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Insulin treatment in type 2 diabetes mellitus patients is still essential and its usage has increased during recent years. Despite this, the level of control continues to be very poor. Insulin treatment is initiated with control levels above the recommendations set by the Clinical Practice Guidelines (CPG) and patients are exposed to very high blood glucose levels during long periods of time. This paper reviews the role of insulin in the different CPG, the criteria for therapy initiation and intensification, the beginning of the intensification and the different types of insulin which are commercialized in our country. Moreover, we discuss insulinization in special situations such as corticosteroid treatment, fragile elderly patients, palliative care situations, chronic kidney disease or during Ramadan. Finally, the problem of therapeutic inertia in insulinization is also addressed.

El carcinoma epidermoide se encuentra entre las neoplasias más frecuentes, de manera que ocupa el lugar 12. Etiológicamente, se encuentra asociado con factores como el tabaquismo, consumo de alcohol, virus de inmunodeficiencia humana y sífilis. Además, el aporte de herramientas como la tomografía o resonancia magnética en el diagnóstico de enfermedades permite la detección de tumores malignos en etapas oportunas. En este trabajo, se presenta el diagnóstico y le evolución de un carcinoma epidermoide en un paciente de 47 años, con hábito de consumo de alcohol y tabaco. La resonancia magnética y la tomografía computarizada permitieron al médico emitir un diagnóstico de cáncer de lengua, cuya lesión ocupante, de dimensiones 86x71x48 mm, se extendió alrededor de un 20%. Palabras clave: carcinoma epidermoide, diagnóstico, tomografía, resonancia magnética.

Editorial on the Research Topic. Obesogenic Environmental Conditions Affect Neurodevelopment and Neurodegeneration

Producción Científica, Diabetic macular oedema (DMO) is one of the leading causes of vision loss associated with diabetic retinopathy (DR). New insights in managing this condition have changed the paradigm in its treatment, with intravitreal injections of antivascular endothelial growth factor (anti-VEGF) having become the standard therapy for DMO worldwide. However, there is no single standard therapy for all patients DMO refractory to anti-VEGF treatment; thus, further investigation is still needed. The key obstacles in developing suitable therapeutics for refractory DMO lie in its complex pathophysiology; therefore, there is an opportunity for further improvements in the progress and applications of new drugs. Previous studies have indicated that Rho-associated kinase (Rho-kinase/ROCK) is an essential molecule in the pathogenesis of DMO. This is why the Rho/ROCK signalling pathway has been proposed as a possible target for new treatments. The present review focuses on the recent progress on the possible role of ROCK and its therapeutic potential in DMO. A systematic literature search was performed, covering the years 1991 to 2021, using the following keywords: “rho-Associated Kinas-es”, “Diabetic Retinopathy”, “Macular Edema”, “Ripasudil”, “Fasudil” and “Netarsudil”. Better insight into the pathological role of Rho-kinase/ROCK may lead to the development of new strategies for refractory DMO treatment and prevention.

Background Reflex testing of antibodies and viral load in the same sample for diagnosing hepatitis C virus infection speeds up access to treatment. However, how hepatitis C is diagnosed in Spanish hospitals is unknown. Objective To describe the available resources and procedures for the diagnosis of hepatitis C virus infection in Spain. Methods Survey sent to public and private Spanish hospitals with teaching accreditation with at least 200 beds. Results Of the 160 hospitals that met the inclusion criteria, 90 centres (response rate 56.3%) completed the survey. Two hospitals (2.2%) have no diagnostic resources, 15 (16.7%) can only test for anti-hepatitis C virus(Ab), 9 (10.0%) for Ab and viral load, 47 (52.2%) for Ab, viral load and genotype, 2 (2.2%) for Ab, viral load and core antigen, and 15 (16.7%) can perform Ab, core antigen, viral load and genotype tests. When an Ab test is positive, 28 (31.1%) hospitals perform reflex testing. When an active infection is diagnosed, some communication strategy is used in 62 (68.9%) hospitals. Approximately 44.2% of the respondents believe that all determinations needed to reach a definitive diagnosis should be done on a single blood sample. Conclusion Although 81% of Spanish hospitals have the resources to perform reflex hepatitis C virus infection testing, it is only done in 31%, and less than a half of respondents believe that the definitive diagnosis should be performed on a single sample.

