for early-onset breast cancer.

Circulating miRNAs have been extensively used in studies of neurological diseases. Thus, methods to extract high quantity total RNA for RNA sequencing (RNA-seq) and real-time quantitative polymerase chain reaction (RT-qPCR) are needed. However, the extraction of sufficient high-quality nucleic acids from circulating blood is difficult. Differences in eccentricity, cryopreservation conditions and extraction methods may affect RNA quantity and quality. Here, we systematically compared six blood-RNA extraction protocols (protocols 1, 2, 3, 4, 5, and 6; see the methods section for details).

Protocol 1 yielded the highest quality and quantity of RNA; protocol 2, protocol 5 and protocol 6 produced RNA of intermediate quality; and protocols 3 and 4 yielded the lowest quality RNA. The RNA integrity number (RIN) for isolated RNA was > 9.0 when protocol 1 or protocol 2 was used, > 8.0 when protocol 5 was used, and > 7.0 when protocol 6 was used; lower values were obtained when protocol 3 or 4 was used. The RNA extracted from circulating blood using protocol 1 was most intact and suitable for RT-qPCR and RNA-seq.

The quality of RNA extracted from circulating blood is affected by high-speed centrifugation and cryopreservation. Adding an RNA stabilizer during the cryopreservation of circulating blood significantly improved RNA quality and quantity. The quality of extracted RNA from circulating blood is improved when using TRIzol relative to that attained with a commercial kit.

The quality of RNA extracted from circulating blood is affected by high-speed centrifugation and cryopreservation. Adding an RNA stabilizer during the cryopreservation of circulating blood significantly improved RNA quality and quantity. The quality of extracted RNA from circulating blood is improved when using TRIzol relative to that attained with a commercial kit.

Results are presented from 2 to 3 trials investigating oral octreotide capsules (OOC) as an alternative to injectable somatostatin receptor ligands (iSRLs) in the treatment of acromegaly.

CH-ACM-01 was an open-label trial (N = 155) and CHIASMA OPTIMAL was a double-blind placebo-controlled (DPC) trial (N = 56), both investigating OOC as maintenance therapy for patients with acromegaly who were biochemical responders receiving iSRLs.

Baseline characteristics in both trials reflected those expected of patients with acromegaly responding to treatment and were similar between trials, despite differences in inclusion criteria. OOC demonstrated a consistent degree of biochemical response across trials, with 65% of patients in CH-ACM-01 maintaining response during the core period and 64% of patients in CHIASMA OPTIMAL at the end of the DPC. Mean insulin-like growth factor I (IGF-I) levels remained within inclusion criteria at the end of treatment in both trials. Of 110 patients entering the fixed-dose phase in CH-ACM-01, 80% maintained or improved acromegaly symptoms from baseline to the end of treatment. Over 85% of patients in both trials elected to continue into the extension phases. OOC were found to be well tolerated across both trials, and no dose-related adverse events were observed.

OOC demonstrated remarkably consistent results for biochemical response, durability of response, and preference to continue with oral treatment across these 2 complementary landmark phase 3 trials, despite differences in the design of each. Trial registration NCT03252353 (August 2017), NCT01412424 (August 2011).

OOC demonstrated remarkably consistent results for biochemical response, durability of response, and preference to continue with oral treatment across these 2 complementary landmark phase 3 trials, despite differences in the design of each. Trial registration NCT03252353 (August 2017), NCT01412424 (August 2011).

Frailty is a state of physiological vulnerability that negatively influences surgical outcomes. The effect of frailty on pituitary adenoma surgery, however, is not clear, and patients may be wrongly denied surgery because they are „too frail”. We examined the effects of frailty on surgical outcome and quality-of-life (QoL) in patients undergoing endoscopic transsphenoidal resection of pituitary adenomas.

A prospective, consecutive cohort of surgically managed pituitary adenoma was analysed. Frailty was defined by the 5-factor modified Frailty Index (mFI-5) and the Charlson Comorbidity Index (CCI). QoL was measured by the anterior skull base questionnaire (ASBQ) and sinonasal outcomes test (SNOT).

Of 304 patients with pituitary adenomas, 42 (13.8%) were frail (mFI5 of > 1). Frail patients tended to have smaller adenomas (p < 0.0001) with less suprasellar extension (p < 0.0001). Both overall (ASBQ) and sinonasal-specific (SNOT) QoL were not affected by frailty on multivariate analysis. Endocrine and visual outcomes were similarly not worsened by frailty. Overall, medical complications were uncommon, and perioperative morbidity or mortality was not significantly greater in the frail group.

Frail patients experience the same QoL benefits from surgery as their non-frail counterparts, and have equivalently successful visual and endocrine outcomes. Frailty should not be seen as a barrier to successful surgical management of pituitary adenomas.

