bluuebunny/crossref_metadata_2025 huggingface dataset:
Promising Strategies for the Development of Advanced In Vitro Models with High Predictive Power in Ischaemic Stroke Research
Authors: Van Breedam Elise , Ponsaerts Peter
Published: June 2022

Although stroke is one of the world’s leading causes of death and disability, and more than a thousand candidate neuroprotective drugs have been proposed based on extensive in vitro and animal-based research, an effective neuroprotective/restorative therapy for ischaemic stroke patients is still missing. In particular, the high attrition rate of neuroprotective compounds in clinical studies should make us question the ability of in vitro models currently used for ischaemic stroke research to recapitulate human ischaemic responses with sufficient fidelity. The ischaemic stroke field would greatly benefit from the implementation of more complex in vitro models with improved physiological relevance, next to traditional in vitro and in vivo models in preclinical studies, to more accurately predict clinical outcomes. In this review, we discuss current in vitro models used in ischaemic stroke research and describe the main factors determining the predictive value of in vitro models for modelling human ischaemic stroke. In light of this, human-based 3D models consisting of multiple cell types, either with or without the use of microfluidics technology, may better recapitulate human ischaemic responses and possess the potential to bridge the translational gap between animal-based in vitro and in vivo models, and human patients in clinical trials.
Broad Spectrum Functional Activity of Structurally Related Monoanionic Au(III) Bis(Dithiolene) Complexes
Authors: Le Gal Yann , Filatre-Furcate Agathe , Lorcy Dominique , Jeannin Olivier , Roisnel Thierry , Dorcet Vincent , Fontinha Diana , Francisco Denise , Prudncio Miguel , Martins Marta , Soeiro Catarina , Sousa Sílvia A. , Leitão Jorge H. , Morais Tnia S. , Bártolo Ins , Taveira Nuno , Guerreiro Joana F. , Marques Fernanda
Published: June 2022

The biological properties of sixteen structurally related monoanionic gold (III) bis(dithiolene/ diselenolene) complexes were evaluated. The complexes differ in the nature of the heteroatom connected to the gold atom (AuS for dithiolene, AuSe for diselenolene), the substituent on the nitrogen atom of the thiazoline ring (Me, Et, Pr, iPr and Bu), the nature of the exocyclic atom or group of atoms (O, S, Se, C(CN)2) and the counter-ion (Ph4P+ or Et4N+). The anticancer and antimicrobial activities of all the complexes were investigated, while the anti-HIV activity was evaluated only for selected complexes. Most complexes showed relevant anticancer activities against Cisplatin-sensitive and Cisplatin-resistant ovarian cancer cells A2780 and OVCAR8, respectively. After 48 h of incubation, the IC50 values ranged from 0.1–8 μM (A2780) and 0.8–29 μM (OVCAR8). The complexes with the Ph4P+ ([P]) counter-ion are in general more active than their Et4N+ ([N]) analogues, presenting IC50 values in the same order of magnitude or even lower than Auranofin. Studies in the zebrafish embryo model further showed that, despite their marked anticancer effect, the complexes with [P] counter-ion exhibited low in vivo toxicity. In general, the exocyclic exchange of sulfur by oxygen or ylidenemalononitrile (C(CN)2) enhanced the compounds toxicity. Most complexes containing the [P] counter ion exhibited exceptional antiplasmodial activity against the Plasmodium berghei parasite liver stages, with submicromolar IC50 values ranging from 400–700 nM. In contrast, antibacterial/fungi activities were highest for most complexes with the [N] counter-ion. Auranofin and two selected complexes [P][AuSBu(=S)] and [P][AuSEt(=S)] did not present anti-HIV activity in TZM-bl cells. Mechanistic studies for selected complexes support the idea that thioredoxin reductase, but not DNA, is a possible target for some of these complexes. The complexes [P] [AuSBu(=S)], [P] [AuSEt(=S)], [P] [AuSEt(=Se)] and [P] [AuSeiPr(=S)] displayed a strong quenching of the fluorescence intensity of human serum albumin (HSA), which indicates a strong interaction with this protein. Overall, the results highlight the promising biological activities of these complexes, warranting their further evaluation as future drug candidates with clinical applicability.
GenericConv: A Generic Model for Image Scene Classification Using Few-Shot Learning
Authors: Soudy Mohamed , Afify Yasmine M. , Badr Nagwa
Published: June 2022

Scene classification is one of the most complex tasks in computer-vision. The accuracy of scene classification is dependent on other subtasks such as object detection and object classification. Accurate results may be accomplished by employing object detection in scene classification since prior information about objects in the image will lead to an easier interpretation of the image content. Machine and transfer learning are widely employed in scene classification achieving optimal performance. Despite the promising performance of existing models in scene classification, there are still major issues. First, the training phase for the models necessitates a large amount of data, which is a difficult and time-consuming task. Furthermore, most models are reliant on data previously seen in the training set, resulting in ineffective models that can only identify samples that are similar to the training set. As a result, few-shot learning has been introduced. Although few attempts have been reported applying few-shot learning to scene classification, they resulted in perfect accuracy. Motivated by these findings, in this paper we implement a novel few-shot learning model—GenericConv—for scene classification that has been evaluated using benchmarked datasets: MiniSun, MiniPlaces, and MIT-Indoor 67 datasets. The experimental results show that the proposed model GenericConv outperforms the other benchmark models on the three datasets, achieving accuracies of 52.16 ± 0.015, 35.86 ± 0.014, and 37.26 ± 0.014 for five-shots on MiniSun, MiniPlaces, and MIT-Indoor 67 datasets, respectively.
Varroa Appears to Drive Persistent Increases in New Zealand Colony Losses
Authors: Stahlmann-Brown Philip , Hall Richard J. , Pragert Hayley , Robertson Thomas
Published: June 2022

