Let's focus more on regional diversity of acromegaly.
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ABSTRACT:
SUBMITTER: Stormann S
PROVIDER: S-EPMC9469124 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Publications
Let's focus more on regional diversity of acromegaly.
Annals of translational medicine 20220801 16
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Project description:BackgroundIn acromegaly, expert surgery is curative in only about 60% of patients. Postoperative radiation therapy is associated with a high incidence of hypopituitarism and its effect on growth hormone (GH) production is slow, so that adjuvant medical treatment becomes of importance in the management of many patients.ObjectiveTo delineate the role of lanreotide in the treatment of acromegaly.MethodsSearch of Medline, Embase, and Web of Science databases for clinical studies of lanreotide in acromegaly.ResultsTreatment with lanreotide slow release and lanreotide Autogel((R)) normalized GH and insulin-like growth factor-I (IGF-I) concentrations in about 50% of patients. The efficacy of 120 mg lanreotide Autogel((R)) on GH and IGF-I levels was comparable with that of 20 mg octreotide LAR. There were no differences in improvement of cardiac function, decrease in pancreatic beta-cell function, or occurrence of side effects, including cholelithiasis, between octreotide LAR and lanreotide Autogel(R). When postoperative treatment with somatostatin analogs does not result in normalization of serum IGF-I and GH levels after noncurative surgery, pegvisomant alone or in combination with somatostatin analogs can control these levels in a substantial number of patients.
| S-EPMC2721386 | biostudies-literature
Project description:Acromegaly is a complex disease with excessive growth hormone and insulin-like growth factor 1 (IGF-1) causing multisystem effects, particularly cardiovascular, respiratory, and metabolic. Psychological concerns and poor quality of life (QoL) are also major disease consequences. This review is intended for clinicians and focuses on the latest developments related to respiratory and QoL effects of long-term growth hormone excess. Along with biochemical disease control, patient treatment satisfaction and outcomes have become major treatment objectives; current knowledge and tools to evaluate and manage this aspect of the disease are described. Sleep apnea syndrome and other derangements of lung function and apparatus, from pathophysiology to treatment, and evaluation tools and determinants of QoL in patients with acromegaly are discussed.
| S-EPMC7391012 | biostudies-literature
Project description:ObjectiveTo report the final long-term safety and efficacy analyses of patients with acromegaly treated with pegvisomant from the ACROSTUDY.DesignGlobal (15 countries), multicentre, non-interventional study (2004-2017).MethodsThe complete ACROSTUDY cohort comprised patients with acromegaly, who were being treated with pegvisomant (PEGV) prior to the study or at enrolment. The main endpoints were long-term safety (comorbidities, adverse events (AEs), pituitary tumour volumes, liver tests) and efficacy (IGF1 changes).ResultsPatients (n = 2221) were treated with PEGV for a median of 9.3 years (range, 0-20.8 years) and followed up for a median of 7.4 years (range, 0-13.9 years). Before PEGV, 96.3% had received other acromegaly treatments (surgery/radiotherapy/medications). Before PEGV treatment, 87.2% of patients reported comorbidities. During ACROSTUDY, 5567 AEs were reported in 56.5% of patients and of these 613 were considered treatment-related (in 16.5% of patients) and led to drug withdrawal in 1.3%. Pituitary imaging showed a tumour size increase in 7.1% of patients; the majority (71.1%) reported no changes. Abnormal AST or ALT liver tests occurred in 3.2% of patients. IGF1 normalization rate improved over time, increasing from 11.4% at PEGV start to 53.7% at year 1, and reaching 75.4% at year 10 with the use of ≥30 mg PEGV/day in an increasing proportion of patients.ConclusionThis comprehensive review of the complete cohort in ACROSTUDY confirmed the overall favourable benefit-to-risk profile and high efficacy of PEGV as mono- and combination therapy in patients with an aggressive course/uncontrolled/active acromegaly requiring long-term medical therapy for control.
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Project description:IntroductionRacial bias in health care is well documented. Research shows the presence of racial bias among health care providers. There is a paucity of workshops focused on racial bias effects in health professions educators.MethodTwo to three workshops were delivered to a diverse group of clinical educators from three programs at a major academic institution. Each workshop included a brief multimedia presentation followed by a facilitated group discussion. Participants completed the online Implicit Association Test (IAT), a baseline demographic questionnaire, and a brief post-then-pre questionnaire.ResultsTwenty-four faculty participated in the study (six physicians, eight nurse practitioners, 10 physician assistants). Nineteen (90%) were women, 18 (86%) were White, nine (43%) had more than 10 years of experience as educators, and seven (35%) had previously participated in a biases program. Seventeen completed the IAT. Sixteen educators agreed or strongly agreed that bias has a significant impact on patients' outcomes at the end of the workshop compared to 17 before the workshop. Seventeen educators agreed or strongly agreed that recognizing their own racial bias would positively alter their teaching practice after the workshop compared to 15 before the workshop.DiscussionThis series of workshops was created to fill a gap regarding the impact of racial bias on patient outcomes, health disparities, and health professions education. The impact of racial bias in health professions education and the long-term impact of awareness and knowledge of racial bias in education are areas needing further evaluation.