Frail patients experience the same QoL benefits from surgery as their non-frail counterparts, and have equivalently successful visual and endocrine outcomes. Frailty should not be seen as a barrier to successful surgical management of pituitary adenomas.Aiming to slow down the spread of the COVID-19, a lockdown was declared in the first term of 2020 in many European countries, applying different restrictions measures. Although the psychological effects of home confinement in children have been described, there is a lack of longitudinal research examining the impact of the confinement over time. The present study analyzes the evolution of the psychological wellbeing of children and adolescents from three European countries with different restrictions. Parents of 624 Italian, Spanish, and Portuguese children and adolescents aged 3 to 18 years old completed the „Impact Scale of COVID-19 and Home Confinement on Children and Adolescents” two, five, and eight weeks after the lockdown. Results show a different pattern for each country. Children from Italy, the first European country that applied a lockdown, were better adapted than Spanish and Portuguese children the first two weeks after confinement but they were more psychologically impacted by home confinement at the eight-week assessment. Portuguese children, who followed a general duty of home confinement, were the best adapted to the situation, with no significant differences over time. A significant change was found in anxiety symptoms in Spanish children, with a decrease at the last assessment. Findings suggest that long confinements and hard restrictions affect children, so prevention measures should be applied during confinements to prevent psychological problems in children.Parental Reflective Functioning (PRF) refers to parents’ capacity to view their child’s and their own behavior considering inner mental states, like thoughts, desires, and intentions. This study’s objective was to examine whether PRF acted as a moderator for the relationships between maternal depression and child internalizing and externalizing problems. The sample was comprised of 685 Iranian mothers with preschoolers (3 to 5 years old) and school-aged (6-10 years old) children. To assess PRF, the PRF questionnaire was used. Child internalizing and externalizing difficulties were assessed with the Child Behavior Checklist, and maternal depression was assessed with the Beck Depression Inventory- second version. Results indicated significant relationships between maternal depression and PRF (specifically pre-mentalizing and certainty in mental states). Also, mothers of school-aged children showed significantly higher levels of pre-mentalizing than mothers of preschoolers. Furthermore, certainty about mental states moderated the relationship between maternal depression and child externalizing behaviors in school-aged children. However, no moderating effect was found for pre-mentalizing or interest and curiosity in mental states in any age group.This article examines the compatibility and relevance of Gabriel Marcel’s phenomenology of hope in interdisciplinary research on the role of hope in end-of-life (EOL) care. Our analysis is divided into three thematic topics which examine the various shades of hope observed in Marcel’s phenomenology of hope and in the collection of 20 EOL studies on hope as experienced by adult palliative care (PC) patients, health care professionals (HCP) and parents of terminally ill children. The three topics defining the shades of hope are the meaning of hope in its dynamic aspects, the dialectics of hope and despair, and the transcendent facets of hope. We analyse how Marcel’s understanding of hope is reflected in EOL studies, and how this perception can enrich the philosophy of PC and significantly deepen and broaden HCPs’ understanding of hope. Our findings prove that despite terminological differences between Marcelian phenomenology and the concepts of hope in the 20 EOL studies, hope emerges as a resourceful movement towards being. Implementing Marcelian hope within communication in EOL care could help in HCPs’ interpersonal approach to patients as his concept harbors a holistic perception of the existential situation of a person. Equally, introducing Marcel’s phenomenology of hope into the clinical encounter could play a beneficial role in improving the ability of patients to adapt to the difficult conditions of their disease and PC treatment.Background Despite common use, anticholinergic medications have been associated with serious health risks. Interventions to reduce their use are being developed and there is a need to understand their implementation into clinical care. Aim of review This systematic review aims to identify and analyse qualitative research studies exploring the barriers and facilitators to reducing anticholinergic burden. Methods Medline (OVID), EMBASE (OVID), CINAHL (EMBSCO) and PsycINFO (OVID) were searched using comprehensive search terms. Peer reviewed studies published in English presenting qualitative research in relation to the barriers and facilitators of deprescribing anticholinergic medications, involving patients, carers or health professionals were eligible. Normalization Process Theory was used to explore and explain the data. Results Of 1764 identified studies, two were eligible and both involved healthcare professionals (23 general practitioners, 13 specialist clinicians and 12 pharmacists). No studies were identified that involved patients or carers. Barriers to collaborative working often resulted in poor motivation to reduce anticholinergic use. Low confidence, system resources and organisation of care also hindered anticholinergic burden reduction. Good communication and relationships with patients, carers and other healthcare professionals were reported as important for successful anticholinergic burden reduction. Having a named person for prescribing decisions, and clear role boundaries, were also important facilitators. Conclusions This review identified important barriers and facilitators to anticholinergic burden reduction from healthcare provider perspectives which can inform implementation of such deprescribing interventions. Studies exploring patient and carer perspectives are presently absent but are required to ensure person-centeredness and feasibility of future interventions.Cancer continues to be the most dangerous disease around the world; it causes electrolyte imbalance as well as metabolic changes. There is a complicated relationship between electrolyte disorder and cancer. Cancer patients commonly pass with abnormalities in serum electrolyte levels such as hypokalemia, hyperkalemia, hyponatremia, and hypercalcemia. So, these electrolyte imbalances indicate the existence of paraneoplastic processes and help come to a more informed prognosis. Hypokalemia is defined as a serum potassium concentration below 3.5 mmol/L and it is the second common electrolyte imbalance seen in patients with malignant diseases. In this paper, the contribution of serum potassium concentration to tumor progression was studied by applying a promising and non-invasive technique called laser-induced breakdown spectroscopy (LIBS). It was found that there is a correlation between hypokalemia and the colorectal cancer problem. Also, significant serum potassium concentration differences were detected among two different stages of the same cancer and also between two groups of the same stage of a cancer held in common but one of them suffers from hypercalcemia. In addition, the optimum conditions of LIBS setup were arranged such that it will be suitable to work with serum samples on glass substrate.

The impact of transanal local excision (TAE) of early rectal cancer (ERC) on subsequent completion rectal resection (CRR) for unfavorable histology or margin involvement is unclear. The aim of this study was to provide a comprehensive review of the literature on the impact of TAE on CRR in patients without neoadjuvant chemoradiotherapy (CRT).

