bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrolyzed–Reduced Water: Review I. Molecular Hydrogen Is the Exclusive Agent Responsible for the Therapeutic Effects
Authors: LeBaron Tyler W. , Sharpe Randy , Ohno Kinji
Published: November 2022

Numerous benefits have been attributed to alkaline-electrolyzed–reduced water (ERW). Sometimes these claims are associated with easily debunked concepts. The observed benefits have been conjectured to be due to the intrinsic properties of ERW (e.g., negative oxidation–reduction potential (ORP), alkaline pH, H2 gas), as well enigmatic characteristics (e.g., altered water structure, microclusters, free electrons, active hydrogen, mineral hydrides). The associated pseudoscientific marketing has contributed to the reluctance of mainstream science to accept ERW as having biological effects. Finally, through many in vitro and in vivo studies, each one of these propositions was examined and refuted one-by-one until it was conclusively demonstrated that H2 was the exclusive agent responsible for both the negative ORP and the observed therapeutic effects of ERW. This article briefly apprised the history of ERW and comprehensively reviewed the sequential research demonstrating the importance of H2. We illustrated that the effects of ERW could be readily explained by the known biological effects of H2 and by utilizing conventional chemistry without requiring any metaphysical conjecture (e.g., microclustering, free electrons, etc.) or reliance on implausible notions (e.g., alkaline water neutralizes acidic waste). The H2 concentration of ERW should be measured to ensure it is comparable to those used in clinical studies.
Schizophyllum commune Reduces Expression of the SARS-CoV-2 Receptors ACE2 and TMPRSS2
Authors: Sun Te-Kai , Huang Wen-Chin , Sun Yu-Wen , Deng Jeng-Shyan , Chien Liang-Hsuan , Chou Ya-Ni , Jiang Wen-Ping , Lin Jaung-Geng , Huang Guan-Jhong
Published: November 2022

The current global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of COVID-19 has infected hundreds of millions of people, killed millions, and continues to pose a threat. It has become one of the largest epidemics in human history, causing enormous damage to people’s lives and economies in the whole world. However, there are still many uncertainties and continued attention to the impact of SARS-CoV-2 on human health. The entry of SARS-CoV-2 into host cells is facilitated by the binding of the spike protein on the virus surface to the cell surface receptor angiotensin-converting enzyme 2 (ACE2). Furthermore, transmembrane protease serine 2 (TMPRSS2) is a host surface protease that cleaves and proteolytically activates its S protein, which is necessary for viral infection. Thus, SARS-CoV-2 uses the ACE2 receptor for cell entry and initiates the S protein using the protease TMPRSS2. Schizophyllum commune (SC) is one of the most widely distributed fungi, often found on the rotten wood of trees that has been found to have various health benefits, including anticancer, antimicrobial activity, antiparasitic, and immunomodulatory function. In this article, SC significantly diminished the expression ACE2 and TMPRSS2 protein in vitro and in vivo without cell damage. In addition, adenosine from SC was also proven in this experiment to reduce the ACE2 and TMPRSS2 expression. Thus, our findings suggest that SC and adenosine exhibit potential for the repression of SARS-CoV-2 infection via the ACE2 and TMPRSS2 axis.
Understanding In Vitro Pathways to Drug Discovery for TDP-43 Proteinopathies
Authors: Cheng Hei W. A. , Callis Timothy B. , Montgomery Andrew P. , Danon Jonathan J. , Jorgensen William T. , Ke Yazi D. , Ittner Lars M. , Werry Eryn L. , Kassiou Michael
Published: November 2022

The use of cellular models is a common means to investigate the potency of therapeutics in pre-clinical drug discovery. However, there is currently no consensus on which model most accurately replicates key aspects of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) pathology, such as accumulation of insoluble, cytoplasmic transactive response DNA-binding protein (TDP-43) and the formation of insoluble stress granules. Given this, we characterised two TDP-43 proteinopathy cellular models that were based on different aetiologies of disease. The first was a sodium arsenite-induced chronic oxidative stress model and the second expressed a disease-relevant TDP-43 mutation (TDP-43 M337V). The sodium arsenite model displayed most aspects of TDP-43, stress granule and ubiquitin pathology seen in human ALS/FTD donor tissue, whereas the mutant cell line only modelled some aspects. When these two cellular models were exposed to small molecule chemical probes, different effects were observed across the two models. For example, a previously disclosed sulfonamide compound decreased cytoplasmic TDP-43 and increased soluble levels of stress granule marker TIA-1 in the cellular stress model without impacting these levels in the mutant cell line. This study highlights the challenges of using cellular models in lead development during drug discovery for ALS and FTD and reinforces the need to perform assessments of novel therapeutics across a variety of cell lines and aetiological models.
Oxidative Status as an Attribute for Selective Antitumor Activity of Platinum-Containing Nanoparticles against Hepatocellular Carcinoma
Authors: Wawrowicz Kamil , Majkowska-Pilip Agnieszka , Szwed Marzena , Żelechowska-Matysiak Kinga , Chajduk Ewelina , Bilewicz Aleksander
Published: November 2022

