Inositols: From established knowledge to novel approaches

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects

When one size does not fit all: Reconsidering PCOS etiology, diagnosis, clinical subgroups, and subgroup-specific treatments

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects a large proportion of women. Due to its heterogeneity, the best diagnostic strategy has been a matter of contention. Since 1990 scientific societies in the field of human reproduction have tried to define the pivotal criteria for the diagnosis of PCOS. The consensus Rotterdam diagnostic criteria included the presence of hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology (PCOM), and have now been updated to evidence based diagnostic criteria in the 2018 and 2023 International Guideline diagnostic criteria endorsed by 39 societies internationally. Within the Rotterdam Criteria, at least two out of three of the above-mentioned features are required to be present to diagnose PCOS, resulting in four phenotypes being identified: phenotype A, characterized by the presence of all the features, phenotype B, exhibiting hyperandrogenism and oligo-anovulation, phenotype C, presenting as hyperandrogenism and PCOM and finally the phenotype D that is characterized by oligo-anovulation and PCOM, lacking the hyperandrogenic component. However, it is the hypothesis of the EGOI group that the Rotterdam phenotypes A, B, and C have a different underlying causality to phenotype D. Recent studies have highlighted the strong correlation between insulin resistance and hyperandrogenism, and the pivotal role of these factors in driving ovarian alterations, such as oligo-anovulation and follicular functional cyst formation. This new understanding of PCOS pathogenesis has led the authors to hypothesis that phenotypes A, B, and C are endocrine-metabolic syndromes with a metabolic clinical onset. Conversely, the absence of hyperandrogenism and metabolic disturbances in phenotype D suggests a different origin of this condition, and point towards novel pathophysiological mechanisms; however, these are still not fully understood. Further questions have been raised regarding the suitability of the “phenotypes” described by the Rotterdam Criteria by the publication by recent GWAS studies, which demonstrated that these phenotypes should be considered clinical subtypes as they are not reflected in the genetic picture. Hence, by capturing the heterogeneity of this complex disorder, current diagnostic criteria may benefit from a reassessment and the evaluation of additional parameters such as insulin resistance and endometrial thickness, with the purpose of not only improving their diagnostic accuracy but also of assigning an appropriate and personalized treatment. In this framework, the present overview aims to analyze the diagnostic criteria currently recognized by the scientific community and assess the suitability of their application in clinical practice in light of the newly emerging evidence

Some Aspects of Conflicts’ Regulation of Contractual Commitments in the International Private Law of Georgia

Legal regulations, adjusting contractual commitments, play a significant role in the International Private Law (further IPL). They regulate quite a broad sphere of civil and legal relations, complicated by a foreign element (factor). To take into consideration the significance of present international legal acts, regulating various spheres of external economic relations, it should be noted, that a certain number of issues remain out of the field of International contracts regulation. So they have to be adjusted by the rules of the domestic law, which are established by means of conflict norm. The problem of the selection the law, applicable for this or another private legal relation, complicated by the foreign element, is the fundamental problem for the International Private Law. This issue is particularly vital for countries, which, having gained their independence at the end of the past century and have entered into International relations, while in process of their own legal system build up.The article represents the analysis of the mechanism of the private law regulations of contractual commitments in the national legislation of Georgia

COVID-19 Pregnancy and Psycho-neurological Disturbance: Single Hospital Case Report

31 years old pregnant woman at 38 1/7 week of gestation with fever has been admitted to the TSMU   First University Clinic Emergency, with positive COVID-19 PCR test. With characteristic complains of COVID-19 infection.  Family history not significant. Personal history reveals childhood seizure as a result of fever. Vital signs at the admission within normal ranges. All protocol based laboratory tests has been done and protocol based treatment initiated. On the seventh day of Covid-19 infection because of episodes of desaturation and termed gestation, pregnancy termination by induction has been done successfully. At the end of early puerperal period because of hypoxemia resistant to oxygen therapy and CT scan diagnosed severe viral induced pneumonia, with symptoms of encephalopathy has been documented.  Later patient transferred to the mechanical ventilation, protocol based lab tests, diagnostic procedures and treatment initiated. After 1 month with improved condition patient has been transferred to the ob/gyn department for ongoing treatment and rehabilitation at this time severely expressed symptoms of encephalopathy were documented.The underlying mechanisms of neurologic complications in patients with COVID-19 are diverse and, in some cases, multifactorial. Neurologic complications may arise from direct effects of the virus as well as systemic response to the infection or as a result of long lasting inadequate oxygenation of all tissues. Although mechanical ventilation is highly complicated by brain damage, covid-19 induced encephalopathies are as well documented and need more scientifically proved facts of the viral role in this complication

