bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Combined Gentamicin and Furosemide Treatment on Cochlear Macrophages
Authors: Sargsyan Liana , Swisher Austin R. , Hetrick Alisa P. , Li Hongzhe
Published: July 2022

Combining aminoglycosides and loop diuretics often serves as an effective ototoxic approach to deafen experimental animals. The treatment results in rapid hair cell loss with extended macrophage presence in the cochlea, creating a sterile inflammatory environment. Although the early recruitment of macrophages is typically neuroprotective, the delay in the resolution of macrophage activity can be a complication if the damaged cochlea is used as a model to study subsequent therapeutic strategies. Here, we applied a high dose combination of systemic gentamicin and furosemide in C57 BL/6 and CBA/CaJ mice and studied the ototoxic consequences in the cochlea, including hair cell survival, ribbon synaptic integrity, and macrophage activation up to 15-day posttreatment. The activity of macrophages in the basilar membrane was correlated to the severity of cochlear damage, particularly the hair cell damage. Comparatively, C57 BL/6 cochleae were more vulnerable to the ototoxic challenge with escalated macrophage activation. In addition, the ribbon synaptic deterioration was disproportionately limited when compared to the degree of outer hair cell loss in CBA/CaJ mice. The innate and differential otoprotection in CBA/CaJ mice appears to be associated with the rapid activation of cochlear macrophages and a certain level of synaptogenesis after the combined gentamicin and furosemide treatment.
Inclusion Body Myositis and Neoplasia: A Narrative Review
Authors: Damian Laura , Login Cristian Cezar , Solomon Carolina , Belizna Cristina , Encica Svetlana , Urian Laura , Jurcut Ciprian , Stancu Bogdan , Vulturar Romana
Published: July 2022

Inclusion body myositis (IBM) is an acquired, late-onset inflammatory myopathy, with both inflammatory and degenerative pathogenesis. Although idiopathic inflammatory myopathies may be associated with malignancies, IBM is generally not considered paraneoplastic. Many studies of malignancy in inflammatory myopathies did not include IBM patients. Indeed, IBM is often diagnosed only after around 5 years from onset, while paraneoplastic myositis is generally defined as the co-occurrence of malignancy and myopathy within 1 to 3 years of each other. Nevertheless, a significant association with large granular lymphocyte leukemia has been recently described in IBM, and there are reports of cancer-associated IBM. We review the pathogenic mechanisms supposed to be involved in IBM and outline the common mechanisms in IBM and malignancy, as well as the therapeutic perspectives. The terminally differentiated, CD8+ highly cytotoxic T cells expressing NK features are central in the pathogenesis of IBM and, paradoxically, play a role in some cancers as well. Interferon gamma plays a central role, mostly during the early stages of the disease. The secondary mitochondrial dysfunction, the autophagy and cell cycle dysregulation, and the crosstalk between metabolic and mitogenic pathways could be shared by IBM and cancer. There are intermingled subcellular mechanisms in IBM and neoplasia, and probably their co-existence is underestimated. The link between IBM and cancers deserves further interest, in order to search for efficient therapies in IBM and to improve muscle function, life quality, and survival in both diseases.
Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction
Authors: Jasiński Tomasz , Zdrojkowski Łukasz , Ferreira-Dias Graça , Kautz Ewa , Juszczuk-Kubiak Edyta , Domino Małgorzata
Published: July 2022

Endometrosis is a frequently occurring disease decreasing mares’ fertility. Thus, it is an important disease of the endometrium associated with epithelial and stromal cell alterations, endometrium gland degeneration and periglandular fibrosis. Multiple degenerative changes are found in uterine mucosa, the endometrium. However, their pathogenesis is not well known. It is thought that nuclear factor-κB (NF-κB), a cell metabolism regulator, and its activation pathways take part in it. The transcription of the profibrotic pathway genes of the NF-κB in fibrotic endometria differed between the follicular (FLP) and mid-luteal (MLP) phases of the estrous cycle, as well as with fibrosis progression. This study aimed to investigate the transcription of genes of estrogen (ESR1, ESR2) and progesterone receptors (PGR) in equine endometria to find relationships between the endocrine environment, NF-κB-pathway, and fibrosis. Endometrial samples (n = 100), collected in FLP or MLP, were classified histologically, and examined using quantitative PCR. The phase of the cycle was determined through the evaluation of ovarian structures and hormone levels (estradiol, progesterone) in serum. The transcription of ESR1, ESR2, and PGR decreased with the severity of endometrial fibrosis and degeneration of the endometrium. Moreover, differences in the transcription of ESR1, ESR2, and PGR were noted between FLP and MLP in the specific categories and histopathological type of equine endometrosis. In FLP and MLP, specific moderate and strong correlations between ESR1, ESR2, PGR and genes of the NF-κB pathway were evidenced. The transcription of endometrial steroid receptors can be subjected to dysregulation with the degree of equine endometrosis, especially in both destructive types of endometrosis, and mediated by the canonical NF-κB pathway depending on the estrous cycle phase.
Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation
Authors: Zamri Muhammad Harith Bin , Ujihara Yoshihiro , Nakamura Masanori , Mofrad Mohammad R. K. , Sugita Shukei
Published: July 2022