New Zealand’s temperate climate and bountiful flora are well suited to managed honey bees, and its geographic isolation and strict biosecurity laws have made sure that some pests and diseases affecting bees elsewhere are not present. Nevertheless, given the importance of pollination and high-value export honey to the economy, New Zealand began systematically measuring winter colony losses in 2015. The New Zealand Colony Loss Survey is modelled on the COLOSS survey but has been adapted to the New Zealand apicultural context. Some 49% of New Zealand beekeepers completed the winter 2021 survey. Between 2015 and 2021, overall colony loss rates increased monotonically from 8.37% [95% CI: 7.66%, 9.15%] to 13.59% [95% CI: 13.21%, 13.99%]. Whereas beekeepers most commonly attributed losses to queen problems between 2015 and 2020, attributions to varroa have escalated year-on-year to become the largest attributed cause of colony loss. Losses to varroa are perhaps amplified by the 23.4% of respondents who did not monitor mite loads and the 4.4% of beekeepers who did not treat varroa during the 2020/21 season. Indeed, most beekeepers consider their treatment to be effective and note that treating at the wrong time and reinvasion were major drivers of losses to varroa.
The Effect of Substrate on the Nutrient Content and Fatty Acid Composition of Edible Insects
Authors: Riekkinen Kati , Väkeväinen Kati , Korhonen Jenni
Published: June 2022

Demand for new food sources and production methods is increasing due to overall population growth, as well as the aim towards more sustainable use of natural resources and circular economy. Edible insects already used in many parts of the world have recently attracted interest as a new protein source in Europe, and novel food acceptance procedures are ongoing in the European Union for several insect species. In this paper, the effects of substate on the nutritional value, especially the fatty acid composition, of edible insects were reviewed and correlation calculations performed. The nutritional value of edible insects is an important health aspect, in particular, a high content of good-quality protein and unsaturated fatty acids with essential fatty acids, and an optimal fatty acid n6/n3 ratio. On the basis of our findings, the nutrient content of insects can be modified by using a feed substrate carefully designed for each individual insect species. In addition, our correlation calculations demonstrated that the contents of linoleic and alpha linolenic acids in insects reflected the contents of these acids in the substrate. In conclusion, optimizing the composition and structure of the substrate and rearing conditions and duration for each insect species might also aid standardization of the nutritional composition of edible insects.
Effectiveness of Lateral Elbow Tendinopathy Treatment Depends on the Content of Biologically Active Compounds in Autologous Platelet-Rich Plasma
Authors: Dejnek Maciej , Moreira Helena , Płaczkowska Sylwia , Barg Ewa , Reichert Paweł , Królikowska Aleksandra
Published: June 2022

Autologous platelet-rich plasma (PRP) injection is an alternative treatment option for patients with lateral elbow tendinopathy. The treatment is supposed to accelerate tissue regeneration by providing high concentrations of growth factors derived from platelets. The aim of the study was to assess the relationship between the content of biologically active compounds in PRP and the clinical effect of the treatment. Thirty patients with lateral elbow tendinopathy treated with a single PRP injection, were evaluated. The pain intensity (measured by a visual analogue scale (VAS)), the pressure pain threshold (PPT), the grip strength and strength of the main arm and forearm muscle groups, and the functional outcome (measured by the Disability of Arm, Shoulder and Hand (DASH) and Patient-Rated Tennis Elbow Evaluation (PRTEE) questionnaires), were assessed before PRP injection and at one- and three-months follow-up. Flow cytometry measurements of the growth factors and inflammatory cytokines in PRP were performed, and the results were used to establish the relationship between those molecules and the clinical outcome. After three months from the intervention, the minimal clinically important difference in pain reduction and functional improvement was observed in 67% and 83% of patients, respectively. Positive correlations were found between the extent of pain reduction after three months and concentrations in the PRP of platelets, epidermal growth factor (EGF), vascular endothelial growth factor, and platelet-derived growth factors. The concentration of EGF in the PRP significantly correlated with an improvement in grip strength, strength of wrist extensors, and the size of functional improvement measured by the PRTEE. The local injection of PRP is a safe and effective treatment option for lateral elbow tendinopathy, and the clinical outcome is correlated with concentrations of its biologically active compounds.
Gynecological Cancers in Lynch Syndrome: A Comparison of the Histological Features with Sporadic Cases of the General Population
Authors: Bounous Valentina Elisabetta , Robba Elisabetta , Perotto Stefania , Pasini Barbara , Tomasi Cont Nicoletta , Ricci Maria Teresa , Ditto Antonino , Vitellaro Marco , Raspagliesi Francesco , Biglia Nicoletta
Published: June 2022