We performed a systematic review of the literature up to March 2020. Medline and Cochrane libraries were searched for studies reporting outcomes of CRR after TAE for ERC. We excluded patients who had neoadjuvant CRT and endoscopic local excision. Surgical, functional, pathological and oncological outcomes were assessed. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed.

Sixteen studies involving 353 patients were included. Pathology following TAE was as follows T0 = 2 (0.5%); T1 = 154 (44.7%); T2 = 142 (41.2%); T3 = 43 (12.5%); Tx = 3 (0.8%); T not reported = 9. Fifty-three percent were > T1. Abdominoperineag of malignant rectal tumors in patients scheduled for TAE.

The data are incomplete and of low quality. There was a tendency towards an increased risk of APR and poor specimen quality. It is necessary to improve the accuracy of preoperative staging of malignant rectal tumors in patients scheduled for TAE.

LEM domain containing 1 (LEMD1) is a novel factor involved in the development of oral squamous cell carcinoma (OSCC). We previously performed a microarray analysis and found that serpin peptidase inhibitor, clade E, member 2 (SERPINE2) is an LEMD1-related signal. SERPINE2 is an extracellular serine proteinase inhibitor with secretory capacity. Although SERPINE2 displays tumor-promoting properties in many cancers, some reports indicate that SRPINE2 also has a tumor-suppressing function. Therefore, there are many unclear points about its role in cancer. In this study, we investigated SERPINE2 expression in OSCC.

The gene expression and secretion levels of SERPINE2 were examined in 42 frozen specimens of OSCC, and SERPINE2 immunostaining was investigated in 167 cases of OSCC. Furthermore, the effect of SERPINE2 on angiogenesis and lymphangiogenesis was analyzed using OSCC cells and endothelial cells.

In the frozen specimens, the gene expression (P < 0.0001) and secretion levels (P < 0.0001) of SERPINE2 were higher in OSCC than in the normal oral mucosa. According to the immunohistochemical analysis, SERPINE2 expression was correlated with the depth of invasion (P = 0.0163), nodal metastasis (P = 0.0085), microvessel density (P < 0.0001), and lymphovessel density (P < 0.0001). Additionally, univariate and multivariate analyses indicated that the SERPINE2 expression level was an independent poor prognostic factor for OSCC. In vitro studies using OSCC cells revealed that SERPINE2 promotes angiogenesis and lymphangiogenesis.

These results suggest that SRPX2 might be a useful tumor marker for OSCC.

These results suggest that SRPX2 might be a useful tumor marker for OSCC.Tweety-homolog 1 protein (Ttyh1) is abundantly expressed in neurons in the healthy brain, and its expression is induced under pathological conditions. In hippocampal neurons in vitro, Ttyh1 was implicated in the regulation of primary neuron morphology. However, the mechanisms that underlie transcriptional regulation of the Ttyh1 gene in neurons remain elusive. The present study sought to identify the promoter of the Ttyh1 gene and functionally characterize cis-regulatory elements that are potentially involved in the transcriptional regulation of Ttyh1 expression in rat dissociated hippocampal neurons in vitro. We cloned a 592 bp rat Ttyh1 promoter sequence and designed deletion constructs of the transcription factors specificity protein 1 (Sp1), E2F transcription factor 3 (E2f3), and achaete-scute homolog 1 (Ascl1) that were fused upstream of a luciferase reporter gene in pGL4.10[luc2]. The luciferase reporter gene assay showed the possible involvement of Ascl1, Sp1, and responsive cis-regulatory elements in Ttyh1 expression. These findings provide novel information about Ttyh1 gene regulation in neurons.Epilepsy represents a hazardous neurological disorder, underpinned by a pathophysiological process that is yet to be fully understood. Here, we aimed to elucidate the effect of methyl-CpG-binding domain protein 3 (MBD3) on hippocampal neuronal damage in epileptic mice by targeting the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. The expression of MBD3 was determined by Western blot in a hippocampal neuronal culture (HNC) epileptic model established using the low Mg2+ECF culture method. The interaction between MBD3 and DNA methyltransferase 1 (DNMT1) was determined via co-immunoprecipitation and mass spectrometry analysis. Bisulfite modification and sequencing was performed to evaluate the degree of methylation of triggering receptor expressed on myeloid cells 2 (TREM2). The viability and apoptosis of hippocampal neurons were detected by CCK-8 and TUNEL assays, respectively. Finally, the effect of MBD3 was verified in vivo. MBD3 was highly expressed in the HNC model of epilepsy, with its interaction with DNMT1 found to promote the hypermethylation of TREM2 at site cg25748868. Additionally, decreased TREM2 and inhibited PI3K/Akt pathway was observed in the HNC epileptic model. Simultaneous inhibition of MBD3 and DNMT1 decreased the methylation level at cg25748868, up-regulated TREM2 expression, and activated the PI3K/Akt pathway, thereby arresting neuronal damage. Inhibition of MBD3 reduced the level of epileptic seizures, down-regulated cg25748868 methylation, activated TREM2-mediated signaling pathways, and alleviated hippocampal neuronal damage in the acute seizure mouse models. The present study unveiled that MBD3 and DNMT1 synergistically enhanced hypermethylation of cg25748868 in TREM2, and promoted the onset of epilepsy via inhibition of the PI3K/Akt pathway.Ovarian cancer (OVC) is often diagnosed at the advanced stage resulting in a poor overall outcome for the patient. The disease mechanisms, prognosis, and treatment require imperative elucidation. A rank-based module-centric framework was proposed to analyze the key modules related to the development, prognosis, and treatment of OVC. The ovarian cancer cell line microarray dataset GSE43765 from the Gene Expression Omnibus database was used to construct the reference modules by weighted gene correlation network analysis. Twenty-three reference modules were tested for stability and functionally annotated. Furthermore, to demonstrate the utility of reference modules, two more OVC datasets were collected, and their gene expression profiles were projected to the reference modules to generate a module-level expression. An epithelial-mesenchymal transition module was activated in OVC compared to the normal epithelium, and a pluripotency module was activated in ovarian cancer stroma compared to ovarian cancer epithelium. Seven differentially expressed modules were identified in OVC compared to the normal ovarian epithelium, with five up-regulated, and two down-regulated. One module was identified to be predictive of patient overall survival. Four modules were enriched with SNP signals. Based on differentially expressed modules and hub genes, five candidate drugs were screened. The hub genes of those modules merit further investigation. We firstly propose the reference module-based analysis of OVC. The utility of the analysis framework can be extended to transcriptome data of other kinds of diseases.