Producción Científica, Silicone oil (SO) still represents the main choice for long-term intraocular tamponade in complicated vitreoretinal surgery. This review compared the complications associated with the use of SO and other vitreous substitutes after pars plana vitrectomy in patients with different underlying diseases. Meta-analysis was conducted in accordance with PRISMA guidelines. We retrieved randomized clinical trials (RCTs), retrospective case–control and cohort studies evaluating the risk of using SO, published between 1994 and 2020, conducting a computer-based search of the following databases: PubMed, Web of Science, Scopus and Embase. Primary outcome was the rate of complications such as intraocular hypertension, retinal re-detachment, unexpected vision loss or hypotony. Secondary outcome was to compare the rate of adverse events of different SO viscosities, especially emulsification. Forty-three articles were included. There were significant differences in intraocular hypertension (p = 0.0002, OR = 1.66; 95% CI = 1.27–2.18) and the rate of retinal re-detachment (p

Background Chronic venous disease (CVD) patients can present with a spectrum of clinical manifestations ranging from severe ulcerations, thrombosis, and varicose vein hemorrhage to milder ones such as telangiectasias. Some CVD patients have a minimal degree of telangiectasias that are almost invisible to the physician. In spite of successful treatment of these telangiectasias, there are patients that might insist on continuing treatment, focusing excessive attention on what they perceive to be persistent telangiectasias that, in their opinion, must be removed. In these cases, one might be facing a possible body dysmorphic disorder (BDD) diagnosis. Methods This is a multicentric study performed in 223 patients with telangiectasias (C1s) seeking treatment; the Body Dysmorphic Disorder Questionnaire (BDDQ) was answered in private by all the patients. Furthermore, each questionnaire was evaluated in accordance with the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria for BDD. Results From a consecutive sample of 223 patients, 38 patients had criteria for BDD according to the DSM-V; indicating that the prevalence of BDD in patients with telangiectasias is 17%. Conclusions Telangiectasias can be a stress trigger that changes the way patients perceive their own appearance. BDD patients tend to focus their attention excessively upon these types of veins and demand unnecessary treatment for minimal telangiectasias in order to diminish their discomfort with their physical appearance. Body dysmorphic disorder occurs in patients with limbs with C1s disease in considerable proportion and, upon evaluation, these patients should be referred to a psychiatrist. The initiation of any treatment for telangiectasias prior to the psychiatric assessment should be avoided.

RATIONALE: Post-traumatic stress disorder (PTSD) is a devastating anxiety-related disorder which develops subsequent to a severe psychologically traumatic event. Only ~ 9% of people who experience such a trauma develop PTSD. It is clear that a number of factors, including genetics, influence whether an individual will develop PTSD subsequent to a trauma. The 129S1/SvImJ (S1) inbred mouse strain displays poor fear extinction and may be useful to model this specific aspect of PTSD. The metabotropic glutamate receptor 7 (mGlu(7) receptor) has previously been shown to be involved in cognitive processes and anxiety-like behaviour placing it in a key position to regulate fear extinction processes. We sought to compare mGlu(7) receptor mRNA levels in the S1 strain with those in the robustly extinguishing C57BL/6J (B6) inbred strain using in situ hybridisation (ISH) in three brain regions associated with fear extinction: the amygdala, hippocampus and prefrontal cortex (PFC). RESULTS: Compared to the B6 strain, S1 mice had increased mGlu(7) receptor mRNA levels in the lateral amygdala (LA) and basolateral amygdala (BLA) subdivisions. An increase was also seen in the hippocampal CA1 and CA3 subregions of S1 mice. No difference in mGlu(7) receptor levels were seen in the central nucleus (CeA) of the amygdala, dentate gyrus (DG) of the hippocampus or prefrontal cortex. CONCLUSIONS: These data show altered mGlu(7) receptor expression in key brain regions associated with fear extinction in two different inbred mouse strains which differ markedly in their fear extinction behaviour. Altered mGlu(7) receptor levels may contribute to the deficit fear extinction processes seen in fear extinction in the S1 strain.

