bluuebunny/crossref_metadata_2025 huggingface dataset:
Polygalae Radix Oligosaccharide Esters May Relieve Depressive-like Behavior in Rats with Chronic Unpredictable Mild Stress via Modulation of Gut Microbiota
Authors: Chen Qijun , Jia Tanrong , Wu Xia , Chen Xiaoqing , Wang Jiajia , Ba Yinying
Published: September 2023

Polygalae radix (PR) is a well-known traditional Chinese medicine that is used to treat depression, and polygalae radix oligosaccharide esters (PROEs) are the main active ingredient. Although gut microbiota are now believed to play key role in depression, the effects of PROEs on depression via modulation of gut microbiota remain unknown. In this article, we investigate the effect of PROEs on the gut microbiota of a depression rat and the possible mechanism responsible. The depression rat model was induced by solitary rearing combined with chronic unpredictable mild stress (CUMS). The depression-like behavior, the influence on the hypothalamic–pituitary–adrenal (HPA) axis, the contents of monoamine neurotransmitter in the hippocampus, and the quantity of short-chain fatty acids (SCFAs) in the feces were each assessed, and the serum levels of lipopolysaccharide (LPS) and interleukin-6 (IL-6) were measured by ELISA. Additionally, ultrastructural changes of the duodenal and colonic epithelium were observed under transmission electron microscope, and the gut microbiota were profiled by using 16S rRNA sequencing. The results show that PROEs alleviated the depression-like behavior of the depression model rats, increased the level of monoamine neurotransmitters in the brain, and reduced the hyperfunction of the HPA axis. Furthermore, PROEs regulated the imbalance of the gut microbiota in the rats, relieving intestinal mucosal damage by increasing the relative abundance of gut microbiota with intestinal barrier protective functions, and adjusting the level of SCFAs in the feces, as well as the serum levels of LPS and IL-6. Thus, we find that PROEs had an antidepressant effect through the restructuring of gut microbiota that restored the function of the intestinal barrier, reduced the release of intestinal endotoxin, and constrained the inflammatory response.
Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet
Authors: Filipe Rosa Louisa , Rings Andreas , Stolzer Iris , Koeninger Louis , Wehkamp Jan , Beisner Julia , Günther Claudia , Nordkild Peter , Jensen Benjamin A. H. , Bischoff Stephan C.
Published: September 2023

Obesity and metabolic comorbidities are associated with gut permeability. While high-fructose and Western-style diet (WSD) disrupt intestinal barrier function, oral administration of human α-defensin 5 (HD5) and β-defensin 2 (hBD2) is believed to improve intestinal integrity and metabolic disorders. Eighty-four male C57BL/6J mice were fed a WSD or a control diet (CD) ± fructose (F) for 18 weeks. In week 13, mice were randomly divided into three intervention groups, receiving defensin fragment HD51–9, full-length hBD2, or bovine serum albumin (BSA)-control for six weeks. Subsequently, parameters of hepatic steatosis, glucose metabolism, and gut barrier function were assessed. WSDF increased body weight and hepatic steatosis (p < 0.01) compared to CD-fed mice, whereas peptide intervention decreased liver fat (p < 0.05) and number of hepatic lipid droplets (p < 0.01) compared to BSA-control. In addition, both peptides attenuated glucose intolerance by reducing blood glucose curves in WSDF-fed mice. Evaluation of gut barrier function revealed that HD51–9 and hBD2 improve intestinal integrity by upregulating tight junction and mucin expression. Moreover, peptide treatment restored ileal host defense peptides (HDP) expression, likely by modulating the Wnt, Myd88, p38, and Jak/STAT pathways. These findings strongly suggest that α- and β-defensin treatment improve hepatic steatosis, glucose metabolism, and gut barrier function.
Fifty Years of Animal Toxin Research at the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry RAS
Authors: Tsetlin Victor , Shelukhina Irina , Kozlov Sergey , Kasheverov Igor
Published: September 2023

This review covers briefly the work carried out at our institute (IBCh), in many cases in collaboration with other Russian and foreign laboratories, for the last 50 years. It discusses the discoveries and studies of various animal toxins, including protein and peptide neurotoxins acting on the nicotinic acetylcholine receptors (nAChRs) and on other ion channels. Among the achievements are the determination of the primary structures of the α-bungarotoxin-like three-finger toxins (TFTs), covalently bound dimeric TFTs, glycosylated cytotoxin, inhibitory cystine knot toxins (ICK), modular ICKs, and such giant molecules as latrotoxins and peptide neurotoxins from the snake, as well as from other animal venoms. For a number of toxins, spatial structures were determined, mostly by 1H-NMR spectroscopy. Using this method in combination with molecular modeling, the molecular mechanisms of the interactions of several toxins with lipid membranes were established. In more detail are presented the results of recent years, among which are the discovery of α-bungarotoxin analogs distinguishing the two binding sites in the muscle-type nAChR, long-chain α-neurotoxins interacting with α9α10 nAChRs and with GABA-A receptors, and the strong antiviral effects of dimeric phospholipases A2. A summary of the toxins obtained from arthropod venoms includes only highly cited works describing the molecules’ success story, which is associated with IBCh. In marine animals, versatile toxins in terms of structure and molecular targets were discovered, and careful work on α-conotoxins differing in specificity for individual nAChR subtypes gave information about their binding sites.
Performance of Zr-Based Metal–Organic Framework Materials as In Vitro Systems for the Oral Delivery of Captopril and Ibuprofen
Authors: Cretu Carmen , Nicola Roxana , Marinescu Sorin-Alin , Picioruș Elena-Mirela , Suba Mariana , Duda-Seiman Corina , Len Adel , Illés Levente , Horváth Zsolt Endre , Putz Ana-Maria
Published: September 2023

