bluuebunny/crossref_metadata_2025 huggingface dataset:
Surfactin and Capric Acid Affect the Posaconazole Susceptibility of Candida albicans Strains with Altered Sterols and Sphingolipids Biosynthesis
Authors: Derkacz Daria , Grzybowska Monika , Cebula Liliana , Krasowska Anna
Published: December 2023

Infections caused by Candida spp. pose a continuing challenge for modern medicine, due to widespread resistance to commonly used antifungal agents (e.g., azoles). Thus, there is considerable interest in discovering new, natural compounds that can be used in combination therapy with conventional antibiotics. Here, we investigate whether the natural compounds surfactin and capric acid, in combination with posaconazole, enhance the growth inhibition of C. albicans strains with alterations in sterols and the sphingolipids biosynthesis pathway. We demonstrate that combinations of posaconazole with surfactin or capric acid correspond with the decreased growth of C. albicans strains. Moreover, surfactin and capric acid can independently contribute to the reduced adhesion of C. albicans strains with altered ergosterol biosynthesis to abiotic surfaces (up to 90% reduction in adhesion). A microscopic study of the C. albicans plasma membrane revealed that combinations of those compounds do not correspond with the increased permeabilization of the plasma membrane when compared to cells treated with posaconazole alone. This suggests that the fungistatic effect of posaconazole in combination with surfactin or capric acid is related to the reduction in adhesion of C. albicans.
Cannabidiol at Nanomolar Concentrations Negatively Affects Signaling through the Adenosine A2A Receptor
Authors: Raïch Iu , Lillo Jaume , Ferreiro-Vera Carlos , Sánchez de Medina Verónica , Navarro Gemma , Franco Rafael
Published: December 2023

Cannabidiol (CBD) is a phytocannabinoid with potential as a therapy for a variety of diseases. CBD may act via cannabinoid receptors but also via other G-protein-coupled receptors (GPCRs), including the adenosine A2A receptor. Homogenous binding and signaling assays in Chinese hamster ovary (CHO) cells expressing the human version of the A2A receptor were performed to address the effect of CBD on receptor functionality. CBD was not able to compete for the binding of a SCH 442416 derivative labeled with a red emitting fluorescent probe that is a selective antagonist that binds to the orthosteric site of the receptor. However, CBD reduced the effect of the selective A2A receptor agonist, CGS 21680, on Gs-coupling and on the activation of the mitogen activated kinase signaling pathway. It is suggested that CBD is a negative allosteric modulator of the A2A receptor.
Assessment of the Purity of IMM-H014 and Its Related Substances for the Treatment of Metabolic-Associated Fatty Liver Disease Using Quantitative Nuclear Magnetic Resonance Spectroscopy
Authors: Zhang Hanyilan , Zhu Haowen , Wu Song , Tang Haoyang , Zhang Wenxuan , Gong Xiaoliang , Wang Tiesong , Wang Yinghong , Yang Qingyun
Published: December 2023

An accurate, rapid, and selective quantitative nuclear magnetic resonance method was developed and validated to assess the purity of IMM-H014, a novel drug for the treatment of metabolic-associated fatty liver disease (MAFLD), and four related substances (impurities I, II, III, and IV). In this study, we obtained spectra of IMM--H014 and related substances in deuterated chloroform using dimethyl terephthalate (DMT) as the internal standard reference. Quantification was performed using the 1H resonance signals at δ 8.13 ppm for DMT and δ 6.5–7.5 ppm for IMM-H014 and its related substances. Several key experimental parameters were investigated and optimized, such as pulse angle and relaxation delay. Methodology validation was conducted based on the International Council for Harmonization guidelines and verified with satisfactory specificity, precision, linearity, accuracy, robustness, and stability. In addition, the calibration results of the samples were consistent with those obtained from the mass balance method. Thus, this research provides a reliable and practical protocol for purity analysis of IMM-H014 and its critical impurities and contributes to subsequent clinical quality control research.
CD6 and Its Interacting Partners: Newcomers to the Block of Cancer Immunotherapies
Authors: Aragón-Serrano Lucía , Carrillo-Serradell Laura , Planells-Romeo Violeta , Isamat Marcos , Velasco-de Andrés María , Lozano Francisco
Published: December 2023

Cancer management still requires more potent and safer treatments, of which immunomodulatory receptors on the lymphocyte surface have started to show promise in new cancer immunotherapies (e.g., CTLA-4 and PD-1). CD6 is a signal-transducing transmembrane receptor, mainly expressed by all T cells and some B and NK cell subsets, whose endogenous ligands (CD166/ALCAM, CD318/CDCP-1, Galectins 1 and 3) are overexpressed by malignant cells of different lineages. This places CD6 as a potential target for novel therapies against haematological and non-haematological malignancies. Recent experimental evidence for the role of CD6 in cancer immunotherapies is summarised in this review, dealing with diverse and innovative strategies from the classical use of monoclonal antibodies to soluble recombinant decoys or the adoptive transfer of immune cells engineered with chimeric antigen receptors.
Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD)
Authors: Zhao Ying , Zhou Yanni , Wang Dan , Huang Ziwei , Xiao Xiong , Zheng Qing , Li Shengfu , Long Dan , Feng Li
Published: December 2023

Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common disease in Western countries and has become the major cause of liver cirrhosis or hepatocellular carcinoma (HCC) in addition to viral hepatitis in recent decades. Furthermore, studies have shown that NAFLD is inextricably linked to the development of extrahepatic diseases. However, there is currently no effective treatment to cure NAFLD. In addition, in 2020, NAFLD was renamed metabolic dysfunction fatty liver disease (MAFLD) to show that its pathogenesis is closely related to metabolic disorders. Recent studies have reported that the development of MAFLD is inextricably associated with mitochondrial dysfunction in hepatocytes and hepatic stellate cells (HSCs). Simultaneously, mitochondrial stress caused by structural and functional disorders stimulates the occurrence and accumulation of fat and lipo-toxicity in hepatocytes and HSCs. In addition, the interaction between mitochondrial dysfunction and the liver–gut axis has also become a new point during the development of MAFLD. In this review, we summarize the effects of several potential treatment strategies for MAFLD, including antioxidants, reagents, and intestinal microorganisms and metabolites.
Biocontrol Potential of Streptomyces odonnellii SZF-179 toward Alternaria alternata to Control Pear Black Spot Disease
Authors: Zhang Fei , Wen Shaohua , Wang Beibei , Zhang Zhe , Liu Fang , Ye Ting , Wang Kaimei , Hu Hongju , Yang Xiaoping , Fang Wei
Published: December 2023

Pear black spot disease, caused by Alternaria alternata, is a devastating disease in pears and leads to enormous economic losses worldwide. In this investigation, we isolated a Streptomyces odonnellii SZF-179 from the rhizosphere soil of pear plants in China. Indoor confrontation experiments results showed that both SZF-179 and its aseptic filtrate had excellent inhibitory effects against A. alternata. Afterwards, the main antifungal compound of SZF-179 was identified as polyene, with thermal and pH stability in the environment. A microscopic examination of A. alternata mycelium showed severe morphological abnormalities caused by SZF-179. Protective studies showed that SZF-179 fermentation broth could significantly reduce the diameter of the necrotic lesions on pear leaves by 42.25%. Furthermore, the potential of fermentation broth as a foliar treatment to control black leaf spot was also evaluated. Disease indexes of ‘Hosui’ and ‘Wonwhang’ pear plants treated with SZF-179 fermentation broth were lower than that of control plants. Overall, SZF-179 is expected to be developed into a safe and broad-spectrum biocontrol agent. No studies to date have evaluated the utility of S. odonnellii for the control of pear black spot disease; our study fills this research gap. Collectively, our findings provide new insights that will aid the control of pear black spot disease, as well as future studies of S. odonnellii strains.
Role of the CB2 Cannabinoid Receptor in the Regulation of Food Intake: A Systematic Review
Authors: Rodríguez-Serrano Luis Miguel , Chávez-Hernández María Elena
Published: December 2023

The CB2 cannabinoid receptor has been found in brain areas that are part of the reward system and has been shown to play a role in food intake regulation. Herein, we conducted a systematic review of studies assessing the role of the CB2 receptor in food intake regulation. Records from the PubMed, Scopus, and EBSCO databases were screened, resulting in 13 studies that were used in the present systematic review, following the PRISMA guidelines. A risk of bias assessment was carried out using the tool of the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE). The studies analyzed used two main strategies: (1) the intraperitoneal or intracerebroventricular administration of a CB2 agonist/antagonist; and (2) depletion of CB2 receptors via knockout in mice. Both strategies are useful in identifying the role of the CB2 receptor in food intake in standard and palatable diets. The conclusions derived from animal models showed that CB2 receptors are necessary for modulating food intake and mediating energy balance.
Combating Black Fungus: Using Allicin as a Potent Antifungal Agent against Mucorales
Authors: Schier Christina , Gruhlke Martin C. H. , Reucher Georg , Slusarenko Alan J. , Rink Lothar
Published: December 2023

Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstrated. Mathematical modeling showed that the efficacy of allicin vapor is comparable to direct contact with the commercially available antifungal agent amphotericin B (ampB). Furthermore, the study revealed a synergistic interaction between allicin and the non-volatile ampB. The toxicity of allicin solution to human cell lines was evaluated and it was found that the half maximal effective concentration (EC50) of allicin was 25–72 times higher in the cell lines as compared to the fungal spores. Fungal allicin sensitivity depends on the spore concentration, as demonstrated in a drop test. This study shows the potential of allicin, a sulfur-containing defense compound from garlic, to combat zygomycete fungi. The findings underscore allicin’s promise for applications in infections of the nasopharynx via inhalation, suggesting a novel therapeutic avenue against challenging fungal infections.
Shear Stress and Endothelial Mechanotransduction in Trauma Patients with Hemorrhagic Shock: Hidden Coagulopathy Pathways and Novel Therapeutic Strategies
Authors: Chalkias Athanasios
Published: December 2023

Massive trauma remains a leading cause of death and a global public health burden. Post-traumatic coagulopathy may be present even before the onset of resuscitation, and correlates with severity of trauma. Several mechanisms have been proposed to explain the development of abnormal coagulation processes, but the heterogeneity in injuries and patient profiles makes it difficult to define a dominant mechanism. Regardless of the pattern of death, a significant role in the pathophysiology and pathogenesis of coagulopathy may be attributed to the exposure of endothelial cells to abnormal physical forces and mechanical stimuli in their local environment. In these conditions, the cellular responses are translated into biochemical signals that induce/aggravate oxidative stress, inflammation, and coagulopathy. Microvascular shear stress-induced alterations could be treated or prevented by the development and use of innovative pharmacologic strategies that effectively target shear-mediated endothelial dysfunction, including shear-responsive drug delivery systems and novel antioxidants, and by targeting the venous side of the circulation to exploit the beneficial antithrombogenic profile of venous endothelial cells.
Isoform-Directed Control of c-Myc Functions: Understanding the Balance from Proliferation to Growth Arrest
Authors: Kubickova Agata , De Sanctis Juan , Hajduch Marian
Published: December 2023

