bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Utility of Hysteroscopic Biopsy in Cases of Suspected Lobular Endocervical Glandular Hyperplasia and Comparison with Cervical Conization
Authors: Shiro Reona , Kotani Yasushi , Ohta Mamiko , Sato Hanako , Kashima Yoko , Murakami Kosuke , Kawasaki Kaoru , Nakai Hidekatsu , Matsumura Noriomi
Published: June 2023

Background: Cervical cystic lesions encompass a range of benign and malignant pathologies. Magnetic resonance imaging or cytology alone cannot provide a definitive diagnosis, and conventional practice involves performing a cervical biopsy by conization to confirm the histology in cases exhibiting potential signs of lobular endocervical glandular hyperplasia (LEGH) or malignancy. However, as postoperative complications resulting from conization can impact future fertility and pregnancy, alternative diagnostic methods are needed for reproductive-age patients. This study aimed to establish the efficacy of a hysteroscopic biopsy for diagnosing cervical cystic lesions and compare it with conization. Methods: Thirteen patients with cervical cystic lesions suspected of LEGH or malignancy underwent a hysteroscopic biopsy, while 23 underwent conization. Patient background information, preoperative evaluation, histology, and postoperative outcomes were collected and compared retrospectively. Results: No significant differences were found between the hysteroscopy and conization groups in terms of mean patient age (45 vs. 48 years), operating time (23 vs. 35 min), blood loss (small amount vs. 43 mL), and postoperative hospitalization (1.1 vs. 1.6 days). Conclusion: A hysteroscopic biopsy allows for targeted resection of the cervix while maintaining diagnostic accuracy. It may serve as an efficient method for diagnosing cervical cystic lesions.
Biomechanical Assessments in Woodwind Musicians: A Systematic Review
Authors: López-Pineda Javier , Rodríguez-Martínez María Carmen , Gómez-Rodríguez Rosa , García-Casares Lucía , García-Casares Natalia
Published: June 2023

Biomechanical methods are frequently used to provide information about the kinematics and kinetics of posture and movement during musical performance. The aim of this review was to identify and analyze the biomechanical methods performed on woodwind musicians to understand their musculoskeletal demands. A systemic review was carried out following the guidelines of the document Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). It was registered in PROSPERO (code 430304).The databases PubMed, Cochrane, CINAHL, Scopus, and Web of Science were consulted between January 2000 and March 2022. The search in the databases identified 1625 articles, and 16 different studies were finally included in the review, with a sample size of 390 participants. Pressure sensors, surface electromyography, infrared thermography, goniometry in two dimensions, and ultrasound topometry in three dimensions were biomechanical methods useful to broaden the knowledge of musculoskeletal demands during musical practice. Piezoresistive pressure sensors were the most widely used method. The great heterogeneity of the studies limited the comparability of the results. The findings raised the need to increase both the quantity and the quality of studies in future research.
Acupuncture Treatment for Hip Pain: A Systematic Review and Meta-Analysis
Authors: Park Hyun Suk , Jeong Hye In , Sung Soo-Hyun , Kim Kyeong Han
Published: June 2023

Acupuncture treatment (AT) is an effective treatment for pain relief; however, there are few systematic reviews that have reported on the effectiveness of AT for hip pain. This systematic review aimed to evaluate the efficacy and safety of AT of hip pain. We searched eight databases for randomised controlled trials (RCTs) evaluating the effect of AT on hip pain until August 2022. Twelve RCTs (806 patients) were included: two reported a significant effect of AT compared with that of conventional medicine (CM) alone for hip pain; two reported significant effects of AT + CM compared with that of CM alone in terms of Visual Analogue Scale (VAS); two reported a significant effect of AT + CM compared with that of Sham AT + CM in terms of anaesthetic dosage; two reported a significant effect of AT + CM compared with that of Sham AT + CM in terms of the side effects associated with analgesic use; one study reported a significant effect of AT compared to that of no-treatment. No serious adverse events were reported. Our findings demonstrate the potential of AT in managing hip pain. Given the low quality and small sample sizes of the studies, the evidence supporting AT for hip pain management was weak. Further clinical trials and systematic reviews are required. The protocol of the current study was registered in the PROSPERO International prospective register of systematic reviews (CRD42017079586).
Perceived Stress among Healthcare Students and Its Association with Anxiety and Depression: A Cross-Sectional Study in Saudi Arabia
Authors: Alwhaibi Monira , Alotaibi Ameerah , Alsaadi Budoor
Published: June 2023

Introduction. Healthcare students are subjected to high-stress levels due to different academic, social, and financial stressors. Persistent and severe stress might predispose students to depression and anxiety. Therefore, this research aims to investigate the level of perceived stress among healthcare students and its relation to anxiety and depression. Methods. A prospective cross-sectional study using a validated questionnaire was conducted among healthcare students in Saudi Arabia. The 14-item Perceived Stress Scale (PSS) was used to evaluate perceived stress, and depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). All statistical analyses were carried out using PSPP Statistical Analysis Software version 1.2.0. Results. A total of 701 respondents participated in this study. The average age of the students was 20.9 years old, and 59.3% were female. Almost three-quarters of students perceive themselves as stressed. Around two-thirds were categorized as having borderline/cases of depression or anxiety. Perceived stress was four times more likely among students with cases of anxiety [Adjusted Odds Ratio (AOR) = 4.83; 95% CI 2.89, 8.06], depression [AOR = 4.79; 95% CI 2.68, 8.53] as compared with those without these conditions. Conclusions. Stress is highly prevalent among healthcare students, and it is strongly associated with female gender and students’ anxiety and depression. Therefore, the mental health of healthcare students is an essential factor affecting perceived stress and at-risk individuals. Therefore, preventative mental health interventions targeting healthcare students are necessary to help improve mental health and cope with stressors in academic education.
Validation of the Health Consciousness Scale among the Czech Population
Authors: Remr Jiri
Published: June 2023