In response to hydrostatic pressure, the cation channel transient receptor potential vanilloid 1 (TRPV1) is essential in signaling pathways linked to glaucoma. When activated, TRPV1 undergoes a gating transition from a closed to an open state that allows the influx of Ca2+ ions. However, the gating mechanism of TRPV1 in response to hydrostatic pressure at the molecular level is still lacking. To understand the effect of hydrostatic pressure on the activation of TRPV1, we conducted molecular-dynamics (MD) simulations on TRPV1 under different hydrostatic pressure configurations, with and without a cell membrane. The TRPV1 membrane-embedded model is more stable than the TPRV1-only model, indicating the importance of including the cell membrane in MD simulation. Under elevated pressure at 27.6 mmHg, we observed a more dynamic and outward motion of the TRPV1 domains in the lower-gate area than in the simulation under normal pressure at 12.6 mmHg. While a complete closed-to-open-gate transition was not evident in the limited course of our MD simulations, an increase in the channel radius at the lower gate was observed at 27.6 mmHg versus that at 12.6 mmHg. These findings provide novel information regarding the effect of hydrostatic pressure on TRPV1 channels.
Overexpression of the Bam Complex Improves the Production of Chlamydia trachomatis MOMP in the E. coli Outer Membrane
Authors: Huynh Dung T. , Jong Wouter S. P. , Koningstein Gregory M. , van Ulsen Peter , Luirink Joen
Published: July 2022

A licensed Chlamydia trachomatis (Ct) vaccine is not yet available. Recombinant Chlamydia trachomatis major outer membrane protein (Ct-MOMP), the most abundant constituent of the chlamydial outer membrane complex, is considered the most attractive candidate for subunit-based vaccine formulations. Unfortunately, Ct-MOMP is difficult to express in its native structure in the E. coli outer membrane (OM). Here, by co-expression of the Bam complex, we improved the expression and localization of recombinant Ct-MOMP in the E. coli OM. Under these conditions, recombinant Ct-MOMP appeared to assemble into a β-barrel conformation and express domains at the cell surface indicative of correct folding. The data indicate that limited availability of the Bam complex can be a bottleneck for the production of heterologous OM vaccine antigens, information that is also relevant for strategies aimed at producing recombinant OMV-based vaccines.
Identification of Bacterial Membrane Selectivity of Romo1-Derived Antimicrobial Peptide AMPR-22 via Molecular Dynamics
Authors: Kim Hana , Yoo Young Do , Lee Gi Young
Published: July 2022

The abuse or misuse of antibiotics has caused the emergence of extensively drug-resistant (XDR) bacteria, rendering most antibiotics ineffective and increasing the mortality rate of patients with bacteremia or sepsis. Antimicrobial peptides (AMPs) are proposed to overcome this problem; however, many AMPs have attenuated antimicrobial activities with hemolytic toxicity in blood. Recently, AMPR-11 and its optimized derivative, AMPR-22, were reported to be potential candidates for the treatment of sepsis with a broad spectrum of antimicrobial activity and low hemolytic toxicity. Here, we performed molecular dynamics (MD) simulations to clarify the mechanism of lower hemolytic toxicity and higher efficacy of AMPR-22 at an atomic level. We found four polar residues in AMPR-11 bound to a model mimicking the bacterial inner/outer membranes preferentially over eukaryotic plasma membrane. AMPR-22 whose polar residues were replaced by lysine showed a 2-fold enhanced binding affinity to the bacterial membrane by interacting with bacterial specific lipids (lipid A or cardiolipin) via hydrogen bonds. The MD simulations were confirmed experimentally in models that partially mimic bacteremia conditions in vitro and ex vivo. The present study demonstrates why AMPR-22 showed low hemolytic toxicity and this approach using an MD simulation would be helpful in the development of AMPs.
Identification of BcARR Genes and CTK Effects on Stalk Development of Flowering Chinese Cabbage
Authors: Ou Xi , Wang Yudan , Zhang Jiewen , Xie Zhenbin , He Bing , Jiang Zhehao , Wang Yuting , Su Wei , Song Shiwei , Hao Yanwei , Chen Riyuan
Published: July 2022

Flowering Chinese cabbage (Brassica campestris L. ssp. Chinensis var. utilis Tsen et Lee) is an important and extensively cultivated vegetable in south China, whose major food product is the stalk. In the process of stalk formation, its initiation and development are regulated by a series of hormonal signals, such as cytokinin and gibberellin. In this study, we analyzed the effects of zeatin (ZT) and gibberellin A3 (GA3), and their interaction, on the bolting of flowering Chinese cabbage. The results indicated that the three-true-leaf spraying of ZT and GA synthesis inhibitor (PAC) inhibited plant height but increased stem diameter. Cytokinin (CTK) synthesis inhibitor (YZJ) and GA3 treatment increased plant height and decreased stem diameter. In addition, ZT and GA3 co-treated plants displayed antagonistic effect. Further, 19 type-B authentic response regulators (ARR-Bs), the positive regulators of cytokinin signal transduction were identified from flowering Chinese cabbage. Comprehensive analysis of phylogeny showed BcARR-Bs clustered into three subfamilies with 10 conserved motifs. Analysis of their expression patterns in different tissues and at various growth stage, and their response to hormone treatment suggest that ARR1-b localized in the nucleus displayed unique highest expression patterns in stem tips, are responsive both to ZT and GA, suggesting a significant role in mediating the crosstalk of ZT and GA in the bolting of flowering Chinese cabbage.
Biomimetic Modification of Water-Borne Polymer Coating with Carnauba Wax for Controlled Release of Urea
Authors: Ge Cong , Xu Xuebin , Ma Fei , Zhou Jianmin , Du Changwen
Published: July 2022