Objective To assess the degree of compliance with the recommendations of the 2009 and 2015 versions of the Spanish guidelines for managing asthma (Guia Espanola para el Manejo del Asma [GEMA]) and the effect of this compliance on controlling the disease. Material and methods We conducted an observational ambispective study between September 2015 and April 2016 in which 314 primary care physicians and 2864 patients participated. Results Using retrospective data, we found that 81 of the 314 physicians (25.8%; 95% CI 21.3–30.9) stated that they complied with the GEMA2009 recommendations. At the start of the study, 88 of the 314 physicians (28.0%; 95% CI 23.4–33.2) complied with the GEMA2015 recommendations. Poorly controlled asthma (OR, 0.19; 95% CI 0.13–0.28) and persistent severe asthma at the start of the study (OR, 0.20; 95% CI 0.12–0.34) were negatively associated with having well-controlled asthma by the end of the follow-up. In contrast, compliance with the GEMA2015 recommendations was positively associated with a greater likelihood that the patient would have well-controlled asthma by the end of the follow-up (OR, 1.70; 95% CI 1.40–2.06). Conclusions Low compliance with the clinical guidelines for managing asthma is a common problem among primary care physicians. Compliance with these guidelines is associated with a better asthma control. Actions need to be taken to improve primary care physician compliance with the asthma management guidelines.

A growing number of investigations report the association between gut permeability and intestinal or extra-intestinal disorders under the basis that translocation of gut luminal contents could affect tissue function, either directly or indirectly. Still, in many cases it is unknown whether disruption of the gut barrier is a causative agent or a consequence of these conditions. Adequate experimental models are therefore required to further understand the pathophysiology of health disorders associated to gut barrier disruption and to develop and test pharmacological treatments. Here, we review the current animal models that display enhanced intestinal permeability, and discuss (1) their suitability to address mechanistic questions, such as the association between gut barrier alterations and disease and (2) their validity to test potential treatments for pathologies that are characterized by enhanced intestinal permeability.

The National AIDS Plan and the Spanish AIDS study group (GESIDA) proposes "preferred regimens" (PR) of antiretroviral treatment (ART) as initial therapy in HIV-infected patients. In 2013, the recommended regimens were all triple therapy regimens. The Gardel Study assessed the efficacy of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) plus lamivudine (3TC). Our objective is to evaluate the GESIDA PR and the DT regimen LPV/r+3TC cost/efficacy ratios.Decision tree models were built.probability of having viral load50 copies/mL at week 48. ART regime cost: costs of ART, adverse effects, and drug resistance tests during the first 48 weeks.Cost/efficacy ratios varied between 5,817 and 13,930 euros per responder at 48 weeks, for the DT of LPV/r+3TC and tenofovir DF/emtricitabine+raltegravir, respectively.Taking into account the official Spanish prices of ART, the most efficient regimen was DT of LPV/r+3TC, followed by the triple therapy with non-nucleoside containing regimens.

