GH/IGF-1 Abnormalities and Muscle Impairment : from basic research to clinical practice

The impairment of skeletal muscle function is one of the most debilitating least understood co-morbidity that accompanies acromegaly (ACRO). Despite being one of the major determinants of these patients' poor quality of life, there is limited evidence related to the underlying mechanisms and treatment options. Although growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels are associated, albeit not indisputable, with the presence and severity of ACRO myopathies the precise effects attributed to increased GH or IGF-1 levels are still unclear. Yet, cell lines and animal models can help us bridge these gaps. This review aims to describe the evidence regarding the role of GH and IGF-1 in muscle anabolism, from the basic to the clinical setting with special emphasis on ACRO. We also pinpoint future perspectives and research lines that should be considered for improving our knowledge in the field

What else can we do to prevent diabetic retinopathy?

Diabetic retinopathy; Modifiable risk factors; Neurovascular unitRetinopatía diabética; Factores de riesgo modificables; Unidad neurovascularRetinopatia diabètica; Factors de risc modificables; Unitat neurovascularThe classical modifiable factors associated with the onset and progression of diabetic retinopathy are the suboptimal control of blood glucose levels and hypertension, as well as dyslipidaemia. However, there are other less recognised modifiable factors that can play a relevant role, such as the presence of obesity or the abnormal distribution of adipose tissue, and others related to lifestyle such as the type of diet, vitamin intake, exercise, smoking and sunlight exposure. In this article we revisit the prevention of diabetic retinopathy based on modulating the modifiable risk factors, as well as commenting on the potential impact of glucose-lowering drugs on the condition. The emerging concept that neurodegeneration is an early event in the development of diabetic retinopathy points to neuroprotection as a potential therapeutic strategy to prevent the advanced stages of the disease. In this regard, the better phenotyping of very early stages of diabetic retinopathy and the opportunity of arresting its progression using treatments targeting the neurovascular unit (NVU) are discussed.Open Access Funding provided by Universitat Autonoma de Barcelona

Inflammation: The Link between Neural and Vascular Impairment in the Diabetic Retina and Therapeutic Implications

Diabetic retinopathy; Inflammation; RetinaRetinopatia diabètica; Inflamació; RetinaRetinopatía diabética; Inflamación; RetinaThe etiology of diabetic retinopathy (DR) is complex, multifactorial and compromises all the elements of the retinal neurovascular unit (NVU). This diabetic complication has a chronic low-grade inflammatory component involving multiple inflammatory mediators and adhesion molecules. The diabetic milieu promotes reactive gliosis, pro-inflammatory cytokine production and leukocyte recruitment, which contribute to the disruption of the blood retinal barrier. The understanding and the continuous research of the mechanisms behind the strong inflammatory component of the disease allows the design of new therapeutic strategies to address this unmet medical need. In this context, the aim of this review article is to recapitulate the latest research on the role of inflammation in DR and to discuss the efficacy of currently administered anti-inflammatory treatments and those still under development.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects ICI20/00129 and PI22/01670 and co-funded by the European Union. Hugo Ramos is the recipient of a grant from the Ministerio de Economía y Competitividad (BES-2017-081690)

Pituitary Apoplexy: Risk Factors and Underlying Molecular Mechanisms

Apoplexy; Growth factors; Matrix metalloproteinaseApoplejía; Factores de crecimiento; Metaloproteinasa de la matrizApoplexia; Factors de creixement; Metaloproteinasa de la matriuPituitary apoplexy is a rare syndrome, graded from asymptomatic subclinical apoplexy to a life-threatening condition due to pituitary ischemia or haemorrhage of an enlarged pituitary gland. The risk factors and the molecular underlying mechanisms are yet to be elucidated. We provide an overview of the general concepts, the potential factors associated with pituitary adenoma susceptibility for apoplectic events and the molecular mechanisms that could be involved such as HIF-1α/VEGF pathways and metalloproteinases activation, among others. The knowledge of the molecular mechanisms that could participate in the pathogenesis of pituitary apoplexy is crucial to advancement in the identification of future diagnostic tools and therapeutic targets in this rare but sometimes fatal condition

Molecular Pathways in Prolactinomas: Translational and Therapeutic Implications

Dopamine; Lactotroph tumour; ProlactinomaDopamina; Tumor lactòtrof; ProlactinomaDopamina; Tumor lactotrofo; ProlactinomaProlactinoma has the highest incidence rate among patients with functional pituitary tumours. Although mostly benign, there is a subgroup that can be aggressive. Some clinical, radiological and pathology features have been associated with a poor prognostic. Therefore, it can be considered as a group of heterogeneous tumours. The aim of this paper is to give an overview of the molecular pathways involved in the behaviour of prolactinoma in order to improve our approach and gain deeper insight into the better understanding of tumour development and its management. This is essential for identifying patients harbouring aggressive prolactinoma and to establish personalised therapeutics options.This research received no external funding

New methods for the diagnosis and monitoring of cognitive function in patients with type 2 diabetes