Benefitting from the special structure of the leaf cuticle layer, plants have natural hydrophobicity and anti-fouling abilities. Inspired by the leaf surface structure, a biomimetic modification strategy was raised to improve the surface hydrophobicity of polyacrylate coating for controlled release fertilizer. Double-layer (polyacrylate and carnauba wax) coated fertilizer was obtained after biomimetic modification. The quality of controlled release fertilizer modified with the carnauba wax was greatly enhanced, and the coating material was effectively saved. The surface appearance of polyacrylate-coated fertilizer was improved for the surface blemish was repaired by the loaded carnauba wax. The characterizations by Fourier transform infrared spectroscopy indicated that the hydrogen bonds were formed between the water-based polyacrylate membrane and the carnauba wax layers. By optimizing the content of polyacrylate and carnauba wax, the release duration of the fertilizer was effectively prolonged, which was improved from 1 month to more than 2 months after the biomimetic modification. Therefore, biological wax as an environmentally-friendly natural material that has showed a broad potential in the application of coated controlled release fertilizer.
G6PD Deficiency Is Crucial for Insulin Signaling Activation in Skeletal Muscle
Authors: Jiang Aiwen , Guo Hongyun , Jiang Xiaoyu , Tao Jingli , Wu Wangjun , Liu Honglin
Published: July 2022

Glucose 6-P dehydrogenase (G6PD) is the first rate-limiting enzyme in pentose phosphate pathway (PPP), and it is proverbial that G6PD is absent in skeletal muscle. However, how and why G6PD is down-regulated during skeletal muscle development is unclear. In this study, we confirmed the expression of G6PD was down-regulated during myogenesis in vitro and in vivo. G6PD was absolutely silent in adult skeletal muscle. Histone H3 acetylation and DNA methylation act together on the expression of G6PD. Neither knock-down of G6PD nor over-expression of G6PD affects myogenic differentiation. Knock-down of G6PD significantly promotes the sensitivity and response of skeletal muscle cells to insulin; over-expression of G6PD significantly injures the sensitivity and response of skeletal muscle cells to insulin. High-fat diet treatment impairs insulin signaling by up-regulating G6PD, and knock-down of G6PD rescues the impaired insulin signaling and glucose uptake caused by high-fat diet treatment. Taken together, this study explored the importance of G6PD deficiency during myogenic differentiation, which provides new sight to treat insulin resistance and type-2 diabetes.
The Zebrafish, an Outstanding Model for Biomedical Research in the Field of Melatonin and Human Diseases
Authors: Aranda-Martínez Paula , Fernández-Martínez José , Ramírez-Casas Yolanda , Guerra-Librero Ana , Rodríguez-Santana César , Escames Germaine , Acuña-Castroviejo Darío
Published: July 2022

The zebrafish has become an excellent model for the study of human diseases because it offers many advantages over other vertebrate animal models. The pineal gland, as well as the biological clock and circadian rhythms, are highly conserved in zebrafish, and melatonin is produced in the pineal gland and in most organs and tissues of the body. Zebrafish have several copies of the clock genes and of aanat and asmt genes, the latter involved in melatonin synthesis. As in mammals, melatonin can act through its membrane receptors, as with zebrafish, and through mechanisms that are independent of receptors. Pineal melatonin regulates peripheral clocks and the circadian rhythms of the body, such as the sleep/wake rhythm, among others. Extrapineal melatonin functions include antioxidant activity, inducing the endogenous antioxidants enzymes, scavenging activity, removing free radicals, anti-inflammatory activity through the regulation of the NF-κB/NLRP3 inflammasome pathway, and a homeostatic role in mitochondria. In this review, we introduce the utility of zebrafish to analyze the mechanisms of action of melatonin. The data here presented showed that the zebrafish is a useful model to study human diseases and that melatonin exerts beneficial effects on many pathophysiological processes involved in these diseases.
Identification of Spliceogenic Variants beyond Canonical GT-AG Splice Sites in Hereditary Cancer Genes
Authors: Dragoš Vita Šetrajčič , Strojnik Ksenija , Klančar Gašper , Škerl Petra , Stegel Vida , Blatnik Ana , Banjac Marta , Krajc Mateja , Novaković Srdjan
Published: July 2022

Pathogenic/likely pathogenic variants in susceptibility genes that interrupt RNA splicing are a well-documented mechanism of hereditary cancer syndromes development. However, if RNA studies are not performed, most of the variants beyond the canonical GT-AG splice site are characterized as variants of uncertain significance (VUS). To decrease the VUS burden, we have bioinformatically evaluated all novel VUS detected in 732 consecutive patients tested in the routine genetic counseling process. Twelve VUS that were predicted to cause splicing defects were selected for mRNA analysis. Here, we report a functional characterization of 12 variants located beyond the first two intronic nucleotides using RNAseq in APC, ATM, FH, LZTR1, MSH6, PALB2, RAD51C, and TP53 genes. Based on the analysis of mRNA, we have successfully reclassified 50% of investigated variants. 25% of variants were downgraded to likely benign, whereas 25% were upgraded to likely pathogenic leading to improved clinical management of the patient and the family members.
Metabolic Reprogramming in Sickle Cell Diseases: Pathophysiology and Drug Discovery Opportunities
Authors: Alramadhani Dina , Aljahdali Anfal S. , Abdulmalik Osheiza , Pierce B. Daniel , Safo Martin K.
Published: July 2022

