Dear Colleagues! We are glad to present the8th Editionof Standards of Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation. The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), American Diabetes Association (ADA, 2012, 2017), American Association of Clinical Endocrinologists (AACE, 2017), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014) and Russian Association of Endocrinologists (RAE, 2011, 2012, 2015). Current edition of the Standards also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EMPA-REG OUTCOME, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals. Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 415 million patients by the end of 2015. According to the current estimation by the International Diabetes Federation, 642 million patients will be suffering from DM by 2040. These observations resulted in the UN Resolution on Diabetes 61/225 passed on 20.12.2006, and in 2011 - UN Political Declaration, addressed to national health systems, calling for the establishment of multidisciplinary strategy in the prevention and control of non-communicable diseases, where special attention is drawn to the problem of diabetes as one of the leading causes of disability and mortality. Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4.35 million patients with DM in this country by the end of 2016 (3% of population) with 92% (4 million) Type 2 DM, 6% (255 th) Type 1 DM and 2% (75 th) other types of DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that only 50% of Type 2 DM are diagnosed. So real prevalence of patients with DM in Russia is no less than 8-9 million patients (about 6% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they dont receive any treatment ant have high risk of vascular complications. Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral, coronary and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death. Current edition of the Standards emphasizes the patient-oriented approach in making decisions on therapeutic goals, such as levels of glycaemia and blood pressure. It also features updated guidelines on the management of Type 2 DM and its vascular complications, added information about bariatric surgery as a method of treatment of DM with morbide obesity. This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discussions held at national meetings and forums. These guidelines are intended for endocrinologists and diabetologists, primary care physicians, cardiologists and other medical professionals involved in prevention and treatment of DM. On behalf of the Working Group
Detection of specific female pheromones stimulates courtship behavior in Drosophila melanogaster males, but the chemosensory molecules, cells and mechanisms involved remain poorly understood. Here we show that ppk25, a DEG/ENaC ion channel subunit required for normal male response to females, is expressed at highest levels in a single sexually dimorphic gustatory neuron of most taste hairs on legs and wings, but not in neurons that detect courtship-inhibiting pheromones or food. Synaptic inactivation of ppk25-expressing neurons, or knockdown of ppk25 expression in all gustatory neurons significantly impairs male response to females, whereas gustatory expression of ppk25 rescues the courtship behavior of ppk25 mutant males. Remarkably, the only other detectable albeit significantly weaker expression of ppk25 occurs in olfactory neurons implicated in modulation of courtship behavior. However, expression of ppk25 in olfactory neurons is not required for male courtship under our experimental conditions. These data show that ppk25 functions specifically in peripheral taste neurons involved in activation of courtship behavior, an unexpected function for this type of channel. Furthermore, our work identifies a small subset of gustatory neurons with an essential role in activation of male courtship behavior, most likely in response to female pheromones.
Dear Colleagues! We are glad to present the 9th Edition (revised) of Standards of Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation. The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), American Diabetes Association (ADA, 2018, 2019), American Association of Clinical Endocrinologists (AACE, 2019), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014, 2018) and Russian Association of Endocrinologists (RAE, 2011, 2012, 2015). Current edition of the Standards also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals. Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 463 million patients by the end of 2019. According to the current estimation by the International Diabetes Federation, 578 million patients will be suffering from diabetes mellitus by by 2030 and 700 million by 2045. Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 584 575 patients with DM in this country by the end of 2018 (3,1% of population) with 92% (4 238 503) Type 2 DM, 6% (256 202) Type 1 DM and 2% (89 870) other types of DM, including 8 006 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) con- firmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 9 million patients (about 6% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they dont receive any treatment ant have high risk of vascular complications. Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral, coronary and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death. In сurrent edition of the Standards: New goals of glycemic control for the elderly, based on the presence of functional dependence, as well as for pregnant women, children and adolescents, are given. Added a snippet that describes the continuous glucose monitoring. Only low-density lipoprotein cholesterol level is used as a target for lipid metabolism. Proposes more stringent target levels of blood pressure. It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes: the excess of the initial level of HbA1c over the target level was used as a criterion. In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages. Recommendations for psychosocial support are added. The position of metabolic surgery as a method of treatment of DM with morbid obesity is updated. Recommendations for diagnostic and treatment of hypogonadism syndrome in men with DM are added. For the first time, evidence levels of confidence and credibility levels of recommendations for diagnostic, therapeutic, rehabilitative and preventive interventions based on a systematic review of the literature are given in accordance with the recommendations of the Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation. This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discus- sions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians and other medical professionals involved in the treatment of DM. On behalf of the Working Group
Odorants and pheromones as well as sweet-and bitter-tasting small molecules are perceived through activation of G proteincoupled chemosensory receptors. In contrast, gustatory detection of salty and sour tastes may involve direct gating of sodium channels of the DEG͞ENaC family by sodium and hydrogen ions, respectively. We have found that ppk25, a Drosophila melanogaster gene encoding a DEG͞ENaC channel subunit, is expressed at highest levels in the male appendages responsible for gustatory and olfactory detection of female pheromones: the legs, wings, and antennae. Mutations in the ppk25 gene reduce or even abolish male courtship response to females in the dark, conditions under which detection of female pheromones is an essential courtshipactivating sensory input. In contrast, the same mutations have no effect on other behaviors tested. Importantly, ppk25 mutant males that show no response to females in the dark execute all of the normal steps of courtship behavior in the presence of visible light, suggesting that ppk25 is required for activation of courtship behavior by chemosensory perception of female pheromones. Finally, a ppk25 mutant allele predicted to encode a truncated protein has dominant-negative properties, suggesting that the normal Ppk25 protein acts as part of a multiprotein complex. Together, these results indicate that ppk25 is necessary for response to female pheromones by D. melanogaster males, and suggest that members of the DEG͞ENaC family of genes play a wider role in chemical senses than previously suspected.courtship ͉ behavior ͉ olfaction ͉ taste A s in most other animals, pheromones play key roles in the regulation of sexual behaviors of Drosophila melanogaster (1-3). In particular, several pheromones modulate male courtship of the female, which involves a stereotyped series of behaviors. By analogy with olfactory and gustatory perception of organic molecules in both insects and vertebrates (4), perception of these pheromones most likely involves interactions with seven-transmembrane receptors and subsequent activation of a G protein-coupled signal transduction pathway. Indeed, a male-specific member of the seven-transmembrane gustatory receptor family has been identified as a putative receptor for female courtship-stimulating pheromones (5). In contrast, gustatory perception of hydrogen and sodium ions, perceived as sour and salty tastes, respectively, has been suggested to involve direct gating of sodium channels of the DEG͞ENaC family (6, 7). In support of this possibility, inactivation of ppk11 or ppk19, two Drosophila DEG͞ENaC subunit genes, results in loss of behavioral and electrophysiological responses to salt (8). Here we report the unexpected finding that another Drosophila DEG͞ENaC subunit gene, ppk25, is specifically required for male response to courtshipactivating female pheromones. This observation suggests that members of this protein family play more diverse roles in chemical senses than previously suspected. Experimental ProceduresMutant and Transgenic Flies. Deletio...
In insects, increasing evidence suggests that small secreted pheromone binding proteins (PBPs) and odorant binding proteins (OBPs) are important for normal olfactory detection of airborne pheromones and odorants far from their source. In contrast, it is unknown whether extracellular ligand binding proteins participate in perception of less volatile chemicals, including many pheromones, that are detected by direct contact with chemosensory organs. CheB42a, a small Drosophila melanogaster protein unrelated to known PBPs or OBPs, is expressed and likely secreted in only a small subset of gustatory sensilla on males' front legs, the site of gustatory perception of contact pheromones. Here we show that CheB42a is expressed specifically in the sheath cells surrounding the taste neurons expressing Gr68a, a putative gustatory pheromone receptor for female cuticular hydrocarbons that stimulate male courtship. Surprisingly, however, CheB42a mutant males attempt to copulate with females earlier and more frequently than control males. Furthermore, CheB42a mutant males also attempt to copulate more frequently with other males that secrete female-specific cuticular hydrocarbon pheromones, but not with females lacking cuticular hydrocarbons. Together, these data indicate that CheB42a is required for a normal gustatory response to female cuticular hydrocarbon pheromones that modulate male courtship.
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