Overcoming the limitations for efficient and selective drug delivery is one of the most challenging obstacles for newly designed anticancer agents. In this study, we present two types of platinum-based nanoparticles (NP), ultrasmall 2 nm PtNPs and core-shell 30 nm Au@Pt, which can be highly cytotoxic in an oxidative environment and remain biologically inactive in cells with lower oxidative status. Our research highlighted the differences in platinum nanoparticle-induced chemotoxicity and is the first study examining its mechanism as a substantial aspect of Au@Pt/PtNPs biological activity. Selectively induced oxidative stress was found to be a primary trigger of NPs’ toxicity. Significant differences between Au@Pt and PtNPs were observed especially during 24 h treatment, due to successful intranuclear PtNPs location (~13% of internalized fraction). Reactive oxygen species (ROS)-level induced from both NPs types were similar, while reduction of reduced glutathione (GSH) intracellular content was stronger after treatment with PtNPs. Any biological activity was found in HER2+ breast cancer cells, which have only slightly increased oxidative status. Platinum-containing nanoparticles are an interesting tool for the improvement of selectivity in anticancer therapies against hepatocellular carcinoma (HCC). Due to intranuclear uptake, 2 nm PtNPs seems to be more promising for further research for HCC therapy.
Protein 3D Hydration: A Case of Bovine Pancreatic Trypsin Inhibitor
Authors: Kruchinin Sergey E. , Kislinskaya Ekaterina E. , Chuev Gennady N. , Fedotova Marina V.
Published: November 2022

Characterization of the hydrated state of a protein is crucial for understanding its structural stability and function. In the present study, we have investigated the 3D hydration structure of the protein BPTI (bovine pancreatic trypsin inhibitor) by molecular dynamics (MD) and the integral equation method in the three-dimensional reference interaction site model (3D-RISM) approach. Both methods have found a well-defined hydration layer around the protein and revealed the localization of BPTI buried water molecules corresponding to the X-ray crystallography data. Moreover, under 3D-RISM calculations, the obtained positions of waters bound firmly to the BPTI sites are in reasonable agreement with the experimental results mentioned above for the BPTI crystal form. The analysis of the 3D hydration structure (thickness of hydration shell and hydration numbers) was performed for the entire protein and its polar and non-polar parts using various cut-off distances taken from the literature as well as by a straightforward procedure proposed here for determining the thickness of the hydration layer. Using the thickness of the hydration shell from this procedure allows for calculating the total hydration number of biomolecules properly under both methods. Following this approach, we have obtained the thickness of the BPTI hydration layer of 3.6 Å with 369 water molecules in the case of MD simulation and 3.9 Å with 333 water molecules in the case of the 3D-RISM approach. The above procedure was also applied for a more detailed description of the BPTI hydration structure near the polar charged and uncharged radicals as well as non-polar radicals. The results presented for the BPTI as an example bring new knowledge to the understanding of protein hydration.
Sex Steroid Hormone Analysis in Human Tear Fluid Using a Liquid Chromatography—Mass Spectrometry Method
Authors: Robciuc Alexandra , Savolainen-Peltonen Hanna , Haanpää Mikko , Moilanen Jukka A. O. , Mikkola Tomi S.
Published: November 2022

The marked sexual dimorphism prevalent in inflammatory/autoimmune diseases is mostly due to sex hormone actions. One common eye disease that disproportionately affects women is dry eye. Thus, our aim was to optimise our highly sensitive liquid chromatography–tandem mass spectrometry method for steroid hormone quantification in tear fluid (TF). We used tears and matched serum samples from 10 heathy individuals. Estrone, estradiol testosterone, progesterone, androstenedione, and dehydroepiandrosterone, were quantified with an HPLC coupled with a Triple Quad 5500 MS. Estrone was measured in 80% of female and 20% of male TF samples (mean ± SD, 68.9 ± 62.2 pmol/L), whereas estradiol was undetectable in tears. Progesterone was identified in half of the female tear samples (2.91 ± 3.47 nmol/L) but in none of the male samples, whereas testosterone was quantifiable only in male tears (0.24 ± 0.1 nmol/L). TF hormone levels were, on average, from 1.4% to 55% of systemic values. Estrone, progesterone, and testosterone levels in tears correlated with the matching serum samples (r = 0.82, 0.79, and 0.85, respectively), but androstenedione and dehydroepiandrosterone showed no correlations. Our LC–MS/MS method could detect five out of the six steroid hormones studied in individual human TF samples and could therefore be used to analyse the role of sex steroids in eye diseases.
RvD1n-3 DPA Downregulates the Transcription of Pro-Inflammatory Genes in Oral Epithelial Cells and Reverses Nuclear Translocation of Transcription Factor p65 after TNF-α Stimulation
Authors: Balta Maria G. , Schreurs Olav , Halder Rashi , Küntziger Thomas M. , Saetre Frank , Blix Inger Johanne S. , Baekkevold Espen S. , Glaab Enrico , Schenck Karl
Published: November 2022

Specialized pro-resolving mediators (SPMs) are multifunctional lipid mediators that participate in the resolution of inflammation. We have recently described that oral epithelial cells (OECs) express receptors of the SPM resolvin RvD1n-3 DPA and that cultured OECs respond to RvD1n-3 DPA addition by intracellular calcium release, nuclear receptor translocation and transcription of genes coding for antimicrobial peptides. The aim of the present study was to assess the functional outcome of RvD1n-3 DPA–signaling in OECs under inflammatory conditions. To this end, we performed transcriptomic analyses of TNF-α-stimulated cells that were subsequently treated with RvD1n-3 DPA and found significant downregulation of pro-inflammatory nuclear factor kappa B (NF-κB) target genes. Further bioinformatics analyses showed that RvD1n-3 DPA inhibited the expression of several genes involved in the NF-κB activation pathway. Confocal microscopy revealed that addition of RvD1n-3 DPA to OECs reversed TNF-α-induced nuclear translocation of NF-κB p65. Co-treatment of the cells with the exportin 1 inhibitor leptomycin B indicated that RvD1n-3 DPA increases nuclear export of p65. Taken together, our observations suggest that SPMs also have the potential to be used as a therapeutic aid when inflammation is established.
Osteomalacia Is Not a Single Disease
Authors: Cianferotti Luisella
Published: November 2022

