Stališča za obravnavo otrok, mlajših od 18 let, z akutno zgolj periferno okvaro obraznega živca

V prispevku predlagamo stališča za obravnavo otrok, mlajših od 18 let, z akutno osamljeno periferno okvaro obraznega živca. Priporočila temeljijo na podatkih iz literature in na lastnih izkušnjah za obravnavo otrok z akutno osamljeno periferno okvaro obraznega živca

implications of glycemic control

Funding Information: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the Slovenian Research and Innovation Agency ARIS (P3-0343, and J7-1820). It was partially funded by the ISPAD JDRF Fellowship Grant 2018. JG was supported by the ESPE fellowship grant. Publisher Copyright: Copyright © 2024 Čugalj Kern, Kovač, Šket, Tesovnik, Jenko Bizjan, Galhardo, Battelino, Bratina and Dovč.Background: Prolonged hyperglycemia causes diabetes-related micro- and macrovascular complications, which combined represent a significant burden for individuals living with diabetes. The growing scope of evidence indicates that hyperglycemia affects the development of vascular complications through DNA methylation. Methods: A genome-wide differential DNA methylation analysis was performed on pooled peripheral blood DNA samples from individuals with type 1 diabetes (T1D) with direct DNA sequencing. Strict selection criteria were used to ensure two age- and sex-matched groups with no clinical signs of chronic complications according to persistent mean glycated hemoglobin (HbA1c) values over 5 years: HbA1c8% (N=10). Results: Between the two groups, 8385 differentially methylated CpG sites, annotated to 1802 genes, were identified. Genes annotated to hypomethylated CpG sites were enriched in 48 signaling pathways. Further analysis of key CpG sites revealed four specific regions, two of which were hypermethylated and two hypomethylated, associated with long non-coding RNA and processed pseudogenes. Conclusions: Prolonged hyperglycemia in individuals with T1D, who have no clinical manifestation of diabetes-related complications, is associated with multiple differentially methylated CpG sites in crucial genes and pathways known to be linked to chronic complications in T1D.publishersversionpublishe

Exploring early DNA methylation alterations in type 1 diabetes: implications of glycemic control

BackgroundProlonged hyperglycemia causes diabetes-related micro- and macrovascular complications, which combined represent a significant burden for individuals living with diabetes. The growing scope of evidence indicates that hyperglycemia affects the development of vascular complications through DNA methylation.MethodsA genome-wide differential DNA methylation analysis was performed on pooled peripheral blood DNA samples from individuals with type 1 diabetes (T1D) with direct DNA sequencing. Strict selection criteria were used to ensure two age- and sex-matched groups with no clinical signs of chronic complications according to persistent mean glycated hemoglobin (HbA1c) values over 5 years: HbA1c<7% (N=10) and HbA1c>8% (N=10).ResultsBetween the two groups, 8385 differentially methylated CpG sites, annotated to 1802 genes, were identified. Genes annotated to hypomethylated CpG sites were enriched in 48 signaling pathways. Further analysis of key CpG sites revealed four specific regions, two of which were hypermethylated and two hypomethylated, associated with long non-coding RNA and processed pseudogenes.ConclusionsProlonged hyperglycemia in individuals with T1D, who have no clinical manifestation of diabetes-related complications, is associated with multiple differentially methylated CpG sites in crucial genes and pathways known to be linked to chronic complications in T1D