Introduction: About 5% of endometrial cancers (ECs) are attributed to an inherited predisposition, for which Lynch syndrome (LS) accounts for the majority of cases. Women with LS have a 40–60% predicted lifetime risk of developing EC, in addition to a 40–80% lifetime risk of developing colorectal cancer and other cancers. In this population, the lifetime risk of developing ovarian cancer (OC) is 10–12%. Object: to compare the histopathological features of LS-associated EC and OC with sporadic cancers in order to evaluate whether there are differences in terms of age at diagnosis, site of occurrence in the uterus, histological type, stage at diagnosis, and tumor grading. Materials and methods: we compared data obtained from 96 patients with LS-associated gynecological cancers (82 with EC and 14 with OC) to a control group (CG) of 209 patients who developed sporadic EC, and a CG of 187 patients with sporadic OC. Results: The mean age at diagnosis of LS-associated EC and OC was much lower than in the control groups. In both groups with EC, the endometrioid histotype was the most frequently occurring histotype. However, among LS women there was a significantly higher incidence of clear cell tumors (11% versus 2.4% in the CG, p = 0.0001). Similar to the sporadic cancer cases, most of the LS-associated ECs presented at an early stage (89% of cases at FIGO I-II stage). In the LS group, the tumor frequently involved only the inner half of the endometrium (77% of cases, p < 0.01). In the LS group, 7.3% of ECs were localized to the lower uterine segment (LUS), whereas no cancer developed in the LUS in the CG. No serous OCs were diagnosed in the LS group (versus 45.5% in the CG, p = 0.0009). Most of the LS-associated OCs presented at an early stage (85% of cases at FIGO I-II stages, p < 0.01). Conclusion: LS-associated EC and OC seem to have peculiar features, occurring at a younger age and at an earlier stage. In LS, EC less frequently involves the outer half of the endometrium, with a more frequent occurrence in the LUS. The presence of clear cell EC was more frequently observed, whereas in OC, the predominant histotype was endometrioid.
Epidemiology, Physiology and Clinical Approach to Sleepiness at the Wheel in OSA Patients: A Narrative Review
Authors: Bonsignore Maria R. , Lombardi Carolina , Lombardo Simone , Fanfulla Francesco
Published: June 2022

Sleepiness at the wheel (SW) is recognized as an important factor contributing to road traffic accidents, since up to 30 percent of fatal accidents have been attributed to SW. Sleepiness-related motor vehicle accidents may occur both from falling asleep while driving and from behavior impairment attributable to sleepiness. SW can be caused by various sleep disorders but also by behavioral factors such as sleep deprivation, shift work and non-restorative sleep, as well as chronic disease or the treatment with drugs that negatively affect the level of vigilance. An association between obstructive sleep apnea (OSA) and motor vehicle accidents has been found, with an increasing risk in OSA patients up to sevenfold in comparison to the general population. Regular treatment with continuous positive airway pressure (CPAP) relieves excessive daytime sleepiness and reduces the crash risk. Open questions still remain about the physiological and clinical determinants of SW in OSA patients: the severity of OSA in terms of the frequency of respiratory events (apnea hypopnea index, AHI) or hypoxic load, the severity of daytime sleepiness, concomitant chronic sleep deprivation, comorbidities, the presence of depressive symptoms or chronic fatigue. Herein, we provide a review addressing the epidemiological, physiological and clinical aspects of SW, with a particular focus on the methods to recognize those patients at risk of SW.
Accuracy of Catheter Positioning during Left Subclavian Venous Access: A Randomized Comparison between Radiological and Topographical Landmarks
Authors: Kim Sun Key , Ahn Jung Hwan , Lee Yoon Kyung , Hwang Bo Young , Lee Min Kyung , Kim Il Seok
Published: June 2022

Left subclavian venous access increases the risk of vascular damage and thrombosis based on the catheter course and location of the catheter tip. We investigated the accuracy of tip positioning with conventional landmarks using transesophageal echocardiography. The carina as a radiological landmark and the right third intercostal space as a topographical landmark were selected for tip positioning within the target zone, defined as 2 cm above and 1 cm below the right atrial junction. A total of 120 participants were randomized into two groups. The catheter insertion depth was determined as 1.5 cm more than the distance between the venous insertion point and the carina via the right first intercostal space in the radiological group, and between the venous insertion point and the right third intercostal space via the right first intercostal space in the topographical group. The determined insertion depth and actual distance to the right atrial junction of the radiological and topographical groups were 19.5 cm and 20.5 cm, and 19.8 cm and 20.4 cm, respectively. Acceptable positioning was more frequent in the topographical group (96.4% vs. 85.7%; p = 0.047). The catheter tip is more accurately positioned in the distal superior vena cava using topographical landmarks than radiological landmarks.
Two Patterns of White Matter Connection in Multiple Gliomas: Evidence from Probabilistic Fiber Tracking
Authors: Zhang Simin , Su Xiaorui , Kemp Graham J. , Yang Xibiao , Wan Xinyue , Tan Qiaoyue , Yue Qiang , Gong Qiyong
Published: June 2022

Background: Multiple lesions are uncommon in brain gliomas, and their pathophysiology is poorly understood. Invasive growth along white matter tracts is an important clinicopathological characteristic of gliomas, and a major factor in a poor therapeutic outcome. Here, we used probabilistic fiber tracking and cluster analysis to investigate the inter-focal connectivity relationships of multiple gliomas, in order to seek inferential evidence of common origin. Methods: MRI scans of 46 patients with multiple gliomas were retrospectively analyzed. Before surgery, all patients underwent multimodal functional MR imaging, including diffusion tensor imaging, enhanced 3D T1-weighted imaging, diffusion-weighted imaging, 1H MR spectroscopy, and dynamic susceptibility contrast perfusion-weighted imaging. Probabilistic fiber tracking was used to quantify white matter connectivity between neoplastic foci. Hierarchical cluster analysis was performed to identify patterns of white matter connection. Results: Cluster analysis reveals two patterns of connectivity, one with smaller, and one with greater, connectivity (2675 ± 1098 versus 30432 ± 22707, p < 0.0001). The two subgroups show significant differences in relative cerebral blood volume (2.31 ± 0.95 versus 1.73 ± 0.48, p = 0.002) and lipid/creatine ratio (0.32 ± 0.22 versus 0.060 ± 0.051, p = 0.006). Conclusion: Two distinct patterns of white matter connection exist in multiple gliomas. Those with lower connectivity tend to have independent origins, and can be termed true multicentric glioma, whereas those with greater connectivity tend to share common origin, and spread along white matter tracts. True multicentric gliomas have higher vascularity and more intratumoral necrosis. These findings may help to develop personalized therapeutic strategies for multiple gliomas.
Association of Cardiac Autonomic Responses with Clinical Outcomes of Myasthenia Gravis: Short-Term Analysis of the Heart-Rate and Blood Pressure Variability
Authors: Zawadka-Kunikowska Monika , Rzepiński Łukasz , Tafil-Klawe Małgorzata , Klawe Jacek J. , Zalewski Paweł , Słomko Joanna
Published: June 2022

