Historical development of methods for diagnosis and treatment of OSA

Obstructive sleep apnea (OSA) has been known to mankind since ancient times. Medical  documents from 2000 years ago that have been found contain information describing severe snoring (apnea) characteristic of OSA. In order to obtain the information targeted research was carried out in the Scientific databases PubMed, Scopus, ScienceDirect, Web of Science. „History of OSA”, „CPAP”, „Polysomnography” keywords were used in for the search.The aim of this article is to present the historical development of methods for diagnosis and treatment of OSA. In 1981 Sullivan et al. published in the Lancet scientific paper on Obstructive Sleep Apnea “ Reversal of obstructive sleep apnea by continuous airway pressure applied through the nares “ . At the end of the XIX th century, the term “Pickwickian syndrome” was introduced in the medical literature. In 1965, the polysomnographic unit was created and for the first time, with the help of electronic device, sleep apnea was registered in patients. Eventually ambulatory sleep testing was introduced as an alternative to polysomnography. Apnea Graph is a new innovative ambulatory sleep analysis tool that identifies the location of snoring obstruction and OSA. It also determines the type of OSA. In 1981, the first CPAP for treatment OSA was created. Sullivan’s findings prove that CPAP is a very effective device for treating OSA

Artificial intelligence – the new suggestion for biomedicine, dentistry and healthcare

The development of technologies based on Artificial Intelligence (AI) and their application in medicine is growing rapidly. Innovations in digital technology, telemedicine, 5G technology and artificial intelligence (AI) create new opportunities for the development of the healthcare system. The aim of the present study is to explore the possibilities for the application of artificial intelligence in biomedicine, dentistry, healthcare and healthcare. In recent years there have been many major innovations, including the introduction of many new information and communication technologies. Digital innovations, including the further inclusion of telemedicine, the development of 5th generation wireless networks (5G) and artificial intelligence (AI) approaches, create an exceptional ecosystem for new health opportunities. The digital health sector creates a favorable environment for the provision of health services at a very high level

Age as a factor for cognitive decline in patients with glial tumors

Introduction: Cognitive impairment appears in almost all patients with glial tumors during the course of this neuro-oncological disease. There are various reasons for this in regards to the glial tumor: grade of malignancy, rate of growth, molecular nature, mass effect, and presence of perifocal edema. But these factors do not always correlate with the degree of patient’s cognitive impairment. The present study’s aim is to account for age as a factor in the occurrence of cognitive decline in patients with glial tumors.Materials and methods: The study includes thirty two patients diagnosed with a glial tumor, treated operatively in the Neurosurgery Clinic of University hospital „St. Marina“ in Varna between 2019 and 2022 year. Twenty nine of those patients are diagnosed with glioblastoma, two are diagnosed with diffuse astrocytoma and one with astrocytoma grade 3 according to WHO. The mean age of the patients is 58.4 ± 11.4 years. The youngest patient is 25 years old and the oldest is 78 years old. Preoperatively, all patients are subjected to a series of cognitive tests.Results: From the studied sample, patients diagnosed with glioblastoma showed lower cognitive scores compared to the patients diagnosed with other glial tumors. Patients diagnosed with glioblastoma are significantly older than the patients diagnosed with other glial tumors.Conclusion: The older age of patients affected by glioblastoma may be an additional reason beside tumor factors for lower cognitive test outcome compared to patients affected by lower-grade gliomas

Methods of cognitive status research in patients with glioblastoma

Introduction: Glioblastoma is a high-grade, aggressive central nervous system tumor with predominantly astrocytic differentiation, characterized by fast invasive growth into the surrounding brain parenchyma and aggressive clinical course. The short life expectancy of patients diagnosed with glioblastoma necessitates the need to maximize their quality of remaining life. One of the most common reasons for quality of life impairment in these patients is the cognitive deficit accompanying the disease. There is a lack of a unified and standardized method for the assessment of cognitive functions in these patients, which meets all the necessary criteria to be convenient and usable in the wide clinical practice.Aim: The aim of the present study is to compare the Montreal cognitive assessment (MoCA) brief screening test with an extended neuropsychological examination to determine its applicability in patients diagnosed with glioblastoma. Material and methods: The study includes 27 patients undergoing neurosurgical intervention for histologically proven IDH-wildtype glioblastoma in the Department of Neurosurgery, “St. Marina” University Hospital – a tertiary healthcare center, for the period January 2019 to December 2022. Preoperatively, patients were examined with the short MoCA screening test and an extended neuropsychological examination including the following subtests: Issac set test, Trail making test A and B, Luria test, Raven‘s color matrices, Stroop test and Bender test.Results: Of all the patients studied, those with a MoCA score below 26 points present at least one negative test of the extended neuropsychological examination. MoCA patients with scores of 26 or more do not demonstrate cognitive impairment in the extended neuropsychological impairment.Conclusion: The obtained results support the claim that the MoCA short screening test is applicable for preoperative diagnosis of cognitive disorders in patients with glioblastoma. Due to the study‘s small sample size, further research is needed to definitively prove this claim