The transcription factor c-Myc, a key regulator of cellular processes, has long been associated with roles in cell proliferation and apoptosis. This review analyses the multiple functions of c-Myc by examining the different c-Myc isoforms in detail. The impact of different c-Myc isoforms, in particular p64 and p67, on fundamental biological processes remains controversial. It is necessary to investigate the different isoforms in the context of proto-oncogenesis. The current knowledge base suggests that neoplastic lesions may possess the means for self-destruction via increased c-Myc activity. This review presents the most relevant information on the c-Myc locus and focuses on a number of isoforms, including p64 and p67. This compilation provides a basis for the development of therapeutic approaches that target the potent growth arresting and pro-apoptotic functions of c-Myc. This information can then be used to develop targeted interventions against specific isoforms with the aim of shifting the oncogenic effects of c-Myc from pro-proliferative to pro-apoptotic. The research summarised in this review can deepen our understanding of how c-Myc activity contributes to different cellular responses, which will be crucial in developing effective therapeutic strategies; for example, isoform-specific approaches may allow for precise modulation of c-Myc function.
Characterization and Preliminary Application of a Novel Lytic Vibrio parahaemolyticus Bacteriophage vB_VpaP_SJSY21
Authors: Xu Yajin , Sun Jun , Hu Jingjie , Bao Zhenmin , Wang Mengqiang
Published: December 2023

Litopenaeus vannamei is one of the most economically significant aquatic species globally. However, the emergence of acute hepatopancreatic necrosis disease (AHPND) in recent years has resulted in substantial losses within the L. vannamei farming industry. Phage therapy holds promise as an effective strategy for preventing and controlling bacterial infections like AHPND, thereby promoting the healthy and sustainable growth of the shrimp aquaculture sector. In this study, a novel and unique Vibrio parahaemolyticus bacteriophage, named vB_VpaP_SJSY21, was successfully isolated from sewage samples. Using transmission electron microscopy, it was observed that phage SJSY21 has an elongated shell. Notably, phage SJSY21 exhibited high infection efficiency, with an optimal multiplicity of infection (MOI) of only 0.01 and a remarkably short latent period of 10 min, resulting in a lysis quantity of 508. Furthermore, phage SJSY21 demonstrated notable heat resistance and the capacity to withstand high temperatures during preservation, thus holding potential for application in phage therapy. Whole-genome sequencing and analysis confirmed that phage SJSY21 has a genome size of 110,776 bp, classifying it as a new member of the short-tailed bacteriophage family. Additionally, cultivation experiments indicated that phage SJSY21 has the potential to enhance the survival of L. vannamei in culture systems, thereby offering innovative prospects for the application of phage therapy in aquaculture.
Hereditary Spastic Paraplegia Type 11—Clinical, Genetic and Neuroimaging Characteristics
Authors: Chojdak-Łukasiewicz Justyna , Sulima Katarzyna , Zimny Anna , Waliszewska-Prosół Marta , Budrewicz Sławomir
Published: December 2023

Hereditary spastic paraplegia (HSP) is a heterogeneous group of genetically determined diseases, characterised by progressive spastic paraparesis of the lower limbs, associated with degeneration of the corticospinal tract and the posterior column of the spinal cord. HSP occurs worldwide and the estimated prevalence is about 1–10/100,000, depending on the geographic localisation. More than 70 genes responsible for HSP have been identified to date, and reports of new potentially pathogenic variants appear regularly. All possible patterns of inheritance (autosomal dominant, autosomal recessive, X-linked and mitochondrial) have been described in families of HSP patients. Among the autosomal recessive forms of HSP (AR-HSP), hereditary spastic paraplegia type 11 is the most common one. We present a patient with diagnosed HSP 11, with a typical clinical picture and characteristic features in additional diagnostic tests.
Evaluation of Osteogenic Potential for Rat Adipose-Derived Stem Cells under Xeno-Free Environment
Authors: Sun Yuzhu , Jo Jun-Ichiro , Hashimoto Yoshiya
Published: December 2023

This study aimed to develop a novel culture method for rat adipose-derived stem cells (rADSC) and evaluate their osteogenic potential. The rADSC cultured in xeno-free culture medium (XF-rADSCs) or conventional culture medium containing fetal bovine serum (FBS-rADSCs) were combined with micropieces of xeno-free recombinant collagen peptide to form 3-dimensional aggregates (XF-rADSC-CellSaic or FBS-rADSC-CellSaic). Both FBS-rADSC and XF-ADSC in CellSaic exhibited multilineage differentiation potential. Compared to FBS-rADSC-CellSaic, XF-rADSC-CellSaic accelerated and promoted osteogenic differentiation in vitro. When transplanted into rat mandibular congenital bone defects, the osteogenically differentiated XF-rADSC-CellSaic induced regeneration of bone tissue with a highly maturated structure compared to FBS-rADSC-CellSaic. In conclusion, XF-rADSC-CellSaic is a feasible 3-dimensional platform for efficient bone formation.
Insights into the Tumor Microenvironment—Components, Functions and Therapeutics
Authors: Baghy Kornélia , Ladányi Andrea , Reszegi Andrea , Kovalszky Ilona
Published: December 2023