Sickle cell disease (SCD) is a genetic disorder that affects millions of individuals worldwide. Chronic anemia, hemolysis, and vasculopathy are associated with SCD, and their role has been well characterized. These symptoms stem from hemoglobin (Hb) polymerization, which is the primary event in the molecular pathogenesis of SCD and contributes to erythrocyte or red blood cell (RBC) sickling, stiffness, and vaso-occlusion. The disease is caused by a mutation at the sixth position of the β-globin gene, coding for sickle Hb (HbS) instead of normal adult Hb (HbA), which under hypoxic conditions polymerizes into rigid fibers to distort the shapes of the RBCs. Only a few therapies are available, with the universal effectiveness of recently approved therapies still being monitored. In this review, we first focus on how sickle RBCs have altered metabolism and then highlight how this understanding reveals potential targets involved in the pathogenesis of the disease, which can be leveraged to create novel therapeutics for SCD.
The Aero-Thermal Performance of Purge Flow and Discrete Holes Film Cooling of Rotor Blade Platform in Modern High Pressure Gas Turbines: A Review
Authors: Barigozzi Giovanna , Abdeh Hamed , Rouina Samaneh , Franchina Nicoletta
Published: July 2022

Design of cooling systems for rotor platforms is critical due to the complex flow field and heat transfer phenomena related to the secondary flow structures originating at the blade leading edge. Horseshoe vortex and passage vortex are the fluid-dynamic features that largely influence the aerodynamic behaviour and the thermal protection level of the platform. The driving parameter is the coolant to mainstream momentum flux ratio, but several issues have to be considered in the design process of cooling technologies. As well acknowledged, an in-depth understanding of losses and heat transfer phenomena are deemed necessary to design effective cooling systems. In the present review, measurements and predictions on the behaviour of the HPT rotor cooled platform, obtained during the last two decades by several research groups, are gathered, described and analysed in terms of aerodynamic losses and heat transfer performance, and are compared with one another with respect to the effectiveness level that is ensured.
Digital Health Solutions for Chronic Illnesses: A Systematic Review of Mobile Health Apps and Quality Analysis with Mobile App Rating Scale
Authors: Vaitkienė Gintarė , Kuzborska Zyta , Žukauskienė Milda
Published: July 2022

Currently, more than half of the adults worldwide have at least one chronic condition; however, poor medication adherence and self-management are observed. Tools, such as mHealth apps, may play a crucial role for millions of people in increasing the patients’ involvement in the treatment process. The purpose of this study is to evaluate the characteristics and quality of the existing mHealth apps for patients with various chronic conditions. The study was conducted from February 1 to March 31, 2022. The mHealth applications’ search was performed on the iOS platform, and 29 apps were included in the final analysis. The quality of apps was evaluated using Mobile App Rating Scale. The majority of the apps had symptom and medication tracking functionality. The mean score of apps’ overall quality was 3.45 (SD = 0.61) out of five, ranging from 2.04 to 4.50. The highest-rated category was the functionality of the app—3.75 (0.61); followed by aesthetics—3.67 (0.62); subjective quality—3.47 (0.88); engagement—3.33 (0.78); and information—3.04 (0.61). The study revealed that only a few high-quality apps for chronic condition management exist, and there is still some space for improvements.
The Seroprevalence of SARS-CoV-2 IgG Antibodies in Children Hospitalized for Reasons Other Than COVID-19
Authors: Franczak Justyna , Moppert Justyna , Sobolewska-Pilarczyk Małgorzata , Pawłowska Małgorzata
Published: July 2022

The aim of the study was to assess the seroprevalence of SARS-CoV-2 IgG antibodies in children hospitalized for reasons other than COVID-19. The study was conducted among 686 children, aged 2 weeks to 18 years, hospitalized in the Department of Paediatrics, Infectious Diseases, and Hepatology in Bydgoszcz, Poland, in the period from 1 June 2021 to 30 April 2022. The presence of anti-SARS-CoV-2 antibodies was detected in 392 (57%) children. Since December 2021, a significantly larger proportion of children with a positive titer of anti-SARS-CoV-2 antibodies has been observed, constituting as much as 87.5% of patients hospitalized in April 2022. In total, 69% of children with detected anti-SARS-CoV-2 antibodies were children under 5 years of age. The highest mean amounts of titers of anti-SARS-CoV-2 antibodies were observed in children over 10 years of age. The conducted studies showed the presence of anti-SARS-CoV-2 antibodies in a significant group of hospitalized children and an increase in the percentage of these children during the fourth and fifth wave of COVID-19 in Poland caused by the Delta and Omicron variants, respectively. The vast majority of parents of the studied children had no knowledge of the COVID-19 infection in their charges, which may indicate asymptomatic infection or mild course of the disease.
Use of Positron Emission Tomography for Pregnancy-Associated Cancer Assessment: A Review
Authors: Parpinel Giulia , Laudani Maria Elena , Giunta Francesca Paola , Germano Chiara , Zola Paolo , Masturzo Bianca
Published: July 2022

Background. Positron emission tomography (PET) has proven clinical utility both in the initial and relapse staging phase, but this technique is controversial during pregnancy. The objective of this review is to provide a compendium of available information on the use of PET during pregnancy. Materials and methods. A systematic literature review was conducted from 1 January 2004 until 20 May 2021. A total of 4 small series and 9 case reports consisting of 25 cases were selected. Results. During the first trimester, the fetus is most sensitive to ionization damage, so lower doses are recommended (2.6E-02 mGy/MBq). Fetal-effective doses are higher in this period and the average fetal dose (4.06 ± 3.22 mGy) remains significantly below the threshold for deterministic effects. During the second and third trimesters, recommended doses are higher (1.4E-02 mGy/MBq at 6 months, and 6.9E-03 mGy/MBq at 9 months of gestation). 18F-FDG activity was distributed to the whole fetus with a prevalence of myocardial tissue in seven cases. The use of special precautions, such as PET-magnetic resonance (MR) and urinary bladder catheterization, reduces the amount of radioactive tracer. Breastfeeding interruption is not recommended. Conclusions. 18F-FDG PET is not contraindicated in pregnancy, but multidisciplinary discussion is necessary and strict precautions are recommended.
Persistent Idiopathic Facial Pain (PIFP) in Patients Referred to a Multidisciplinary Centre in Italy: A Retrospective Observational Study
Authors: Schweiger Vittorio , Nocini Riccardo , De Santis Daniele , Procacci Pasquale , Zanette Giovanni , Secchettin Erica , Del Balzo Giovanna , Fior Andrea , Martini Alvise , Nizzero Marta , Donadello Katia , Finco Gabriele , Gottin Leonardo , Polati Enrico
Published: July 2022