Glutamine (Gln) is essential for cancer progression, however, few studies have been conducted to investigate the roles of Gln transporters in gastric cancer stem cells (CSCs).

This work aims to explore the roles of Gln transporters in gastric cancer cell stemness.

We collected spheres formed by gastric cancer (GC) cells through a 3-dimensional (3D) semisolid culture system which has been shown to hold CSC-like traits. Lentivirus package was used to construct GC cells with SNAT2 overexpression. Analysis of sphere-formation, stemness marker expression, ALDH activity were used to detect the effects of Gln transporters on GC cell stemness. Determination of reactive oxygen species (ROS) and Gln consumption combined with the methods analyzing cell stemness were performed to explore the underlying mechanisms.

Gln consumption was upregulated in GC spheres compared to the parental GC cells. The Gln transporter SNAT2 was highly expressed in GC spheres compared to that in the parental GC cells. SNAT2 overexpression significantly increased the Gln consumption in GC cells and increased the expression of stemness markers, sphere-formation ability and ALDH activity. Notably, SNAT2-mediated promoting effects on GC cell stemness were rescued by Gln deprivation. What’s more, high expression of SNAT2 was associated with a poor GC patient survival through different online datasets.

SNAT2 can promote the stemness of GC cells in a Gln-dependent manner.