The intestinal barrier function depends on an adequate response to pathogens by the epithelium. Toll-like receptor 3 (TLR-3) recognizes double-stranded RNA, a virus-associated molecular pattern. Activation of TLR-3 with Poly(I:C), a synthetic agonist, modulates tissue repair and permeability in other epithelia; however, the effects of local luminal TLR-3 agonists on gut barrier function are unknown. The aim of this investigation was to evaluate short-term effects of Poly(I:C) on rat ileal and colonic permeability ex vivo. We also studied the acute effects of intrarectal administration of Poly(I:C) on colonic barrier function. Ileum tissues displayed decreased transepithelial electrical resistance (TEER) 1h after incubation with 200μg/mL Poly(I:C); however, the mucosa-to-serosa transit of macromolecules (4.4 and 40kDa dextrans - TD4.4 and FD40, respectively) remained unchanged. Conversely, colon tissue preparations stimulated with 200μg/mL Poly(I:C) showed a decreased thinning of the mucosal layer after 2h and a decreased transit of FD40 after 3h, in comparison to controls. There was no change in colonic TEER after 3h of treatment. In addition, colon tissue taken from rats 6h after an intrarectal administration of 100μg Poly(I:C) also showed decreased permeability to FD40 in the everted gut sac assay at 3h post-extraction. Tissue morphology remained unchanged. Our results suggest that an acute exposure to Poly(I:C) reduces colon permeability to macromolecules but increases ileum permeability to electrolytes/small molecules ex vivo. Although the mechanism associated to these effects needs further investigation, to our knowledge this is the first report of a direct effect of a TLR-3 ligand in intestinal barrier function and may be of significance to understand region-specific interactions between gut mucosa and microbiota.

© 2020 by the authors., Age-related macular degeneration (AMD) is a complex, multifactorial and progressive retinal disease affecting millions of people worldwide. In developed countries, it is the leading cause of vision loss and legal blindness among the elderly. Although the pathogenesis of AMD is still barely understood, recent studies have reported that disorders in the regulation of the extracellular matrix (ECM) play an important role in its etiopathogenesis. The dynamic metabolism of the ECM is closely regulated by matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). The present review focuses on the crucial processes that occur at the level of the Bruch's membrane, with special emphasis on MMPs, TIMPs, and the polymorphisms associated with increased susceptibility to AMD development. A systematic literature search was performed, covering the years 1990-2020, using the following keywords: AMD, extracellular matrix, Bruch's membrane, MMPs, TIMPs, and MMPs polymorphisms in AMD. In both early and advanced AMD, the pathological dynamic changes of ECM structural components are caused by the dysfunction of specific regulators and by the influence of other regulatory systems connected with both genetic and environmental factors. Better insight into the pathological role of MMP/TIMP complexes may lead to the development of new strategies for AMD treatment and prevention.

espanolAntecedentes: la implementacion de estrategias de diagnostico de la hepatitis C en un solo paso contribuiria a disminuir el tiempo de acceso al tratamiento, evitando el progreso de la enfermedad y sus complicaciones y facilitando la eliminacion de la enfermedad. Objetivo: evaluar la validez y la seguridad de las posibles estrategias del diagnostico de la infeccion por virus de la hepatitis C (VHC) en un solo paso, asi como sus costes y eficiencia. Metodos: estudio de evaluacion economica de la eficiencia (coste/eficacia) mediante la construccion de arboles de decision con analisis de sensibilidad determinista. La perspectiva del analisis es la del financiador (Sistema Nacional de Salud), que solo considera los costes directos. Se han considerado unicamente los costes diferenciales (costes de los test analiticos realizados). El ambito del estudio es Espana. Se define la eficacia de una estrategia diagnostica como el porcentaje de pacientes con infeccion activa por VHC con diagnostico positivo y la eficiencia, como el coste de diagnosticar correctamente un paciente con infeccion activa. Resultados: todas las estrategias para el diagnostico de VHC en un solo paso evaluadas presentan validez y seguridad aceptables como consecuencia de la elevada sensibilidad y especificidad que tienen los test utilizados. La estrategia mas eficiente es Ac-Ag, seguida de Ac-Ag-CV y Ac-CV. La estrategia mas eficiente es Ac-Ag debido a su menor coste por paciente testado, pero es menos eficaz que Ac-CV. Conclusion: los hallazgos de este estudio pueden contribuir a establecer las estrategias de diagnostico mas adecuadas en un solo paso teniendo en cuenta su eficacia y eficiencia. EnglishBackground: implementing one-step strategies for hepatitis C diagnosis would help shorten the time to treatment access. Thus avoiding disease progression and complications, while facilitating hepatitis C virus (HCV) elimination. Objective: to assess the validity and certainty of potential one-step strategies for the diagnosis of HCV infection and their associated cost and efficiency. Methods: the study design is an economic appraisal of efficiency (cost/efficacy) using decision trees and deterministic sensitivity analysis. The analysis was performed from the payer perspective (Spanish National Health System), which exclusively considers the direct costs. Only the differential costs (diagnostic testing costs) were taken into account and the study was set in Spain. The efficacy of a diagnostic strategy was defined as the percentage of patients with an active HCV infection who received a positive diagnosis and the efficiency was defined as the cost per patient with a correctly diagnosed and active infection. Results: the one-step strategies evaluated for the diagnosis of HCV had an acceptable validity and certainty due to the high sensitivity and specificity of the considered tests. The Ab-Ag strategy was the most efficient, followed by Ab-Ag-VL and Ab-VL. Ab-Ag was the most efficient due to the lower cost per patient tested, although the efficacy was lower than the Ab-VL efficacy. Conclusion: the study findings may help to establish more appropriate one-step diagnostic approaches whilst considering the efficacy and efficiency.