Introduction: The aim of the study was to assess cardiac and autonomic function in patients with myasthenia gravis (MG) and to explore its relationship with disease outcomes. Methods: Thirty-eight patients with an MG were enrolled (median age 40.5 years; median disease duration 5.5 years). Cardiovascular parameters, baroreflex sensitivity (BRS), spectral indices of short-term heart rate (HRV), and systolic blood pressure variability (SBPV) were compared with age- and gender-matched controls (n = 30). Cardiac autonomic function was assessed during the response to standing (tilt) and deep breathing tests (expiration/inspiration ratio-E/I). Results: HR and BP responses to the tilt test were similar in both groups. MG patients, as compared to controls, were characterized by altered SBPV at rest, significantly reduced HR response to the deep breathing test (p < 0.001), increased sympathovagal balance after tilt (delta LF/HF-RRI, p = 0.037), and lower values of BRS (p = 0.007) and hemodynamic parameters, i.e., cardiac index, index contractility, left ventricular work index, at rest and during tilt. There was no association between disease duration and autonomic parameters. Disease severity, as determined by MGFA (Myasthenia Gravis Foundation of America) corrected for age and sex, was an independent predictor of diminished vagal tone (E/I ratio) and increased sympathetic response to tilt (delta LF/HF-RRI) as measured with HRV. Lower BRS was associated with greater disease severity and older age. Hemodynamic parameters were predominantly predicted by age and sex. Conclusion: Our results confirm cardiac autonomic dysfunction among MG patients with predominant parasympathetic impairment. Clinicians should consider evaluation of autonomic balance in MG patients with, or at risk for, cardiovascular disease.
Achilles Tendon Rupture and Dysmetabolic Diseases: A Multicentric, Epidemiologic Study
Authors: Oliva Francesco , Marsilio Emanuela , Asparago Giovanni , Giai Via Alessio , Biz Carlo , Padulo Johnny , Spoliti Marco , Foti Calogero , Oliva Gabriella , Mannarini Stefania , Rossi Alessandro Alberto , Ruggieri Pietro , Maffulli Nicola
Published: June 2022

Introduction: Achilles tendon ruptures are common. Metabolic disorders, such as diabetes mellitus, hypercholesterolemia, thyroid disorders, and obesity, impair tendons health, leading to Achilles tendinopathy and likely predisposing patients to Achilles tendon ruptures. Materials and methods: Patients who visited the Orthopedic Outpatient Clinics and the Accident and Emergency Departments of five different hospitals in Italy were recruited. Through telephone interviews, we administered a questionnaire to all the patients who had undergone surgical ATR repair, evaluating their past medical history, sport- and work-related activities, drug use, and post-operative rehabilitation outcomes. Results: “Return to work activities/sport” was negatively predicted by the presence of a metabolic disorder (β = −0.451; OR = 0.637) and ‘open’ surgery technique (β = −0.389; OR = 0.678). “Medical complications” were significantly predicted by metabolic disorders (β = 0.600 (0.198); OR = 1.822) and was negatively related to ‘mini-invasive’ surgery (i.e., not ‘open’ nor ‘percutaneous’) (β = −0.621; OR = 0.537). “Immediate weightbearing” and “immediate walking without assistance” were negatively predicted by ‘open’ technique (β = −0.691; OR = 0.501 and β = −0.359 (0.174; OR = 0.698)). Conclusions: Metabolic conditions can strongly affect post-operative outcomes following surgical repair of acute Achilles tendon tears.
High-Intensity Laser Therapy (HILT) as an Emerging Treatment for Vulvodynia and Chronic Musculoskeletal Pain Disorders: A Systematic Review of Treatment Efficacy
Authors: Starzec-Proserpio Małgorzata , Grigol Bardin Marcela , Fradette Julie , Tu Le Mai , Bérubè-Lauzière Yves , Paré Josianne , Carroll Marie-Soleil , Morin Mélanie
Published: June 2022

High-intensity laser therapy (HILT) has been gaining popularity in the treatment of chronic musculoskeletal pain, including vulvodynia. The objective of this study was to critically appraise and synthesize the available evidence on the efficacy of HILT for reducing pain and improving function in vulvodynia and other chronic primary musculoskeletal pain conditions. Electronic databases and the grey literature were searched. Effects on pain intensity, function, and adverse events were assessed. One study investigating HILT in the treatment of vulvodynia and 13 studies on the treatment of chronic musculoskeletal pain were selected. The study assessing vulvodynia showed favorable results for reducing pain. Regarding chronic musculoskeletal pain, 12 out of the 13 studies selected consistently showed that HILT was more effective than the placebo/active comparator for reducing pain and improving function. The available effect sizes for pain showed large to huge effects. Similar effects were observed for function except for two studies showing moderate effects. The GRADE score was moderate. Conclusions: There are insufficient data to support the use of HILT in vulvodynia, but the promising results encourage further research. HILT appears to be effective in musculoskeletal pain conditions. More high-quality studies are needed to identify effective laser protocols.
A Genotype-Phenotype Study of Multiple Hereditary Exostoses in Forty-Three Patients
Authors: Kim Sungmin , Lee Chang-Hyun , Choi Seok-Yong , Kim Myeong-Kyu , Jung Sung Taek
Published: June 2022