Similarly to our healthy organs, the tumor tissue also constitutes an ecosystem. This implies that stromal cells acquire an altered phenotype in tandem with tumor cells, thereby promoting tumor survival. Cancer cells are fueled by abnormal blood vessels, allowing them to develop and proliferate. Tumor-associated fibroblasts adapt their cytokine and chemokine production to the needs of tumor cells and alter the peritumoral stroma by generating more collagen, thereby stiffening the matrix; these processes promote epithelial–mesenchymal transition and tumor cell invasion. Chronic inflammation and the mobilization of pro-tumorigenic inflammatory cells further facilitate tumor expansion. All of these events can impede the effective administration of tumor treatment; so, the successful inhibition of tumorous matrix remodeling could further enhance the success of antitumor therapy. Over the last decade, significant progress has been made with the introduction of novel immunotherapy that targets the inhibitory mechanisms of T cell activation. However, extensive research is also being conducted on the stromal components and other cell types of the tumor microenvironment (TME) that may serve as potential therapeutic targets.
Public Knowledge about Dementia in Poland—A Survey Study
Authors: Skowronek Alicja , Bojkowska-Otrębska Katarzyna , Łabuz-Roszak Beata
Published: December 2023

Background: Based on worldwide estimates, the number of people with dementia will increase significantly in the coming decades. Therefore, knowledge about dementia and its modifiable risk factors plays a crucial role in prevention. Although dementia is still incurable, an early diagnosis might help to slow down its progression and improve the quality of patients’ lives. The aim of the study was to assess public knowledge about dementia and its risk factors in Poland. Methods: The research was conducted in 2022 using a self-constructed questionnaire by applying computer-assisted web interviewing (CAWI). Results: A total of 304 completed surveys were obtained (mean score of 16.95 ± 2.79 points out of 23.6). The scores were significantly higher for people associated with the medical community in comparison to those unrelated to the medical community (18.23 ± 2.61 and 16.15 ± 2.59, respectively; p = 0.0001). A moderate negative correlation was found between the results and the ages of the respondents (R = −0.44; p = 0.001). No statistically significant differences were reported in the results between people involved in providing care to patients with dementia or those who had a patient with dementia in the family and those who were not involved in such care or had no relative with dementia. Conclusions: Knowledge about dementia and its risk factors in Poland is not satisfactory and should be improved. Special attention should be paid to educating the families and caregivers of people with dementia.
Clinical Utility and Validation of the Acoustic Voice Quality and Acoustic Breathiness Indexes for Voice Disorder Assessment in English Speakers
Authors: Castillo-Allendes Adrián , Codino Juliana , Cantor-Cutiva Lady Catherine , Nudelman Charles J. , Rubin Adam D. , Barsties v. Latoszek Ben , Hunter Eric J.
Published: December 2023

Background: While several acoustic voice metrics are available for clinical voice assessment, there remains a significant need for reliable and ecologically valid tools. The Acoustic Voice Quality Index version 03.01 (AVQI-3) and Acoustic Breathiness Index (ABI) hold potential due to their comprehensive assessment approach, incorporating diverse voice aspects. However, these tools still need to be validated in English-speaking populations. Methods: This study assessed the discriminatory accuracy and validity of AVQI-3 and ABI in 197 participants, including 148 with voice disorders. Voice samples were collected, followed by AVQI-3 and ABI calculations. Additionally, auditory-perceptual assessments were conducted by a panel of speech-language pathologists. Results: AVQI-3 and ABI effectively identified disordered voice quality, evidenced by high accuracy (AUCs: 0.84, 0.89), sensitivity, and specificity (thresholds: AVQI-3 = 1.17, ABI = 2.35). Strong positive correlations were observed with subjective voice quality assessments (rs = 0.72, rs = 0.77, p < 0.001). Conclusions: The study highlights AVQI-3 and ABI as promising instruments for clinically assessing voice disorders in U.S. English speakers, underscoring their utility in clinical practice and voice research.
Immersive Virtual Reality Therapy Is Supportive for Orthopedic Rehabilitation among the Elderly: A Randomized Controlled Trial
Authors: Mazurek Justyna , Cieślik Błażej , Wrzeciono Adam , Gajda Robert , Szczepańska-Gieracha Joanna
Published: December 2023

Objective: This research aimed to determine the efficacy of VR therapy in mitigating symptoms of depression, anxiety, and stress among older adults following arthroplasty surgery and to comprehend the influence of psychological improvement on changes in functional outcomes. Methods: Utilizing a parallel-group randomized controlled trial design, the study involved 68 osteoarthritis patients who had recently undergone either total hip or knee arthroplasty. Subjects were split into two groups. The experimental group underwent eight VR therapy sessions during their rehabilitation, while the control group was given standard care. Assessments encompassed both psychological and functional outcomes, with tools like the Hospital Anxiety and Depression Scale, Perceived Stress Scale, and the Barthel Index, among others. The experimental group showcased notable enhancements in both psychological and functional areas compared to the control group. Results: A significant (p value of < 0.001) relationship was found between psychological progress and functional recovery, indicating that psychological factors can serve as predictors for functional outcomes. Conclusions: The findings emphasize the promising role of VR therapy as a beneficial addition to the rehabilitation process for older adults’ post-hip and knee arthroplasty. The integration of psychological interventions in standard rehabilitation practices appears valuable, but further studies are needed to ascertain the long-term advantages of such an approach.
Impact of Breastfeeding Duration on Adenoid Hypertrophy, Snoring and Acute Otitis Media: A Case-Control Study in Preschool Children
Authors: Zwierz Aleksander , Domagalski Krzysztof , Masna Krystyna , Walentowicz Paweł , Burduk Paweł
Published: December 2023