The COVID-19 pandemic has demonstrated the importance of maintaining good health. It became has become apparent that health consciousness is a crucial factor in promoting healthy lifestyles, disease prevention, and the overall well-being of individuals. A higher level of health consciousness is associated with healthy habits, better adherence to medical recommendations, and a higher quality of life. Therefore, health consciousness is a critical construct in health care that reflects the degree to which individuals care about their health. This study, which is based on a representative sample of the adult population (n = 1372), aims to validate the Health Consciousness Scale (HCS) to assess its reliability and validity, and evaluate the factor structure of the translated version of the scale in the Czech language. The validation of the HCS in the Czech context is a significant step forward and provides useful information for healthcare professionals, policymakers, and researchers. The findings of this study contribute to the understanding of health consciousness in the Czech population and provide unique information for the development and evaluation of health interventions aimed at promoting healthy behaviors and attitudes.
Indexing of Speckle Tracking Longitudinal Strain of Right Ventricle to Body Surface Area Does Not Improve Its Efficiency in Diagnosis and Mortality Risk Stratification in Patients with Acute Pulmonary Embolism
Authors: Wiliński Jerzy , Skwarek Anna , Borek Radosław , Medygrał Michał , Chrzan Iwona , Lechowicz-Wilińska Marta , Chukwu Ositadima
Published: June 2023

Background: Acute pulmonary embolism (PE) is associated with a serious mortality rate. Thus, the rapid diagnosis and identification of patients at high risk of death is pivotal. The search for echocardiographic parameters for this purpose continues. Recent publications reveal correlations between myocardial longitudinal strain (LS) and body surface area (BSA). The aim of the study was to evaluate the usefulness of indexing the right ventricular (RV) speckle tracking LS to BSA in detecting PE and stratifying the risk of 30-day all-cause mortality. Methods: the prospective cross-sectional observational study group consisted of 167 consecutive patients (76 men, 45.5%) aged 69.5 ± 15.3 years, and they were referred for computed tomography pulmonary angiography. Patients underwent a transthoracic echocardiographic examination within 24 h of admission to the hospital ward. RVLS and their derivatives indexed to BSA were included in the analysis. Results: PE was confirmed in 88 patients, while 79 patients had no radiological features of PE. The only echocardiographic parameters that differed between subgroups were pulmonary flow acceleration (Act), McConnell’s sign, LS of the middle segment of the RV free wall, and its derivative indexed to BSA. During the 30-day follow-up of a subgroup of subjects with PE, 12 patients died. The mortality predictors with increasing prediction value included a RV free wall mid-segment LS (cut-off value: −21%, Area Under the Curve—AUC 0.6, p = 0.02) and its derivative indexed to BSA (−14 %/m2, AUC 0.62, p = 0.003), body mass index (24.7 kg/m2, AUC 0.63, p = 0.002), D-dimer serum concentration (3559 pg/mL, AUC 0.66, p < 0.001), Act (67 ms, AUC 0.67, p < 0.001), septal basal LS (−15%, AUC 0.68, p = 0.02), RV free wall basal segment LS (−14%, AUC 0.7, p = 0.015), age (66 years, AUC 0.74, p = 0.004), NT-proBNP (1120 pg/mL, AUC 0.75, p = 0.01), troponin T (66 ng/mL, AUC 0.78, p = 0.005), and the complex score of the Pulmonary Embolism Severity Index (AUC 0.88, p < 0.001). Conclusions: indexing of RVLS to BSA does not improve its prognostic value in patients with acute PE.
Spatial Patterns in the Distribution of Hypertension among Men and Women in India and Its Relationship with Health Insurance Coverage
Authors: Kamath Rajesh , Brand Helmut , Ravandhur Arun Harshith , Lakshmi Vani , Sharma Nishu , D’souza Reshma Maria Cocess
Published: June 2023

The present study explores district-level data associated with health insurance coverage (%) and the prevalence of hypertension (mildly, moderately, and severely elevated) observed across men and women as per NFHS 5. Coastal districts in the peninsular region of India and districts in parts of northeastern India have the highest prevalence of elevated blood pressure. Jammu and Kashmir, parts of Gujarat and parts of Rajasthan have a lower prevalence of elevated blood pressure. Intrastate heterogeneity in spatial patterns of elevated blood pressure is mainly seen in central India. The highest burden of elevated blood pressure is in the state of Kerala. Rajasthan is among the states with higher health insurance coverage and a lower prevalence of elevated blood pressure. There is a relatively low positive relationship between health insurance coverage and the prevalence of elevated blood pressure. Health insurance in India generally covers the cost of inpatient care to the exclusion of outpatient care. This might mean that health insurance has limited impact in improving the diagnosis of hypertension. Access to public health centers raises the probability of adults with hypertension receiving treatment with antihypertensives. Access to public health centers has been seen to be especially significant at the poorer end of the economic spectrum. The health and wellness center initiative under Ayushman Bharat will play a crucial role in hypertension control in India.
The Trend of Healthcare Needs among Elders and Its Association with Healthcare Access and Quality in Low-Income Countries: An Exploration of the Global Burden of Disease Study 2019
Authors: Sempungu Joshua Kirabo , Choi Minjae , Lee Eun Hae , Lee Yo Han
Published: June 2023