Historical origin and meaning of the term „glial tumor“

In everyday neurosurgical practice, the term „glial tumor“ is associated with astrocytomas, glioblastomas, and oligodendrogliomas, although historically this has not always been the case. The term „glial tumor“ was first given by Virchow in the 19th century as a term initially combining all primary brain tumors under this name. It derives from the name of the group of „supporting“ nerve cells - glia or neuroglia (from the Greek glia - glue), a group which for many years was wrongly ascribed only a cohesive or supporting function.In 1926, in their classification of glial tumors - A Classification of the Tumors of the Glioma Group on a Histogenetic Basis with a Correlated Study of Prognosis, one of the founding fathers of neuropathology Percival Bailey and the founding father of modern neurosurgery – Harvey Cushing ascribed several different tumors in this group: in addition to neuroepithelioma, spongioblastoma multiforme, astrocytoma and ependymoma, they also add medulloblastoma, astroblastoma, oligodendroglioma and unipolar spongioblastoma. Since then, the classification of glial tumors has undergone many changes to its current form. In the latest classification of brain tumors published in 2021, glial tumors are united in a common group together with glioneuronal and neuronal tumors. Their extensive group includes tumors with different prognosis, age presentation, molecular profile and therapeutic response. From a neurosurgical point of view, the term „glial tumor“ does not carry a prognostic value, but only determines the belonging of the tumor to the astrocyte, oligodendrocyte cell line or their precursor cells. In relation to that an interesting question arises- why the remaining tumors originating from glial cells other than astrocytic, such as ependymomas, lost their belonging to the group of glial tumors, or such as intracranial schwannomas, are not included in it at all

Вейвлет-анализ параметров систем автоматического управления авиационных двигателей

The article deals with wavelet analysis of signals received from the sensors of electronic control systems of aircraft gas turbine engines, which will significantly improve the diagnostics of engine operating condition to prevent failure and ultimately to reduce the economic costs. A block diagram of automatic control of aircraft gas turbine engine is presented.Статья посвящена вопросам вейвлет-анализа сигналов, полученных с датчиков электронных систем управления авиационных газотурбинных двигателей, что позволит заметно улучшить диагностику режимов работы двигателя для предотвращения их выхода из строя и в конечном счете для снижения экономических затрат. Представлена блок-схема автоматического управления авиационным газотурбинным двигателем

Characterisation of the Cullin-3 mutation that causes a severe form of familial hypertension and hyperkalaemia

Deletion of exon 9 from Cullin‐3 (CUL3, residues 403–459: CUL3Δ403–459) causes pseudohypoaldosteronism type IIE (PHA2E), a severe form of familial hyperkalaemia and hypertension (FHHt). CUL3 binds the RING protein RBX1 and various substrate adaptors to form Cullin‐RING‐ubiquitin‐ligase complexes. Bound to KLHL3, CUL3‐RBX1 ubiquitylates WNK kinases, promoting their ubiquitin‐mediated proteasomal degradation. Since WNK kinases activate Na/Cl co‐transporters to promote salt retention, CUL3 regulates blood pressure. Mutations in both KLHL3 and WNK kinases cause PHA2 by disrupting Cullin‐RING‐ligase formation. We report here that the PHA2E mutant, CUL3Δ403–459, is severely compromised in its ability to ubiquitylate WNKs, possibly due to altered structural flexibility. Instead, CUL3Δ403–459 auto‐ubiquitylates and loses interaction with two important Cullin regulators: the COP9‐signalosome and CAND1. A novel knock‐in mouse model of CUL3WT/Δ403–459 closely recapitulates the human PHA2E phenotype. These mice also show changes in the arterial pulse waveform, suggesting a vascular contribution to their hypertension not reported in previous FHHt models. These findings may explain the severity of the FHHt phenotype caused by CUL3 mutations compared to those reported in KLHL3 or WNK kinases

Effect of rearing temperature on physiological measures and antioxidant status of broiler chickens fed stevia (Stevia rebaudiana B.) leaf meal and exogenous xylanase