Among bone-material qualities, mineralization is pivotal in conferring stiffness and toughness to the bone. Osteomalacia, a disease ensuing from inadequate mineralization of the skeleton, is caused by different processes leading to decreased available mineral (calcium and/or phosphate) or enzymatic alterations. Vitamin D deficiency, which remains the major cause of altered mineralization leading to inadequate intestinal calcium and phosphate absorption, may be also associated with other conditions primarily responsible for abnormal mineralization. Given the reality of widespread vitamin D inadequacy, a full biochemical assessment of mineral metabolism is always necessary to rule out or confirm other conditions. Both too-high or too-low serum alkaline phosphatase (ALP) levels are important for diagnosis. Osteomalacic syndrome is reversible, at least in part, by specific treatment. Osteomalacia and bone mineralization themselves constitute largely unexplored fields of research. The true prevalence of the different forms of osteomalacia and the recovery after proper therapy have yet to be determined in the real world. Although non-invasive techniques to assess bone mineralization are not available in clinical practice, the systematic assessment of bone quality could help in refining the diagnosis and guiding the treatment. This review summarizes what is known of osteomalacia recent therapeutic developments and highlights the future issues of research in this field.
Glucagon-like Peptide-1 Receptor in the Human Hypothalamus Is Associated with Body Mass Index and Colocalizes with the Anorexigenic Neuropeptide Nucleobindin-2/Nesfatin-1
Authors: Psilopanagioti Aristea , Nikou Sofia , Logotheti Souzana , Arbi Marina , Chartoumpekis Dionysios V. , Papadaki Helen
Published: November 2022

Data on animals emphasize the importance of the neuronal glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) for feeding suppression, although it is unclear whether astrocytes participate in the transduction of anorectic GLP-1R-dependent signals. In humans, the brain circuitry underlying these effects remains insufficiently investigated. The present study aimed to explore GLP-1R protein expression in the human hypothalamus and its correlation with body mass index (BMI). Sections of hypothalamus from 28 autopsy cases, 11 with normal weight (BMI < 25 kg/m2) and 17 with non-normal weight (BMI ≥ 25 kg/m2), were examined using immunohistochemistry and double immunofluorescence labeling. Prominent GLP-1R immunoexpression was detected in neurons of several hypothalamic nuclei, including paraventricular, supraoptic, and infundibular nuclei; the lateral hypothalamic area (LH); and basal forebrain nuclei. Interestingly, in the LH, GLP-1R was significantly decreased in individuals with BMI ≥ 25 kg/m2 compared with their normal weight counterparts (p = 0.03). Furthermore, GLP-1R was negatively correlated (τb = −0.347, p = 0.024) with BMI levels only in the LH. GLP-1R extensively colocalized with the anorexigenic and antiobesogenic neuropeptide nucleobindin-2/nesfatin-1 but not with the astrocytic marker glial fibrillary acidic protein. These data suggest a potential role for GLP-1R in the regulation of energy balance in the human hypothalamus. In the LH, an appetite- and reward-related brain region, reduced GLP-1R immunoexpression may contribute to the dysregulation of homeostatic and/or hedonic feeding behavior. Possible effects of NUCB2/nesfatin-1 on central GLP-1R signaling require further investigation.
Prognostic Implications of Left Ventricular Ejection Fraction and Left Ventricular End-Diastolic Diameter on Clinical Outcomes in Patients with ICD
Authors: Cheng Sijing , Deng Yu , Huang Hao , Liu Xi , Yu Yu , Chen Xuhua , Gu Min , Niu Hongxia , Hua Wei
Published: November 2022

Background: Left ventricular ejection fraction (LVEF) is a suboptimal indicator of risk stratification for patients with an implantable cardioverter defibrillator (ICD). Studies have shown that left ventricular end-diastolic diameter (LVEDD) was associated with all-cause mortality and ventricular arrhythmias. We examined the quantified prognostic value of LVEF and LVEDD for clinical outcomes, respectively. Method: This study retrospectively enrolled patients with ICD implantation in a single center. The associations between LVEF or LVEDD and all-cause mortality and appropriate shocks were analyzed using Cox regression and Fine-gray competing risk regression, respectively. Result: During a median follow up of 59.6 months, 168/630 (26.7%) patients died. LVEF and LVEDD were strongly associated with all-cause mortality (LVEF per 10%: HR 0.77, 95%CI 0.64–0.93, p = 0.006; LVEDD per 10 mm: HR 1.54, 95%CI 1.27–1.85, p < 0.001). After a median interrogation time of 37.1 months, 156 (24.8%) patients received at least one shock. LVEF was not associated with appropriate shock, whereas larger LVEDD (per 10 mm) was significantly associated with a higher risk of shock (HR: 1.27, 95%CI 1.06–1.52, p = 0.008). The addition of LVEF or LVEDD to clinical factors provided incremental prognostic value and discrimination improvement for all-cause mortality, while only the addition of LVEDD to clinical factors improved prognostic value for shock intervention. Conclusions: Baseline LVEF and LVEDD show a linear relationship with all-cause mortality in patients with ICD. However, whereas LVEF is not associated with shock, a linear relationship exists between LVEDD and appropriate shock. LVEDD adds more predictive value in relation to all-cause mortality and appropriate shocks than LVEF.
Longitudinal Change of Choroidal Thickness after Pars Plana Vitrectomy for Idiopathic Epiretinal Membrane
Authors: Kim Dong-Ik , Bae Ki-Woong , Hwang Daniel Duck-Jin
Published: November 2022