To investigate the trend of healthcare needs among elders in low-income countries (LICs) and how changes in healthcare access and quality (HAQ) have correlated with these changes from 1990 to 2019, this study used estimates from the global burden of disease (GBD) 2019 study, including prevalence, years of life lost (YLLs), years lived with disability (YLDs), life expectancy (LE), health-adjusted life expectancy (HALE) and the HAQ index for years 1990 and 2019. We found increases in numbers of YLLs, YLDs, and prevalent cases due to NCDs, and the rate of increase was higher for all indicators of non-communicable diseases (NCDs) when compared with communicable, maternal, neonatal and nutritional diseases among elders. We also observed increases in LE and HALE among all countries. However, this was also challenged by increases in unhealthy life years (ULYs) and their constant percentage of LE. The HAQ index of LICs was also found to be low, although it had increased during the period. A reduction in the burden of acute diseases explains the increase in LE, but increases in ULYs and the NCD burden were also observed. LICs need to improve their HAQ to counter the growing threat of longer but less healthy lives.
Transcutaneous Tibial Nerve Stimulation for Primary Dysmenorrhea: A Protocol for a Randomized Controlled Trial
Authors: Correyero-León Marta , Llamas-Ramos Rocío , Calvo-Rodrigo Javier , Alvarado-Omenat Jorge Juan , Llamas-Ramos Inés
Published: June 2023

Primary dysmenorrhea (PD) is a painful menstruation that can persist for the duration of a woman’s fertile life. Non-steroidal anti-inflammatory drugs, hormonal therapy, physiotherapy techniques, etc., are the main treatments. The main objective of this study is to evaluate the effectiveness of transcutaneous posterior tibial nerve stimulation (TTNS) in PD patients. The study will consist of a single-blind randomized clinical trial, parallel-assigned with two arms. Women with PD (18–43 years) with regular menstrual cycles and at least 4 points in VAS will be randomly divided into experimental (TTNS) and placebo (simulated stimulation) groups during 12 treatment sessions (1 session/week) and several follow-ups: monthly during treatment and 1, 3 and 6 months after. Maximum and mean pain intensity, pain duration, pain severity, number of anti-inflammatory drugs, quality of life, sleep quality, overall improvement, treatment satisfaction and secondary effects will be measured once a month every 6 months and at 3 and 6 months. The Student’s t-test for independent samples or the Mann–Whitney U test will be used. The literature shows effective physiotherapeutic techniques for PD in the short term, which do not act on causes and have limitations. The TTNS technique can be used in transcutaneous and percutaneous modalities, with similar effectiveness, but the transcutaneous causes less discomfort. TTNS modulates pain, and long-term benefits could be achieved at low cost and without patient discomfort.
Sex-Based Differences in Clinical Profile and Complications among Individuals with Type 2 Diabetes Seen at a Private Tertiary Diabetes Care Centre in India
Authors: Pradeepa Rajendra , Shreya Lal , Anjana Ranjit Mohan , Jebarani Saravanan , Venkatesan Ulagamathesan , Kamal Raj Nithyanantham , Swami Onkar C. , Mohan Viswanathan
Published: June 2023

This study aimed to compare the clinical and biochemical profiles as well as the complications in males and females with type 2 diabetes (T2DM) presenting to a private tertiary diabetes care centre in India. This is a retrospective study, conducted between 1 January 2017 and 31 December 2019, and included 72,980 individuals with T2DM, aged ≥ 18 years (age and sex-matched—males—36,490; females—36,490). Anthropometric measurements, blood pressure, fasting plasma glucose (FPG), post-prandial plasma glucose (PPPG), glycated haemoglobin (HbA1c), lipids, urea, and creatinine were measured. Retinopathy was screened using retinal photography, neuropathy using biothesiometry, nephropathy measuring urinary albumin excretion, peripheral vascular disease (PVD) using Doppler, and coronary artery disease (CAD) based on the history of myocardial infarction and/or drug treatment for CAD and/or electrocardiographic changes. Obesity (73.6% vs. 59.0%) rates were significantly higher in females compared to males. FPG, PPPG, and HbA1c were higher among younger age groups among both sexes, with males having higher values compared to females. However, after the age of 44 years, control of diabetes was worse among females. In addition, only 18.8% of the females achieved glycemic control (HbA1c < 7%) compared to 19.9% in males (p < 0.001). Males had higher prevalence of neuropathy (42.9% vs. 36.9%), retinopathy (36.0% vs. 26.3%), and nephropathy (25.0% vs. 23.3%) compared to females. Males had 1.8- and 1.6-times higher risk of developing CAD and retinopathy compared to females. Hypothyroidism (12.5% vs. 3.5%) and cancers (1.3% vs. 0.6%) were significantly higher in females compared to males. In this large sample of T2DM seen at a chain of private tertiary diabetes centres, females had higher prevalence of metabolic risk factors and poorer diabetes control compared to males, emphasizing the need for better control of diabetes in females. However, males had higher prevalence of neuropathy, retinopathy, nephropathy, and CAD compared to females.
Quantitative Proteomic and Phosphoproteomic Profiling of Lung Tissues from Pulmonary Arterial Hypertension Rat Model
Authors: Luo Ang , Jia Yangfan , Hao Rongrong , Yu Yafang , Zhou Xia , Gu Chenxin , Ren Meijuan , Tang Haiyang
Published: June 2023