SNAT2 can promote the stemness of GC cells in a Gln-dependent manner.Endoscopic third ventriculostomy (ETV) is a well-established surgical procedure for hydrocephalus treatment, but there is sparse evidence on the optimal choice between flexible and rigid approaches. A meta-analysis was conducted to compare efficacy and safety profiles of both techniques in pediatrics and adults. A comprehensive search was conducted on PubMED, EMBASE, and Cochrane until 11/10/2019. Efficacy was evaluated comparing incidence of ETV failure, while safety was defined by the incidence of perioperative complications, intraoperative bleedings, and deaths. Random-effects models were used to pool the incidence. Out of 1365 studies, 46 case series were meta-analyzed, yielding 821 patients who underwent flexible ETV and 2918 who underwent rigid ETV, with an age range of [5 days-87 years]. Although flexible ETV had a higher incidence of failure in adults (flexible 54%, 95%CI 22-82% vs rigid 20%, 95%CI 22-82%) possibly due to confounding due to etiology in adults treated with flexible, a smaller difference was seen in pediatrics (flexible 36%, pediatric 32%). Safety profiles were acceptable for both techniques, with a certain degree of variability for complications (flexible 2%, rigid 18%) and death (flexible 1%, rigid 3%) in pediatrics as well as complications (rigid 9%, flexible 13%), death (flexible 4%, rigid 6%) and intra-operative bleeding events (rigid 6%, flexible 8%) in adults. No clear superiority in efficacy could be depicted between flexible and rigid ETV for hydrocephalus treatment. Safety profiles varied by age but were acceptable for both techniques. Well-designed comparative studies are needed to assess the optimal endoscopic treatment option for hydrocephalus.We studied the immunological status and polymorphic variants of candidate genes in men with disturbances of autonomic nervous regulation under conditions of aerogenic exposure to benzene. The group of men with pathology of the autonomic nervous system (autonomic dysfunction syndrome) living under conditions of aerogenic exposure to benzene is characterized by increased blood contamination with benzene, which 1.5-fold surpassed this parameter in the group of conventionally healthy men (p1; p less then 0.05) with the variant allele of the FOXP3 immune regulation gene (rs3761547) and with wild-type allele of the SOD2 superoxide dismutase gene (rs2758330) and the corresponding homozygous genotypes. The established features of immune regulation (hyperproduction of IgG to benzene, imbalance of apoptosis markers (CD127-, CD3+CD95+, p53, and TNFR) against the background of altered polymorphism of candidate genes (FOXP3, SOD2) form a complex of genetic and immunological markers of autonomic regulation disorders in men living under conditions of aerogenic exposure to benzene.We studied functional changes in rat pituitary-thyroid axis after a short-term shift in deuterium body content. Male Wistar rats consumed deuterium-enriched (500,000 ppm) or deuterium-depleted water (10 ppm) for 24 h. Rats of both experimental groups demonstrated elevated concentration of bound with transport proteins thyroxine and reduced level of thyroid-stimulating hormone in serum. No changes in the rate of thyroxine conversion to triiodothyronine were found. Thus, both the increase and reduction of deuterium body content produced similar changes in the function of the pituitary-thyroid axis with primary affection of the thyroid gland, indicative of its higher sensitivity to shift in deuterium levels.Morphometric and immunohistochemical examination of the vaginal mucosa before and 12 months after installation of polypropylene implants for the correction of stress urinary incontinence was performed in 20 patients with genital prolapse. The research results confirmed good biocompatibility of polypropylene and the formation of full-fledged connective tissue in the vaginal mucosa, but revealed the presence of a weak lymphocytic reaction to polypropylene 12 months after surgery. According to immunohistochemical study, increased contents of B lymphocytes and plasma cells responsible for the inductive and productive stages of the immune response were revealed in the vaginal mucosa around the implants 12 months after surgery. This reaction in the presences of provoking factors can lead to the development of inflammation and erosion, a type of mesh-associated complications.The prospect of using the antioxidant dipeptide carnosine for the treatment of urate nephrolithiasis was evaluated. Urate nephrolithiasis was modeled in rats by intragastric administration of a mixture of oxonic and uric acids. Carnosine was administered intragastrically through a tube in a dose of 15 mg/kg. In rats treated with carnosine, the concentration of TBA-reactive products decreased by 1.4 times, the total antioxidant activity increased by 1.4 times, and catalase activity increased by 1.3 times. By the end of the experiment, the lactate dehydrogenate level in experimental rats was 2-fold lower than in the control, and the number of urate deposits decreased by 1.6 times with a concomitant alleviation of the inflammatory processes. Thus, the use of direct peptide antioxidant carnosine attenuated the manifestations of urate nephrolithiasis.Morphofunctional changes of the brain tissues of Wistar rats were studied based on the development of a multifactor cardiovasorenal model of arterial hypertension using MRI. An increase of the signal on the diffusion brain maps was recorded in 3 months, which indicated fluid accumulation in the intra- and extracellular space of the brain tissue. The data characterize the development of the pathogenetic mechanism of the hypervolemic variant of experimental arterial hypertension. The development of endothelial dysfunction in the brain vessels was manifested by predominance of abnormal constrictor reactions. In 6 months after arterial hypertension simulation, structural changes in the brain developed, such as leukoareosis, cystic encephalomalacia with dilated cerebrospinal fluid spaces and limited blood supply to brain tissue in the basins of the large cerebral arteries.The effect of UV-light (240-390 nm) in doses of 151 and 755 J/m2 on the expression of membrane markers CD5, CD19, CD20 in human peripheral blood B cells was studied by flow cytometry. In 24 h after exposure to UV light, we observed activation of processes accompanied by structural rearrangements of B-cell membranes leading to changes in the expression of receptor molecules the content of of CD19 and CD20 increased due to activation of the synthesis of these proteins, while the content of CD5 decreased. The percentage of CD5+ cells decreased over 24 h after UV-irradiation of lymphocytes, while addition of autologous plasma to the incubation medium produced a photoprotective effect on CD5+ cells.The presence of IgG and IgM antibodies in the venous blood of 76 patients with confirmed COVID-19 infection was determined by ELISA using Russian test systems. Different levels of IgM antibodies to N-protein and receptor binding domain of the Spike protein (RBD) were revealed. The dynamics of IgG antibodies to the whole virion antigen and recombinant antigens showed high values on weeks 4-5 of the disease. The level of IgG antibodies to Nprotein remained low throughout the observation period. The characteristic dynamics of IgG measured using test systems with sorbed whole virion or recombinant spike proteins reflects the duration of the disease.We studied the mechanisms by which microRNA-126 regulates proliferation and migration of human umbilical vein endothelial cells (HUVEC) cultured in a medium with high glucose concentration and treated with chemokine CXCL8. Cell proliferation, apoptosis, and migration