A multinational prospective observational real-world cohort study

Funding Information: The authors thank the ISPAD executive committee and ISPAD JENIOUS members for their support. An abstract with partial study data was presented in June 2021 at the Virtual Advanced Technologies and Treatment for Diabetes (ATTD) conference. There was no commercial sponsor for this study. This study was partially funded by the ISPAD JDRF Fellowship Grant. KD was supported by the Slovenian National Research Agency (grant nos. J3–6798, V3–1505, and P3–0343). Funding Information: ISPAD, Grant/Award Number: ISPAD JDRF Fellowship Grant; Slovenian National Research Agency, Grant/Award Numbers: J36798, V31505, P30343 Funding information Funding Information: KD received honoraria for participation on the speakerʼs bureau of Pfizer, Novo Nordisk, and Eli Lilly. JG received speakerʼs honoraria from Eli Lilly and Sanofi, and clinical trials investigatorʼs payment from Novo Nordisk. RM received advisory board honoraria from Abbott and Novo Nordisk. JP received speakerʼs honoraria from Medtronic. JS serves as a consultant to Cecelia Health, Lexicon, Lilly, Insulet, Medtronic, and Sanofi, is a member of the advisory board for Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic, and the T1D Fund and Vertex, and has had research support from the NIH, JDRF, and the Helmsley Charitable Trust. Her institution has had research support from Medtronic and Insulet. AC received speakerʼs honoraria from Medtronic, Eli Lilly, and Novo Nordisk. TB received speakerʼs honoraria from DexCom, Medtronic, Novo Nordisk, Roche, Sanofi, and Ypsomed, and advisory board honoraria from Ascensia, AstraZeneca, DexCom, Medtronic, and Sanofi.publishersversionpublishe

Continuous glucose monitoring use and glucose variability in very young children with type 1 diabetes ( VibRate ): A multinational prospective observational real‐world cohort study

info:eu-repo/semantics/publishedVersio

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Human papillomavirus infection in patients with inverted papilloma’s of nose and paranasal sinuses and with associated squamous cell carcinoma