This study aimed to investigate changes in choroidal thickness after pars plana vitrectomy (PPV) with and without air tamponade in patients with idiopathic epiretinal membrane (ERM). We retrospectively reviewed 61 patients with ERM who underwent a 25-gauge transconjunctival sutureless PPV. The patients were divided into two groups: the air tamponade group (30 eyes) and the nontamponade group (31 eyes). Subfoveal choroidal thickness (SFCT) was analyzed over 12 months. No significant differences were seen between the two groups at baseline. For all patients, the SFCT was significantly thicker at 1 month after surgery and significantly thinner at 6 and 12 months after surgery than preoperative values. In the subgroup analysis, there was no significant difference in SFCT 3 months after surgery compared with the preoperative values in both groups, but SFCT was significantly lower 6 months after surgery in both groups. In conclusion, our results showed that choroidal thickness temporarily increased after surgery and then gradually decreased until 12 months after the PPV for ERM.
Time Trends and Sex Differences in the Association between Diabetes and Chronic Neck Pain, Chronic Low Back Pain, and Migraine. Analysis of Population-Based National Surveys in Spain (2014–2020)
Authors: Jiménez-García Rodrigo , López-de-Andrés Ana , de Miguel-Diez Javier , Zamorano-León José J. , Carabantes-Alarcón David , Noriega Concepción , Cuadrado-Corrales Natividad , Pérez-Farinos Napoleón
Published: November 2022

(1) Background: To assess the time trend in the prevalence of chronic neck pain (CNP), chronic low back pain (CLBP), and migraine or frequent headache (MFH) among people with diabetes in Spain from 2014 to 2020, this study identified sex differences and compared the prevalence of these pain sites between people with diabetes and age–sex-matched non-diabetic subjects. (2) Methods: The study design included a cross-sectional and a case–control study. The data were obtained from the European Health Interview Surveys for Spain conducted in 2014 and 2020. The presence of diabetes, CNP, CLBP, and MFH was self-reported. Study covariates included sociodemographic characteristics, comorbidities, lifestyles, and pain-related variables. (3) Results: Among people with diabetes, the prevalence of CNP, CLBP, and MFH did not improve from 2014 to 2020. Women with diabetes had a significantly higher prevalence of all the pain sites analyzed than men with diabetes. After matching by sex and age, the prevalence of CNP (26.0% vs. 21.1%; p < 0.001), CLBP (31.2% vs. 25.0%; p < 0.001), and MFH (7.7% vs. 6.5%; p = 0.028) was higher for people with diabetes than for those without diabetes. Self-reported mental disease was independently associated with reporting the three pain sites analyzed in people with diabetes. (4) Conclusions: The prevalence of CNP, CLBP, and MFH has remained stable over time. Remarkable sex differences were found, with a higher prevalence among women than men with diabetes. Diabetes was associated with reporting in all the pain sites analyzed. Self-reported mental disease was associated with reporting CNP, CLBP, and MFH.
Opioid Free Anesthesia in Thoracic Surgery: A Systematic Review and Meta Analysis
Authors: D’Amico Filippo , Barucco Gaia , Licheri Margherita , Valsecchi Gabriele , Zaraca Luisa , Mucchetti Marta , Zangrillo Alberto , Monaco Fabrizio
Published: November 2022

Introduction: Recent studies showed that balanced opioid-free anesthesia is feasible and desirable in several surgical settings. However, in thoracic surgery, scientific evidence is still lacking. Thus, we conducted the first systematic review and meta-analysis of opioid-free anesthesia in this field. Methods: The primary outcome was the occurrence of any complication. Secondary outcomes were the length of hospital stay, recovery room length of stay, postoperative pain at 24 and 48 h, and morphine equivalent consumption at 48 h. Results: Out of 375 potentially relevant articles, 6 studies (1 randomized controlled trial and 5 observational cohort studies) counting a total of 904 patients were included. Opioid-free anesthesia compared to opioid-based anesthesia, was associated with a lower rate of any complication (74 of 175 [42%] vs. 200 of 294 [68%]; RR = 0.76; 95% CI, 0.65–0.89; p < 0.001; I2 = 0%), lower 48 h morphine equivalent consumption (MD −14.5 [−29.17/−0.22]; p = 0.05; I2 = 95%) and lower pain at 48 h (MD −1.95 [−3.6/0.3]; p = 0.02, I = 98%). Conclusions: Opioid-free anesthesia in thoracic surgery is associated with lower postoperative complications, and less opioid demand with better postoperative analgesia at 48 h compared to opioid-based anesthesia.
Safety and Feasibility of Catheter Ablation Procedures in Patients with Bleeding Disorders
Authors: Feher Marcel , Saguner Ardan M. , Kirstein Bettina , Vogler Julia , Eitel Charlotte , Phan Huong-Lan , Keelani Ahmad , Cimen Tolga , Hatahet Sascha , Trajanoski Darko , Samara Omar , Kuck Karl-Heinz , Tilz Roland R. , Heeger Christian-H.
Published: November 2022