Background: Persistent Idiopathic Facial Pain (PIFP), previously named Atypical Facial Pain (AFP) is a poorly understood condition, often diagnosed after several inconclusive investigations. The aim of this retrospective study was to evaluate the demographic and clinical characteristics of patients with PIFP referred to a Facial Pain Center. Methods: Between May 2011 and September 2014, data on 41 PIFP patients were analyzed regarding temporal, topographical and descriptive pain features, including onset, localization, pain descriptors and intensity. Pharmacological pain treatments were also registered. Finally, the presence and type of previous minor oro-surgery procedures in the painful area were investigated. Results: Demographic and clinical characterization were similar to PIFP patients reported in literature. The presence of previous minor oro-surgery procedures in the painful area was reported in most of these patients, in particular endodontic treatments and tooth extractions. Conclusions: This retrospective analysis showed a high prevalence of minor oro-surgery procedures in our population, while its role in PIFP pathophysiology remains unknown. A new classification of PIFP built around the main discriminant factor of presence of these procedures in the painful area could be considered while available data were still insufficient to define specific diagnostic criteria.
Moesin Serves as Scaffold Protein for PD-L1 in Human Uterine Cervical Squamous Carcinoma Cells
Authors: Doukuni Rina , Kobori Takuro , Tanaka Chihiro , Tameishi Mayuka , Urashima Yoko , Ito Takuya , Obata Tokio
Published: July 2022

Immune checkpoint blockade (ICB) therapy targeting the programmed death ligand-1 (PD-L1)/PD-1 axis has emerged as a promising treatment for uterine cervical cancer; however, only a small subset of patients with uterine cervical squamous cell carcinoma (SCC) derives clinical benefit from ICB therapies. Thus, there is an urgent unmet medical need for novel therapeutic strategies to block the PD-L1/PD-1 axis in patients with uterine cervical SCC. Here, we investigated the involvement of ezrin/radixin/moesin (ERM) family scaffold proteins, which crosslink several plasma membrane proteins with the actin cytoskeleton, on the plasma membrane localization of PD-L1 in BOKU and HCS-2 cells derived from human uterine cervical SCC. Immunofluorescence analysis showed that PD-L1 colocalized with all three ERM proteins in the plasma membrane. Gene knockdown of moesin, but not ezrin and radixin, substantially reduced the plasma membrane expression of PD-L1, with limited effect on mRNA expression. An immunoprecipitation assay demonstrated the molecular interaction between PD-L1 and moesin. Moreover, phosphorylated, i.e., activated, moesin was highly colocalized with PD-L1 in the plasma membrane. In conclusion, moesin may be a scaffold protein responsible for the plasma membrane expression of PD-L1 in human uterine cervical SCC.
Implications of Decreased Expression of miR-125a with Respect to Its Variant Allele in the Pathogenesis of Recurrent Pregnancy Loss: A Study in a High Incidence Zone
Authors: Manzoor Usma , Pandith Arshad A. , Amin Ina , Wani Saima , Sanadhya Dheera , Lone Tawseef A. , Mir Hyder , Paray Bilal Ahamad , Gulnaz Aneela , Anwar Iqra , Ahmad Abida , Aein Qurat Ul
Published: July 2022

Pregnancy is controlled by several types of genes and the regulation of their expression is tightly controlled by miRNAs. The present study was carried out to explore the association between miR-125a polymorphic sequence variation and its expression and recurrent pregnancy loss (RPL) compared to full-term healthy controls. A total of 150 women that had experienced two or more RPLs and 180 healthy controls (two or more full-term pregnancies) were recruited, along with 50 product of conception (POC) samples from the corresponding RPL patients, and evaluated for miR-125a SNPs by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP), which was confirmed by high resolution melting (HRM)/DNA sequencing. Additionally, the expression of miR-125a was quantified with q–PCR in the maternal plasma of 40 corresponding RPL patients against healthy controls. The frequency of variant genotype CC was significantly higher in RPL cases (19.3%) than controls (10.5%), with an odds ratio of >2 (p = 0.025). The expression levels of miR-125a were markedly decreased in RPL cases compared to healthy controls (p < 0.05). Variant genotype CC was found significantly more often in RPL cases than controls (0.34 vs. 0.20; p < 0.05).In this study, miR-125a rs12976445 C/T revealed that the homozygous CC genotype and C allele were associated with the risk of RPL and significant expression indicates that miR-125a has an important role in RPL etiopathogenesis.
Transcutaneous Spinal Cord Stimulation: Advances in an Emerging Non-Invasive Strategy for Neuromodulation
Authors: Hofstoetter Ursula S. , Minassian Karen
Published: July 2022

Recent studies of epidural electrical spinal cord stimulation have shown the enabling and, in some cases, the recovery of motor functions thought to be irreversibly lost due to severe spinal cord injury [...]
Exploring Enhanced Cell-Based Therapy for Ischemic Heart Disease and Heart Failure
Authors: Madonna Rosalinda
Published: July 2022