Pulmonary arterial hypertension (PAH) is a rare but fatal disease characterized by elevated pulmonary vascular resistance and increased pressure in the distal pulmonary arteries. Systematic analysis of the proteins and pathways involved in the progression of PAH is crucial for understanding the underlying molecular mechanism. In this study, we performed tandem mass tags (TMT)-based relative quantitative proteomic profiling of lung tissues from rats treated with monocrotaline (MCT) for 1, 2, 3 and 4 weeks. A total of 6759 proteins were quantified, among which 2660 proteins exhibited significant changes (p-value < 0.05, fold change < 0.83 or >1.2). Notably, these changes included several known PAH-related proteins, such as Retnla (resistin-like alpha) and arginase-1. Furthermore, the expression of potential PAH-related proteins, including Aurora kinase B and Cyclin-A2, was verified via Western blot analysis. In addition, we performed quantitative phosphoproteomic analysis on the lungs from MCT-induced PAH rats and identified 1412 upregulated phosphopeptides and 390 downregulated phosphopeptides. Pathway enrichment analysis revealed significant involvement of pathways such as complement and coagulation cascades and the signaling pathway of vascular smooth muscle contraction. Overall, this comprehensive analysis of proteins and phosphoproteins involved in the development and progression of PAH in lung tissues provides valuable insights for the development of potential diagnostic and treatment targets for PAH.
Extracellular Vesicles as Markers of Liver Function: Optimized Workflow for Biomarker Identification in Liver Disease
Authors: Paluschinski Martha , Loosen Sven , Kordes Claus , Keitel Verena , Kuebart Anne , Brandenburger Timo , Schöler David , Wammers Marianne , Neumann Ulf P. , Luedde Tom , Castoldi Mirco
Published: June 2023

Liver diseases represent a significant global health burden, necessitating the development of reliable biomarkers for early detection, prognosis, and therapeutic monitoring. Extracellular vesicles (EVs) have emerged as promising candidates for liver disease biomarkers due to their unique cargo composition, stability, and accessibility in various biological fluids. In this study, we present an optimized workflow for the identification of EVs-based biomarkers in liver disease, encompassing EVs isolation, characterization, cargo analysis, and biomarker validation. Here we show that the levels of microRNAs miR-10a, miR-21, miR-142-3p, miR-150, and miR-223 were different among EVs isolated from patients with nonalcoholic fatty liver disease and autoimmune hepatitis. In addition, IL2, IL8, and interferon-gamma were found to be increased in EVs isolated from patients with cholangiocarcinoma compared with healthy controls. By implementing this optimized workflow, researchers and clinicians can improve the identification and utilization of EVs-based biomarkers, ultimately enhancing liver disease diagnosis, prognosis, and personalized treatment strategies.
C- and N-Phosphorylated Enamines—An Avenue to Heterocycles: NMR Spectroscopy
Authors: Larina Lyudmila
Published: June 2023

The review presents extensive data (from the works of the author and literature) on the structure of C- and N-chlorophosphorylated enamines and the related heterocycles obtained by multipulse multinuclear 1H, 13C, and 31P NMR spectroscopy. The use of phosphorus pentachloride as a phosphorylating agent for functional enamines enables the synthesis of various C- and N-phosphorylated products that are heterocyclized to form various promising nitrogen- and phosphorus-containing heterocyclic systems. 31P NMR spectroscopy is the most convenient, reliable and unambiguous method for the study and identification of organophosphorus compounds with different coordination numbers of the phosphorus atom, as well as for the determination of their Z- and E-isomeric forms. An alteration of the coordination number of the phosphorus atom in the phosphorylated compounds from 3 to 6 leads to a drastic screening of the 31P nucleus from about +200 to −300 ppm. The unique structural features of nitrogen–phosphorus-containing heterocyclic compounds are discussed.
Clay Nanotubes Loaded with Diazepam or Xylazine Permeate the Brain through Intranasal Administration in Mice
Authors: Yanamadala Yaswanthi , Saleh Mahdi Y. , Williams Afrika A. , Lvov Yuri , Murray Teresa A.
Published: June 2023

The blood–brain barrier (BBB) is an obstacle to the permeation of most therapeutic drugs into the brain, limiting treatments for neurological disorders. Drugs loaded within nanocarriers that pass through the BBB can overcome this limitation. Halloysite consists of naturally occurring biocompatible clay nanotubes of 50 nm diameter and 15 nm lumen, allowing the loading and sustained release of loaded drugs. These have demonstrated the ability to transport loaded molecules into cells and organs. We propose to use halloysite nanotubes as a “nano-torpedo” for drug delivery through the BBB due to their needle-like shape. To determine if they can cross the BBB using a non-invasive, clinically translatable route of administration, we loaded halloysite with either diazepam or xylazine and delivered these intranasally to mice daily over six days. The sedative effects of these drugs were observed in vestibulomotor tests conducted at two, five, and seven days after the initial administration. Behavioral tests were conducted 3.5 h after administration to show that the effects were from halloysite/delivered drugs and not from the drug alone. As expected, the treated mice performed more poorly than the sham, drug alone, and halloysite-vehicle-treated mice. These results confirm that halloysite permeates the BBB to deliver drugs when administered intranasally.
Emission and Migration of Nanoscale Particles during Osseointegration and Disintegration of Dental Implants in the Clinic and Experiment and the Influence on Cytokine Production
Authors: Labis Varvara , Bazikyan Ernest , Sizova Svetlana , Oleinikov Vladimir , Trulioff Andrey , Serebriakova Maria , Kudryavtsev Igor , Khmelenin Dmitry , Zhigalina Olga , Dyachkova Irina , Zolotov Denis , Asadchikov Victor , Mrugova Tatyana , Zurochka Aleksandr , Khaidukov Sergey , Kozlov Ivan G.
Published: June 2023