Background: The aim of this study was to analyze the relationship between breastfeeding duration and adenoid size, snoring and acute otitis media (AOM). Methods: We analyzed the medical history of children admitted to the ENT outpatient clinic in 2022 and 2023, reported symptoms, ear, nose and throat (ENT) examination, and flexible nasopharyngoscopy examination of 145 children aged 3–5 years. Results: Breastfeeding duration of 3 and 6 months or more had a significant effect on the reduction of snoring (p = 0.021; p = 0.039). However, it had no effect on the adenoid size, mucus coverage and sleeping with an open mouth. Snoring was correlated with open mouth sleeping (p < 0.001), adenoid size with a 75% A/C ratio or more (p < 0.001), and adenoid mucus coverage in the Mucus of Adenoid Scale by Nasopharyngoscopy Assessment—MASNA scale (p = 0.009). Children who were breastfed for less than 3 months had more than a four-fold greater risk of snoring. There was a statistically significant correlation between AOM and gender (p = 0.033), breastfeeding duration in groups fed 1, 3 or 6 months or more (p = 0.018; p = 0.004; p = 0.004) and those fed with mother’s breast milk 3 or 6 months or more (p = 0.009; p = 0.010). Moreover, a correlation was found between adenoid size and mucus coverage, tympanogram, and open-mouth sleeping (p < 0.001). Independent factors of snoring in 3- to 5-year-old children were breastfeeding duration of less than 3 months (p = 0.032), adenoid size with an A/C ratio of 75% or more (p = 0.023) and open mouth sleeping (p = 0.001). Conclusions: Children breastfed for 3 and 6 months or more exhibited reduced rates of snoring. There was no effect of breastfeeding duration on adenoid size in children aged 3 to 5 years, suggesting that the link between breastfeeding duration and snoring is primarily associated with craniofacial development and muscle tone stimulation. A breastfeeding duration of 1 month or more plays a key role in reducing the rate of AOM. The mother’s milk plays a protective role against AOM. The presence of mucus might be responsible for snoring in preschool children. A medical history of breastfeeding should be taken into consideration when snoring children are suspected of adenoid hypertrophy.
Nighttime versus Fulltime Brace Treatment for Adolescent Idiopathic Scoliosis: Which Brace to Choose? A Retrospective Study on 358 Patients
Authors: Capek Vojtech , Baranto Adad , Brisby Helena , Westin Olof
Published: December 2023

The purpose of this study is to retrospectively compare the effectiveness of fulltime Boston Brace (BB) and Providence Nighttime Brace (PNB) treatments in moderate scoliotic curves (20–40°) at a single institution and to carry out analyses for different subgroups. Inclusion criteria: idiopathic scoliosis, age ≥ 10 years, curve 20–40°, Risser ≤ 3 or Sanders stage ≤ 6 and curve apex below T6 vertebra. Exclusion criteria: incomplete radiological or clinical follow-up and previous treatment. The primary outcome was failure according to the SRS outcome assessment: increase in main curve > 5° and/or increase in main curve beyond 45° and/or surgery. The subgroup analyses were secondary outcomes. In total, 249 patients in the PNB and 109 in the BB groups were included. The BB showed a higher success rate compared to the PNB (59% and 46%, respectively) in both crude and adjusted comparisons (p = 0.029 and p = 0.007, respectively). The subgroup analyses showed higher success rates in pre-menarchal females, thoracic curves and curves > 30° in the BB group compared to the PNB group. Based on the findings, fulltime braces should be the treatment of choice for more immature patients and patients with larger and thoracic curves while nighttime braces might be sufficient for post-menarchal females and patients with lumbar and smaller curves.
The Relationship between Pulmonary Artery Pressure and Mortality in Type 2 Diabetes: A Fremantle Diabetes Study Phase II and National Echocardiographic Database of Australia Data Linkage Study
Authors: Nundlall Nishant , Playford David , Strange Geoff , Davis Timothy M. E. , Davis Wendy A.
Published: December 2023

An elevated estimated right ventricular systolic pressure (eRVSP) identified on echocardiography is present in one-third of individuals with type 2 diabetes, but its prognostic significance is unknown. To assess the relationship between eRVSP and mortality, prospective data from 1732 participants in the Fremantle Diabetes Study Phase II were linked with the National Echocardiographic Database of Australia. Of this cohort, 416 (mean age 70.6 years, 47.4% males) had an eRVSP measured and 381 (91.4%) had previously confirmed type 2 diabetes. Receiver- operating characteristic analysis of the relationship between eRVSP and all-cause mortality was conducted. Survival analyses were performed for participants with type 2 diabetes diagnosed before first measured eRVSP (n = 349). Cox regression identified clinical and echocardiographic associates of all-cause mortality. There were 141 deaths (40.4%) during 2348 person-years (mean ± SD 6.7 ± 4.0 years) of follow-up. In unadjusted Kaplan–Meier analysis, mortality rose with higher eRVSP (log-rank test, p < 0.001). In unadjusted pairwise comparisons, eRVSP >30 to 35, >35 to 40, and >40 mmHg had significantly increased mortality compared with eRVSP ≤ 30 mmHg (p = 0.025, p = 0.001, p < 0.001, respectively). There were 50 deaths in 173 individuals (29.1%) with eRVSP ≤ 30 mmHg, and 91 in 177 (51.4%) with eRVSP > 30 mmHg (log-rank test, p < 0.001). In adjusted models including age, Aboriginal descent, Charlson Comorbidity Index ≥ 3 and left heart disease, eRVSP > 30 mmHg predicted a two-fold higher all-cause mortality versus ≤ 30 mmHg. An eRVSP > 30 mmHg predicts increased all-cause mortality in type 2 diabetes. Where available, eRVSP could inform type 2 diabetes outcome models.
Predictors of Long-COVID and Chronic Impairment of Exercise Tolerance in Spiroergometry in Patients after 15 Months of COVID-19 Recovery
Authors: Gryglewska-Wawrzak Katarzyna , Sakowicz Agata , Banach Maciej , Bielecka-Dabrowa Agata
Published: December 2023