Inositols: From Established Knowledge to Novel Approaches

International audienceMyo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects

Экологические проблемы мобильной связи в Грузии

თანამედროვე მეცნიერებისათვის ჯერ კიდევ ბოლომდე გაურკვეველია რეალური საფრთხე ელექტრომაგნიტური გამოსხივების ცოცხალ ორგანიზმებზე ზემოქმედებისა. თემა განსაკუთრებით აქტუალური ხდება მობილური ტელეფონებისა და ერთიანი მსოფლიო საკომუნიკაციო სისტემების სულ უფრო ფართო დამკვიდრებით ყოველდღიურ ცხოვრებაში. ზოგადი დამოკიდებულება ზემოქმედების რისკებისა გამოსხივების პარამეტრებზე ასე თუ ისე ნათელია; არაცალსახია ჯანმრტელობაზე ზემოქმედების გამოვლინებები. მსოფლიო ჯანდაცვის ორგანიზაცია მოგვიწოდებს ვიხელმძღვანელოთ „გონიერი შეზღუდვის პრინციპით“

When one size does not fit all: Reconsidering PCOS etiology, diagnosis, clinical subgroups, and subgroup-specific treatments

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects a large proportion of women. Due to its heterogeneity, the best diagnostic strategy has been a matter of contention. Since 1990 scientific societies in the field of human reproduction have tried to define the pivotal criteria for the diagnosis of PCOS. The consensus Rotterdam diagnostic criteria included the presence of hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology (PCOM), and have now been updated to evidence based diagnostic criteria in the 2018 and 2023 International Guideline diagnostic criteria endorsed by 39 societies internationally. Within the Rotterdam Criteria, at least two out of three of the above-mentioned features are required to be present to diagnose PCOS, resulting in four phenotypes being identified: phenotype A, characterized by the presence of all the features, phenotype B, exhibiting hyperandrogenism and oligo-anovulation, phenotype C, presenting as hyperandrogenism and PCOM and finally the phenotype D that is characterized by oligo-anovulation and PCOM, lacking the hyperandrogenic component. However, it is the hypothesis of the EGOI group that the Rotterdam phenotypes A, B, and C have a different underlying causality to phenotype D. Recent studies have highlighted the strong correlation between insulin resistance and hyperandrogenism, and the pivotal role of these factors in driving ovarian alterations, such as oligo-anovulation and follicular functional cyst formation. This new understanding of PCOS pathogenesis has led the authors to hypothesis that phenotypes A, B, and C are endocrine-metabolic syndromes with a metabolic clinical onset. Conversely, the absence of hyperandrogenism and metabolic disturbances in phenotype D suggests a different origin of this condition, and point towards novel pathophysiological mechanisms; however, these are still not fully understood. Further questions have been raised regarding the suitability of the “phenotypes” described by the Rotterdam Criteria by the publication by recent GWAS studies, which demonstrated that these phenotypes should be considered clinical subtypes as they are not reflected in the genetic picture. Hence, by capturing the heterogeneity of this complex disorder, current diagnostic criteria may benefit from a reassessment and the evaluation of additional parameters such as insulin resistance and endometrial thickness, with the purpose of not only improving their diagnostic accuracy but also of assigning an appropriate and personalized treatment. In this framework, the present overview aims to analyze the diagnostic criteria currently recognized by the scientific community and assess the suitability of their application in clinical practice in light of the newly emerging evidence