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Project description:Despite the study of subterranean biodiversity facing harsh sampling and mapping challenges, the huge diversity of taxa, ecological adaptations and evolutionary trajectories in subterranean environments is gaining increasing attention. Yet, the spatial and environmental factors driving the composition of groundwater communities are still poorly understood. To partially fill this knowledge gap, we collected copepod crustaceans from 12 caves along the Italian peninsula between 2019 and 2022, sampling each cave twice. The resulting presence-absence data were analysed to assess: (i) between-cave taxonomic beta diversity, also partitioning between turnover and nestedness-resultant dissimilarity; (ii) the relative weight of geographic distance and climatic differences in shaping observed beta diversity. Seventy-one species of copepods were collected overall. Pairwise beta diversity was high for most pairs of caves, with turnover being the major component. Geographic distance-decay models partially explained total beta diversity and turnover patterns. However, in Generalized Dissimilarity Models (GDM), including surface climatic conditions as predictors, the contribution of seasonal temperature averages was generally higher than that of geographic distance. Further, the explanatory and predictive performance of the GDMs notably increased, along with temperature contribution, when widening the spatial extent from which climate data were gathered. Our results confirmed a high spatial turnover in groundwater copepods' assemblages and strengthened the link between regional climate and subterranean biodiversity.
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Project description:Parkinson's disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminergic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the disease progression. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk. In this review we assess current clinical trials targeting two enzymes, leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), which are encoded by two most common PD risk genes. Because the details of the pathogenic processes coupled to the different LRRK2 and GBA risk variants are not fully understood, we ask if these precision medicine-based intervention strategies will prove "precise" or "personalized" enough to modify the disease process in PD patients. We also consider at what phases of the disease that such strategies might be effective, in light of the genes being primarily associated with the risk of developing disease in the first place, and less clearly linked to the rate of disease progression. Finally, we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients, beyond those that actually carry risk variants of these genes.
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Project description:The mechanisms of B-cell diversification differ greatly between aves and mammals, but both produce B cells and antibodies capable of supporting an effective immune response. To see how differences in the generation of diversity might affect overall repertoire diversity, we have compared the diversity characteristics of immunoglobulin genes from domestic chickens to those from humans. Both use V(D)J gene rearrangement and somatic hypermutation, but only chickens use somatic gene conversion. A range of diversity analysis tools were used to investigate multiple aspects of amino acid diversity at both the germline and repertoire levels. The effect of differing amino acid usages on antibody characteristics was assessed. At both the germline and repertoire levels, chickens exhibited lower amino acid diversity in comparison to the human immunoglobulin genes, especially outside of the complementarity-determining region (CDR). Chickens were also found to possess much larger and more hydrophilic CDR3s with a higher predicted protein binding potential, suggesting that the antigen-binding site in chicken antibodies is more flexible and more polyreactive than that seen in human antibodies.
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Project description:The transition to agriculture is regarded as a major turning point in human history. In the present contribution we propose to look at it through the lens of ethnographic data by means of a machine learning approach. More specifically, we analyse both the subsistence economies and the socioecological context of 1290 societies documented in the Ethnographic Atlas with a threefold purpose: (i) to better understand the variability and success of human economic choices; (ii) to assess the role of environmental settings in the configuration of the different subsistence economies; and (iii) to examine the relevance of fishing in the development of viable alternatives to cultivation. All data were extracted from the publicly available cross-cultural database D-PLACE. Our results suggest that not all subsistence combinations are viable, existing just a subset of successful economic choices that appear recurrently in specific ecological systems. The subsistence economies identified are classified as either primary or mixed economies in accordance with an information-entropy-based quantitative criterion that determines their degree of diversification. Remarkably, according to our results, mixed economies are not a marginal choice, as they constitute 25% of the cases in our data sample. In addition, fishing seems to be a key element in the configuration of mixed economies, as it is present across all of them.
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Project description:Our understanding of broad-scale biodiversity and functional trait patterns is largely based on plants, and relatively little information is available on soil arthropods. Here, we investigated the distribution of termite diversity globally and morphological traits and diversity across China. Our analyses showed increasing termite species richness with decreasing latitude at both the globally, and within-China. In addition, we detected obvious latitudinal trends in the mean community value of termite morphological traits on average, with body size and leg length decreasing with increasing latitude. Furthermore, temperature, NDVI and water variables were the most important drivers controlling the variation in termite richness, and temperature and soil properties were key drivers of the geographic distribution of termite morphological traits. Our global termite richness map is one of the first high resolution maps for any arthropod group and especially given the functional importance of termites, our work provides a useful baseline for further ecological analysis.
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Project description:The classical myeloproliferative neoplasms (MPNs) are a group of clonal diseases comprising essential thrombocythaemia (ET), polycythaemia vera (PV) and primary myelofibrosis (PMF). PMF is the rarest disease sub type and has been challenging to address due to the lack of a specific genetic marker, inadequate risk identification models and a highly variable clinical course. Continuous efforts have over time, seen the inclusion of cytogenetic information in prognostic scoring models that have resulted in improved risk stratification models providing further rationale for therapeutic management. Technological advances using single nucleotide polymorphism arrays increased the detection of known and novel MPN related changes and variant detection by massively parallel sequencing provided a large scale screening tool for the multitude of somatic gene mutations that have more recently been described in MPN. Some of these mutations show an association with specific cytogenetic changes or phenotypes. While PMF occurs mainly in adults, it has also been described in paediatric cases and shows distinct histopathological, genetic and clinical features in comparison. This review provides an overview of the genomics landscape of PMF and current developments in MPN therapy.
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