Background: The aim of the study was to identify factors that may cause the presence of long COVID and to assess factors that affect chronic limited exercise tolerance in spiroergometry after one-year follow-up in patients who had recovered from COVID-19. Methods: Of 146 patients hospitalised in the Cardiology Department, 82 completed a one-year follow-up (at least 15 months post-COVID-19 recovery). We compared their conditions at initial screening and follow-up to analyse the course of long COVID and exercise intolerance mechanisms. Clinical examinations, laboratory tests, echocardiography, cardiopulmonary exercise testing, and body composition analysis were performed. Results: The patients, after one-year follow-up, had significantly higher levels of high-sensitivity cardiac troponin T (hs-cTnT) (p = 0.03), left atrium diameter (LA) (p = 0.03), respiratory exchange ratio (RER) (p = 0.008), and total body water content percentage (TBW%) (p < 0.0001) compared to the 3-month assessment. They also had lower forced vital capacity in litres (FVC) (p = 0.02) and percentage (FVC%) (p = 0.001). The factors independently associated with a decline in maximum oxygen uptake (VO2max) after one-year follow-up included the percentage of fat (OR 2.16, 95% CI: 0.51–0.77; p = 0.03), end-diastolic volume (EDV) (OR 2.38, 95% CI 0.53–0.78; p = 0.02), and end-systolic volume (ESV) (OR 2.3, 95% CI: 0.52–0.78; p = 0.02). Conclusions: Higher left ventricular volumes and fat content (%) were associated with a reduced peak VO2max when assessed 15 months after COVID-19 recovery.
Striving for Perfection: How Stable Is Orthodontic Treatment When Excellent Outcomes Are Achieved? A 9-Year Post-Treatment Retrospective Study
Authors: Cornelis Marie A. , Gera Arwa , Gera Shadi , Isenshtat Alona , Cattaneo Paolo M.
Published: December 2023

(1) Aims: The main objective of this retrospective study was to assess the long-term stability of difficult orthodontic treatments treated to an excellent result and to correlate stability to possible prognostic factors. Secondary objectives were to observe the changes in retention protocol over time and to assess Oral Health-related Quality of Life (OHRQoL) after a long-term post-treatment follow-up. (2) Methods: Cases presented for final examination by orthodontic postgraduate students were retrospectively screened for eligibility. Eligible patients were recalled for a post-treatment recall appointment (T2), consisting of a clinical examination and intraoral scan, and were asked to complete the Oral Health Impact Profile-14 (OHIP-14-DK). Gender, age at treatment commencement (T0), treatment modality and duration, and retention protocol were extracted from the records. At T2, the duration of the retention period was recorded, and retainers in place were clinically compared to the original retention protocol. The following variables were assessed on the sets of models at T0, T1 (end of treatment), and T2: arch length and width, overjet and overbite, Dental Aesthetic Index (DAI), Peer Assessment Rating score (PAR), and Little’s Irregularity Index (LII). Multiple regression models were conducted. (3) Results: Eighty-five subjects attended T2. The mean post-treatment follow-up was 9.4 years +/− 2.4. In the upper arch, at T1, 74 patients had a combination of fixed and removable retainers, while at T2, 55 had a fixed retainer only. In the lower arch, at T1, 67 patients had a fixed retainer only, with this number increasing to 76 at T2. From T0 to T1, the PAR score improved by 96.1%, with the improvement remaining at 77.5% at T2. The stability of lower inter-canine and upper inter-premolar widths was significantly correlated with the extent of changes during treatment. The presence of a lower fixed retainer at T2 and a low LII at T1 were prognostic factors for stability. The mean weighted total OHIP-14 score at T2 was very low (1.6 ± 2.4 points). (4) Conclusions: In a sample with an initial high-severity malocclusion and treated to an excellent outcome, long-term stability was very good. Good stability can be retained when a lower fixed retainer is present at T2 and when a low LII is achieved at T1.
The Role of the Supine Empty Stress Test in the Evaluation of Women with Stress Urinary Incontinence: A Retrospective Cohort Study
Authors: Varlı Bulut , Çetinkaya Şerife Esra , Seval Mehmet Murat , Dökmeci Fulya
Published: December 2023

The International Continence Society recommends the supine empty stress test (SEST) as an accessory test in the evaluation of women with urinary incontinence, especially for the presence of intrinsic sphincter deficiency (ISD). The aim of this study was to investigate the relationship between the SEST and clinical findings in women diagnosed with stress urinary incontinence with single voiding cycle ambulatory urodynamics (AUM). AUM tracings of patients with lower urinary tract symptoms (LUTS = Lower urinary tract symptoms) (n = 513) were retrospectively reviewed, and 364 charts with urodynamic SUI were analyzed. Demographics, examination findings, scores of the Sandvik Incontinence Severity Index and validated questionnaires, and AUM findings were compared between SEST-positive and -negative groups. Additionally, the diagnostic accuracy of the SEST in the diagnosis of low abdominal leak point pressure (ALPP ≤ 60 cm H2O) in women with pure urodynamic SUI was calculated. The SEST was positive in 41.8% (n = 152) of the cohort. Women with a positive SEST had higher scores on the Sandvik severity index (9.2 ± 3.6 vs. 7.5 ± 3.8, p = 0.003) and lower ALPP (79.6 ± 29.3 vs. 98.4 ± 31.3, p < 0.001). The negative predictive value of the SEST for ISD was found to be 92.4%. Thus, the SEST seems to be an objective clinical test reflecting urinary incontinence severity while excluding the presence of ISD.
Radiographic Evaluation and Changes in Bone Density of the Humeral Side after Reverse Total Shoulder Arthroplasty
Authors: Soma Daisuke , Ichiseki Toru , Ueda Shusuke , Sakurai Masaru , Kawahara Norio
Published: December 2023