Background The global climate is warming. Heat stress, as a result of high ambient temperatures, may negatively impact physiology and reduce growth performance of poultry. Stevia is a perennial shrub indigenous to South America where its phytochemical extracts have been used as a natural sweetener for hundreds of years. Its physiological effects, including antioxidant properties, on poultry are well known, however, the translation of these to improved growth performance is variable. Combining stevia with a commercial xylanase to enhance feed digestibility could therefore form a feeding strategy to partially mitigate the negative impact of rearing birds under high ambient temperatures. Purpose The study aimed to compare the growth performance, dietary energy and nutrient availability, oxidative status, gastrointestinal tract development, and caecal short chain fatty acid concentration; at two ambient rearing temperatures, when feeding diets containing stevia and exogenous xylanase, alone or in combination, to broiler chickens. Study design/Methods: Day-old chicks (n = 105) were reared in a single floor pen following breeder recommendations for the first 7 days, whereupon birds (n = 96) were randomly allocated to one of four experimental diets (negative control, stevia at 20 g/kg diet, xylanase at 100 FXU/kg diet, stevia at 20 g/kg diet + xylanase at 100 FXU/kg diet), in one of two environmental conditions (high ambient temperature at 32 ± 2 °C or regular rearing at breeder recommendations), in a 2 × 2 × 2 factorial design. Results Rearing birds at high ambient temperature reduced daily feed intake (p = 0.02). Birds fed stevia and reared at regular temperature had similar weight gain to birds reared in high ambient temperatures, although birds on the control diet housed at regular temperatures had the greatest weight gain (P < 0.05). Exogenous xylanase improved overall dietary metabolisable energy and improved nitrogen retention in the high ambient temperature group only (P < 0.05). Dietary stevia reduced caecal digesta butyric acid: acetic acid at regular temperature, but xylanase increased the butyric acid concentration at high ambient temperature (P < 0.05). Dietary stevia increased (P < 0.001) the hepatic carotenoid concentrations and xylanase improved (P < 0.05) hepatic vitamin E concentrations. Conclusions Rearing temperature is an important environmental factor in broiler production. Exogenous xylanase supplementation can increase feed efficiency and dietary metabolisable energy. Feeding xylanase or stevia improves hepatic antioxidant status in broilers by increasing hepatic vitamin E and carotenoids, respectively, suggesting that either may be effective in counteracting oxidative stress

Time separation as a hidden variable to the Copenhagen school of quantum mechanics

The Bohr radius is a space-like separation between the proton and electron in the hydrogen atom. According to the Copenhagen school of quantum mechanics, the proton is sitting in the absolute Lorentz frame. If this hydrogen atom is observed from a different Lorentz frame, there is a time-like separation linearly mixed with the Bohr radius. Indeed, the time-separation is one of the essential variables in high-energy hadronic physics where the hadron is a bound state of the quarks, while thoroughly hidden in the present form of quantum mechanics. It will be concluded that this variable is hidden in Feynman's rest of the universe. It is noted first that Feynman's Lorentz-invariant differential equation for the bound-state quarks has a set of solutions which describe all essential features of hadronic physics. These solutions explicitly depend on the time separation between the quarks. This set also forms the mathematical basis for two-mode squeezed states in quantum optics, where both photons are observable, but one of them can be treated a variable hidden in the rest of the universe. The physics of this two-mode state can then be translated into the time-separation variable in the quark model. As in the case of the un-observed photon, the hidden time-separation variable manifests itself as an increase in entropy and uncertainty.Comment: LaTex 10 pages with 5 figure. Invited paper presented at the Conference on Advances in Quantum Theory (Vaxjo, Sweden, June 2010), to be published in one of the AIP Conference Proceedings serie

Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors.

It is generally assumed that recurrent mutations within a given cancer driver gene elicit similar drug responses. Cancer genome studies have identified recurrent but divergent missense mutations affecting the substrate-recognition domain of the ubiquitin ligase adaptor SPOP in endometrial and prostate cancers. The therapeutic implications of these mutations remain incompletely understood. Here we analyzed changes in the ubiquitin landscape induced by endometrial cancer-associated SPOP mutations and identified BRD2, BRD3 and BRD4 proteins (BETs) as SPOP-CUL3 substrates that are preferentially degraded by endometrial cancer-associated SPOP mutants. The resulting reduction of BET protein levels sensitized cancer cells to BET inhibitors. Conversely, prostate cancer-specific SPOP mutations resulted in impaired degradation of BETs, promoting their resistance to pharmacologic inhibition. These results uncover an oncogenomics paradox, whereby mutations mapping to the same domain evoke opposing drug susceptibilities. Specifically, we provide a molecular rationale for the use of BET inhibitors to treat patients with endometrial but not prostate cancer who harbor SPOP mutations