bluuebunny/crossref_metadata_2025 huggingface dataset:
Selecting the superior late-leafing genotypes of Persian walnut (Juglans regia L.) using morphological and pomological evaluations
Authors: Soveili Somayeh , Khadivi Ali
Published: August 2023

Background

Late-spring frost is one of the major factors limiting and reducing yield of Persian walnut (Juglans regia L.) in temperate regions, including Iran. Therefore, in the present study, seedling-originated genotypes of walnut were investigated to identify late-leafing genotypes with high-quality kernels for direct cultivation in orchards or as parents in breeding programs. In the first step, the variation of the selected trees was investigated in terms of traits related to phenology, vegetation, and fruit. In the second step, late-leafing trees were identified and their traits related to kernel quality were investigated to identify superior genotypes.

Results

Strong variabilities were exhibited among the studied genotypes based on the traits recorded. The genotypes showed high variation based on dates of leafing, full male flowering date, and full female flowering date, including very early, early, moderate, and late. After recording the leafing date, 21 late-leaf genotypes were identified and evaluated to select the superiors among them in terms of kernel quantity and quality. Among them, the values of nut-related traits ranged as follows: nut length: 30.12–49.74 mm, nut width: 29.31–37.17 mm, nut weight: 8.77–16.47 g, and shell thickness: 1.15–2.25 mm. The values of kernel-related traits ranged as follows: kernel length: 22.35–35.73 mm, kernel width: 21.79–29.03 mm, kernel weight: 3.22–8.17 g, and kernel percentage: 35.08–53.95%.

Conclusions

According to the ideal values and situations of commercial characteristics of walnut, twelve promising late-leafing genotypes (No. 9, 13, 32, 33, 72, 77, 78, 82, 83, 86, 92, and 98) were identified and are recommended for cultivation in orchards.
Association between serum Klotho concentration and hypertension in postmenopausal women, a cross-sectional study from NHANES 2013–2016
Authors: Yu Jingli , Li Jinfeng , Li Mingxia , Wang Ling , Xu Xia , Li Miao
Published: August 2023

Background

The objective of this study was to examine the correlation between serum Klotho protein concentration and postmenopausal hypertension.

Methods

A cross-sectional study design was used, in which 1713 postmenopausal women who participated in the National Health and Nutrition Examination Survey (NHANES) 2013–2016 were included. Multivariate logistic regression models were applied to assess the association between serum Klotho concentration and postmenopausal hypertension.

Results

A weighted analysis was executed, revealing a noteworthy hypertension prevalence rate of 53.44% among the study participants. Participants with lower quartile of serum Klotho concentration had a higher prevalence of hypertension than those in higher quartiles (Q1:62.29% vs. Q2: 48.52% vs. Q3: 47.33% vs. Q4: 55.02%, p < 0.001). Furthermore, a multivariate logistic regression analysis confirmed that participants with higher quartiles of serum Klotho concentration had a significantly reduced risk of postmenopausal hypertension compared to those in the lowest quartile. Subgroup analysis displayed consistent findings in those following subgroups: aged ≥ 65 years, obesity, nonsmokers, individuals without diabetes and coronary heart disease, and those with higher levels of estradiol and estimated glomerular filtration rate. Based on the results, we concluded that there is a significant association between serum Klotho concentration and postmenopausal hypertension.

Conclusion

The findings of this study revealed a significant inverse association between serum Klotho concentration and hypertension among postmenopausal women. Serum Klotho concentration may serve as a valuable biomarker for risk stratification in postmenopausal women who are at risk of developing hypertension.
Indwelling catheter vs intermittent catheterization: is there a difference in UTI susceptibility?
Authors: Neumeier Vera , Stangl Fabian P. , Borer Joëlle , Anderson Collene E. , Birkhäuser Veronika , Chemych Oksana , Gross Oliver , Koschorke Miriam , Marschall Jonas , McCallin Shawna , Mehnert Ulrich , Sadri Helen , Stächele Lara , Kessler Thomas M. , Leitner Lorenz
Published: August 2023

Background

Patients with neurogenic lower urinary tract dysfunction (NLUTD) often rely on some type of catheterization for bladder emptying. Intermittent catheterization (IC) is considered the gold standard and is preferred over continuous catheterization, since it is considered to cause fewer urinary tract infections (UTIs) than indwelling catheterization. The main objective of our study was to describe UTI prevalence (at visit) and incidence (within the last 12 months) and urine culture characteristics between patients using an indwelling catheter versus (vs) those performing IC.

Methods

In this cross-sectional study, we prospectively evaluated from 02/2020 to 01/2021 patients with NLUTD undergoing urine cultures for prophylactic reasons or due to UTI symptoms. At visit, all patients underwent a standardized interview on current UTI symptoms as well as UTI history and antibiotic consumption within the past year. Patients using an indwelling catheter (n = 206) or IC (n = 299) were included in the analysis. The main outcome was between-group differences regarding UTI characteristics.

Results

Patients using an indwelling catheter were older (indwelling catheter vs IC: median 66 (Q1-Q3: 55—77) vs 55 (42—67) years of age) and showed a higher Charlson comorbidity index (indwelling catheter vs IC: median 4 (Q1-Q3: 2–6) vs 2 (1–4) (both p < 0·001).

A total of 40 patients from both groups were diagnosed with a UTI at visit (indwelling catheters vs IC: 8% (16/206) vs 8% (24/299); p = 0·782), and the number of UTIs within the past 12 months was not significantly different between groups. Overall, Escherichia coli (21%), Enterococcus faecalis (17%), and Klebsiella spp. (12%) were the most frequently detected bacteria.