Invertirani papilomi (IP) nosu in obnosnih votlin so redki benigni epitelni lokalno agresivni tumorji. Za IP so značilne nagnjenost k ponovitvam, povezava s prehodom v ploščatocelični karcinom (PCK) in zmožnost destrukcije kostnine. Etiologija IP še ni pojasnjena. Podatki številnih raziskav o povezavi okužbe s človeškimi papilomavirusi (HPV) in nastankom IP so nasprotujoči si in še vedno nezadostni, da bi potrdili povezavo. Opazna odsotnost klasičnih genskih sprememb v IP je nakazala možnost, da maligno alteracijo in nastanek PCK v IP lahko povzročajo visokorizični genotipi HPV. Do danes vloga HPV v PCK v IP še ni pojasnjena. Skupino genotipov virusov iz družine Papillomaviridae, ki so pomembni v humani medicini, imenujemo človeški papilomavirusi. Izmed petih rodov, v katere uvrščamo genotipe HPV, je najpomembnejši rod alfa. Glede na onkogeni potencial jih delimo na nizko- in visokorizične genotipe, ki izražajo tropizem za sluznico ali kožo. Povzročajo lahko navadne ali ploščate, kožne ali anogenitalne bradavice, papilome v ustni votlini ali grlu in rak materničnega vratu, zadnjika, penisa, vulve, nožnice, ustnega žrela in nosne votline. Namen naše raziskave je bil ugotoviti prisotnost HPV DNA pri bolnikih z IP, PCK v IP in pri kontrolni skupini. Samo dokaz HPV DNA v IP in PCK v IP ne zadošča za opredelitev HPV kot enega od etioloških dejavnikov v nastanku bolezni. HPV je lahko namreč le naključno prisoten (by stander). Zato smo želeli ugotoviti tudi morebitno integracijo virusne DNA v človeški genom in s tem povezano transkripcijsko aktivnost HPV v IP in PCK v IP. Dodatno smo pri naših bolnikih pridobili podatke o lokalizaciji IP in vplivu vrste kirurškega zdravljenja na ponovitev bolezni. V raziskavo smo vključili biopsijske vzorce 83 bolnikov z IP, 5 bolnikov s PCK v IP in 61 bolnikov kontrolne skupine, pri katerih smo ob operaciji nosnega pretina odstranili tudi del kompenzatorno zadebeljene sluznice v spodnji nosni školjki. Z dvema občutljivima različicama PCR (GP5+/GP6+ in CPI/CPIIg) na 218 tkivnih vzorcih 146 bolnikov z IP, PCK v IP ali kontrolne skupine nam je HPV DNA uspelo dokazati v tkivnih vzorcih 22 bolnikov z IP, 3 bolnikov s PCK v IP in 7 bolnikov iz kontrolne skupine. Ugotovili smo, da je okužba s HPV pri bolnikih z IP ali PCK v IP v nosu in obnosnih votlinah statistično pomembno pogostejša kot v kontrolni skupini. Z metodo ISH mRNA E6/E7 HPV smo transkripcijsko aktivnost dokazali pri dveh bolnikih z IP. HPV je bil pri naših bolnikih z IP redko prisoten v integrirani transkripcijsko aktivni obliki in najverjetneje ni eden od pomembnih dejavnikov v etiologiji IP. Prisotnost HPV DNA pri bolnikih z IP, pri katerih je prišlo do ponovitve IP po kirurškem zdravljenju, ni bila pogostejša kot pri bolnikih, pri katerih ni prišlo do ponovitve bolezni, tako da ni napovedni dejavnik za ponovitev. V naši raziskavi nismo ugotovili statistično pomembnih razlik med pogostostjo HPV DNA med bolniki s PCK v IP in bolniki z IP. Z metodo ISH mRNA E6/E7 HPV smo transkripcijsko aktivnost dokazali pri enem bolniku s PCK v IP. Glede na rezultate ISH mRNA E6/E7 HPV menimo, da HPV najverjetneje ni eden od glavnih etioloških dejavnikov v nastanku PCK v IP, da pa pri PCK v IP kljub temu obstajajo primeri, v katerih je integriran in transkripcijsko aktiven HPV lahko vpleten v etiopatogenezo PCK. S kombinacijo imunohistokemičnega izražanja beljakovine p16 in odsotnosti izražanja beljakovine pRb smo v naši raziskavi potrdili z metodo ISH za E6/E7 mRNA dokazano integrirano in transkripcijsko aktivno okužbo s HPV pri bolniku s PCK v IP. Imunohistokemično izražanje beljakovine p16 je bilo prisotno pri dveh naših bolnikih s PCK v IP. Samo pri enem je bila z metodo ISH za E6/E7 mRNA dokazana integracija in transkripcijska aktivnost. Pri naših bolnikih s PCK v IP glede na samostojen izvid p16 torej ne moremo sklepati o morebitni integraciji in transkripcijski aktivnosti HPV. Metoda izražanja p16 je lahko samo komplementarna metodi ISH za E6/E7 mRNA. Pri naših bolnikih z IP so bile ponovitve po kirurškem zdravljenju z zunanjim pristopom pogostejše kot pri bolnikih, zdravljenih endoskopsko. Odstotek ponovitev je približno enak odstotku ponovitev v objavljenih raziskavah, zato kirurško zdravljenje naših bolnikov z IP lahko ocenimo kot uspešno.Inverted papilloma (IP) is a rare benign epithelial sinonasal lesion with a propensity for locally invading the surrounding tissues. They have strong tendency to recur and malignant transformation is reported. Pressure erosion of bone may also be apparent. Several studies have proposed human papillomaviruses (HPV) infection to be involved in the etiology of IPs, but the reports are contradictory and still insufficient to prove the connection. The notable absence of conventional genetic alterations in IPs has suggested the possibility of high-risk human papillomavirus (HPV) as an alternative driver of malignant transformation. To date, however, the role of HPV in carcinomatous transformation of IP is unresolved. The group of viruses from Papillomaviridae family which are important in human medicine are named human papillomaviruses. Out of five viral genera in which this family is further divided, the alpha genus is the most important. They are further divided in low-risk and high-risk genotypes which can show tissue tropism or predilection for infecting mucous membrane or skin. They can cause common or flat warts, skin or anogenital warts, mouth papilloma, laryngeal papillomatosis and cancer of the cervix, anus, penis, vulva, vagina, oropharynx and sinonasal tract. The aim of our study was to find out the presence of HPV DNA in IPs, IPs associated with squamous cell carcinoma (IPsSCC) and in control group. However, simply finding HPV DNA cannot distinguish HPV infections that are truly causative from those that are clinically insignificant (&#698passenger&#698HPV). That is why we wanted to identify integration of viral DNA and HPV transcriptional activity in IPs and in IPsSCC. In our study we have additionally collected the data on location of IPs and the influence of type of the treatment on recurrence after surgical treatment. Our study included tissue samples from 83 patients with IP, 5 patients with IPsSCC and 61 patients from control group in whom we removed a part of inferior turbinate during the surgery for deviated nasal septum. Using two primer sets (GP5+/GP6+ in CPI/CPIIg), PCR amplification was performed on 218 tissue samples from 146 patients with IPs, IPsPCC or control group and HPV DNA was detected in tissue samples from 22 patients with IP, 3 patients with IPsCC and 7 patients from control group. The presence of HPV DNA was statistically higher in patients with IPs and patients with IPsSCC in comparison with the control group. Using the in situ hybridization (ISH) for detecting HPV E6/E7 mRNA transcripts we found transcriptional activity in 2 patients with IP. In our patients with IPs HPV was rarely present in integrated and transcriptionally active form and most probably isn’t one of the important etiological factors of IPs. The presence of HPV DNA in patients with recurrence of IP after surgical treatment was not statistically higher in comparison to patients with no recurrence and is not a risk factor of the recurrence. In our study we did not find statistically significant differences in the presence of HPV DNA between patients with IPs and patients with IPsSCC. Using detection of the HPV E6/E7 mRNA transcripts we have demonstrated integration and transcriptional activity in one patient with IPsSCC. According to the results of ISH mRNA E6/E7 HPV we believe that HPV is not one of the most important etiological factors in development of IPsSCC but furthermore we do believe that there are the cases in which integrated and transcriptionally active HPV can be involved in the etiopathogenesis of IPsSCC. Protein expression was analysed by immunohistochemistry. In our study the combination of high expression of p16 and low expression of pRb additionally confirmed integrated and transcriptionally active HPV infection in patient with IPsSCC. Expression of p16 was immunohistochemically present in 2 patients with IPsSCC. Only one had with ISH mRNA E6/E7 HPV proven integration and transcriptional activity. In our patients with IPsSCC immunostaining for p16 cannot substitute ISH mRNA E6/E7 HPV for HPV testing. Immunostaining for p16 can only be used as a complimentary procedure for HPV testing in IPsSCC. In our patients with IP the recurrences after surgery were more common after external approach than after endoscopic treatment. The percentage of recurrences and treatment success is comparable to published studies and we consider the treatment of our patients as successful