Zr-based metal–organic framework materials (Zr-MOFs) with increased specific surface area and pore volume were obtained using chemical (two materials, Zr-MOF1 and Zr-MOF3) and solvothermal (Zr-MOF2) synthesis methods and investigated via FT-IR spectroscopy, TGA, SANS, PXRD, and SEM methods. The difference between Zr-MOF1 and Zr-MOF3 lies in the addition of reactants during synthesis. Nitrogen porosimetry data indicated the presence of pores with average dimensions of ~4 nm; using SANS, the average size of the Zr-MOF nanocrystals was suggested to be approximately 30 nm. The patterns obtained through PXRD were characterized by similar features that point to well-crystallized phases specific for the UIO-66 type materials; SEM also revealed that the materials were composed of small and agglomerate crystals. Thermogravimetric analysis revealed that both materials had approximately two linker deficiencies per Zr6 formula unit. Captopril and ibuprofen loading and release experiments in different buffered solutions were performed using the obtained Zr-based metal–organic frameworks as drug carriers envisaged for controlled drug release. The carriers demonstrated enhanced drug-loading capacity and showed relatively good results in drug delivery. The cumulative percentage of drug release in phosphate-buffered solution at pH 7.4 was higher than that in buffered solution at pH 1.2. The release rate could be controlled by changing the pH of the releasing solution. Different captopril release behaviors were observed when the experiments were performed using a permeable dialysis membrane.
Genotypes Distribution of Epstein–Barr Virus among Lymphoma Patients in Ethiopia
Authors: Teshome Seifegebriel , Ahmed Elshafa Hassan , Zealiyas Kidist , Abubeker Abdulaziz , Tadesse Fisihatsion , Weigel Christoph , Baiocchi Robert A. , Abebe Tamrat
Published: September 2023

Epstein–Barr virus (EBV) is an oncogenic herpes virus associated with several human malignancies. Two main EBV genotypes (type 1 and type 2) distinguished by the differences in EBV nuclear antigens are known. Geographic variability in these genetic differences has been observed in the incidence of some EBV-related tumors. Here, we investigated the genetic variation of EBV in lymphoma specimens collected in Ethiopia. A total of 207 DNA samples were used for EBV detection and typing, and EBNA1 and EBNA3C genes were used to detect and subtype the EBV genome, respectively. EBV genotype 1 was detected in 52.2% of lymphoma patients. EBV genotype 2 was detected in 38.2% of the lymphoma patients, and 9.7% were coinfected by both EBV genotypes. Overall, 52.8% of the Hodgkin’s lymphoma (HL) patients and 51.8% of non-Hodgkin’s lymphoma (NHL) patients showed the presence of genotype 1. Meanwhile, 42.8% and 2.3% of HL patients and 35.8% and 12.4% of NHL patients showed EBV genotype 2 and both genotypes, respectively. Significant associations between the age groups and EBV genotypes were observed (p = 0.027). However, no significant association was seen between EBV genotypes and other sociodemographic and clinical characteristics. This study showed that the distribution of EBV genotype 1 was higher in Ethiopian lymphoma patients.
Regulation of Embden–Meyerhof–Parnas (EMP) Pathway and Tricarboxylic Acid (TCA) Cycle Concerning Aberrant Chilling Injury Behavior in Postharvest Papaya (Carica papaya L.)
Authors: Huang Lijin , Tao Shoukui , Zhu Yi , Pan Yonggui , Zhang Zhengke , Yu Zhiqian , Chen Yezhen
Published: September 2023

Postharvest abnormal chilling injury (CI) behavior in papaya (Carica papaya L.) fruit is a rare phenomenon that may be associated with respiratory metabolism. This study thus aimed to investigate the impacts of storage temperatures (1 and 6 °C) on the respiratory metabolism of postharvest papaya and its impact on CI development. Results demonstrated that 1 °C storage reduced the activities of hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), citrate synthase (CS), and α-ketoglutarate dehydrogenase (α-KGDH) and regulated the expression of corresponding enzymes in the Embden–Meyerhof–Parnas (EMP) pathway and tricarboxylic acid (TCA) cycle compared with 6 °C storage, resulting in a lower respiration rate of the EMP-TCA pathway and mitigating the development of CI. Meanwhile, lower contents of nicotinamide adenine dinucleotide (hydrogen) (NAD(H)) were observed in papaya fruit stored at 1 °C. Notably, papaya fruit stored at 1 °C maintained higher activity and transcriptional levels of SDH and IDH during the whole storage period. These findings suggest that 1 °C storage reduced the respiration rate of the EMP-TCA pathway by reducing the expression level and activity of related enzymes, which is conducive to the reduction of respiration substrate consumption and finally alleviating the occurrence of CI.
The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function
Authors: Falah Ghadeer , Sharvit Lital , Atzmon Gil
Published: September 2023

Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the GH receptor (GHR), which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR isoform, which lacks exon 3 has recently been related to longevity; individuals carrying this isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the wild type (WT) isoform (flGHR). Further, studies performed in patients with acromegaly, Prader–Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR isoform may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.
Endothelial Dysfunction in Primary Sjögren’s Syndrome: Correlation with Serum Biomarkers of Disease Activity
Authors: Caraba Alexandru , Iurciuc Stela , Nicolin Mihaela , Iurciuc Mircea
Published: September 2023

To assess the relationship between endothelial dysfunction and serum cytokines, anti-SSA and anti-SSB antibodies, beta-2 microglobulin levels, focus score and EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) in primary Sjögren’s syndrome (pSS) patients. The study included 90 patients with pSS and 45 healthy subjects, matched for age and gender, as controls. Serum beta-2 microglobulin, total cholesterol, HDL-cholesterol, triglycerides, TNF-α, and IL-6 were analyzed in both the groups. Patients with pSS were also tested for antinuclear antibodies, anti-SAA (anti-Sjögren’s syndrome-related antigen A) antibodies, anti-SSB (anti-Sjögren syndrome related antigen B) antibodies, and focus score (the histopathologic one, based on minor salivary gland biopsy). Endothelial dysfunction was assessed by means of flow-mediated dilation (FMD) in the brachial artery. Data are presented as mean ± standard deviation. Statistical analysis was performed using the t-test and the Pearson’s correlation. Differences were considered to be statistically significant if the value of p < 0.05. Endothelial dysfunction was identified in pSS patients (p < 0.00001). The serum levels of cytokines (TNF-α, respective IL-6) and beta-2 microglobulin were increased in pSS patients compared with controls (p < 0.00001). Endothelial dysfunction (expressed as FMD%) was correlated with focus score, ESSDAI, levels of anti-SSA and anti-SSB antibodies, beta-2 microglobulin, IL-6, and TNF-α, with statistical significance. Endothelial dysfunction is present in pSS patients and is associated with a high focus score and activity as well as increased concentrations of antibodies, pro-inflammatory cytokines, and beta 2-microglobulin.
Supplementation with Vitamin D3 Protects against Mitochondrial Dysfunction and Loss of BDNF-Mediated Akt Activity in the Hippocampus during Long-Term Dexamethasone Treatment in Rats
Authors: Korewo-Labelle Daria , Karnia Mateusz Jakub , Myślińska Dorota , Kaczor Jan Jacek
Published: September 2023

Dexamethasone (DEXA) is a commonly used steroid drug with immunosuppressive and analgesic properties. Unfortunately, long-term exposure to DEXA severely impairs brain function. This study aimed to investigate the effects of vitamin D3 supplementation during chronic DEXA treatment on neurogenesis, mitochondrial energy metabolism, protein levels involved in the BDNF-mediated Akt activity, and specific receptors in the hippocampus. We found reduced serum concentrations of 25-hydroxyvitamin D3 (25(OH)D3), downregulated proBDNF and pAkt, dysregulated glucocorticosteroid and mineralocorticoid receptors, impaired mitochondrial biogenesis, and dysfunctional mitochondria energy metabolism in the DEXA-treated group. In contrast, supplementation with vitamin D3 restored the 25(OH)D3 concentration to a value close to that of the control group. There was an elevation in neurotrophic factor protein level, along with augmented activity of pAkt and increased citrate synthase activity in the hippocampus after vitamin D3 administration in long-term DEXA-treated rats. Our findings demonstrate that vitamin D3 supplementation plays a protective role in the hippocampus and partially mitigates the deleterious effects of long-term DEXA administration. The association between serum 25(OH)D3 concentration and BDNF level in the hippocampus indicates the importance of applying vitamin D3 supplementation to prevent and treat pathological conditions.
A Novel Gamification Application for High School Student Examination and Assessment to Assist Student Engagement and to Stimulate Interest
Authors: Gianni Anna Maria , Antoniadis Nikolaos
Published: September 2023

Formal education in high school focuses primarily on knowledge acquisition via traditional classroom teaching. Younger generations of students tend to lose interest and to disengage from the process. Gamification, the use of gaming elements in the training process to stimulate interest, has been used lately to battle this phenomenon. The use of an interactive environment and the employment of tools familiar to today’s students aim to bring the student closer to the learning process. Even though there have been several attempts to integrate gaming elements in the teaching process, few applications in the student assessment procedure have been reported so far. In this article, a new approach to student assessment is implemented using a gamified quiz as opposed to standard exam formats, where students are asked to answer questions on the material already taught, using various gaming elements (leaderboards, rewards at different levels, etc.). The results show that students are much more interested in this interactive process and would like to see this kind of performance assessment more often in their everyday activity in school. The participants are also motivated to learn more about the subject of the course and are generally satisfied with this novel approach compared to standard forms of exams.
Shared Decision Making and Cardioneuroablation Allow Discontinuation of Permanent Pacing in Patients with Vagally Mediated Bradycardia
Authors: Stec Sebastian , Wileczek Antoni , Reichert Agnieszka , Śledź Janusz , Kosior Jarosław , Jagielski Dariusz , Polewczyk Anna , Zając Magdalena , Kutarski Andrzej , Karbarz Dariusz , Zyśko Dorota , Nowarski Łukasz , Stodółkiewicz-Nowarska Edyta
Published: September 2023