Aims/Objectives: Patients with bleeding disorders are a rare and complex population in catheter ablation (CA) procedures. The most common types of bleeding disorders are von Willebrand disease (VWD) and hemophilia A (HA). Patients with VWD or HA tend to have a higher risk of bleeding complications compared to other patients. There is a lack of data concerning peri- and postinterventional coagulation treatment. We sought to assess the optimal management of patients with VWD and HA referred for catheter ablation procedures. Methods and Results: In this study, we analyzed patients with VWD or HA undergoing CA procedures at two centers in Germany and Switzerland between 2016 and 2021. Clotting factors were administered in conjunction with hemostaseological recommendations. CA was performed as per the institutional standard. During the procedure, unfractionated heparin (UFH) was given intravenously with respect to the activated clotting time (ACT). Primary endpoints included the feasibility of the procedure, bleeding complications, and thromboembolic events during the procedure. Secondary endpoints included bleeding complications and thromboembolic events up to one year after catheter ablation. A total of seven patients (three VWD Type I, one VWD Type IIa, three HA) underwent 10 catheter ablation procedures (pulmonary vein isolation (PVI): two × radiofrequency (RF), one × laser balloon (LB), one × cryoballoon (CB); PVI + cavotricuspid isthmus (CTI): one × RF; PVI + left atrial appendage isolation (LAAI): one × RF; Premature ventricular contraction (PVC): three × RF; Atrioventricular nodal reentrant tachycardia (AVNRT): one × RF). VWD patients received 2000–3000 IE Wilate i.v. 30 to 45 min prior to ablation. Patients with HA received 2000–3000 IE factor VIII before the procedure. All patients undergoing PVI received UFH (cumulative dose 9000–18,000 IE) with a target ACT of >300 s. All patients after PVI were started on oral anticoagulation (OAC) 12 h after ablation. Two patients received aspirin (acetylsalicylic acid; ASA) for 4 weeks after the ablation of left-sided PVCs. No anticoagulation was prescribed after slow pathway modulation in a case with AVNRT. No bleeding complications or thromboembolic events were reported. During a follow-up of one year, one case of gastrointestinal bleeding occurred following OAC withdrawal after LAA occlusion. Conclusions: After the substitution of clotting factors, catheter ablation in patients with VWD and HA seems to be safe and feasible.
The Battle against Cardiogenic Shock
Authors: Rahamim Eldad , Carasso Shemy , Amir Offer , Elbaz-Greener Gabby
Published: November 2022

Cardiogenic shock (CS) is a life-threatening condition characterized by hypoperfusion and hypoxia caused by low cardiac output [...]
Analysis of the Frequency and Correlated Factors of Midpalatal Suture Maturation Stages in Young Adults, Based on Cone Beam Computed Tomography Imaging
Authors: Silva-Montero Juan Carlos , Faus-Matoses Ignacio , Ribas-Pérez David , Pourhamid Hourieh , Solano-Mendoza Beatriz
Published: November 2022

Background: The choice of whether to perform a palatal disjunction in constricted maxilla has traditionally been decided based on the age of the patients, although there are gradually increasing references to the fact that this is not a determining factor. The main goal of this study was to evaluate the frequency of the different stages of midpalatal suture maturation in a sample of young adults between 15 and 30 years of age. Other objectives also included analyzing the possible correlation the maturation stages could maintain with sex and age groups. Methods: 142 Cone Beam Computed Tomography (CBCT) scans of young adults were performed. The images were divided into four age groups based on age ranges of 15–18, 19–22, 23–26, and 27–30 years. Each group consisted of 26, 41, 39, and 36 patients, respectively, which were classified using Angelieri’s method. In addition, sex and age groups were considered as variables, and the possible correlation of the prevalence of each one, according to age and sex, was studied. Results: the sample was classified into 4.9% stage B; 52.1% stage C; 27.5% stage D; and 15.5% stage E. In addition, no statistically significant correlation between sex and the maturation stages was found, but more advanced stages did appear to be related to the chronological age of the subjects. Conclusions: The frequency of maturational stages where the suture is shown to be consolidated did not appear to be as high as expected; therefore, the idea of rejecting transverse plane treatment in a conventional manner in an out-of-growth patient should be discarded.
Quality of Life and Sexual Satisfaction in Women with Breast Cancer Undergoing a Surgical Treatment and in Their Male Partners
Authors: Martins Renato , Otero Patricia , Torres Ángela J. , Vázquez Fernando L.
Published: November 2022

This study aimed to determine the quality of life and sexual satisfaction in a sample of 389 women with breast cancer who underwent a surgical treatment and 366 men who were these women’s partners. The sample was recruited from the Portuguese League Against Cancer by 10 trained psychologists who assessed the quality of life and sexual satisfaction of the participants. Data on the sociodemographic variables, diagnosis and treatment in the female participants, relationship with their partner, anxiety and depression, and body image were also collected. It was found that 76.6% and 54.2% of the women had low physical and mental health, respectively, while 100% of partners had acceptable physical and mental health. The predictors of women’s physical health were months since surgery, current treatment, completed treatments, satisfaction with the current relationship with their partner, lower anxiety and depression, and better body image. The predictors of women’s mental health were months since diagnosis and treatment completion, satisfaction with partner support during the illness, lower anxiety and depression, and better body image. The predictors of both physical and mental health of partners were lower anxiety and depression. In addition, 88.4% of women and 100% of partners presented with sexual dysfunction. The predictors of women’s sexual satisfaction were being older, satisfaction with their relationship with their partner before the illness, lower anxiety and depression, and better body image. The predictors of sexual satisfaction of the male partners were psychological/psychiatric support, satisfaction with their current relationship with their partner, and lower anxiety and depression. These findings suggest that interventions targeted at the quality of life of women and sexual satisfaction with a couple perspective are needed.
Research Evidence of the Role of the Glymphatic System and Its Potential Pharmacological Modulation in Neurodegenerative Diseases
Authors: Verghese Joji Philip , Terry Alana , de Natale Edoardo Rosario , Politis Marios
Published: November 2022