The emission of nanoscale particles from the surfaces of dental implants leads to the cumulative effect of particle complexes in the bone bed and surrounding soft tissues. Aspects of particle migration with the possibility of their involvement in the development of pathological processes of systemic nature remain unexplored. The aim of this work was to study protein production during the interaction of immunocompetent cells with nanoscale metal particles obtained from the surfaces of dental implants in the supernatants. The ability to migrate nanoscale metal particles with possible involvement in the formation of pathological structures, in particular in the formation of gallstones, was also investigated. The following methods were used: microbiological studies, X-ray microtomography, X-ray fluorescence analysis, flow cytometry, electron microscopy, dynamic light scattering, and multiplex immunofluorescence analysis. For the first time, titanium nanoparticles in gallstones were identified by X-ray fluorescence analysis and electron microscopy with elemental mapping. The multiplex analysis method revealed that the physiological response of the immune system cells, in particular neutrophils, to nanosized metal particles significantly reduced TNF-a production both through direct interaction and through double lipopolysaccharide-induced signaling. For the first time, a significant decrease in TNF-a production was demonstrated when supernatants containing nanoscale metal particles were co-cultured with proinflammatory peritoneal exudate obtained from the peritoneum of the C57Bl/6J inbred mice line for one day.
IGFBP7 Fuels the Glycolytic Metabolism in B-Cell Precursor Acute Lymphoblastic Leukemia by Sustaining Activation of the IGF1R–Akt–GLUT1 Axis
Authors: Artico Leonardo Luís , Ruas Juliana Silveira , Teixeira Júnior José Ricardo , Migita Natacha Azussa , Seguchi Gustavo , Shi Xinghua , Brandalise Silvia Regina , Castilho Roger Frigério , Yunes José Andrés
Published: June 2023

Increased glycolytic metabolism plays an important role in B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL). We previously showed that IGFBP7 exerts mitogenic and prosuvival effects in ALL by promoting IGF1 receptor (IGF1R) permanence on the cell surface, thus prolonging Akt activation upon IGFs/insulin stimulation. Here, we show that sustained activation of the IGF1R–PI3K–Akt axis concurs with GLUT1 upregulation, which enhances energy metabolism and increases glycolytic metabolism in BCP-ALL. IGFBP7 neutralization with a monoclonal antibody or the pharmacological inhibition of the PI3K–Akt pathway was shown to abrogate this effect, restoring the physiological levels of GLUT1 on the cell surface. The metabolic effect described here may offer an additional mechanistic explanation for the strong negative impact seen in ALL cells in vitro and in vivo after the knockdown or antibody neutralization of IGFBP7, while reinforcing the notion that it is a valid target for future therapeutic interventions.
Intramolecular Hydrogen Bonding in N6-Substituted 2-Chloroadenosines: Evidence from NMR Spectroscopy
Authors: Berzina Maria Ya. , Eletskaya Barbara Z. , Kayushin Alexei L. , Dorofeeva Elena V. , Lutonina Olga I. , Fateev Ilya V. , Zhavoronkova Olga N. , Bashorin Arthur R. , Arnautova Alexandra O. , Smirnova Olga S. , Antonov Konstantin V. , Paramonov Alexander S. , Dubinnyi Maxim A. , Esipov Roman S. , Miroshnikov Anatoly I. , Konstantinova Irina D.
Published: June 2023

Two forms were found in the NMR spectra of N6-substituted 2-chloroadenosines. The proportion of the mini-form was 11–32% of the main form. It was characterized by a separate set of signals in COSY, 15N-HMBC and other NMR spectra. We assumed that the mini-form arises due to the formation of an intramolecular hydrogen bond between the N7 atom of purine and the N6–CH proton of the substituent. The 1H,15N-HMBC spectrum confirmed the presence of a hydrogen bond in the mini-form of the nucleoside and its absence in the main form. Compounds incapable of forming such a hydrogen bond were synthesized. In these compounds, either the N7 atom of the purine or the N6–CH proton of the substituent was absent. The mini-form was not found in the NMR spectra of these nucleosides, confirming the importance of the intramolecular hydrogen bond in its formation.
Neurological Phenotypes in Mouse Models of Mitochondrial Disease and Relevance to Human Neuropathology
Authors: Olkhova Elizaveta A. , Smith Laura A. , Bradshaw Carla , Gorman Gráinne S. , Erskine Daniel , Ng Yi Shiau
Published: June 2023