Ischemic heart disease (IHD) and heart failure (HF) remain the leading causes of death worldwide [...]
Effects of HIV Infection in Plasma Free Fatty Acid Profiles among People with Non-Alcoholic Fatty Liver Disease
Authors: Martínez-Sanz Javier , Calvo María Visitación , Serrano-Villar Sergio , Montes María Luisa , Martín-Mateos Rosa , Burgos-Santamaría Diego , Díaz-Álvarez Jorge , Talavera-Rodríguez Alba , Rosas Marta , Moreno Santiago , Fontecha Javier , Sánchez-Conde Matilde
Published: July 2022

Despite its high prevalence, the mechanisms underlying non-alcoholic fatty liver disease (NAFLD) in people living with HIV (PLWH) are still unclear. In this prospective cohort study, we aim to evaluate differences in plasma fatty acid profiles between HIV-infected and HIV-uninfected participants with NAFLD. We included participants diagnosed with NAFLD, both HIV-infected and HIV-uninfected. Fatty acid methyl esters were measured from plasma samples. Ratios ([product]/[substrate]) were used to estimate desaturases and elongases activity. We used linear regression for adjusted analyses. We included 31 PLWH and 22 HIV-uninfected controls. We did not find differences in the sum of different types of FA or in FA with a greater presence of plasma. However, there were significant differences in the distribution of some FA, with higher concentrations of ALA, trans-palmitoleic, and behenic acids, and a lower concentration of lignoceric acid in PLWH. PLWH had lower C24:0/C22:0 and C16:0/C14:0 ratios, which estimates the activity of elongases ELOVL1 and ELOVL6. Both groups had similar fatty acid distribution, despite differences in traditional risk factors. PLWH had a lower proportion of specific ratios that estimate ELOVL1 and ELOVL6 activity, which had been previously described for other inflammatory conditions, such as psoriasis.
Obesity Impact on SARS-CoV-2 Infection: Pros and Cons “Obesity Paradox”—A Systematic Review
Authors: Vulturar Damiana-Maria , Crivii Carmen-Bianca , Orăsan Olga Hilda , Palade Emanuel , Buzoianu Anca-Dana , Zehan Iulia Georgiana , Todea Doina Adina
Published: July 2022

Background: During the last years, the COVID-19 pandemic meets the pandemic generated by obesity, raising many questions regarding the outcomes of those with severe forms of infection. Methods: The present systematic review summarises and analyses the data providing evidence for or against the “obesity-paradox” in COVID-19 patients. After applying the inclusion and exclusion criteria, 23 studies were included. We also analysed the presumably underlying basic mechanisms. Results: The patients with a body mass index (BMI) of 30–40 kg/m2 presented severe symptoms that led to intensive care unit (ICU) admission but not increased death rate. Those with a higher degree of obesity, with a BMI higher than 40 kg/m2, led to a rise in the death rate, particularly in young patients. Obesity was associated with a higher rate of ICU admission but was not determined as an independent predictor of increased mortality. In contrast, some studies suggest a strong association between obesity or morbid obesity and the risk of death. Conclusions: The existence of “obesity-paradox” cannot be stated; our study presents obesity as a critical risk factor in the evolution of COVID-19.
Influence of Depression and Sleep Quality on Postoperative Outcomes after Total Hip Arthroplasty: A Prospective Study
Authors: Longo Umile Giuseppe , De Salvatore Sergio , Greco Alessandra , Marino Martina , Santamaria Giulia , Piergentili Ilaria , De Marinis Maria Grazia , Denaro Vincenzo
Published: July 2022

The trend of Total Hip Arthroplasty (THA) is projected to grow. Therefore, it has become imperative to find new measures to improve the outcomes of THA. Several studies have focused attention on the influence of psychological factors and sleep quality on surgical outcomes. The consequences of depressive states may affect outcomes and also interfere with rehabilitation. In addition, sleep quality may be an essential factor in determining surgical outcomes. To our knowledge, few articles focus on the influence of these factors on THA results. The present study investigates a possible correlation between preoperative depression or sleep quality and postoperative outcomes of THA. This study was conducted with 61 consecutive patients undergoing THA from January 2020 to January 2021. Patients were assessed preoperatively using GDS and PSQI, and six months postoperatively using FJS-12, SF-36, WOMAC, PSQI, and GDS. To simplify comparisons, the overall scores were normalized to range from 0 (worst condition) to 100 points (best condition). A total of 37 patients (60.7%) were classified as depressed and 24 as not depressed (39.3 %) in the preoperative assessment. A low–moderate positive correlation between preoperative GDS score and FJS-12 (rho = 0.22, p = 0.011), SF-36-PCS (rho = 0.328, p = 0.01), and SF-36-MCS (rho = 0.293, p = 0.022) scores at six-month follow-up was found. When the normalized preoperative GDS score was high (no depression), the FJS-12, SF-36-PCS, and SF-36-MCS scores tended to increase more compared to the other group. Statistically significant differences between the two groups were found in postoperative FJS-12 (p = 0.001), SF-36-PCS (p = 0.017), and SF-36-MCS scores (p = 0.016). No statistically significant correlation between preoperative PSQI score and postoperative outcome measures was found. Preoperatively depressed patients had a low–moderate positive correlation with postoperative SF-36 and FJS-12 scores. There was no correlation between sleep quality and postoperative outcome measures of THA.
Lack of Objective Measurement in the Initial Screening and Follow-Up of Patients Who Report Whiplash Injury—Is Elastography of the Trapezius Muscle an Answer?
Authors: Aljinović Jure , Barun Blaž , Benzon Benjamin , Poljičanin Ana , Vlak Tonko
Published: July 2022