The glymphatic system is a unique pathway that utilises end-feet Aquaporin 4 (AQP4) channels within perivascular astrocytes, which is believed to cause cerebrospinal fluid (CSF) inflow into perivascular space (PVS), providing nutrients and waste disposal of the brain parenchyma. It is theorised that the bulk flow of CSF within the PVS removes waste products, soluble proteins, and products of metabolic activity, such as amyloid-β (Aβ). In the experimental model, the glymphatic system is selectively active during slow-wave sleep, and its activity is affected by both sleep dysfunction and deprivation. Dysfunction of the glymphatic system has been proposed as a potential key driver of neurodegeneration. This hypothesis is indirectly supported by the close relationship between neurodegenerative diseases and sleep alterations, frequently occurring years before the clinical diagnosis. Therefore, a detailed characterisation of the function of the glymphatic system in human physiology and disease would shed light on its early stage pathophysiology. The study of the glymphatic system is also critical to identifying means for its pharmacological modulation, which may have the potential for disease modification. This review will critically outline the primary evidence from literature about the dysfunction of the glymphatic system in neurodegeneration and discuss the rationale and current knowledge about pharmacological modulation of the glymphatic system in the animal model and its potential clinical applications in human clinical trials.
Unattended versus Attended Blood Pressure Measurement: Relationship with Retinal Microcirculation
Authors: Paini Anna , Agabiti Rosei Claudia , De Ciuceis Carolina , Aggiusti Carlo , Bertacchini Fabio , Cacciatore Marco , Capellini Sara , Gatta Roberto , Malerba Paolo , Stassaldi Deborah , Rizzoni Damiano , Salvetti Massimo , Muiesan Maria Lorenza
Published: November 2022

Though the relationship between both “attended” and “unattended” BP and several forms of target organ damage have been evaluated, data on retinal arteriolar alterations are lacking. The aim of our study was to evaluate the relationship between “attended” or “unattended” BP values and retinal arteriolar changes in consecutive individuals undergoing a clinical evaluation and assessment of retinal fundus at an ESH Excellence Centre. An oscillometric device programmed to perform 3 BP measurements, at 1 min intervals and after 5 min of rest was used on all individuals to measure BP with the patient alone in the room (“unattended”) or in the presence of the physician (“attended”) in the same day in a random order. The retinal arteriole’s wall thickness (WT) was measured automatically by a localization algorithm as the difference between external (ED) and internal diameter (ID) by adaptive optics (RTX-1, Imagine Eyes, Orsay, Francia). Media-to-lumen ratio (WLR) of the retinal arterioles and cross-sectional area (WCSA) of the vascular wall were calculated. Results: One-hundred-forty-two patients were examined (mean age 57 ± 12 yrs, 48% female, mean BMI 26 ± 4). Among them, 60% had hypertension (84% treated) and 11% had type 2 diabetes mellitus. Unattended systolic BP (SBP) was lower as compared to attended SBP (129 ± 14.8. vs. 122.1 ± 13.6 mmHg, p < 0.0001). WLR was similarly correlated with unattended and attended SBP (r = 0.281, p < 0.0001 and r = 0.382, p < 0.0001) and with unattended and attended diastolic BP (r = 0.34, p < 0.001 and r = 0.29, p < 0.0001). The differences between correlations were not statistically significant (Steiger’s Z test). Conclusion: The measurement of “unattended” or “attended” BP provides different values, and unattended BP is lower as compared to attended BP. In this study a similar correlation was observed between attended and unattended BP values and structural changes of retinal arterioles.
The Advantage of Immunohistochemical Staining for Evaluating Lymphovascular Invasion Is Limited for Patients with Esophageal Squamous Cell Carcinoma Invading the Muscularis Mucosa
Authors: Dobashi Akira , Aizawa Daisuke , Hara Yuko , Furuhashi Hiroto , Matsui Hiroaki , Futakuchi Toshiki , Ono Shingo , Toyoizumi Hirobumi , Bazerbachi Fateh , Yamauchi Takashi , Suka Machi , Sumiyama Kazuki
Published: November 2022

The cumulative metastasis rate of esophageal squamous cell carcinoma (ESCC) pathologically invading the muscularis mucosae (pT1a-MM), based on lymphovascular invasion (LVI) evaluated by immunohistochemical (IHC) staining is unknown. This retrospective study included patients with endoscopically resected pT1a-MM ESCC. The primary endpoint was the metastasis rate of pT1a-MM based on LVI, evaluated using IHC and additional prophylactic therapy. The secondary endpoint was the identification of independent factors for metastasis based on lesion characteristics. The prognosis was also analyzed considering the impact of head and neck cancer. A total of 104 patients were analyzed, with a median follow-up of 74 months. The positive rate for LVI was 43.3% (45/104). In 33 patients, IHC was not performed at the time of clinical evaluation, 8 of whom exhibited LVI. However, these patients did not exhibit metastasis. The metastasis rates of patients without LVI, those with LVI and additional therapy, and those with LVI without additional therapy were 5.1%, 20.8%, and 0%, respectively. Lesion size ≥ 25 mm was the only independent factor for metastasis in multivariate analysis. The advantage of IHC for determining additional prophylactic therapy is limited for patients with pT1a-MM ESCC.
Coexistence of Multiple Myositis-Specific Antibodies in Patients with Idiopathic Inflammatory Myopathies
Authors: Huang Hung-Ling , Lin Wen-Chih , Tsai Wei-Lun , Weng Chia-Tse , Weng Meng-Yu , Wu Chun-Hsin , Sun Yuan-Ting
Published: November 2022