Dementia; Retinal microperimetry; Type 2 diabetesDemencia; Microperimetría retiniana; Diabetes tipo 2Demència; Microperimetria retiniana; Diabetis tipus 2The presence of type 2 diabetes acts as an accelerator of cognitive impairment (mild cognitive impairment and later dementia), with a significant impact on the management of the disease and its complications. Therefore, it is recommended to perform an annual evaluation of cognitive function in patients with diabetes older than 65 years. Current guidelines still recommend the use of the Minimental State Evaluation Test (MMSE) as screening test, but it has a modest sensitivity and specificity for identifying mild cognitive impairment. This represents an important gap because patients with mild cognitive impairment are at risk of progressing to dementia. The neurocognitive diagnosis is based on complex neuropsychological tests, which require specifically trained personnel and are time consuming, making its routine incorporation into daily clinical practice unfeasible. Therefore, at present there are no reliable biomarkers to identify patients with type 2 diabetes at increased risk of developing cognitive impairment. Since the brain and the retina have a common embryological origin, our Research Group, has worked over the last 10 years evaluating the usefulness of the retina as a “window” to the brain. We provided evidence that retinal microperimetry is a simple, feasible and useful tool for screening and monitoring cognitive function in patients with type 2 diabetes. We propose a review of actual tests recommended for screening of cognitive impairment as well as an update of new emerging methods, such as retinal microperimetry

Iron Overload in Diabetic Retinopathy: A Cause or a Consequence of Impaired Mechanisms?

Iron is an essential ion for life, playing a central role in many metabolic processes. The most important property of free iron is its capacity to be reversibly oxidized and reduced, but at same time this make it highly pro-oxidant molecule. In this regard, iron is able to generate powerful reactive oxygen species (ROS). For this reason, careful control on iron availability is central to the maintenance of normal cell function in the retina. In the diabetic eye there is an impairment of iron homeostasis, thus leading to iron overload. The mechanisms involved in this process include: (1) Destruction of heme molecules induced by hyperglycemia (2) Intraretinal and vitreal hemorrhages (3) Overexpression of the renin-angiotensin system. The main consequences of iron overload are the following: (1) Retinal neurodegeneration due to the increase of oxidative stress (2) Increase of AGE-RAGE binding (3) Defective phagocytosis of retinal pigment epithelium, which generates the accumulation of autoantigens and the synthesis of proinflammatory cytokines. Further studies addressed to explore not only the role of iron in the pathogenesis of diabetic retinopathy, but also to design novel therapeutic strategies based on the regulation of iron homeostasis are needed

Pregnancy-Specific Stress during the First Lockdown of the COVID-19 Pandemic: Assessing Face-to-Face versus Online Recruitment

The study aims to assess pregnancy-specific stress among pregnant women in Spain during the first lockdown of the COVID-19 pandemic. Two samples of pregnant women from the south of Spain (Andalusia) were assessed using the Prenatal Distress Questionnaire (PDQ) and a sociodemographic and obstetric questionnaire. Group 1 (N = 155) was recruited face-to-face, whereas Group 2 (N = 78) was recruited online. Pregnancy-specific stress levels were significantly different in both groups. The face-to-face group (Group 1) had higher pregnancy-specific stress levels than the online group (Group 2). The online sample over-represents young adult pregnant women with high education levels and a high number of previous miscarriages. The face-to-face study seems more accessible to racially and ethnically diverse groups. The main concern among both groups was the risk of having a sick neonate. Research during the COVID-19 pandemic can benefit from using online resources to collect data to screen and identify perinatal mental health problems in a crisis environment. Nevertheless, researchers should be aware of the potential limitations this strategy can have, for example, certain groups of people may have limited access to the internet

Genetics in Diabetic Retinopathy : Current Concepts and New Insights

There is emerging evidence which indicates the essential role of genetic factors in the development of diabetic retinopathy (DR). In this regard it should be highlighted that genetic factors account for 25-50% of the risk of developing DR. Therefore, the use of genetic analysis to identify those diabetic patients most prone to developing DR might be useful in designing a more individualized treatment. In this regard, there are three main research strategies: candidate gene studies, linkage studies and Genome-Wide Association Studies (GWAS). In the candidate gene approach, several genes encoding proteins closely related to DR development have been analyzed. The linkage studies analyze shared alleles among family members with DR under the assumption that these predispose to a more aggressive development of DR. Finally, Genome-Wide Association Studies (GWAS) are a new tool involving a massive evaluation of single nucleotide polymorphisms (SNP) in large samples. In this review the available information using these three methodologies is critically analyzed. A genetic approach in order to identify new candidates in the pathogenesis of DR would permit us to design more targeted therapeutic strategies in order to decrease this devastating complication of diabetes. Basic researchers, ophthalmologists, diabetologists and geneticists should work together in order to gain new insights into this issue

Neurovascular Unit: A New Target for Treating Early Stages of Diabetic Retinopathy

Retinopatía diabética; Neurodegeneración; Unidad neurovascularRetinopatia diabètica; Neurodegeneració; Unitat neurovascularDiabetic retinopathy; Neurodegeneration; Neurovascular unitThe concept of diabetic retinopathy as a microvascular disease has evolved and is now considered a more complex diabetic complication in which neurovascular unit impairment plays an essential role and, therefore, can be considered as a main therapeutic target in the early stages of the disease. However, neurodegeneration is not always the apparent primary event in the natural story of diabetic retinopathy, and a phenotyping characterization is recommendable to identify those patients in whom neuroprotective treatment might be of benefit. In recent years, a myriad of treatments based on neuroprotection have been tested in experimental models, but more interestingly, there are drugs with a dual activity (neuroprotective and vasculotropic). In this review, the recent evidence concerning the therapeutic approaches targeting neurovascular unit impairment will be presented, along with a critical review of the scientific gaps and problems which remain to be overcome before our knowledge can be transferred to clinical practice.This research was funded by grants from the Instituto de Salud Carlos III (DTS18/0163, PI19/01215, and ICI20/00129). The funders had no role in the design of the study; in the collection, analyses, or the interpretation of the data; in the writing of the manuscript, or in the decision to publish the results