Background: Painfully decreased cervical range of motion accompanied by muscle spasm is a common presentation of whiplash injury of the neck. Stiffness of the cervical muscles can be assessed by ultrasound shear wave elastography (SWE), expressed in kilopascals (kPa). The hypothesis: SWE of the trapezius muscle is an objective measurement suitable for the initial screening and follow-up of patients who report whiplash injury. Methods and results: A total of 99 patients after whiplash injury were compared to 75 control participants. Mean trapezius stiffness was 82.24 ± 21.11 vs. 57.47 ± 13.82 for whiplash patients and controls, respectively. The cut-off value of SWE of 75.8 kPa showed 77% accuracy in correctly assigning patients to the whiplash or control group. To evaluate whether SWE can be used as a follow-up method of recovery after a whiplash injury, initial and endpoint SWE (after six months, n = 24) was carried out. Patients reporting no recovery showed similar SWE values as completely recovered patients. This finding refutes the second part of our hypothesis. Conclusions: SWE is a method that can be used for the initial screening of patients with whiplash injury, but we are still searching for an objective measurement that can be used in the follow-up of recovery.
Impact of Cardiopulmonary Resuscitation of Donors on Days Alive and Out of Hospital after Orthotopic Heart Transplantation
Authors: Roth Sebastian , M’Pembele René , Nucaro Anthony , Stroda Alexandra , Tenge Theresa , Lurati Buse Giovanna , Sixt Stephan U. , Westenfeld Ralf , Rellecke Philipp , Tudorache Igor , Hollmann Markus W. , Aubin Hug , Akhyari Payam , Lichtenberg Artur , Huhn Ragnar , Boeken Udo
Published: July 2022

Background: The number of patients waiting for heart transplantation (HTX) is increasing. Optimizing the use of all available donor hearts is crucial. While mortality seems not to be affected by donor cardiopulmonary resuscitation (CPR), the impact of donor CPR on days alive and out of hospital (DAOH) is unclear. Methods: This retrospective study included adults who underwent HTX at the University Hospital Duesseldorf, Germany from 2010–2020. Main exposure was donor-CPR. Secondary exposure was the length of CPR. The primary endpoint was DAOH at one year. Results: A total of 187 patients were screened and 171 patients remained for statistical analysis. One-year mortality was 18.7%. The median DAOH at one year was 295 days (interquartile range 206–322 days). Forty-two patients (24.6%) received donor-CPR hearts. The median length of CPR was 15 (9–21) minutes. There was no significant difference in DAOH between patients with donor-CPR hearts versus patients with no-CPR hearts (CPR: 291 days (211–318 days) vs. no-CPR: 295 days (215–324 days); p = 0.619). Multivariate linear regression revealed that there was no association between length of CPR and DAOH (unstandardized coefficients B: −0.06, standard error: 0.81, 95% CI −1.65–1.53, p = 0.943). Conclusions: Donor CPR status and length of CPR are not associated with reduced DAOH at one year after HTX.
Is Hartmann’s Pouch an Option in the Management of Acute Severe Ulcerative Colitis?
Authors: Renaud Myriam , Ayav Ahmet , Caron Bénédicte , Peyrin-Biroulet Laurent , Germain Adeline
Published: July 2022

Background: The surgical management of remnant rectosigmoid after subtotal colectomy with end ileostomy for acute severe ulcerative colitis remains controversial with respect to the need to perform sigmoidostomy or Hartmann’s pouch. The aim of this retrospective study was to investigate whether Hartmann’s pouch may be a safe option. Methods: Thirty-eight Hartmann’s pouches were performed between January 2003 and December 2015. We looked at morbidity (with a focus on the occurrence of pelvic sepsis and leakage of the rectal stump) and the rate of restored intestinal continuity. Results: Nineteen patients had surgical complications. Seven had an intra-abdominal collection, only one of which was in the pelvis, and the patient had to be reoperated. Only one patient had a reopening of the rectal stump, which was revealed by rectal bleeding. Twenty-six patients (68.4%) underwent further proctectomy with ileal J-pouch anal anastomosis with no difficulty in localizing or mobilizing the rectal stump and no major surgical complications. Conclusions: Hartmann’s pouch may be considered in patients with acute severe ulcerative colitis, with low rates of morbidity and pelvic sepsis. The restoration of intestinal continuity is possible after this procedure without any special difficulty.
Diagnosis of DSD in Children—Development of New Tools for a Structured Diagnostic and Information Management Program within the Empower-DSD Study
Authors: Wechsung Katja , Marshall Louise , Jürgensen Martina , Neumann Uta ,   on behalf of the Empower-DSD Study Group
Published: July 2022

Background: Current recommendations define a structured diagnostic process, transparent information, and psychosocial support by a specialized, multi-professional team as central in the care for children and adolescents with genital variations and a suspected difference of sex development (DSD). The active involvement of the child and their parents in shared decision-making should result in an individualized care plan. So far, this process has not been standardized. Methods: Within the Empower-DSD study, a team of professionals and representatives of patient advocacy groups developed a new diagnostic and information management program based on current recommendations and existing patient information. Results: The information management defines and standardizes generic care elements for the first weeks after a suspected DSD diagnosis. Three different tools were developed: a guideline for the specialized multiprofessional team, a personal health record and information kit for the child with DSD and their family, and a booklet for medical staff not specialized in DSD. Conclusions: The new information management offers guidance for patients and professionals during the first weeks after a DSD diagnosis is suspected. The developed tools’ evaluation will provide further insight into the diagnostic and information-sharing process as well as into all of the involved stakeholders’ needs.
Electromyographic Response of the Abdominal Muscles and Stabilizers of the Trunk to Reflex Locomotion Therapy (RLT). A Preliminary Study
Authors: Pérez-Robledo Fátima , Sánchez-González Juan Luis , Bermejo-Gil Beatriz María , Llamas-Ramos Rocío , Llamas-Ramos Inés , de la Fuente Antonio , Martín-Nogueras Ana María
Published: July 2022