Multiple hereditary exostoses (MHE) is a rare autosomal dominant skeletal disorder with a variety of clinical manifestations. We aimed to evaluate the general clinical phenotypic severity of MHE using our own scoring system and analyzed the risk factors associated with severe clinical phenotypes. In this study, 43 patients from 30 families were analyzed. The mutations were identified by direct sequencing of polymerase chain reaction-amplified genomic DNA or by multiplex ligation-dependent probe amplification. According to a new scoring system devised by the authors, the severity of the phenotype was assessed as mild, moderate, or severe based on the deformity of each segment, number of exostoses, leg length discrepancy, and functional limitations. Of 43 patients from 30 families, 39 patients (90.7%) and 24 families (80%) presented with EXT1 or EXT2 mutations. Patients with EXT1 mutations had a significantly worse phenotype than that of patients with EXT2 mutations or without any detectable mutation. The mean clinical score of patients with an EXT1 mutation (5.76; range, 2.0–8.0; SD = 1.60) was higher than that of patients with an EXT2 mutation (4.06; range, 2.0–7.0; SD = 1.47) or of those without any detectable mutation (4.63; range, 3.0–6.0; SD = 1.44; p = 0.005). According to our classification system, more patients with EXT1 mutations had ‘severe disease’ than those with EXT2 mutations. Deformity scores were also higher in patients with EXT1 mutations (p = 0.018). In the multivariate analysis, the deformity score was found to be associated with the ‘severe’ class (p = 0.031). In conclusion, 90.7% of patients with MHE showed EXT mutations. Our scoring system showed reliable results. We suggest that the extent of deformity is an important factor in determining the phenotype of MHE and close monitoring for the development of severe disease is recommended in patients with high deformity scores.
The Risk of Developing Alzheimer’s Disease and Parkinson’s Disease in Patients with Inflammatory Bowel Disease: A Meta-Analysis
Authors: Szandruk-Bender Marta , Wiatrak Benita , Szeląg Adam
Published: June 2022

Recently, a growing body of research has linked gut microbiota dysbiosis to central nervous system diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and has suggested that AD and PD pathology may take its origin from chronic inflammation in the gastrointestinal tract. Thus, this study aimed to elucidate whether inflammatory bowel disease (IBD) is associated with a higher risk of developing AD and PD as compared to the non-IBD population by conducting a meta-analysis. A thorough search of Pubmed and Embase databases was performed to identify all relevant articles. The quality of included studies was assessed using the Newcastle-Ottawa Scale. The odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed using a fixed-effect model. To assess publication bias and heterogeneity among the studies, Egger’s test and L’Abbé plots were used, respectively. A total of eight eligible studies were included in this meta-analysis. No significant heterogeneity or significant publication bias was detected. The risk of developing AD in IBD patients was higher than in non-IBD patients (OR = 0.37; 95% CI = 0.14–1.00; p = 0.05), and there was a relationship between the occurrence of AD and Crohn’s disease or ulcerative colitis (OR = 0.11; 95% CI = 0.04–0.30; p < 0.0001, OR = 0.14; 95% CI = 0.04–0.49; p = 0.0024, respectively). The risk of developing both of the most common neurodegenerative diseases, AD and PD, was also significantly higher in patients diagnosed with Crohn’s disease or ulcerative colitis (OR = 0.21; 95% CI = 0.09–0.49; p = 0.0003, OR = 0.25; 95% CI = 0.13–0.51; p = 0.0001, respectively). This meta-analysis revealed a higher risk of AD and PD among CD and UC patients compared to the general population. It may suggest a key role for the gut microbiota in the pathogenesis of not only Crohn’s disease and ulcerative colitis but also AD and PD. The identification of this potential risk may provide earlier preventive measures to be implemented to reduce comorbidity and mortality rate.
The Effectiveness of Hydrodissection with 5% Dextrose for Persistent and Recurrent Carpal Tunnel Syndrome: A Retrospective Study
Authors: Chao Ta-Chung , Reeves Kenneth Dean , Lam King Hei Stanley , Li Tsung-Ying , Wu Yung-Tsan
Published: June 2022

Patients with failure of primary surgery for carpal tunnel syndrome (CTS) present a frustrating clinical problem because there are no relevant treatment guidelines, and the effect of current conservative management or revision surgery is unsatisfactory. Hydrodissection with 5% dextrose is emerging as an effective treatment for primary CTS and may be an effective alternative treatment method for persistent or recurrent post-surgical CTS. We retrospectively investigated the long-term effectiveness of hydrodissection with 5% dextrose for persistent or recurrent CTS. Thirty-six of forty consecutively-treated patients with either persistent or recurrent symptoms of CTS after surgery, who were treated with ultrasound-guided hydrodissection of the median nerve using 10 mL of 5% dextrose, were available to provide outcome data by a structured phone interview at least six months after treatment completion. Symptom relief ≥ 50% represented an effective outcome, while symptom relief < 50% was rated as a poor outcome. Nearly 2/3 (61.1%) of patients reported an effective outcome after a mean of 3.1 injections, with a post-injection follow-up mean of 33 (6–67) months. A non-significant trend toward a more frequently-effective outcome was observed in those with recurrent versus persistent symptoms following CTS (76.9% vs. 52.2%, p = 0.165). However, a significantly higher percentage of those with recurrent symptoms reported an excellent outcome, defined as a greater than 70% improvement (8/13 [61.6%] vs. 3/23 [13%], p = 0.006). The percentage of patients achieving an effective outcome was not significantly different between <2, 2–4, and >4 years of post-treatment follow-up (36.4% vs. 77.8% vs. 57.1%; p = 0.077). Hydrodissection with 5% dextrose may result in a clinically important and durable benefit in those experiencing persistent or recurrent CTS after surgery.
Reshaping Treatment of Heart Failure with Preserved Ejection Fraction
Authors: Karamichalakis Nikolaos , Xanthopoulos Andrew , Triposkiadis Filippos , Paraskevaidis Ioannis , Tsougos Elias
Published: June 2022