The mutual exclusivity of myositis-specific antibodies (MSAs) has been reported before, but the coexistence of 2 or more MSAs was still found in a few case reports. This study aims to confirm the existence and prevalence of double MSAs in patients with idiopathic inflammatory myopathy (IIM) and to clarify the clinical features of these patients. One hundred fifty-one patients with IIM diagnosed from 1 July 2018 to 31 July 2022, at National Cheng Kung University Hospital, Taiwan, were enrolled and divided into two groups, patients with ≤1 MSA (n = 128, 84.8%) and those with ≥2 MSAs (n = 23, 15.2%) according to the initial serology results. After being re-examined by ANA-IIF assay, 8 out of 23 patients were confirmed to have ≥2 MSAs. The demographic data and clinical features were presented. The prevalence of double-positive MSAs among IIM was 5.3% in this cohort. The coexistence of two MSAs in an IIM patient does exist but is rare. Patients with two MSAs belonging to two distinct IIM subtypes presented clinical features skewed to one subtype instead of “mixed phenotypes”. No apparent difference in clinical severity was found between patients with ≥2 MSAs and ≤1 MSA. Longer follow-ups and more studies are required to characterize the patients of IIM with ≥2 MSAs.
Comparison between School-Age Children with and without Obesity in Nutritional and Inflammation Biomarkers
Authors: Kassem Eias , Na’amnih Wasef , Shapira Maanit , Ornoy Asher , Muhsen Khitam
Published: November 2022

Childhood obesity is a major health problem. We examined differences between children with obesity and normal weight in nutritional and inflammation biomarkers. A cross-sectional study was conducted among healthy children aged 10–12 years from Arab villages in Israel. Parents were interviewed regarding sociodemographic and children’s health status. Body weight and height measurements were performed and weight categories were defined using the 2007 WHO growth curves. Blood samples were tested for complete blood count, levels of iron, ferritin, lipids, uric acid, and C-reactive protein (CRP). Overall, 146 children (59.0% males, mean age = 11.3 [SD = 0.5]) were enrolled. In total 43.8%, 14.1% and 42.3% of the participants had normal weight, overweight and obesity, respectively. A multivariable logistic regression model showed that children with overweight and obesity had lower iron, and HDL-C levels than children with normal weight. Levels of CRP, uric acid, LDL-C and lymphocytes were higher among children with overweight and obesity. In conclusion, our findings highlight the worse metabolic and nutritional status in overweight and obese children. Such markers play a role in metabolic syndrome, thus suggesting that metabolic syndrome might start in childhood.
Benefits of Robotic Assisted vs. Traditional Laparoscopic Partial Nephrectomy: A Single Surgeon Comparative Study
Authors: Bray Gerard , Bahadori Arya , Mao Derek , Ranasinghe Sachinka , Tracey Christopher
Published: November 2022

Purpose: The current study aims to compare peri-operative and post-operative outcomes between robotic assisted vs. laparoscopic partial nephrectomy. Multiple reviews of the current literature have detailed the lack of single surgeon studies in this domain. To limit inter-operator bias, we utilise a single surgeon experienced in both approaches to reduce this bias seen in other multi-centre studies. Methods and Materials: We retrospectively compared patient demographics, tumour characteristics, peri-operative and post-operative outcomes of all partial nephrectomies undertaken by a single surgeon between 2014 and 2021 with experience in both laparoscopic and robotic surgery. The Da Vinci surgical system was utilized. Statistical analysis was carried out using GraphPad prism software version 7.03, San Diego, CA, USA. Results: Warm ischemia time was reduced by 2.6 min, length of stay reduced by 1.3 days and acute renal function deterioration was reduced by 55% with all these results being significant with robotic assisted partial nephrectomy compared to laparoscopic partial nephrectomy. Conclusion: This study highlights the benefits of robotic assisted in comparison to laparoscopic partial nephrectomy. Further large-scale prospective studies and cost-benefit analysis of robotic assisted partial nephrectomy would be valuable in confirming these findings and justifying the usage against their financial cost.
Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review of the Most Updated Literature
Authors: Faccioli Eleonora , Verzeletti Vincenzo , Perazzolo Marra Martina , Boscolo Annalisa , Schiavon Marco , Navalesi Paolo , Rea Federico , Dell’Amore Andrea
Published: November 2022

Pulmonary endarterectomy (PEA) is the treatment of choice in case of chronic thromboembolic pulmonary hypertension (CTEPH). PEA is performed by an increasing number of surgeons; however, the reported outcomes are limited to a few registries or to individual centers’ experiences. This systematic review focuses on pre-operative evaluation, intra-operative procedure and post-operative results in patients submitted to PEA for CTEPH. The literature included was searched using a formal strategy, combining the terms “pulmonary endarterectomy” AND “chronic pulmonary hypertension” and focusing on studies published in the last 5 years (2017–2022) to give a comprehensive overview on the most updated literature. The selection of the adequate surgical candidate is a crucial point, and the decision should always be performed by expert multidisciplinary teams composed of surgeons, pulmonologists and radiologists. In all the included studies, the surgical procedure was performed through a median sternotomy with intermittent deep hypothermic circulatory arrest under cardiopulmonary bypass. In case of residual pulmonary hypertension, alternative combined treatments should be considered (balloon angioplasty and/or medical therapy until lung transplantation in highly selected cases). Short- and long-term outcomes, although not homogenous across the different studies, are acceptable in highly experienced CTEPH centers.
Targeted Resequencing of Otosclerosis Patients from Different Populations Replicates Results from a Previous Genome-Wide Association Study
Authors: Tavernier Lisse J. M. , Vanpoucke Thomas , Schrauwen Isabelle , Van Camp Guy , Fransen Erik
Published: November 2022