were analyzed by the CCK-8 assay, Annexin V-PI staining, and Transwell assay, respectively. The ratios of p-ERK/ERK, p-P38/P38, p-JNK/JNK were determined by ELISA. HUVEC cells cultured in the presence of high glucose concentration (30 mmol/ml) and treated with CXCL8 (50 ng/ml) demonstrated more intensive proliferation, migration, and p-ERK/ERK, p-P38/P38, and p-JNK/JNK ratios and significantly lower apoptosis rate than control cells (high glucose, no treatment) and cells treated with CXCL8 and transfected with microRNA-126-mimic. Thus, microRNA-126 regulates proliferation and migration of HUVEC cells cultured in the presence of high glucose concentrations and treated with CXCL8 through inhibition of MAPK signaling pathway.Spike activity of neurons in the ventromedial nucleus (VMN) of the hypothalamus in adult (6-8 months) and aged (2 years) male rats was studied by the in vivo extracellular method using stereotaxic insertion of microelectrodes. In all animals, firing frequency of most VMN neurons increased in response to glucose administration. However, in aged rats, the mean baseline and glucose-induced spike frequencies of VMN neurons were lower than in adult animals. These results support the hypothesis that aging is associated with a decrease in the functional activity of hypothalamic neurons.The presence of mutations in the gene encoding isocitrate dehydrogenase (IDH1), parameters of pro- and antioxidant activity in glioma tumor tissue, and their correlation were studied using bioinformatic analysis using STRING, IntAct, BioGrid, UniProt, SwissProt databases. The rate of detection of IDH1 gene mutations varied in different degree of anaplasia, being maximum in grade III gliomas. The intensity of free radical oxidation and activities of superoxide dismutase and catalase in the tumor tissue were significantly higher than in the control. The dependence of these parameters on the degree of anaplasia was shown. Mutations in IDH1 are associated with a decrease in antioxidant activity in the tissues of gliomas, which is critically important for the initial diagnosis, the choice of treatment options, and prediction of patient survival.We studied the effect of nanostructured clathrate complex 9-phenyl-symm-octahydoselenoxanthene (selenopyran) with β-cyclodextrin on the generation of ОН· radicals in the Fenton system and parameters of oxidative stress in rat liver cells incubated at 37°С for 1 h. The complex inhibits the development of free-radical oxidative processes induced by ROS and the most toxic ОН· radicals, reduces the increased level of ROS induced by prooxidants, and exhibits antioxidant activity.Changes in pulmonary microcirculation were studied in isolated perfused rabbit lungs during modelling pulmonary thromboembolism under conditions of acetylcholine infusion against the background of treatment with M1 acetylcholine receptor blocker pirenzepine or blockade of muscarinic acetylcholine receptors with atropine. In the first case, the increase in pulmonary artery pressure was less pronounced than in case of atropine treatment. In response to pulmonary embolism after acetylcholine infusion against the background of pirenzepine pretreatment, the capillary hydrostatic pressure and postcapillary resistance did not change, while after atropine treatment, these parameters increased. In case of pulmonary embolism after acetylcholine infusion combined with selective blockade of M1 muscarinic acetylcholine receptors, the capillary filtration coefficient increased to a greater extent, than in the control and after blockade of muscarinic acetylcholine receptors.We studied the influence of microorganisms isolated from permafrost on the psychophysiological parameters of birds. Significant effect of the microbiota of the paleoecosystems of the cryolithozone on locomotor activity, psycho-emotional state, and psychophysiological lateralization of brain function of Gallus gallus chickens. The involvement of both the autonomic and the higher central nervous systems in this regulatory process via synthesis of neuropeptides by symbionts is discussed.Histological and morphometric studies of brain autopsy material showed that the development of hypoxic changes in miners starts at the early stages of working in the dusty atmosphere. Edema of the pericellular and perivascular zones and the pia mater, degenerative changes in some nerve cells and even their loss and formation of gliosis foci were identified. The revealed changes in neurons progressed with increasing the duration of working under hazardous conditions.Atomic force microscopy is not very popular in practical health care, therefore, its potential is not studied enough, for example, in obstetrics when studying the „mother-placenta-fetus” system. Our study summarizes the possibilities of using atomic force microscopy for detection of various circulatory disorders and vascular changes at the microscopic level in the uterus (endometrium and myometrium), placenta, and umbilical cord in the main variants of obstetric and endocrine pathology. For instance, in the case of endocrine pathologies, changes in the form of stasis, sludge, diapedesis, ischemia, destruction and separation of endotheliocytes in villous blood vessels were found in the mother. The oxygen content in erythrocytes also naturally decreased in pathologies; poikilo- and anisocytosis were observed.We developed a model of retinal degeneration in rabbits based on exposure to light with a wavelength of 405 nm. This model allows reproducing structural and functional disorders in the central parts of the retina, including primarily degeneration of the outer layers of the retina (retinal pigment epithelium and layer of photoreceptor cells), and is designed to study the mechanisms of formation, progression and effectiveness of new drugs and methods of treatment of degenerative diseases of the retina.Neuroprotective peptides are promising candidate molecules for the treatment of Alzheimer’s disease (AD). Oral application of KED (Lys-Glu-Asp) improved memory and attention in elderly individuals with functional CNS disorders. Peptide KED also restores synaptic plasticity in in vitro model of AD. This review is focused on the analysis of the influence of KED peptide on the expression of genes and synthesis of proteins regulating apoptosis, aging, neurogenesis, and involved in AD pathogenesis. Analysis of published reports and our experimental findings suggests that KED regulates the expression of genes of cell aging and apoptosis (р16, р21), genes (NES, GAP43) and proteins (nestin, GAP43) of the neuronal differentiation, and genes involved in AD pathogenesis (SUMO, APOE, and IGF1). The study the effectiveness of neuroprotective peptide KED in animal models of AD seems to be very important.The effects of hydrogen sulfide baths and sulfide-silt mud applications on the abdominal wall were studied in outbred white rats. Heart preparations stained with hematoxylin and eosin were analyzed and the mean numbers of cells expressing Ki-67, Nkx-2.5, and mesenchymal stem cell markers were determined. Hydrogen sulfide balneotherapy promoted the development of blood capillaries in rat hearts and an increased the expression of CD34. A decrease in the regenerative potential of the myocardium was found due to a decrease in the content of proliferating cells and cells expressing CD73, CD90, and CD105, and also due to the absence of cells stained for cardiomyogenic differentiation marker Nkx-2.5.Using rat and mouse models of neurogenic, ethanol-induced, and indometacin-induced damage to the gastric mucosa we demonstrated that course preventive treatment with flavonoid complex from aerial parts of Lychnis chalcedonica L. increased the resistance of gastric mucosa to ulcerogenic factors of different