After artificial joint surgery, bone density may decrease around the artificial joint; thus, postoperative bone density evaluation around the artificial joint is crucial. We investigated changes in bone mineral density and performed radiographic evaluation around the stem after reverse shoulder arthroplasty (RSA) surgery in 17 males (18 shoulders) and 19 females (19 shoulders), aged >65 years, with >1-year follow-up. In total, 20 and 17 cases involved massive rotator cuff tears and rotator cuff tear arthropathy, respectively. The Comprehensive Reverse Shoulder System (Standard Ingrowth) was used for all cases and cement was used in eight patients due to bone fragility. We examined lucent lines, loosening, bone resorption, and spot welds in non-cemented cases using plain radiography and postoperative bone density changes around the stem using dual-energy X-ray absorptiometry (DEXA). Lucent lines and bone resorption occurred in 5 (13.5%) and 19 (51.4%) shoulders, respectively. No loosening occurred. Compared to stem bone density at 2 weeks postoperatively, the decrease rate was the largest in the proximal medial humerus. One-year postoperative bone density was not related to sex, age, cement use, or preoperative diagnosis. Higher preoperative bone density was better maintained postoperatively. Furthermore, 1 year post RSA, spot welds were observed in approximately 48.2% of cases at the distal medial portion of the stem coating, and bone resorption occurred in the proximal medial humerus in 43.2% of cases. Therefore, postoperative bone density is related to preoperative bone density, suggesting the importance of maintaining high preoperative bone density.
Effects of SARS-CoV-2 Vaccination on Menstrual Cycle: An Italian Survey-Based Study
Authors: Granese Roberta , Incognito Giosuè Giordano , Gulino Ferdinando Antonio , Casiraro Giorgia , Porcaro Paola , Alibrandi Angela , Martinelli Canio , Ercoli Alfredo
Published: December 2023

Vaccination against SARS-CoV-2 has played a critical role in controlling the spread of the pandemic. The main side effects of SARS-CoV-2 vaccination include fever and fatigue; however, the potential impacts on menstrual cycles are to be determined. Given the limited number of studies suggesting menstrual changes post vaccination, this study investigates the correlation between COVID-19 vaccines and menstrual cycle changes in fertile-aged Italian women. A questionnaire was distributed from 1 October to 31 November 2022, focusing on menstrual rhythm and flow changes post vaccination. The analysis involved 471 participants. The study observed a shift from a regular to an irregular menstrual rhythm (p < 0.001), and changes in menstrual duration (p = 0.008 and p < 0.001 for first and second doses, respectively) and flow volume (p < 0.001). Most patients with irregular rhythms were vaccinated in the proliferative phase of their cycle. Within six months post vaccination, 74.2% of women with irregular post-vaccination rhythms reported a return to normality. These findings indicate primarily transient menstrual changes following mRNA COVID-19 vaccination, suggesting the vaccines’ safety for women of reproductive age.
When Atrial Fibrillation Meets Cerebral Amyloid Angiopathy: Current Evidence and Strategies
Authors: Merella Pierluigi , Casu Gavino , Chessa Paola , Atzori Enrico , Bandino Stefano , Deiana Gianluca
Published: December 2023

Non-valvular atrial fibrillation (AF) and cerebral amyloid angiopathy (CAA) are two common diseases in elderly populations. Despite the effectiveness of oral anticoagulant therapy in cardioembolic stroke prevention, intracranial hemorrhage represents the most serious complication of these therapies. Cerebral amyloid angiopathy is one of the main risk factors for spontaneous intracranial bleeding, and this risk is highly increased by age and concomitant antithrombotic therapies. Cerebral amyloid angiopathy can be silent for years and then manifest with clinical features simulating TIA (TIA-mimics) or stroke in AF patients, pushing clinicians to rapidly start VKAs or DOACs, thus increasing the risk of intracranial bleeding if the diagnosis of CAA was unknown. Because the cerebral amyloid angiopathy is easily diagnosed with non-contrast MRI, suspecting the disease can avoid catastrophic complications. In this review, we will provide physicians managing anticoagulant therapies with key tips to familiarize themselves with cerebral amyloid angiopathy, with a focus on the possible clinical presentations and on the diagnostic criteria.
Emergent Conversion to Open Heart Surgery during Transcatheter Aortic Valve Implantation: The Presence of a Rescue Team Improves Outcomes
Authors: Nasso Giuseppe , Vignaroli Walter , Contegiacomo Gaetano , Marchese Alfredo , Fattouch Khalil , D’Alessandro Pasquale , Brigiani Mario Siro , Vitobello Vincenza , Triggiani Vera , Demola Maria Antonietta , Tonioni Stefano , Paparella Domenico , Sechi Stefano , Bonifazi Raffaele , Santarpino Giuseppe , Resta Fabrizio , Bartolomucci Francesco , Lorusso Roberto , Larosa Claudio , Valenti Giovanni , Tito Antonio , Moscarelli Marco , Margari Vito , Fiore Flavio , Condello Ignazio , Speziale Giuseppe
Published: December 2023