Background: Safe discontinuation of pacemaker therapy for vagally mediated bradycardia is a dilemma. The aim of the study was to present the outcomes of a proposed diagnostic and therapeutic process aimed at discontinuing or not restoring pacemaker therapy (PPM) in patients with vagally mediated bradycardia. Methods: The study group consisted of two subgroups of patients with suspected vagally mediated bradycardia who were considered to have PPM discontinued or not to restore their PPM if cardioneuroablation (CNA) would successfully treat their bradycardia. A group of 3 patients had just their pacemaker explanted but reimplantation was suggested, and 17 patients had preexisting pacemakers implanted. An invasive electrophysiology study was performed. If EPS was negative, extracardiac vagal nerve stimulation (ECVS) was performed. Then, patients with positive ECVS received CNA. Patients with an implanted pacemaker had it programmed to pace at the lowest possible rate. After the observational period and control EPS including ECVS, redo-CNA was performed if pauses were induced. The decision to explant the pacemaker was obtained based on shared decision making (SDM). RESULTS: After initial clinical and electrophysiological evaluation, 17 patients were deemed eligible for CNA (which was then performed). During the observational period after the initial CNA, all 17 patients were clinically asymptomatic. The subsequent invasive evaluation with ECVS resulted in pause induction in seven (41%) patients, and these patients underwent redo-CNA. Then, SDM resulted in the discontinuation of pacemaker therapy or a decision to not perform pacemaker reimplantation in all the patients after CAN. The pacemaker was explanted in 12 patients post-CNA, while in 2 patients explantation was postponed. During a median follow-up of 18 (IQR: 8–22) months, recurrent syncope did not occur in the CNA recipients. Conclusions: Pacemaker therapy in patients with vagally mediated bradycardia could be discontinued safely after CNA.
Dissecting Airborne Allergens
Authors: Torres-Borrego Javier , Sánchez-Solís Manuel
Published: September 2023

Asthma is a heterogeneous and very complex group of diseases, and includes different clinical phenotypes depending on symptoms, progression, exacerbation patterns, or responses to treatment, among other characteristics. The allergic phenotype is the most frequent, especially in pediatric asthma. It is characterized by sensitization (the production of specific IgEs) to allergens and frequent comorbidity with rhinitis as well as atopic dermatitis. Given the complexity of allergic asthma, knowledge of it must be approached from different points of view: clinical, histological, physiological, epidemiological, biochemical, and immunological, among others. Since partial approaches do not allow for the understanding of this complexity, it is necessary to have multidimensional knowledge that helps in performing the optimal management of each case, avoiding a “blind men and elephant parable” approach. Allergens are antigens that trigger the production of specific IgE antibodies in susceptible individuals, who present symptoms that will depend on the type and intensity of the allergenic load as well as the tissue where the interaction occurs. Airborne allergens cause their effects in the respiratory tract and eyes, and can be indoor or outdoor, perennial, or seasonal. Although allergens such as mites, pollens, or animal dander are generally considered single particles, it is important to note that they contain different molecules which could trigger distinct specific IgE molecules in different patients. General practitioners, pediatricians, and other physicians typically diagnose and treat asthma based on clinical and pulmonary function data in their daily practice. This nonsystematic and nonexhaustive revision aims to update other topics, especially those focused on airborne allergens, helping the diagnostic and therapeutic processes of allergic asthma and rhinitis.
Serum Inflammatory and Oxidative Stress Markers in Patients with Vitiligo
Authors: Kassab Asma , Khalij Yassine , Ayed Yosra , Dar-Odeh Najla , Kokandi Amal A. , Denguezli Meriam , Youssef Monia
Published: September 2023

