified. Much of this historical information is available in a number of recent reviews.(Chen et al., 2010b; Deangelis et al., 2011; Fafowora and Gorin, 2012b; Francis and Klein, 2011; Kokotas et al., 2011) Large meta analysis of AMD GWAS has added new loci and variants to this collection.(Chen et al., 2010a; Kopplin et al., 2010; Yu et al., 2011) This paper will focus on the ongoing controversies that are confronting AMD genetics at this time, rather than attempting to summarize this field, which has exploded in the past 5 years