To evaluate the degree of glycemic control and its relationship with disease characteristics and antidiabetic treatment in patients with type 2 diabetes mellitus (DM), as well as the frequency of A1c use.For this purpose, an observational, cross-sectorial, and multicenter study was performed. A total of 443 patients were monitored in 17 Spanish primary healthcare centers. Demographic and clinical variables were recorded from the clinical history of patients.Mean age was 68.9±12.0 years. Time of evolution of DM was 9.2±6.4 years. Mean A1c was 7.38±1.34% and 45% of patients achieved A1c7%. There was a no significant relationship between the degree of control and time of evolution of DM. In 16% of patients no A1c determination was performed in the previous twelve months. In those patients in whom A1c was determined, 95% received pharmacologic treatment, and 31% insulin therapy. 66% of patients on monotherapy attained A1C7%, compared with 39% and 23% of those receiving double- and triple-oral therapy, respectively (p0.001). Only 21% of patients on insulin therapy achieved A1c7%. The worst-controlled patients were those receiving oral antidiabetic agents and insulin (24% had A1c levels ≥9%).A large proportion of patients are poorly controlled. Poor control increases according to complexity of treatment. A1c is underdetermined in many patients, likely related to clinical inertia.

People with type 2 diabetes mellitus have a 2 to 4 times higher risk of developing cardiovascular diseases when compared to general population of similar age and sex. This risk remains after adjustment of other traditional cardiovascular risk factors. The dyslipidemia associated with type 2 diabetes mellitus is present in up to 60% of people with diabetes and contributes greatly to increased cardiovascular, morbidity and mortality risk in these patients. Diabetic dyslipidemia is a disorder of lipid metabolism characterized by an excess of triglycerides, a decrease in HDL-cholesterol and altered lipoprotein composition, consisting mainly in an excess of small, dense LDL particles. Multiple clinical trials have demonstrated the benefits of drug treatment of dyslipidemia (mainly statins) to prevent cardiovascular events and mortality in people with diabetes, both in primary and secondary prevention. This consensus document, developed by general practitioners, members of the Diabetes Group of the Spanish Society of Primary Care Physicians (SEMERGEN), aims to assist in the management of patients with diabetes and dyslipidemia in accordance with the most recent recommendations.