Background: Vitiligo is a common chronic hypomelanotic skin disorder. An intricate pool of markers associated with a complex combination of biological and environmental factors is thought to be implicated in etiology. This study aims to investigate the most important markers associated with vitiligo pathogenesis, including redox status, inflammation, and immune profile, in patients with vitiligo. Materials and Methods: The study included a total of 96 subjects: 30 patients with active non-segmental vitiligo, 30 patients with stable non-segmental vitiligo, and 36 controls. The vitiligo area severity index (VASI) and vitiligo disease activity score (VIDA) were determined. The following serum parameters were assessed: antioxidant status (TAS), superoxide dismutase activity (SOD), catalase activity (CAT), glutathione peroxidase activity (GPx), glutathione-S-transferase activity (GST), malondialdehyde (MDA), advanced oxidation protein products (AOPP), C reactive protein (CRP), interleukin-15 (IL-15), and chemokines (CXCL9, CXCL10). Results: The VASI score was not significantly different between active and stable vitiligo patients, as it was approximately 0.1. TAS, CAT, GPx, and GST were significantly lower in vitiligo patients compared to controls (p < 0.05). They were also significantly lower in active vitiligo when compared to stable vitiligo (p < 0.05). However, SOD levels were significantly higher in vitiligo patients than in controls and in the active vitiligo group than in the stable vitiligo group (p < 0.05). MDA and AOPP levels were significantly higher in patients with active and stable vitiligo compared to controls (p < 0.05). However, they did not significantly differ between active and stable vitiligo patients (p < 0.05). In both active and stable vitiligo, CRP and IL-15 were significantly higher than controls (p < 0.05). Whereas CRP was significantly higher in active (range = 2.0–7.2, mean = 4.46 ± 1.09) than in stable vitiligo (range = 1.6–6.7, mean = 3.75 ± 1.08) (p < 0.05). There was no significant difference in IL-15 levels between active and stable vitiligo. In both active and stable vitiligo, CXCL9 and CXCL10 were significantly higher than controls (p < 0.05), and they were significantly higher in active than stable vitiligo (p < 0.05). Conclusions: In vitiligo, oxidative damage induces an increase in pro-inflammatory IL-15, which in turn promotes IFN-γ-inducible chemokines such as CXCL9 and CXCL10. Further, there seems to be a link between the VASI score and IL-15 levels. These data imply that inhibiting IL-15 could be a promising method for developing a potentially targeted treatment that suppresses the early interplay between oxidant stress and IL-15 keratinocyte production, as well as between resident and recirculating memory T cells.
MDS-Related Anemia Is Associated with Impaired Quality of Life but Improvement Is Not Always Achieved by Increased Hemoglobin Level
Authors: Haring Yael , Goldschmidt Noa , Taha Shaimaa , Stemer Galia , Filanovsky Kalman , Hellman Ilana , Okasha Doaa , Krayem Baher , Levi Itai , Rosenbaum Hanna , Koren-Michowitz Maya , Yagna Shai , Nemets Anatoly , Gino-Moor Sharon , Saban Revital , Cohen Joseph , Halperin Erez , Wolach Ofir , Dally Najib , Merkel Drorit , Oster Howard S. , Mittelman Moshe
Published: September 2023

Quality of life is impaired in MDS, but the role of hemoglobin level is unclear. To study the Hb–QoL correlation at diagnosis and 1 year later, patients filled out the EQ-5D questionnaire, assessing their mobility, self care, daily activities, pain/discomfort, and anxiety/depression, using scores of 0 (normal), 1 (mild/moderate), or 2 (poor). They also evaluated their health using a visual analogue scale, scoring from 0 (poor) to 100 (excellent). The anemia subgroups were: none/normal (Hb ≥ 12.5 g/dL), mild (10 ≤ Hb < 12.5), moderate (9 ≤ Hb < 10), severe (8 ≤ Hb < 9), or very severe (Hb < 8). LR-MDS patients (n = 127) and inpatient controls (n = 141) participated. The anemic patients had a poor QoL and the MDS patients had a lower QoL with a lower Hb. The controls had no QoL difference among the various anemia subgroups. In addition, the MDS QoL sharply decreased with an Hb of < 9. The MDS patients showed a wide QoL variability, i.e., different QoL scores in the same Hb subgroup, suggesting that other factors affect QoL (e.g., age and comorbidities). After 1 year (n = 61), the QoL was still poor for most MDS patients (including 27 patients with an increased Hb). In summary: (1) a poor QoL in MDS-anemia is non-linear, suggesting other influencing factors on QoL. (2) The sharp QoL drop with Hb < 9 g/dL challenges the transfusion Hb threshold. (3) The QoL in anemic MDS patients might differ from that in non-MDS patients. (4) Raising Hb, while recommended, does not guarantee an improved QoL.
Oral Microbiota in Children with Cleft Lip and Palate: A Systematic Review
Authors: Świtała Jacek , Sycińska-Dziarnowska Magdalena , Spagnuolo Gianrico , Woźniak Krzysztof , Mańkowska Katarzyna , Szyszka-Sommerfeld Liliana
Published: September 2023

Background: Cleft in the lip and/or palate (CLP) is a congenital facial deformity that significantly impacts the oral cavity’s structure and function. This malformation can affect the oral microbiota. The objective of this systematic review was to examine and consolidate the current scientific evidence on the oral microflora in children with CLP. Methods: The search strategy included the PubMed, PubMed Central, Web of Science, Scopus, and Embase databases. The inclusion criteria were studies assessing oral microbiota in children with CLP. The Newcastle–Ottawa Scale (NOS) was used to evaluate the quality of the included studies. Results: The search strategy identified 422 potential articles. Twelve papers met the inclusion criteria. High heterogeneity was observed in methodologies, sample sites, and patient characteristics. Eight studies assessed the levels of Streptococcus mutans and Lactobacillus in saliva, with some reporting significantly higher levels in the cleft group compared to controls, while others found no differences. One study reported a significantly higher colonization rate of Candida species in patients with cleft lip and/or palate. Conclusion: The results of the available studies are unclear. Further research is needed to gain a comprehensive understanding of the oral microbiota and potential implications for oral health management in this population. The review was not registered Registration Statement.
Efficacy of a Cognitive Behavioral Intervention for the Prevention of Depression in Nonprofessional Caregivers Administered through a Smartphone App: A Randomized Controlled Trial
Authors: Vázquez Fernando L. , Blanco Vanessa , Hita Isabel , Torres Ángela J. , Otero Patricia , Páramo Mario , Salmerón Mar
Published: September 2023