Mitochondrial diseases represent the most common inherited neurometabolic disorders, for which no effective therapy currently exists for most patients. The unmet clinical need requires a more comprehensive understanding of the disease mechanisms and the development of reliable and robust in vivo models that accurately recapitulate human disease. This review aims to summarise and discuss various mouse models harbouring transgenic impairments in genes that regulate mitochondrial function, specifically their neurological phenotype and neuropathological features. Ataxia secondary to cerebellar impairment is one of the most prevalent neurological features of mouse models of mitochondrial dysfunction, consistent with the observation that progressive cerebellar ataxia is a common neurological manifestation in patients with mitochondrial disease. The loss of Purkinje neurons is a shared neuropathological finding in human post-mortem tissues and numerous mouse models. However, none of the existing mouse models recapitulate other devastating neurological phenotypes, such as refractory focal seizures and stroke-like episodes seen in patients. Additionally, we discuss the roles of reactive astrogliosis and microglial reactivity, which may be driving the neuropathology in some of the mouse models of mitochondrial dysfunction, as well as mechanisms through which cellular death may occur, beyond apoptosis, in neurons undergoing mitochondrial bioenergy crisis.
Influence of Mechanical Flower Thinning on Fruit Set and Quality of ‘Arisoo’ and ‘Fuji’ Apples
Authors: Win Nay Myo , Song Yang-Yik , Nam Jong-Chul , Yoo Jingi , Kang In-Kyu , Cho Young Sik , Yang Sang-Jin , Park Juhyeon
Published: June 2023

This study aimed to identify the efficiency of mechanical flower thinning (MFT) and its influence on apple fruit quality. In the first experiment, ‘Arisoo’ apple flowers were subjected to MFT with one hundred sixty-two (half) and three hundred twenty-four (full) strings at the same rotor (300 rpm) and tractor (6 km/h) speeds. Hand thinning was performed as a control. The number of removed flowers in each terminal and lateral flower cluster was slightly higher in MFT with full-strings than that of MFT with half-strings. The fruit set rate was lower in MFT with full-strings than that of MFT with half-strings. However, the use of full-strings during mechanical thinning increased the leaf damage rate compared to half-strings. Except a* value, MFT with full-strings improved flesh firmness, soluble solids content (SSC) and titratable acidity (TA), and reduced starch pattern index of fruits at harvest compared to the control. In the second experiment, ‘Fuji’ apple flowers were subjected to chemical thinning, MFT (300 rpm, 6 km/h), and MFT + chemical thinning treatments and compared with hand thinning (control). The thinning efficiency of MFT was similar to that of chemical thinning and MFT + chemical thinning treatments in terms of the removal of flowers and fruit set rates. Compared to the control, MFT, chemical thinning, and their combined treatments improved flesh firmness and SSC of fruits at harvest. TA was highest in the chemical thinning treatment compared to other thinning treatments. However, fruit size, weight, and a* value were unaffected by any treatment. In conclusion, the use of full-strings during MFT achieved optimal results in ‘Arisoo’ apples. In ‘Fuji’ apples, MFT treatment alone achieved effective results and the addition of chemical thinning after MFT had no supportive role in thinning efficiency and fruit quality.
Exploring the Potential of Plant-Based CTB-INS Oral Vaccines in Treating Type 1 Diabetes
Authors: Mbongue Jacques C. , Vanterpool Elaine , Langridge William H. R.
Published: June 2023

The 19th century saw the development of vaccines, which were biological preparations designed to enhance immunity against specific diseases. Edible vaccines function by stimulating both systemic and mucosal immune responses against foreign pathogens, and they may potentially protect the host from autoimmunity. The mucosal surfaces provide a convenient and rapid route for delivering therapeutic small molecules. This is due to their large surface areas and easy administration. The effectiveness of mucosal immunization relies on the fact that mucous membranes represent the body’s largest immunogenic organ. Within this interface, there is a well-organized lymphatic structure known as MALT (mucosa-associated lymphoid tissue), which includes both T and B cells and encompasses the adaptive arms of the immune system. Oral vaccines specifically stimulate immune responses in the gut-associated lymphoid tissue (GALT), which consists of lymph nodes, Payer’s patches (where B cells make up about 75% of the population and T cells account for approximately 20%), and isolated lymphoid follicles within the gastrointestinal tract (GIT). However, a significant challenge in developing vaccines is the rapid degradation of antigens within the harsh environment of the digestive tract, which hampers effective protein delivery to the GIT. In light of recent proteomic analysis revealing strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1) in DCs inoculated with the Cholera toxin B-subunit-Insulin fusion protein vaccine (CTB-INS), we are interested in investigating the effects of transgene integration into a selected plant cell as an edible vaccine.
Efficacy of the Fumigants Propylene Oxide and Ethyl Formate to Control Two Pest Species of Dry-Cured Hams
Authors: Maille Jacqueline M. , Schilling M. Wes , Phillips Thomas W.
Published: June 2023

The ham mite Tyrophagus putrescentiae and the red-legged ham beetle Necrobia rufipes are harmful pests to several high-valued stored products. The regulatory phase-out of the fumigant methyl bromide necessitates the search for alternative fumigants. Propylene oxide (PPO) and ethyl formate (EF) were therefore evaluated in the laboratory for controlling these pests of dry-cured hams. Concentration–mortality studies at 25 °C of PPO and EF found that the mobile stages of the mites were very susceptible to low concentrations of 10 mg/L and less of each gas, while mite eggs were very tolerant and required 20 mg/L for PPO and 80 mg/L of EF for 100% mortality. Mixed life stage cultures of mites and beetles were treated for 24 h with either PPO or EF at 1× and 2× the estimated 99% lethal doses and confirmed effectiveness for controlling simulated pest populations. The sorptive properties of each gas in chambers with ham pieces, dog food kibbles, or fish meal were minimal for a reduction in mite toxicity when compared to treatments in empty chambers. There was no evidence that any desorbed gas occurred at a level toxic to mite eggs in any of the fumigated commodities. These fumigation studies with ham pests support further work with PPO and EF on any changes in the sensory quality of dry-cured hams for human taste and for commercial-scale fumigations toward regulatory approval.
Mosquito Larvicidal Activity and Cytotoxicity of the Extracts of Aromatic Plants from Malaysia
Authors: Lim Huimei , Lee Sook Yee , Ho Lai Yee , Sit Nam Weng
Published: June 2023