The objective of this study is to investigate two internal fixation surgical techniques for mandibular fractures in order to compare modified lag screw techniques with standard miniplates. This is an observational prospective study. Three hundred eighteen patients were operated on for mandibular fractures. The patients were divided into two groups according to the type of surgical technique used: modified lag screws (155 patients) and traditional miniplates (163 patients). Analyses were made of sociodemographic and preoperative variables, the parameters related to the fracture type and postoperative data. There were no differences between the two groups regarding their sociodemographic characteristics. The modified lag screws were primarily used with double fractures, while conventional miniplates were more often used with simple fractures. The number of complications was higher with the miniplate technique. The unfavorable fractures had an OR of 5.75 due to postoperative complications; double fractures had an OR of 8.87 and simple fractures an OR of 19.53, which, in both cases, were lower with conventional miniplates than with modified lag screws. Modified lag screws provide a rigid fixation system that is as secure as miniplates, but with greater compression between the fragments, less postsurgical gap, faster ossification, and fewer postoperative complications. The modified screw technique is a safe tool that does not require any specific osteosynthesis materials not found in a basic traumatology kit and has a lower cost, due to the reduced amount of material used.

Objective: To describe the prevalence of known and ignored type 2 diabetes mellitus (T2DM) among primary care physicians (PCP), as well as the treatment used and the degree of metabolic control reached. Material and methods: Descriptive cross-sectional study on national level. The participants were randomly selected PCPs, members of the redGDPS Foundation. A total of 495 PCP were enrolled. Capillary HbA(1c) measurement was done with a A1CNow+(R) device and a diabetes-related survey specifically designed for the study was administered to the participants. Results: The total prevalence of T2DM was 11.1% (95% CI 8.33-13.9) (known disease 8.1% and ignored disease 3.0%). The prevalence of prediabetes was 16.2% (95% CI 13.0-19.4). A total of 62.5% of PCPs with known T2DM reached HbA(1c) < 7% and 15% had HbA(1c) > 8.5%. Control of blood pressure (BP < 140/90 mmHg) was reached in 87.5% and control of LDL cholesterol < 130 mg/dl with no history of cardiovascular disease was reached in 88.6% of cases of known T2DM. In the PCPs with a history of macrovascular disease, good control of LDL was reached in 42.9% of the cases. A total of 12.5% were active smokers. A total of 71.4% of PCPs with known T2DM self-treated their own disease, usually with 2 or more drugs (51.4%). The most commonly used drug was metformin (74.3%) followed by iDPP4 (48.6%). Conclusions: PCPs with T2DM have better metabolic control than the general population. It is necessary to study whether PCPs with T2DM may have greater adherence to treatment and do they achieve a better metabolic control. (C) 2017 SEEN. Published by Elsevier Espana, S.L.U. All rights reserved.

SummaryBackground Central nervous system (CNS) development and physiopathology are greatly affected by environmental stimuli. The intestinal barrier restricts the entrance of toxins, pathogens, and antigens while modulating the expression of various neuroactive compounds. The existence of a rich gut-to-brain communication raises the possibility that intestinal barrier alterations may take part in the pathophysiology of CNS disorders. Aim To review evidence associating intestinal barrier dysfunction with the development of CNS disorders. Methods Literature search was conducted on PubMed using the following terms: intestinal barrier, intestinal permeability, central nervous system, mental disorders, schizophrenia, autism, stress, anxiety, depression, and neurodegeneration. Results Clinical and animal model studies of the association between intestinal barrier and schizophrenia, autism spectrum disorders, neurodegenerative diseases or depression were reviewed. The majority of reports concentrated on schizophrenia and autism spectrum disorders. About half of these described increased intestinal permeability/mucosal damage in patients compared with healthy controls, with up to 43% of children with autism spectrum disorders and up to 35% of schizophrenia patients displaying abnormally high urinary excretion of the sugars used as permeability markers. However, another substantial group of studies did not find such differences. In autism spectrum disorders, some reports show that the use of diets such as the gluten-free casein-free diet may contribute to the normalisation of lactulose/mannitol ratio, but to date there is no adequately controlled study showing improvement in behavioural symptoms following these dietary interventions. Conclusions Evidence of altered intestinal permeability in individuals suffering from CNS disorders is limited and cannot be regarded as proven. Moreover the efficacy of targeting gut barrier in the management of neurological and behavioural aspects of CNS disorders has not yet been established, and needs further investigation.