Due to the limited availability of in-person interventions for caregivers, the development of effective programs that use new technologies to prevent depression is needed. The goal of this research was to assess the efficacy of a cognitive behavioral intervention for the prevention of depression, administered to nonprofessional caregivers through a smartphone application (app). One hundred and seventy-five caregivers were randomly assigned to either an app-based cognitive behavioral intervention (CBIA), the CBIA intervention plus a telephone conference call (CBIA + CC), or an attention control group (ACG). At post-intervention, the incidence of depression was lower in the CBIA and CBIA + CC compared to the ACG (1.7% and 0.0% vs. 7.9%, respectively). The absolute risk, relative risk, and number needed to treat compared to the ACG were 6.2%, 21.6%, and 16 for the CBIA, whilst they were 8%, 0.0%, and 13 for the CBIA + CC. Depressive symptomatology was significantly lower in the CBIA and CBIA + CC compared to the ACG (d = 0.84, Cliff’s δ = 0.49; d = 1.56, Cliff’s δ = 0.72), as well as in the CBIA + CC compared to the CBIA (d = 0.72, Cliff’s δ = 0.44). The prevention of depression was more likely in participants who received the CBIA, and adding the conference call in the CBIA + CC group improved the likelihood of this.
Editorial: New Advances in Cerebrovascular Disorders
Authors: Karapanayiotides Theodoros , Krogias Christos
Published: September 2023

Cerebrovascular disorders constitute major causes of disability and mortality worldwide [...]
Rehabilitation of Peripheral Neuropathies: From Lexical Analysis of the Literature to Identification of Clinical Protocols
Authors: Coraci Daniele , Romano Marcello , Ragazzo Lisa , Restivo Domenico Antonio , Cipriani Martina , Gottardello Federica , Pizzolato Martina , Maccarone Maria Chiara , Masiero Stefano
Published: September 2023

Peripheral nervous system diseases are a complex and heterogenous group of diseases affecting the different nerves with various severity and impact on quality of life. The current literature does not provide a structured guide for the rehabilitation of these conditions. We performed a lexical literature evaluation based on graph theory to clarify this topic. We performed a search on PubMed and calculated the frequencies of the words indicating rehabilitation approaches, nerves, and diseases. We found the usefulness of exercises and different physical agents, like laser and ultrasound therapy and neuromuscular stimulation vibration therapy. Orthoses are useful for entrapment, trauma, and hereditary diseases. Correct knowledge and assessment of the neuropathies are fundamental for the therapeutic decision and to guide rehabilitation. Despite the usefulness shown by the different approaches to modulating pain, improving muscle strength and endurance, and ameliorating balance and the sensory system, further studies are needed to define the best-personalized protocols.
Periodic Limb Movements during Sleep in Acute Stroke: Prevalence, Severity and Impact on Post-Stroke Recovery
Authors: Plomaritis Panagiotis , Theodorou Aikaterini , Michalaki Vasiliki , Stefanou Maria-Ioanna , Palaiodimou Lina , Papagiannopoulou Georgia , Kotsali-Peteinelli Vasiliki , Bregianni Marianna , Andreadou Elissavet , Paraskevas Georgios , Giannopoulos Sotirios , Tsivgoulis Georgios , Bonakis Anastasios
Published: September 2023

Background: Periodic Limb Movements during Sleep (PLMS) have been described to be frequently present in stroke patients. We aimed to evaluate the prevalence and severity of PLMS in acute stroke patients and clarify the association between PLMS and coexisting Sleep Disordered Breathing (SDB). Additionally, we focused on identifying variables that could independently predict the presence of PLMS in patients with acute stroke. The potential impact of PLMS on stroke outcome at three months was investigated as well. Methods: In this study, we performed overnight polysomnography on consecutive stroke patients within 72 h from symptom onset. Data regarding clinical and imaging characteristics were prospectively collected. National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Epworth-Sleepiness Scale (ESS) were used to evaluate stroke severity on admission, stroke outcome at three months and history of daytime sleepiness, respectively. We documented PLMS and SDB using standard polysomnography criteria. Results: We prospectively assessed 126 patients with acute stroke [109 with ischemic and 17 with hemorrhagic stroke, mean age 60 ± 11 years, 68% men, median NIHSS score on admission: 3 (IQR: 2–7)]. The overall rate of PLMS in our cohort was 76%, and the rate of SDB among patients with PLMS was 83%. PLMS detection rates differed significantly (p-value: <0.001) according to SDB, with PLMS prevalence increasing with greater SDB severity. SDB could independently (OR:4.869, 95% CI: 1.884–12.784, p-value: 0.001) predict the presence of PLMS in the acute stroke phase in multivariable analyses adjusting for potential confounders. Moreover, baseline stroke severity (NIHSS-score increase in per-1 point: OR: 0.819, 95% CI: 0.737–0.895, p-value < 0.001) and PLMS (OR:0.099, 95% CI: 0.009–0.482, p-value = 0.015) were significantly associated with the likelihood of excellent functional outcome (mRS-scores: 0–1) at 3 months. Conclusion: The common presence of mostly severe PLMS in patients with acute stroke and their negative effect on stroke outcomes point out the necessity for early PLMS detection and treatment.
Intraocular Pressure Variations in Postural Changes: Comparison between Obese and Non-Obese Controls
Authors: De Bernardo Maddalena , Pilone Vincenzo , Di Paola Ilenia , Cione Ferdinando , Cembalo Giovanni , Calabrese Pietro , Rosa Nicola
Published: September 2023