Current data indicate that in the community, approximately 50% of patients with heart failure (HF) have preserved left ventricular (LV) ejection fraction (LVEF)—the so-called HFpEF. Treatment of HFpEF has been considered an unmet need for decades. We believe that the main underlying reasons have been (a) the ever-changing LVEF cut-offs used for HF classification; (b) controversies regarding the definition of the LVEF normal range; (c) the fact that HFpEF does not represent a phenotype, but a category of diseases with entirely different characteristics (hypertensive heart disease, valvular heart disease (VHD), hypertrophic cardiomyopathy (HCM) etc.); (d) the lack of recognition that hypertensive HFpEF is the most common and important HFpEF phenotype; (e) the assumption that neurohormonal overactivity is absent in HF patients with a LVEF > 45–50% which has been proven to be wrong. Current HFpEF trials, in which the vast majority of the participants suffered from hypertension (HTN), whereas VHD and HCM were absent, demonstrated that neurohormonal and sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective in HF patients over a wide LVEF range. Thus, restricting these lifesaving treatments to HF patients with reduced LVEF is not justified anymore and it should be additionally considered for HFpEF patients suffering from HTN.
Methods for Determination of Individual PEEP for Intraoperative Mechanical Ventilation Using a Decremental PEEP Trial
Authors: Girrbach Felix , Zeutzschel Franziska , Schulz Susann , Lange Mirko , Beda Alessandro , Giannella-Neto Antonio , Wrigge Hermann , Simon Philipp
Published: June 2022

(1) Background: Individual PEEP settings (PEEPIND) may improve intraoperative oxygenation and optimize lung mechanics. However, there is uncertainty concerning the optimal procedure to determine PEEPIND. In this secondary analysis of a randomized controlled clinical trial, we compared different methods for PEEPIND determination. (2) Methods: Offline analysis of decremental PEEP trials was performed and PEEPIND was retrospectively determined according to five different methods (EIT-based: RVDI method, Global Inhomogeneity Index [GI], distribution of tidal ventilation [EIT VT]; global dynamic and quasi-static compliance). (3) Results: In the 45 obese and non-obese patients included, PEEPIND using the RVDI method (PEEPRVD) was 16.3 ± 4.5 cm H2O. Determination of PEEPIND using the GI and EIT VT resulted in a mean difference of −2.4 cm H2O (95%CI: −1.2;−3.6 cm H2O, p = 0.01) and −2.3 cm H2O (95% CI: −0.9;3.7 cm H2O, p = 0.01) to PEEPRVD, respectively. PEEPIND selection according to quasi-static compliance showed the highest agreement with PEEPRVD (p = 0.67), with deviations > 4 cm H2O in 3/42 patients. PEEPRVD and PEEPIND according to dynamic compliance also showed a high level of agreement, with deviations > 4 cm H2O in 5/42 patients (p = 0.57). (4) Conclusions: High agreement of PEEPIND determined by the RVDI method and compliance-based methods suggests that, for routine clinical practice, PEEP selection based on best quasi-static or dynamic compliance is favorable.
Genetic Aspects of Small for Gestational Age Infants Using Targeted-Exome Sequencing and Whole-Exome Sequencing: A Single Center Study
Authors: Park Su-Jung , Lee Narae , Jeong Seong-Hee , Jeong Mun-Hui , Byun Shin-Yun , Park Kyung-Hee
Published: June 2022

Background: The etiology of small for gestational age (SGA) is multifactorial and includes maternal/uterine-placental factors, fetal epigenetics, and genetic abnormalities. We evaluated the genetic causes and diagnostic effectiveness of targeted-panel sequencing (TES) or whole-exome sequencing (WES) in SGA infants without a known cause. Methods: A prospective study was conducted on newborn infants born with a birth weight of less than the 10th percentile for gestational age between January 2019 and December 2020 at the Pusan National University Hospital. We excluded infants with known causes of SGA, including maternal causes or major congenital anomalies or infections. SGA infants without a known etiology underwent genetic evaluation, including karyotyping, chromosomal microarray (CMA), and TES/WES. Results: During the study period, 82 SGA infants were born at our hospital. Among them, 61 patients were excluded. A total of 21 patients underwent karyotyping and chromosomal CMA, and aberrations were detected in two patients, including one chromosomal anomaly and one copy number variation. Nineteen patients with normal karyotype and CMA findings underwent TES or WES, which identified three pathogenic or likely pathogenic single-gene mutations, namely LHX3, TLK2, and MED13L. Conclusions: In SGA infants without known risk factors, the prevalence of genetic causes was 22% (5/21). The diagnostic yield of TES or WES in SGA infants with normal karyotype and CMA was 15.7% (3/19). TES or WES was quite helpful in identifying the etiology in SGA infants without a known cause.
Hemostasis Disturbances in Continuous-Flow Left Ventricular Assist Device (CF-LVAD) Patients—Rationale and Study Design
Authors: Kuczaj Agnieszka , Hudzik Bartosz , Kaczmarski Jacek , Przybyłowski Piotr
Published: June 2022