Despite ongoing control efforts, the mosquito population and diseases vectored by them continue to thrive worldwide, causing major health concerns. There has been growing interest in the use of botanicals as alternatives to insecticides due to their widespread insecticidal properties, biodegradability, and adaptability to ecological conditions. In this study, we investigated the larvicidal activity and cytotoxicity effects of solvent extracts from three aromatic plants—Curcuma longa (turmeric), Ocimum americanum (hoary basil), and Petroselinum crispum (parsley)—against Aedes albopictus. Subsequently, we examined the phytochemical composition of the extracts through gas chromatography–mass spectrometry (GC–MS) analysis. Results revealed that the hexane extracts of O. americanum and P. crispum exhibited the greatest larvicidal activity with the lowest median lethal concentration (LC50) values (<30 µg/mL) at 24 h post-treatment, with the former found to be significantly less toxic towards African monkey kidney (Vero) cells. The GC–MS analysis of the said extract indicated the presence of different classes of metabolites, including phenylpropanoids, very long-chain alkanes, fatty acids and their derivatives, and terpenes, with the most abundant component being methyl eugenol (55.28%), most of which, have been documented for their larvicidal activities. These findings provide valuable insights into the potential use and development of bioinsecticides, particularly from O. americanum.
Performance Modeling and Optimization for a Fog-Based IoT Platform
Authors: Tang Shensheng
Published: June 2023

A fog-based IoT platform model involving three layers, i.e., IoT devices, fog nodes, and the cloud, was proposed using an open Jackson network with feedback. The system performance was analyzed for individual subsystems, and the overall system was based on different input parameters. Interesting performance metrics were derived from analytical results. A resource optimization problem was developed and solved to determine the optimal service rates at individual fog nodes under some constraint conditions. Numerical evaluations for the performance and the optimization problem are provided for further understanding of the analysis. The modeling and analysis, as well as the optimization design method, are expected to provide a useful reference for the design and evaluation of fog computing systems.
Pediatric Flatfoot: Is There a Need for Surgical Referral?
Authors: Vergillos Luna Manuel , Khal Adyb-Adrian , Milliken Kara A. , Solla Federico , Rampal Virginie
Published: June 2023

Pediatric foot deformities are a common finding, concerning up to 44% of preschool aged children. The absence of accepted international guidelines, as well as heterogeneity in definitions and measurements, makes management of pediatric flatfoot a challenge, and decisions surrounding specialized care referral confusing and biased. The objective of this narrative review is to provide guidance to primary care physicians treating these patients. A non-systematic review of the literature regarding the development, etiology, and clinical and radiographic assessment of flatfeet using the PubMed and Cochrane Library databases was performed. The exclusion criteria for the review were adult populations, papers detailing the outcome of a specific surgical procedure, and publications prior to 2001. The included articles showed great heterogeneity in definition and proposed management, which makes the study of pediatric flatfoot challenging. Flatfoot is a common finding in children under 10 years old, and should not be considered pathological unless stiffness or functional limitation are present. Surgical referral should be reserved to children with stiff or painful flatfoot, while simple observation is indicated for flexible, asymptomatic flatfeet.
Poor Adherence to Self-Applied Topical Drug Treatment Is a Common Source of Low Lesion Clearance in Patients with Actinic Keratosis—A Cross-Sectional Study
Authors: Koch Elias A. T. , Steeb Theresa , Bender-Säbelkampf Sophia , Busch Dorothee , Feustel Janina , Kaufmann Matthias D. , Maronna Andreas , Meder Christine , Ronicke Moritz , Toussaint Frédéric , Wellein Hedwig , Berking Carola , Heppt Markus V.
Published: June 2023

Background: Many treatments for actinic keratosis (AK) have been proven efficient in clinical trials. However, patients with AK may still experience unsatisfactory therapeutic outcomes in clinical practice. Objectives: To investigate patient adherence to self-applied topical interventions for AK and to explore factors associated with adherence in a real-world setting. Methods: A cross-sectional study was conducted. Patients presenting with AK were asked to complete a self-administered questionnaire about their last topical AK treatment. Results: A total of 113 patients participated with a median age of 78.5 years (range 58–94). Fifty-four patients (47.8%) received topical diclofenac, ten (8.8%) imiquimod, nine (8%) 5-fluorouracil, nine (8%) 5-fluorouracil plus salicylic acid, and eight (7.1%) photodynamic therapy. The non-adherence rate was 46.9% (n = 53), and only 30.9% (n = 35) used the topical treatments according to the summary of product characteristics (SmPC). These subgroups were compared. Patients of the non-compliant group were significantly less informed about the application time of the specific topical intervention (p = 0.002) and adjusted the timeframe (p < 0.001) and application frequency of the therapy (p = 0.02) independently of their physician. Conversely, patients reporting a sufficient pre-treatment consultation (p = 0.019) generally complied with the SmPC compliance application. Conclusions: A thorough pre-treatment consultation can help to increase treatment adherence and ensure lesion clearance.
Sodium Glucose Cotransporter-2 Inhibitor Empagliflozin Increases Antioxidative Capacity and Improves Renal Function in Diabetic Rats
Authors: Yaribeygi Habib , Hemmati Mohammad Amin , Nasimi Fatemeh , Maleki Mina , Jamialahmadi Tannaz , Reiner Ivan , Reiner Željko , Sahebkar Amirhossein
Published: June 2023