Background: Comparing intraocular pressure (IOP) changes (ΔIOP) between obese subjects and non-obese controls in relation to different positions: standing, sitting, supine. Methods: the IOP was measured in both obese patients and non-obese controls groups with Tono-Pen AVIA in different positions following this sequence: after 5 min (5′) in the standing position, sitting, supine, supine after 5 min (supine 5′) and immediately after standing. ΔIOP values obtained comparing all positions were, therefore, evaluated. Results: 92 eyes of 46 obese subjects aged between 18 and 59 years (mean 38.07 ± 11.51 years) and of a Body Mass Index (BMI) between 31.84 and 60.65 (mean 41.84 ± 7.05) were evaluated. A total of 48 eyes of 24 non-obese controls aged between 23 and 55 (mean 35.21 ± 11.96 years) and of a BMI between 18.20 and 26.79 (mean 21.04 ± 2.36) were also recruited. In obese subjects, there were statistically significant differences between the IOP in the supine position and the supine positions 5′ with all other IOP measurements (p < 0.05). There were statistically significant differences between ΔIOP in both supine positions and prolonged standing positions obtained by obese subjects and non-obese controls (p < 0.05). Conclusions: In obese subjects, there is a statistically significant increase in IOP in the supine positions that is significantly greater than the non-obese population. BMI is weakly correlated with IOP and ΔIOP in postural changes.
Let Us Know Transfusion Triggers for Prophylactic Use of Platelet Concentrate—Analysis of Compliance with Recent Transfusion Guidelines in a Large Academic Medical Center
Authors: Czempik Piotr F. , Herzyk Jan , Wilczek Dawid
Published: September 2023

Platelet concentrate (PC) is a blood component that is used to prevent or manage bleeding associated with thrombocytopenia or impaired platelet function. The aim of our study was to assess the compliance of ordering physicians with the most recent PC transfusion guidelines in our academic medical center. All PC transfusions performed between January 2019 and December 2022 were analyzed. The appropriateness of PC transfusions was assessed based on the most recent PC transfusion guidelines. During 2019–2022, there were 362 (0.2%) PC recipients out of 161,762 hospitalized patients. There were 971 PCs transfused during the analyzed period. Inappropriate transfusions accounted for 53.3% of cases, and most of them were given prophylactically (80.2%). Compliance with platelet transfusion guidelines varied among departments. The overall percentage of inappropriately transfused PC ranged from 50.7% to 60.8% in successive years. Educational activities should target clinicians performing procedures associated with high rates of inappropriate PC transfusions. Implementing clinical decision support systems can help reduce unnecessary PC transfusions and associated costs. The majority of inappropriate PC transfusions in our medical center were given as prophylaxis against bleeding. Prescribers should be educated about evidence-based transfusion triggers for the prophylactic use of PC in various clinical scenarios.
Blood Vessel Injuries of the Fingers: A Clinical Comparison of One- and Two-Arterial Blood Supply
Authors: Dastagir Nadjib , Obed Doha , Bucher Florian , Murad Shiar , Dastagir Khaled , Vogt Peter M.
Published: September 2023

Traumatic finger injuries are very common in emergency medicine. When patients present with finger injuries, there is often damage to the vascular nerve bundles, which requires subsequent reconstruction. It is unknown if repairing a unilaterally injured artery affects patients’ recovery in a well-perfused finger. This retrospective cohort study compares the clinical outcomes of 11 patients with one-vessel supply (mean age 48.3 years; 7 males, 4 females) to 14 patients with two-vessel supply (mean age 44.5 years; 8 males, 6 females). The patient outcomes were assessed using patient questionnaires (Disabilities of Arm, Shoulder, and Hand (DASH), European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L), and EuroQol visual analog scale (EQ-VAS)) and a clinical examination of hand function and imaging of circulatory efficiency. No significant changes were observed in the DASH, EQ-5D-5L, and EQ-VAS questionnaires. Clinical evaluation of hand function, measured by cold sensitivity, two-point discrimination, pain numerical analog scale, and grip strength also revealed no significant differences between cohorts. Blood flow measurements using thermal imaging revealed no effects on circulation in the affected digit. Collectively, the study finds reconstruction is not absolutely necessary when there is one intact digital artery as it is sufficient for healing and functional outcomes. We recommend finger artery reconstruction when both digital arteries are injured or if an immediate tension-free suture is possible.
Effects of Exercise, Rehabilitation, and Nutritional Approaches on Body Composition and Bone Density in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis
Authors: Rinaldo Natascia , Pasini Alba , Straudi Sofia , Piva Giovanni , Crepaldi Anna , Baroni Andrea , Caruso Lorenzo , Manfredini Fabio , Lamberti Nicola
Published: September 2023