etiology. The gastroprotective effect of the phytocomplex in a dose range of 16-1600 μg/kg was comparable with that of the reference drug plantaglucide and was superior to that of the reference drugs eleutherococcus extract and methyluracil in the therapeutic doses. The antiulcerogenic activity of Lychnis chalcedonica flavonoid complex considerably exceeded activity of Lychnis chalcedonica L. extract demonstrated in our previous experiments.In patients with moderate-to-severe and severe psoriasis and high efficacy of therapy (PASI≥75) with signaling pathway inhibitors (apremilast, tofacitinib), cytokine spectra in the skin and blood plasma were studied using xMAP technology at baseline and on weeks 14 and 26 of treatment. Comparison of cytokine levels in psoriatic lesional skin and plasma samples of patients treated with apremilast or tofacitinib revealed statistical difference only for IFNγ level (р less then 0.05) at week 26.The review presents modern views about the role of oxidative stress reactions in the pathogenesis of types 1 and 2 diabetes mellitus and their complications based on the analysis of experimental and clinical studies. The sources of increased ROS generation in diabetes are specified, including the main pathways of altered glucose metabolism, oxidative damage to pancreatic β-cells, and endothelial dysfunction. The relationship between oxidative stress, carbonyl stress, and inflammation is described. The significance of oxidative stress reactions associated with hyperglycemia is considered in the context of the „metabolic memory” phenomenon. The results of our studies demonstrated significant ethnic and age-related variability of the LPO-antioxidant defense system parameters in patients with diabetes mellitus, which should be considered during complex therapy of the disease. Numerous studies of the effectiveness of antioxidants in diabetes mellitus of both types convincingly proved that antioxidants should be a part of the therapeutic process. Modern therapeutic strategies in the treatment of diabetes mellitus are aimed at developing new methods of personalized antioxidant therapy, including ROS sources targeting combined with new ways of antioxidant delivery.Restenosis remains the main complication after percutaneous coronary interventions in patients with coronary heart disease. The causes of its development include, in particular, genetic factors. We studied polymorphic loci of genes encoding endothelin-1 (EDN1 rs5370), endothelin-1 receptor (EDNRA rs5333), endothelin-converting enzyme (ECE1 rs1076669), and endothelial NO synthase (eNOS rs1549758, eNOS rs1799983, and eNOS rs2070244) in the context of in-stent restenosis development. It was found that the analyzed polymorphisms of the endothelin system genes were more significant for patients aged ≥ 65 years, while the polymorphic loci of the endothelial NO synthase gene (eNOS rs1799983 and eNOS rs1549758) were predominantly associated with time of in-stent restenosis. The obtained results can be useful for comprehensive assessment of the restenosis risk factors and the choice of optimal treatment for patients with coronary heart disease before elective surgical intervention.Remotely Piloted Aerial Systems (RPAS) are poised to revolutionize healthcare in out-of-hospital settings, either from necessity or practicality, especially for remote locations. RPAS have been successfully used for surveillance, search and rescue, delivery, and equipping drones with telemedical capabilities being considered. However, we know of no previous consideration of RPAS-delivered tele-ultrasound capabilities. Of all imaging technologies, ultrasound is the most portable and capable of providing real-time point-of-care information regarding anatomy, physiology, and procedural guidance. Moreover, remotely guided ultrasound including self-performed has been a backbone of medical care on the International Space Station since construction. The TeleMentored Ultrasound Supported Medical Interventions Group of the University of Calgary partnered with the Southern Alberta Institute of Technology to demonstrate RPAS delivery of a smartphone-supported tele-ultrasound system by the SwissDrones SDO50 RPAS. Upon receipt of the sanitized probe, a completely ultrasound-naïve volunteer was guided by a remote expert located 100 km away using online video conferencing (Zoom), to conduct a self-performed lung ultrasound examination. It proved feasible for the volunteer to examine their anterior chest, sides, and lower back bilaterally, correlating with standard recommended examinations in trauma/critical care, including the critical locations of a detailed COVID-19 lung diagnosis/surveillance examination. We contend that drone-delivered telemedicine including a tele-ultrasound capability could be leveraged to enhance point-of-care diagnostic accuracy in catastrophic emergencies, and allow diagnostic capabilities to be delivered to vulnerable populations in remote locations for whom transport is impractical or undesirable, speeding response times, or obviating the risk of disease transmission depending on the circumstances.We develop and evaluate a deep learning algorithm to classify multiple catheters on neonatal chest and abdominal radiographs. A convolutional neural network (CNN) was trained using a dataset of 777 neonatal chest and abdominal radiographs, with a split of 81%-9%-10% for training-validation-testing, respectively. We employed ResNet-50 (a CNN), pre-trained on ImageNet. Ground truth labelling was limited to tagging each image to indicate the presence or absence of endotracheal tubes (ETTs), nasogastric tubes (NGTs), and umbilical arterial and venous catheters (UACs, UVCs). The dataset included 561 images containing two or more catheters, 167 images with only one, and 49 with none. Performance was measured with average precision (AP), calculated from the area under the precision-recall curve. On our test data, the algorithm achieved an overall AP (95% confidence interval) of 0.977 (0.679-0.999) for NGTs, 0.989 (0.751-1.000) for ETTs, 0.979 (0.873-0.997) for UACs, and 0.937 (0.785-0.984) for UVCs. Performance was similar for the set of 58 test images consisting of two or more catheters, with an AP of 0.975 (0.255-1.000) for NGTs, 0.997 (0.009-1.000) for ETTs, 0.981 (0.797-0.998) for UACs, and 0.937 (0.689-0.990) for UVCs. Our network thus achieves strong performance in the simultaneous detection of these four catheter types. Radiologists may use such an algorithm as a time-saving mechanism to automate reporting of catheters on radiographs.This work demonstrates a slow, sustained drug delivery system that provides on-demand delivery bursts through the application of pulsed therapeutic ultrasound (TUS). Insoluble β-cyclodextrin-polymer (pCD) disks were loaded with a saturated antibiotic solution of rifampicin (RIF) and used for drug delivery studies. To obtain on-demand release from the implants, TUS was applied at an intensity of 1.8 W/cm2. The therapeutic efficacy of the combination treatment was assessed in bacterial culture via an in vitro Staphylococcus aureus bioluminescence assay. The results demonstrated that the application of pulsed TUS at 3 MHz and 1.8 W/cm2 to pCD implants leads to a significantly higher short-term burst in the drug release rate compared to samples not treated with TUS. The addition of TUS increased the drug release by 100% within 4 days. The pCD disk + RIF stimulated with TUS showed a comparatively higher bacterial eradication with CFU/mL of 4.277E+09, and 8.00E+08 at 1 and 24 h compared with control treated bacteria at 1.48E+10. Overall, these results suggest that the addition of pulsed TUS could be an effective technology to noninvasively expedite antibiotic release on demand at desired intervals.