In the last few years, the publication of new studies in diabetes, together with the development of new classes of blood glucose-lowering medications, have led to updates of the most prestigious clinical practice guidelines for the treatment of diabetes. Thus, a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes was published in April 2012. An update of one of the evidence-based guidelines issued by the Canadian Diabetes Association appeared in 2013 and this year, 2014, saw the publication of the consensus document of the redGDPS, whose guidelines are those most closely followed by primary care physicians in Spain. The three guidelines highlight the need for an individualized approach to type 2 diabetes mellitus, outlining both target glycemic goals and distinct treatment regimens based on patient characteristics, disease stage and the presence of comorbidities or complications. In the treatment of the disease, the three guidelines also stress the importance of considering patients' opinions and of recommending lifestyle modifications to achieve good disease control. Metformin is identified as the first-line drug, with the addition of other glucose-lowering agents if necessary.

In the past few years, intestinal microbiota has emerged as a novel target for the treatment of gut-brain axis alterations. These include functional gastrointestinal disorders, such as irritable bowel syndrome (IBS), which can be comorbid with stress-related psychiatric conditions. Thus, modulation of the microbiota (e.g. with the use of probiotics) could be proposed as a novel strategy not only for the treatment of IBS but also as an adjuvant for psychiatric treatment of anxiety and depression.

The gut and the brain communicate bidirectionally through anatomic and humoral pathways, establishing what is known as the gut–brain axis. Therefore, interventions affecting one system will impact on the other, giving the opportunity to investigate and develop future therapeutic strategies that target both systems. Alterations in the gut–brain axis may arise as a consequence of changes in microbiota composition (dysbiosis), modifications in intestinal barrier function, impairment of enteric nervous system, unbalanced local immune response and exaggerated responses to stress, to mention a few. In this review we analyze and discuss several novel pharmacological targets within the gut–brain axis, with potential applications to improve intestinal and mental health.

Objectives To estimate the prevalence of known and undiagnosed depression in patients with type 2 diabetes attended in primary care setting in Spain, and to determine the factors associated with the presence of depression. Methods This was a cross-sectional and multicenter study performed in a random sample of patients with type 2 diabetes attended in 21 primary care centers. Depressive symptoms were measured with the self-administered Patient Health Questionnaire (PHQ-9). Results A total of 411 patients were analyzed (mean age 70.8 (SD 10.3) years; 53.8% women). 29.2% of patients met the diagnostic criteria of depression, of whom 17% had known depression and 12.2% undiagnosed depression (PHQ-9 score ≥10, without a previous diagnosis of depression). Depression was more common in women (43.4%; 95% confidence interval [CI] 34.5–52.3%), widow (33.3%; 95% CI 27.9–38.7%), and hypothyroidism (12.5%; 95% CI 8.7–16.3%). Cardiovascular risk factors, the degree of control, complications related to diabetes, antidiabetic therapy and the number of drugs were not associated with the presence of depression. Conclusions The prevalence of depression was high in patients with type 2 diabetes. However, in approximately 40% of patients depression was undiagnosed. The complications related to diabetes and antidiabetic therapy were not associated with the presence of depression.

Schizophrenia is one of the most disabling psychiatric conditions. Current treatments target monoamine receptors but this approach does not address the full complexity of the disorder. Here we explore the possibility of developing new anti-psychotics by targeting microRNAs (miRNAs), single stranded RNA molecules, 21-23 nucleotides in length that are not translated into proteins and regulate gene expression. The present review reveals that research involving schizophrenia and miRNA is very recent (the earliest report from 2007) and miRNAs add a significant layer of complexity to the pathophysiology of the disorder. However, miRNAs offer an exciting potential not only to understand the underlying mechanisms of schizophrenia, but also for the future development of antipsychotics, as the human miRNA system provides a rich and diverse opportunity for pharmacological targeting. However, technology is still developing in order to produce effective strategies to modulate specific and localized changes in miRNA, particularly in relation to the central nervous system and schizophrenia.