People with multiple sclerosis (pwMS) are affected by a wide range of disabilities, including a decrease in bone mineral density (BMD) and a worsening of body composition (BC), which negatively impact their quality of life quality. This study aims to analyze the effects of nonpharmacological interventions—in particular, physical activity, nutritional approaches, and rehabilitation—on BC and BMD in pwMS. This systematic review and meta-analysis was performed following the updated version of the PRISMA guidelines. In July 2022, five databases (MEDLINE, Embase, The Cochrane Library, Google Scholar, Web of Science) and gray literature were screened. Relevant articles published between 1 January 1990 and 1 September 2022 in any language were included. Outcomes of interest were anthropometric, BC measures, and BMD. The RoB 2.0 tool was used to assess the risk of bias. After duplicates elimination, 1120 records were screened, and 36 studies were included. A total of 25 articles were focused on physical activity and rehabilitation, 10 on nutrition, and 1 on multimodal intervention. One-third of the studies were judged to be at high risk of bias. The meta-analysis showed a high degree of heterogeneity due to the high variability in disease severity and intervention duration, intensity, frequency, and type. In general, no intervention showed consistent positive effects on BC. However, the most promising interventions seemed to be high-intensity training and ketogenic diets. Only a few studies considered BMD, and the results are inconsistent. Nevertheless, more studies are needed in order to confirm these results.
Metacognitive Strategy Training Improves Decision-Making Abilities in Amnestic Mild Cognitive Impairment
Authors: Pikouli Foteini Aikaterini , Moraitou Despina , Papantoniou Georgia , Sofologi Maria , Papaliagkas Vasileios , Kougioumtzis Georgios , Poptsi Eleni , Tsolaki Magdalini
Published: September 2023

Mild cognitive impairment (MCI) is associated with deficits in decision-making, which is of utmost importance for daily functioning. Despite evidence of declined decision-making abilities, research on decision-making interventions for MCI is scarce. As metacognition seems to play an important role in decision-making, the present study’s aim was to examine whether a metacognitive strategy training can improve MCI patients’ decision-making abilities. Older adults—patients of a day care center, diagnosed with amnestic MCI (n = 55) were randomly allocated in two groups, which were matched in gender, age and educational level. Τhe experimental group (n = 27, 18 women, mean age = 70.63, mean years of education = 13.44) received the metacognitive strategy training in parallel with the cognitive and physical training programs of the day care center, and the active control group (n = 28, 21 women, mean age = 70.86, mean years of education = 13.71) received only the cognitive and physical training of the center. The metacognitive strategy training included three online meeting sessions that took place once per week. The basis of the intervention was using analytical thinking, by answering four metacognitive-strategic questions, to make decisions about everyday situations. To examine the efficacy of the training, the ability to make decisions about everyday decision-making situations and the ability to apply decision rules were measured. Both groups participated in a pre-test session and a post-test session, while the experimental group also participated in a follow-up session, one month after the post-test session. The results showed that the experimental group improved its ability to decide, based on analytical thinking, about economic and healthcare-related everyday decision-making situations after they received the metacognitive strategy training. This improvement was maintained one month later. However, the ability to apply decision rules, which requires high cognitive effort, did not improve. In conclusion, it is important that some aspects of the analytical decision-making ability of amnestic MCI patients were improved due to the present metacognitive intervention.
An Investigation of the Operating Principles and Power Consumption of Digital-Based Analog Amplifiers
Authors: Richelli Anna , Faustini Paolo , Rosa Andrea , Colalongo Luigi
Published: September 2023

Digital-based differential amplifiers (DDA) are particularly suitable to low voltage digital integrated circuit technologies. This paper presents an exhaustive analysis of digital-based analog amplifiers to take advantage of today’s high-performance digital technologies, and of computer aided design (CAD), which is commonly employed to design integrated circuits. The operating principle and the main mathematical relations of digital-based differential amplifiers are discussed along with an exhaustive explanation of its operating regions and of the corresponding power consumption. These aspects, which are not discussed in the literature, are very important for the circuit designers. Finally, a detailed description of the design procedure of the UMC 180nm standard CMOS technology is provided.
The Genome-Wide Characterization of Alternative Splicing and RNA Editing in the Development of Coprinopsis cinerea
Authors: Xie Yichun , Chan Po-Lam , Kwan Hoi-Shan , Chang Jinhui
Published: September 2023

Coprinopsis cinerea is one of the model species used in fungal developmental studies. This mushroom-forming Basidiomycetes fungus has several developmental destinies in response to changing environments, with dynamic developmental regulations of the organism. Although the gene expression in C. cinerea development has already been profiled broadly, previous studies have only focused on a specific stage or process of fungal development. A comprehensive perspective across different developmental paths is lacking, and a global view on the dynamic transcriptional regulations in the life cycle and the developmental paths is far from complete. In addition, knowledge on co- and post-transcriptional modifications in this fungus remains rare. In this study, we investigated the transcriptional changes and modifications in C. cinerea during the processes of spore germination, vegetative growth, oidiation, sclerotia formation, and fruiting body formation by inducing different developmental paths of the organism and profiling the transcriptomes using the high-throughput sequencing method. Transition in the identity and abundance of expressed genes drive the physiological and morphological alterations of the organism, including metabolism and multicellularity construction. Moreover, stage- and tissue-specific alternative splicing and RNA editing took place and functioned in C. cinerea. These modifications were negatively correlated to the conservation features of genes and could provide extra plasticity to the transcriptome during fungal development. We suggest that C. cinerea applies different molecular strategies in its developmental regulation, including shifts in expressed gene sets, diversifications of genetic information, and reversible diversifications of RNA molecules. Such features would increase the fungal adaptability in the rapidly changing environment, especially in the transition of developmental programs and the maintenance and balance of genetic and transcriptomic divergence. The multi-layer regulatory network of gene expression serves as the molecular basis of the functioning of developmental regulation.