Introduction: There are several pathologic mechanisms involved in diabetic nephropathy, but the role of oxidative stress seems to be one of the most important. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs that might also have some other effects in addition to lowering glucose. The aim of this study was to evaluate the possible effects of the SGLT2 inhibitor empagliflozin on oxidative stress and renal function in diabetes. Methods: Male Wistar rats were randomly divided into four groups: control, control-treated, diabetic, and diabetic-treated (n = 8 per group). Diabetes was induced by a single intraperitoneal dose of streptozotocin (50 mg/kg). The treated animals received empagliflozin for 5 weeks (20 mg/kg/day/po). All groups were sacrificed on the 36th day, and blood and tissue samples were collected. Serum levels of urea, uric acid, creatinine, and glucose levels were determined. The level of malondialdehyde (MDA) and glutathione (GLT), as well as the activity of catalase (CAT) and superoxide dismutase (SOD), was measured in all groups. Data were analyzed using one-way Anova and paired T-tests, and p ≤ 0.05 was considered significant. Results: Diabetes significantly increased urea (p < 0.001), uric acid (p < 0.001), and creatinine (p < 0.001) in the serum, while the activities of CAT (p < 0.001) and SOD (p < 0.001) were reduced. GLT was also reduced (p < 0.001), and MDA was increased (p < 0.001) in non-treated animals. Treatment with empagliflozin improved renal function, as shown by a reduction in the serum levels of urea (p = 0.03), uric acid (p = 0.03), and creatinine (p < 0.001). Empagliflozin also increased the antioxidant capacity by increasing CAT (p = 0.035) and SOD (p = 0.02) activities and GLT content (p = 0.01) and reduced oxidative damage by lowering MDA (p < 0.001). Conclusions: It seems that uncontrolled diabetes induces renal insufficiency by decreasing antioxidant defense mechanisms and inducing oxidative stress. Empagliflozin might have additional benefits in addition to lowering glucose—-reversing these processes, improving antioxidative capacity, and improving renal function.
Outcome of Out-of-Hospital Cardiac Arrest Patients Stratified by Pre-Clinical Loading with Aspirin and Heparin: A Retrospective Cohort Analysis
Authors: Macherey-Meyer Sascha , Heyne Sebastian , Meertens Max M. , Braumann Simon , Niessen Stephan F. , Baldus Stephan , Lee Samuel , Adler Christoph
Published: June 2023

Background: Out-of-hospital cardiac arrest (OHCA) has a high prevalence of obstructive coronary artery disease and total coronary occlusion. Consequently, these patients are frequently loaded with antiplatelets and anticoagulants before hospital arrival. However, OHCA patients have multiple non-cardiac causes and high susceptibility for bleeding. In brief, there is a gap in the evidence for loading in OHCA patients. Objective: The current analysis stratified the outcome of patients with OHCA according to pre-clinical loading. Material and Methods: In a retrospective analysis of an all-comer OHCA registry, patients were stratified by loading with aspirin (ASA) and unfractionated heparin (UFH). Bleeding rate, survival to hospital discharge and favorable neurological outcomes were measured. Results: Overall, 272 patients were included, of whom 142 were loaded. Acute coronary syndrome was diagnosed in 103 patients. One-third of STEMIs were not loaded. Conversely, 54% with OHCA from non-ischemic causes were pretreated. Loading was associated with increased survival to hospital discharge (56.3 vs. 40.3%, p = 0.008) and a more favorable neurological outcome (80.7 vs. 62.6% p = 0.003). Prevalence of bleeding was comparable (26.8 vs. 31.5%, p = 0.740). Conclusions: Pre-clinical loading did not increase bleeding rates and was associated with favorable survival. Overtreatment of OHCA with non-ischemic origin, but also undertreatment of STEMI-OHCA were documented. Loading without definite diagnosis of sustained ischemia is debatable in the absence of reliable randomized controlled data.
Smoking Intensity Increases Diaphragm Muscle Injury: A Clinicopathologic Study
Authors: Nucci Ricardo Aparecido Baptista , Busse Alexandre Leopold , de Souza Romeu Rodrigues , Maifrino Laura Beatriz Mesiano , Pasqualucci Carlos Augusto , Anaruma Carlos Alberto , Leite Renata Elaine Paraizo , Rodriguez Roberta Diehl , Suemoto Claudia Kimie , Jacob-Filho Wilson
Published: June 2023

Background: Studying the effects of smoking intensity is important to evaluate the risk of tobacco use on a range of illnesses, such as as sarcopenia among the elderly. Thus, this study aimed to analyze the effects of pack-years of cigarette smoking on the diaphragm muscle (DIAm) histopathology of postmortem samples. Methods: Subjects were divided into three groups: never-smoker (n = 46); less than 30 pack-years of smoking (n = 12); and more than 30 pack-years of smoking (n = 30). Diaphragm samples were stained with Picrosirius red and hematoxylin and eosin stain for general structure. Results: Participants with more than 30 pack-years of cigarette smoking had a significant increase in adipocytes, blood vessels and collagen deposit, as well as an increase in histopathological alterations. Conclusions: Pack-years of smoking was associated with DIAm injury. However, further clinicopathological studies are needed to confirm our findings.