Left ventricular assist devices are a treatment option for end-stage heart failure patients. Despite advancing technologies, bleeding and thromboembolic events strongly decrease the survival and the quality of life of these patients. Little is known about prognostic factors determining these adverse events in this group of patients. Therefore, we plan to investigate 90 consecutive left ventricular assist device (LVAD) patients and study in vitro fibrin clot properties (clot lysis time, clot permeability, fibrin ultrastructure using a scanning electron microscope) and the calibrated automated thrombogram in addition to the von Willebrand factor antigen, fibrinogen, D-dimer, prothrombin time/international normalized ratio (PT/INR), and activated partial thromboplastin time (APTT) to identify prognostic factors of adverse outcomes during the course of therapy. We plan to assess the hemostasis system at four different time points, i.e., before LVAD implantation, 3–4 months after LVAD implantation, 6–12 months after LVAD implantation, and at the end of the study (at 5 years or at the time of the adverse event). Adverse outcomes were defined as bleeding events (bleeding in general or in the following subtypes: severe bleeding, fatal bleeding, gastrointestinal bleeding, intracranial bleeding), thromboembolic events (stroke or transient ischemic attack, pump thrombosis, including thrombosis within the pump or its inflow or outflow conduits, arterial peripheral thromboembolism), and death.
NKG2A Expression among CD8 Cells Is Associated with COVID-19 Progression in Hypertensive Patients: Insights from the BRACE CORONA Randomized Trial
Authors: Moll-Bernardes Renata , Fortier Sérgio C. , Sousa Andréa S. , Lopes Renato D. , Vera Narendra , Conde Luciana , Feldman André , Arruda Guilherme , Cabral-Castro Mauro , Albuquerque Denílson C. , Paula Thiago C. , Furquim Thyago , Loures Vitor A. , Giusti Karla , Oliveira Nathália , Macedo Ariane , Barros e Silva Pedro , De Luca Fábio , Kotsugai Marisol , Domiciano Rafael , Silva Flávia A. , Santos Mayara F. , Souza Olga F. , Bozza Fernando A. , Luiz Ronir R. , Medei Emiliano
Published: June 2022

Cardiovascular comorbidities and immune-response dysregulation are associated with COVID-19 severity. We aimed to explore the key immune cell profile and understand its association with disease progression in 156 patients with hypertension that were hospitalized due to COVID-19. The primary outcome was progression to severe disease. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and immune cell subsets associated with the primary outcome. Obesity; diabetes; oxygen saturation; lung involvement on computed tomography (CT) examination; the C-reactive protein concentration; total lymphocyte count; proportions of CD4+ and CD8+ T cells; CD4/CD8 ratio; CD8+ HLA-DR MFI; and CD8+ NKG2A MFI on admission were all associated with progression to severe COVID-19. This study demonstrated that increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, is associated with a high risk of COVID-19 progression in hypertensive patients. These findings reinforce the hypothesis of the functional exhaustion of T cells with the increased expression of NKG2A in patients with severe COVID-19, elucidating how severe acute respiratory syndrome coronavirus 2 infection may break down the innate antiviral immune response at an early stage of the disease, with future potential therapeutic implications.
Chronic Pelvic Pain in Endometriosis: Cross-Sectional Associations with Mental Disorders, Sexual Dysfunctions and Childhood Maltreatment
Authors: Netzl Johanna , Gusy Burkhard , Voigt Barbara , Sehouli Jalid , Mechsner Sylvia
Published: June 2022

The aim of this cross-sectional study was to compare the rates of mental disorders, sexual dysfunctions and childhood maltreatment (CM) in women with endometriosis with either chronic pelvic pain (CPP) or minimal to no pelvic pain. Additionally, two models to predict a current mental disorder were tested, including pelvic-pain-related or psychosocial predictor variables. We examined 100 women with confirmed endometriosis (group CPP, n = 50; group NOPAIN, n = 50). Participants responded to a comprehensive questionnaire and the Childhood Trauma Questionnaire. The Diagnostic Interview for Mental Disorders was used to assess mental disorders according to DSM-5 and to screen for sexual dysfunctions. The mean age was 28.8 ± 5.6 (CPP)/2.7 ± 6.3 (NOPAIN). Participants with CPP had higher rates of current mental disorders (p = 0.019), lifetime mental disorders (p = 0.006) and sexual dysfunctions (p < 0.001), but not CM (p = 0.074). In two binary-logistic regression analyses, a greater need for pain relief (aOR = 4.08, p = 0.026) and a sexual dysfunction (aOR = 2.69, p = 0.031) were significant predictors for a current mental disorder. Our findings confirmed the crucial role of pelvic pain for mental and sexual well-being in endometriosis. They highlight the need for pain relief and interdisciplinary care in the treatment of endometriosis.
Optic Nerve Drusen Evaluation: A Comparison between Ultrasound and OCT
Authors: Rosa Nicola , De Bernardo Maddalena , Abbinante Giulia , Vecchio Gianluca , Cione Ferdinando , Capasso Luigi
Published: June 2022

This observational study compared optic coherence tomography (OCT) and B-scan in the detection of optic disc drusen. In total, 86 eyes of 50 patients with optic disc drusen (ODD) (36 bilateral) with a mean age of 34.68 ± 23.81 years, and 54 eyes of 27 patients with papilledema, with a mean age of 35.42 years ± 17.47, were examined. Patients with ODD, diagnosed with ultrasound, underwent spectral-domain OCT evaluation. With US, 28 ODD cases were classified as large (4 buried and 24 superficial), 58 were classified as point-like (6 buried, 49 superficial and 3 mixed). Then, all patients underwent OCT. OCT was able to detect the presence of ODD and/or peripapillary hyperreflective ovoid mass structure (PHOMS) in 69 eyes (p < 0.001). In particular, 7 eyes (8.14%) showed the presence of ODD alone, 25 eyes (29.07%) showed only PHOMS and 37 eyes (43.02%) showed ODD and PHOMS. In 17 eyes (19.77%) no ODD or PHOMS were detected. In the papilledema group, no ODD were observed with both US and OCT. OCT showed the presence of drusen or similar lesions in only 80.23% of the cases highlighted by the US scan, so it does not allow for certain ODD diagnoses, especially in the case of buried ODD.
Stool Elastase as an Independent Prognostic Factor in Patients with Pancreatic Head Cancer
Authors: Hwang Honam , Kim Hongbeom , Sohn Hee Ju , Lee Mirang , Kim Hyeong Seok , Han Youngmin , Kwon Wooil , Jang Jin-Young
Published: June 2022