Objective: Transcatheter aortic valve implant (TAVI) is the gold standard for the high-surgical-risk group of patients with aortic valve disease and it is an alternative to surgery in patients at intermediate risk. Lethal complications can occur, and many of these are manageable only with emergent conversion to open heart surgery. We retrospectively evaluate the outcome of all patients undergoing TAVI in our departments and the impact of a complete cardiac rescue team to reduce 30-day mortality. Methods: Data from all patients undergoing TAVI between January 2020 and August 2023 in our center were analyzed. An expert complete rescue was present in catheter laboratory. Primary outcomes were in-hospital and at 30-day mortality and evaluation of all cases needed for emergent conversion to open heart surgery. Results: 825 patients were enrolled. The total mortality was 19/825 (2.3%). Eleven of the total patients (1.3%) required emergent conversion to open heart surgery. Among them, eight were alive (73%), with a theoretical decrease of 0.98% in overall mortality. Conclusions: surgical treatment is rare during TAVI. The presence of an expert complete rescue team as support means an increase in survival. Surgery must be used only to restore circulatory and to treat complication while percutaneous approaches should complete the procedure.
Diagnostic and Therapeutic Issues in Glioma Using Imaging Data: The Challenge of Numerical Twinning
Authors: Guillevin Rémy , Naudin Mathieu , Fayolle Pierre , Giraud Clément , Le Guillou Xavier , Thomas Clément , Herpe Guillaume , Miranville Alain , Fernandez-Maloigne Christine , Pellerin Luc , Guillevin Carole
Published: December 2023

Glial tumors represent the leading etiology of primary brain tumors. Their particularities lie in (i) their location in a highly functional organ that is difficult to access surgically, including for biopsy, and (ii) their rapid, anisotropic mode of extension, notably via the fiber bundles of the white matter, which further limits the possibilities of resection. The use of mathematical tools enables the development of numerical models representative of the oncotype, genotype, evolution, and therapeutic response of lesions. The significant development of digital technologies linked to high-resolution NMR exploration, coupled with the possibilities offered by AI, means that we can envisage the creation of digital twins of tumors and their host organs, thus reducing the use of physical sampling.
Cancer Risk in Patients with Gaucher Disease Using Real-World Data
Authors: Revel-Vilk Shoshana , Zimran Ari , Istaiti Majdolen , Azani Liat , Shalev Varda , Chodick Gabriel , Manor Orly , Paltiel Ora
Published: December 2023

The association between GD and cancer has been uncertain due to ascertainment bias in previously published studies. We analyzed cancer incidence using the Maccabi Healthcare Service (MHS) electronic health records among 264 patients with GD compared to 3440 matched controls. We ascertained cancers diagnosed before and after the index date (i.e., the first documentation of GD in cases and the corresponding date for controls). Before the index date, cancers were diagnosed in 18 individuals, with 11 (4.2%) in the GD group and 7 (0.2%) in the control group. After the index date, cancers were diagnosed in 57 individuals, with 20 (7.9%) in the GD group and 37 (1.1%) in the control group, with a median follow-up of almost 13 years in both groups. The most common cancers diagnosed in GD were non-melanoma skin cancer (NMSC) and hematological malignancies, with a clustering of diagnoses around the time of GD diagnosis. The incidence of cancers (excluding MNSC) was 4.1 (95% CI 2.2–7.1) and 0.7 (95% CI 0.4–0.9) per 1000 patient-years in the GD and control groups, respectively, with an incidence rate ratio of 6.37 (95% CI 3–12.7). Patients with GD underwent more cancer screening tests than their counterparts in the control group. While our study revealed an increased occurrence of cancers in patients with GD, this finding might be partly attributed to the more rigorous surveillance procedures employed in this patient population.
Evaluation of Neuropathic Pain after Total Knee Arthroplasty: Do Yellow Flags Matter?
Authors: Colovic Danijel , Draschl Alexander , Reinbacher Patrick , Hecker Andrzej , Schittek Gregor , Fischerauer Stefan Franz , Leithner Andreas , Klim Sebastian Martin , Koutp Amir , Wittig Ulrike , Brunnader Kevin , Sandner-Kiesling Andreas , Sadoghi Patrick
Published: December 2023

Up to 20% of total knee arthroplasty (TKA) patients continue to experience chronic postsurgical pain. Various factors have been identified as potential contributors, including so-called “yellow flags”, encompassing symptoms of depression, anxiety, and catastrophizing, which were examined in this study to assess their predictive value concerning functional outcomes after TKA. Methods: Fifty TKA patients were categorized into high-risk and low-risk groups based on clinical assessment, demographic data, medication, and patient-reported outcome measures (DN4, SF-36, WOMAC, NRS, Fibromyalgia Survey Questionnaire, Pain Catastrophizing Scale, and Hospital Anxiety and Depression Scale). Postoperative outcomes within six months after TKA were then compared. Results: Both groups exhibited significant (p < 0.001) improvements in all WOMAC and NRS subscales, as well as in the physical function, role physical, pain, and energy/fatigue subdomains of the SF-36 after six months, while the high-risk group showed lower WOMAC scores regarding stiffness (19.0 ± 18.3 vs. 27.2 ± 20.7, p < 0.001) and pain (13.5 ± 13.3 vs. 15.1 ± 16.3, p = 0.029). The high-risk group showed significantly worse preoperative DN4 scores (1.8 ± 1.3 vs. 3.0 ± 1.1, p = 0.002) than the low-risk group, which persisted for one day (2.3 ± 1.2 vs. 3.5 ± 1.5, p = 0.005) and six weeks (2.2 ± 1.9 vs. 3.6 ± 2.3, p = 0.041) postoperatively. Conclusions: Our results indicate that pre-existing yellow flags contribute to a more challenging early postoperative phase, underscoring the importance of considering individual patient characteristics and psychological factors to optimize TKA outcomes.