Reflex locomotion therapy (RLT) was developed by Vaclav Vojta in 1954 as a diagnostic and treatment tool. This therapy is mainly used to rehabilitate children with motor disorders and risk of cerebral palsy. It is also used for adults with neurological and motor impairment. RLT is based on specific postures and regular stimulation points through which a series of reflex responses are triggered. The neurophysiological mechanisms of this therapy have recently been discovered. This study aims to objectively evaluate muscular responses at the abdominal level after stimulation in the first phase of reflex rolling by showing, with surface electromyography analysis (sEMG), the muscular activity in trunk stabilizing muscles (rectus abdominis, external oblique, internal oblique, and serratus anterior) before, during, and after the application of RLT. A total sample of 27 healthy subjects over 18 years of age was recruited. An experimental study on a cohort was conducted. Two experimental conditions were considered: stimuli according to the Vojta protocol, and a control non-STI condition. Regarding muscular electrical activity, statistically significant differences were determined in all muscles during right-sided stimulation in the VSTI condition (p < 0.001), but not in the non-STI condition. The mean increase in muscle activity in the VSTI condition during the first stimulation ranged from 7% to 20% in the different abdominal muscles. In conclusion, an sEMG response was observed in the abdominal muscles during stimulation of the pectoral area as described in RLT, compared to stimulation of non-described areas.
Preexisting Humoral Immunity Cross-Reacting with SARS-CoV-2 Might Prevent Death Due to COVID-19 in Critical Patients
Authors: Yamashita Taro , Shimakami Tetsuro , Nio Kouki , Terashima Takeshi , Okajima Masaki , Taniguchi Takumi , Wada Takashi , Honda Masao , Gabata Toshifumi , Ota Kenji , Yanagihara Katsunori , Kaneko Shuichi
Published: July 2022

The preexistence of humoral immunity, which cross-reacts with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein due to prior endemic low-pathogenic human coronavirus infection, has been reported, but its role in coronavirus disease 2019 (COVID-19) outcomes remains elusive. We evaluated serum samples obtained from 368 patients before the pandemic and 1423 independent serum samples from patients during the pandemic. We found that approximately 6~13% and 1.5% of patients had IgG cross-reactivity to the SARS-CoV-2 spike and nucleocapsid proteins in both cohorts. We evaluated the IgG cross-reactivity to the SARS-CoV-2 spike and nucleocapsid proteins in 48 severe or critical COVID-19 patients to evaluate if the elevation of IgG was evoked as a primary response (IgG elevation from 10 days after antigen exposure) or boosted as a secondary response (IgG elevation immediately after antigen exposure). Approximately 50% of patients showed humoral immune responses to the nucleocapsid protein of SARS-CoV-2. Importantly, none of the critically ill patients with this humoral immunity died, whereas 40% of patients without this immunity did. Taken together, subjects had humoral immunity to SARS-CoV-2 nucleocapsid but not spike before the pandemic, which might prevent critically ill COVID-19 patients from dying.
Comparative Analyses of the Impact of Different Criteria for Sepsis Diagnosis on Outcome in Patients with Spontaneous Subarachnoid Hemorrhage
Authors: Centner Franz-Simon , Oster Mariella Eliana , Dally Franz-Joseph , Sauter-Servaes Johannes , Pelzer Tanja , Schoettler Jochen Johannes , Hahn Bianka , Fairley Anna-Meagan , Abdulazim Amr , Hackenberg Katharina Antonia Margarete , Groden Christoph , Etminan Nima , Krebs Joerg , Thiel Manfred , Wenz Holger , Maros Máté Elod
Published: July 2022

Data on sepsis in patients with a subarachnoid hemorrhage (SAH) are scarce. We assessed the impact of different sepsis criteria on the outcome in an SAH cohort. Adult patients admitted to our ICU with a spontaneous SAH between 11/2014 and 11/2018 were retrospectively included. In patients developing an infection, different criteria for sepsis diagnosis (Sepsis-1, Sepsis-3_original, Sepsis-3_modified accounting for SAH-specific therapy, alternative sepsis criteria compiled of consensus conferences) were applied and their impact on functional outcome using the modified Rankin Scale (mRS) on hospital discharge and in-hospital mortality was evaluated. Of 270 SAH patients, 129 (48%) developed an infection. Depending on the underlying criteria, the incidence of sepsis and septic shock ranged between 21–46% and 9–39%. In multivariate logistic regression, the Sepsis-1 criteria were not associated with the outcome. The Sepsis-3 criteria were not associated with the functional outcome, but in shock with mortality. Alternative sepsis criteria were associated with mortality for sepsis and in shock with mortality and the functional outcome. While Sepsis-1 criteria were irrelevant for the outcome in SAH patients, septic shock, according to the Sepsis-3 criteria, adversely impacted survival. This impact was higher for the modified Sepsis-3 criteria, accounting for SAH-specific treatment. Modified Sepsis-3 and alternative sepsis criteria diagnosed septic conditions of a higher relevance for outcomes in patients with an SAH.