(1) Background: Patients with pancreatic exocrine insufficiency (PEI) have an increased risk of malnutrition, which in turn increases morbidity and mortality and is frequent in pancreatic head cancer. This study aimed to analyze the utility of PEI measured using the stool elastase (SE) level to predict the prognosis of patients with pancreatic head cancer. (2) Methods: Patients who underwent pancreaticoduodenectomy for pancreatic cancer at our institution between 2011 and 2015 were included. Only patients with data on preoperative SE levels were analyzed. Patients were classified into low and high SE groups based on preoperative SE levels (low < 100 µg/g < high). (3) Results: The median preoperative SE level was 67.2 µg/g, and 84 of 143 (58.7%) patients were included in the low SE group. The two groups had significantly different overall survival (OS) and disease-free survival (DFS), and the low SE group had a worse prognosis. In multivariate analysis, SE level < 100 µg/g and lymph node metastasis were independent poor prognostic factors for OS and DFS. (4) Discussion: PEI measured using SE levels is an independent prognostic factor in patients with pancreatic head cancer undergoing pancreaticoduodenectomy. Since poor nutritional status may be related to prognosis in patients with low levels of stool elastase preoperatively, aggressive treatment may be required.
Lipid, Aqueous and Mucin Tear Film Layer Stability and Permanence within 0.15% Liposome Crosslinked Hyaluronic Acid versus 0.15% Non-Crosslinked Hyaluronic Acid Measured with a Novel Non-Invasive Ocular Surface Analyzer
Authors: Sánchez-González José-María , De-Hita-Cantalejo Concepción , Martínez-Lara Concepción , Sánchez-González María Carmen
Published: June 2022

To evaluate the stability and permanence of the liquid film created after the instillation of 0.15% crosslinked hyaluronic acid with liposomes and crocin versus the effect of 0.15% standard hyaluronic acid, a prospective, longitudinal, single-blind, single-center study was conducted in symptomatic populations with a novel noninvasive ocular surface analyzer. Limbal and bulbar redness classification, lipid layer thickness, tear meniscus height, and first and mean noninvasive break-up time (FNIBUT and MNIBUT) were performed before and 30 and 45 min after liposome-crosslinked hyaluronic acid (LCHA) and standard hyaluronic acid (HA) eye drop instillations. LCHA had a higher lipid layer thickness than HA (grades 2.00 ± 0.83 and 1.17 ± 0.63 on the Guillon pattern, respectively). LCHA achieved a better tear meniscus height than HA (0.23 ± 0.02 and 0.21 ± 0.02 mm, respectively). LCHA improved FNIBUT and MNIBUT more than HA (for FNIBUT, 6.30 ± 0.94 and 4.77 ± 0.89 s, respectively. For MNIBUT, 17.23 ± 5.11 and 12.41 ± 4.18 s, respectively). Crosslinking hyaluronic acid with liposomes and crocin significantly increases the permanence and stability of the lipid, aqueous, and mucin tear film layers. In a short-term period, liposome and crosslinked hyaluronic acid achieved better first and mean noninvasive break-up times than standard hyaluronic acid.
Remodeling of Retinal Arterioles and Carotid Arteries in Heart Failure Development—A Preliminary Study
Authors: Sadowski Janusz , Targonski Ryszard , Cyganski Piotr , Nowek Paulina , Starek-Stelmaszczyk Magdalena , Zajac Katarzyna , Juranek Judyta , Wojtkiewicz Joanna , Rynkiewicz Andrzej
Published: June 2022

Current data indicate that heart failure (HF) is associated with inflammation and microvascular dysfunction and remodeling. These mechanisms could be involved in HF development and progression, especially in HF with preserved ejection fraction (HFpEF). We aimed to compare structural changes in retinal arterioles and carotid arteries between HF patients and patients without heart failure. This preliminary, retrospective, case-control study included 28 participants (14 patients with HFpEF and 14 age- and sex-matched healthy controls). Carotid intima-media thickness to lumen ratio (cIMTLR) was assessed using B-mode ultrasonography. Retinal arterioles wall- to-lumen ratio (rWLR) was assessed by adaptive optics camera rtx1. The HF patients had higher IMTLR (Δmedian [HFpEF–control group] 0.07, p = 0.01) and eWLR (Δmedian 0.03, p = 0.001) in comparison to patients without HF. In the whole study group, rWLR correlated significantly with IMTLR (r = 0.739, p = 0.001). Prevalence of arterial hypertension was similar in both groups, however, patients with HF had a significantly lower office, central and 24-h ambulatory blood pressure (systolic Δmedian −21 to −18 mmHg; diastolic Δmedian −23 to −10 mmHg). Our data suggests gradual and simultaneous progression of vascular remodeling in both retinal arterioles and carotid arteries in HFpEF patients. This process could be a marker of HF development. Significantly lower blood pressure values in HF group may indicate that vascular remodeling could be independent of BP control. Nevertheless, further and larger prospective studies allowing to reduce the impact of confounding and address temporality are warranted.