Mechanisms of premature fracture in modular neck stems made of CoCrMo/Ti6Al4V and Ti6Al4V/Ti6Al4V alloy

In this paper, we present the mechanisms of premature fracture of modular neck stems in two case studies: (I) when the neck and stem are both made of the same Ti6Al4V alloy, and (II) when the neck and stem are made from two different alloys, CoCrMo and Ti6Al4V alloy. Our study integrates two orthopedic patients who have undergone primary uncemented THA for usual indications in two orthopedic centers (Community Health Centre and University Medical Centre). Both centers are part of the national public health care system. Both surgeries were performed by two skilled orthopedic surgeons with more than 10 years of experience in THA. The survivorship of the modular neck of cast CoCrMo alloy was 24 months. The survivorship of the modular neck from Ti6Al4V alloy was 84 months. Multivariate analyses were performed to assess the differences in the fretting, corrosion, and fatigue of the two prematurely failed modular neck stems: stereo light microscopy (SLM), scanning electron microscopy (SEM), X-ray energy-dispersive spectroscopy (EDS), and electron backscatter diffraction (EBSD). Patient demographic information, including sex, age, body mass index, survivorship of implants, and reason for the revision, was collected from medical records. We found that fretting and fatigue occurred on both neck-stem retrievals due to additional galvanic corrosion, but the CoCrMo/Ti6Al4V alloy system suffered more corrosion due to additional galvanic corrosion and fractured earlier than the Ti6Al4V/Ti6Al4V metal alloy system. Both metallic alloy systems used in this application are known to be highly corrosion-resistant, but the bio-tribo-corrosion processes need to be understood in detail and characterized so that appropriate improvements in design and materials can be made