COVID-19 pandemic radically transformed our daily clinical practice, raising the need not to lose close contact with patients without being able to see them face-to-face. These issues are even more felt and evident in fragile patients, as those affected by neuromuscular disease. An important help came from new digital technologies that allow clinicians to remotely monitor health status and any deterioration of chronically ill patients.

In this mini-review, an initiative of the „Digital Technologies, Web and Social Media Study Group” of the Italian Society of Neurology, we propose to analyze the approach to neuromuscular patients by looking over raising evidence on the main cornerstones of Telemedicine (TM) clinician-patient interaction, remote clinical assessment, remote monitoring, and digital therapeutics. In particular, we explored the strategies developed by researchers and their impact on the physical and emotional status of the patients, with particular focusing on their adherence to the program of to everyone.

N-Pep-12 is a dietary supplement with neuroprotective and pro-cognitive effects, as shown in experimental models and clinical studies on patients after ischemic stroke. We tested the hypothesis that N-Pep-12 influences quantitative electroencephalography (QEEG) parameters in patients with subacute to chronic supratentorial ischemic lesions.

We performed secondary data analysis on an exploratory clinical trial (ISRCTN10702895), assessing the efficacy and safety of 90 days of once-daily treatment with 90 mg N-Pep-12 on neurocognitive function and neurorecovery outcome in patients with post-stroke cognitive impairment against a control group. All participants performed two 32-channel QEEG in resting and active states at baseline (30-120 days after stroke) and 90 days later. Power spectral density on the alpha, beta, theta, delta frequency bands, delta/alpha power ratio (DAR), and (delta+theta)/(alpha+beta) ratio (DTABR) were computed and compared across study groups using means comparison and descriptive mets needed to consolidate our findings.Ethyl-acetate is important for the flavor and aroma of the alcoholic beverages, therefore, there have been extensive efforts toward increasing its production by engineering yeast strains. In this study, we reported a new approach to breed non-genetic modified producing yeast strain with higher ethyl-acetate production for beer brewing. First, we demonstrated the positive effect of higher acetic acid concentration on inducing the expression of acetyl-CoA synthetase (ACS). Then, we applied adaptive laboratory evolution method to evolve strain with higher expression level of ACS. As a result, we obtained several evolved strains with increased ACS expression level as well as ethyl-acetate production. In 3 L scale fermentation, the optimal strain EA60 synthesized more ethyl-acetate than M14 at the same time point. At the end of fermentation, the ethyl-acetate production in EA60 was 21.4% higher than M14, while the other flavor components except for acetic acid were changed in a moderate degree, indicating this strain had a bright prospect in industrial application. Moreover, this study also indicated that ACS1 played a more important role in increasing the acetic acid tolerance of yeast, while ACS2 contributed to the synthesis of cytosol acetyl-CoA, thereby facilitating the production of ethyl-acetate during fermentation.Porcine circovirus type 2 (PCV2), an important pig viral pathogen, can cause porcine circovirus-associated disease (PCVAD), resulting in economic losses associated with decreased growth and mortalities. The diagnosis of PCVAD is complex requiring clinical, pathological and virological approaches. This study assessed PCV2 infection using histopathology and immunohistochemistry (IHC) on tissue samples and quantitative polymerase chain reaction (qPCR) on serum samples from 47 grower-finisher pigs allocated in three clinical groups in the Philippines. Typical PCV2 histopathological lesions were observed in mediastinal lymph nodes (MLN) of eight of 47 pigs. Lymphoid depletion was seen in all eight pigs and granulomatous inflammation in one of these pigs. Four of these eight pigs were PCV2 positive by both IHC and qPCR. IHC revealed PCV2 antigen in 8 pigs in at least one of the following tissues MLN (5/8), spleen (3/8), tonsils (4/8) and lungs (5/8). PCV2 antigen was observed in 3/8 MLN with lymphoid depletion and in one MLN with depletion and granulomatous inflammation. The qPCR test showed that 33 sera had a non-detectable level, twelve had  106 PCV2 DNA copies/ml serum. These findings suggest that PCVAD is present in the Philippines and confirm the challenges of PCVAD diagnosis as different patterns of results were obtained from the different tests.

Nonoperative management (NOM) has been widely accepted as one of the standard treatments for patients with acute appendicitis. However, predictive factors for the failure of NOM have not been thoroughly investigated.

A total of 196 patients with acute appendicitis underwent NOM between April 2014 and December 2020. Of these 196 patients, 24 patients failed NOM and required emergency surgery (failure group n = 24), while the other 172 patients were successfully treated with NOM (success group n = 172). These two groups were compared, and the predictive factors for the failure of NOM were investigated.

The number of patients who had a previous history of stroke was significantly increased in the failure group (12.5% vs. 2.9%, p = 0.026). Incarceration of an appendicolith on CT images was significantly associated with the failure group (20.8% vs. 1.7%, p < 0.001), while neither the presence of an appendicolith nor abscess was associated. The presence of periappendiceal fluid was significantly associated with the failure group (50.