Otosclerosis is one of the most common causes of hearing loss in young adults. It has a prevalence of 0.3–0.4% in the European population. Clinical symptoms usually occur between the second and fifth decade of life. Different studies have been performed to unravel the genetic architecture of the disease. Recently, a genome-wide association study (GWAS) identified 15 novel risk loci and replicated the regions of three previously reported candidate genes. In this study, seven candidate genes from the GWAS were resequenced using single molecule molecular inversion probes (smMIPs). smMIPs were used to capture the exonic regions and the 3′ and 5′ untranslated regions (UTR). Discovered variants were tested for association with the disease using single variant and gene-based association analysis. The single variant results showed that 13 significant variants were associated with otosclerosis. Associated variants were found in five of the seven genes studied here, including AHSG, LINC01482, MARK3, SUPT3H and RELN. Conversely, burden testing did not show a major role of rare variants in the disease. In conclusion, this study was able to replicate five out of seven candidate genes reported in the previous GWAS. This association is likely mainly driven by common variants.
Lymphadenopathies before and during the Pandemic COVID-19: Increasing Incidence of Metastases from Solid Tumors
Authors: Trasarti Stefania , Troiano Raffaele , Biglietto Mario , Sorella Silvia , Lisi Chiara , Assanto Giovanni Manfredi , Bizzoni Luisa , Brunetti Gregorio Antonio , Giordano Carla , Rullo Emma , Saracino Mariangela , Saullo Paolina , Vignetti Marco , Martelli Maurizio , Caronna Roberto
Published: November 2022

Since December 2019, the world has experienced a pandemic caused by SARS-CoV-2, a virus which spread throughout the world. Anti-COVID19 measures were applied to limit the spread of the infection, affecting normal clinical practice. In 2020, studies on the possible impact of the pandemic considering the screening programs for early diagnosis of cancer were conducted, resulting in a prediction of delayed diagnosis of cancer. We performed a retrospective monocentric study on patients who present with the onset of lymphadenomegalies evaluated at our Hematological Department from February 2019 to October 2021 and undergoing excisional lymph-node biopsy. Three periods were considered: pre-pandemic, first pandemic period and second pandemic period (Group A, B and C). We included 258 patients who underwent a surgical biopsy and received a histological diagnosis. Hematological evaluation of outpatients sent by the general practitioner and surgical biopsies did not decrease among the three groups, despite limitations placed during this pandemic as well as new diagnoses of hematological malignancies. However, the diagnosis of metastatic cancer significantly increased from 2019 (7.8%) to 2021 (22.1%) (p = 0.042). Our data supports the hypothesis that the pandemic affected the national screening programs of early cancer detection.
Micro-Focused Ultrasound Therapy in Patients with Urogenital Atrophy and Vaginal Laxity
Authors: Kolczewski Piotr , Kozłowski Mateusz , Cymbaluk-Płoska Aneta
Published: November 2022

Vaginal laxity (VL) and genitourinary syndromes of menopause (GSM) create physical, psychological, and functional problem for women and their partners. We aimed to evaluate the efficacy and safety of micro-focused ultrasound (MFU) therapy performed twice in the vaginal canal in a patients with VL and GSM. A total of 20 women with GSM and VL were treated with MFU Ultravera by Hironic. The treatment course consisted of two vaginal applications of MFU at an interval of 6 weeks. The clinical effects of the protocol were evaluated using the Vaginal Laxity Questionnaire (VLQ), the Vaginal Health Index (VHI), and the Female Sexual Function Index (FSFI). The overall values of the vaginal laxity evaluation for the total subject population showed a statistically significant improvement between the baseline and the findings at 3 and 6 months after treatment. The effect of therapy was consistent across all domains of FSFI. It peaked at the 6 week follow-up visit (from 26.5 to 32) and plateaued at 12 weeks and 6 months. There was a significant VHI improvement over time, with the greatest and most significant change between the study entry and 21 days after treatment; the VHI score leveled off up to 3 months after the procedures. MFU therapy, performed twice in the vaginal canal, showed promising efficacy and safety profiles, meriting further investigation.
Effectiveness and Minimal-Invasiveness of Zone 0 Landing Thoracic Endovascular Aortic Repair Using Branched Endograft
Authors: Kudo Tomoaki , Kuratani Toru , Sawa Yoshiki , Miyagawa Shigeru
Published: November 2022

Background: Zone 0 landing thoracic endovascular aortic repair (TEVAR) for the treatment of aortic arch diseases has become a topic of interest. This study aimed to verify whether branced TEVAR (bTEVAR) is an effective and a more minimally invasive treatment by comparing the outcomes of bTEVAR and hybrid TEVAR (hTEVAR) in landing zone 0. Methods: This retrospective, single-center, observational cohort study included 54 patients (bTEVAR, n = 25; hTEVAR, n = 29; median age, 78 years; median follow-up period, 5.4 years) from October 2012 to June 2018. The logistic Euro-SCORE was significantly higher in the bTEVAR group than in the hTEVAR group (38% vs. 21%, p < 0.001). Results: There was no significant difference the in-hospital mortality between the bTEVAR and hTEVAR groups (0% vs. 3.4%, p = 1.00). The operative time (220 vs. 279 min, p < 0.001) and length of hospital stay (12 vs. 17 days, p = 0.013) were significantly shorter in the bTEVAR group than in the hTEVAR group. The 7-year free rates of aorta-related deaths (bTEVAR [95.5%] vs. hTEVAR [86.9%], Log-rankp = 0.390) and aortic reintervention (bTEVAR [86.3%] vs. hTEVAR [86.9%], Log-rankp = 0.638) were not significantly different. Conclusions: The early and mid-term outcomes in both groups were satisfactory. bTEVAR might be superior to hTEVAR in that it is less invasive. Therefore, bTEVAR may be considered an effective and a more minimally invasive treatment for high-risk patients.