Liraglutide is the first once-daily human glucagon-like peptide-1 analog available for use in clinical practice. It has recently been approved by the EMA and the US FDA for treatment of Type 2 diabetes mellitus (T2DM). Initial approval is for use in combination with either metformin or a sulfonylurea, or in combination with metformin plus a sulfonylurea or thiazolidinedione. Liraglutide monotherapy is approved in the USA. Results from the Liraglutide Effect and Action in Diabetes (LEAD) clinical trials program indicate that liraglutide significantly lowers glycosylated hemoglobin (HbA1c) with a low risk of hypoglycemia. Liraglutide is also associated with significant and sustained weight loss, decreased systolic blood pressure, and improvements in other markers of cardiovascular risk. Liraglutide also shows strong potential to preserve β-cell function. Maximum benefits may be achieved when liraglutide treatment is initiated early on in the course of T2DM. Sin financiación 0.213 SJR (2010) Q3, 114/183 Endocrinology, diabetes and metabolism UEM

Early-life experience plays a major role in the stress response throughout life. Neonatal maternal separation (MS) is an animal model of depression with an altered serotonergic response. We hypothesize that this alteration may be caused by differences in 5-HT1A receptor and serotonin transporter (SERT) mRNA expression in brain areas involved in the control of emotions, memory and fear as well as in regions controlling the central serotonergic tone.To test this, Sprague-Dawley rats were subjected to MS for 3h daily during post-natal days 2-12. As control, age matched rats were not separated (NS) from their dams. When animals reached adulthood (11-13 weeks) brain was extracted and mRNA expression of 5-HT1A receptor in amygdala, hippocampus and dorsal raphé nucleus (DRN) and SERT in the DRN was analyzed through in-situ hybridisation.Densitometric analysis revealed that MS increased 5-HT1A receptor mRNA expression in the amygdala, and reduced its expression in the DRN, but no changes were observed in the hippocampus in comparison to NS controls. Also, MS reduced SERT mRNA expression in the DRN when compared to NS rats.These results suggest that early-life stress induces persistent changes in 5-HT1A receptor and SERT mRNA expression in key brain regions involved in the development of stress-related psychiatric disorders. The reduction in SERT mRNA indicates an alteration that is in line with clinical findings such as polymorphic variants in individuals with higher risk of depression. These data may help to understand how early-life stress contributes to the development of mood disorders in adulthood.

Mood disorders and chronic stress are frequently associated with gastrointestinal (GI) symptoms including diarrhoea or constipation. Locally produced serotonin [5-hydroxytryptamine (5-HT)] regulates GI motility and is a key factor in the pathophysiology of stress-associated GI disorders. We aimed to establish whether chronic stress can differentially affect faecal output and colon 5-HT concentration in two inbred mouse strains: BALB/c and C57BL/6 which differ in their ability to cope with stress. Adult male BALB/c and C57BL/6 mice were restrained for 2 h daily for 10 days. Defecation was monitored during each stress session. Twenty-four hours after the last session of stress, plasma corticosterone concentration was higher than control in both strains, indicative of a physiological effect of chronic stress; however, stress-induced diarrhoea was more persistent in C57BL/6 mice. Basal concentration of colon 5-HT was higher in C57BL/6 mice, and stress elicited an increase in colon 5-HT only in this strain. Finally, naïve BALB/c mice had a higher sensitivity (incidence of diarrhoea) to 5-HT (0.33 mg/kg, i.p.) than C57BL/6 mice. Our results suggest that differential defecation responses to stress may be associated with colon 5-HT concentration, which may in turn reflect the individual sensitivity to 5-HT. In addition, C57BL/6 mice emerge as a relevant model for studying GI alterations induced by chronic stress.