Conclusions

In this cohort of patients with NLUTD, we did not find relevant differences in UTI frequency between groups. These results suggest that UTI-related concerns should not be given undue emphasis when counseling patients for catheter-related bladder emptying methods.
Out-of-pocket expenditure and its correlates for institutional deliveries in private and public healthcare sectors in India: findings from NFHS 5
Authors: Manna Sayantani , Singh Damini , Ghosal Shishirendu , Rehman Tanveer , Kanungo Srikanta , Pati Sanghamitra
Published: August 2023

Background

Increased coverage for institutional delivery (ID) is one of the essential factors for improved maternal and child health (MCH). Though, ID increased over time, out-of-pocket expenditure (OOPE) for the care-seeking families had been found to be growing, parallelly. Hence, we estimated OOPE in public and private health centres for ID, along with their sources and attributing factors and compared state and union territory-wise, so that financial risk protection can be improved for MCH related services.

Methods

We used women’s data from the National Family Health Survey, 2019–2021 (NFHS-5). Reproductive aged women (15–49 years) delivering one live child in last 5 years (n = 145,386) in any public or private institutions, were included. Descriptive statistics were presented as frequency and proportions. OOPE, was summarized as median and interquartile range (IQR). To estimate the extent for each covariate’s effect, linear regression model was conducted.

Results

Overall median OOPE for ID was Rs. 4066 (median OOPE: private hospitals: Rs.25600, public hospitals: Rs.2067). Health insurance was not sufficient to slash OOPE down at private facilities. Factors associated significantly to high OOPE were mothers’ education, elderly pregnancy, complicated delivery, birth order of the latest child etc.

Conclusion

A standard norm for ID should be implemented as a component of overseeing and controlling inequality. Aiding the needy is probably just one side of the solution, while the focus is required to be shifted towards reducing disparity among the health facilities, so that the beneficiaries do not need to spend on essential services or during emergencies.
Do locking plugs improve implant strength? Biomechanical comparison of polyaxial locking constructs with and without locking plugs in a fracture gap model
Authors: Viitanen Joni , Quinn Robert , Allen Matthew , Broeckx Bart J. G. , Bartkowiak Tomasz , Haimel Georg
Published: August 2023

Background

The objective of this study was to investigate the effects of locking plugs and the biomechanical properties of a 3.5 mm 8-hole polyaxial locking plate in a fracture gap model. Our hypothesis was that locking plugs would increase the strength and stiffness of the construct. Twelve 3.5 mm 8-hole plates were used to evaluate two different construct designs (with locking plugs vs. without locking plugs) with validated bone substitutes in a 25 mm bridging osteosynthesis gap model. Each construct was subjected to a single cycle four-point bending load to failure using a servo-hydraulic testing machine. Bending stiffness, bending strength, and bending structural stiffness were calculated and compared using an unpaired Student´s t-test.

Results

The plating construct with locking plugs did not show any significant increase in terms of bending stiffness, bending strength, and bending structural stiffness compared to plating construct without locking plugs in a 25 mm gap fracture model during a single cycle four-point bending.

Conclusions

Under the conditions tested, filling empty plate holes with locking plugs in bridging osteosynthesis does not increase stiffness or strength of the plate-bone construct.
Successful implementation of ITN distribution through health facilities in Ghana
Authors: Nuñez Luigi , Skjefte Malia , Asamoah Obed E. , Owusu Prince , Malm Keziah , Miller Jane E.
Published: August 2023

Background

Global efforts to reduce malaria burden include distribution of insecticide-treated mosquito nets through mass campaigns and routine channels. Ghana’s National Malaria Elimination Programme (NMEP) distributes insecticide-treated bed nets (ITNs) through various channels, including to pregnant women at antenatal care (ANC) visits and children at vaccination visits through child welfare clinics (CWC). This study assessed historical ITN distribution throughout ANCs and CWCs across Ghana and the characteristics of high performing facilities.

Methods

Monthly data on routine ITN distribution was provided from Ghana’s national health information management system for the years 2016–2021. Analyses were conducted to assess the performance of ITN distribution at ANC and CWC across time, ecological zone, regions, districts, facility ownership, and facility type. Univariate and multivariate logistic regressions were performed to predict the odds of ANC and CWC issuing rates greater or equal to 80% for a given facility type or ownership.

Results

In 2021, 93% of women who attended their first antenatal care visit and 92% of children under five who received their second dose of the measles-rubella vaccine (MR2) had received an ITN. At the regional level, 94% of regions (n = 15/16) maintained the NSP target issuing rate of 80% throughout 2020 and 2021. While there were no clear differences in issuing rates between ecological zones, district-level differences were present across the six years. All health facility types performed at or above 80% in 2021 for both ANC and CWC. Odds ratios demonstrated differences in the likelihood of meeting the 80% issuing rate goal among different facility types as well as private versus public ownership when comparing ANC and CWC.

Conclusion

By 2021, Ghana had improved its ITN issuing rates since the initial year of analysis, surpassing the 80% target by issuing nets to over 90% of pregnant women and young children attending ANC and CWC. Future work can explore the reasons for national and subnational differences in issuing rates as well as help understand additional characteristics of high performing facilities. Additionally, it is necessary to identify and expand on the drivers for improved performance over the time period.
A case of bacteremia and pneumonia caused by Streptococcus equi subspecies equi infection in a 70-year-old female following horse exposure in rural Wyoming
Authors: Bohlman Tristan , Waddell Heith , Schumaker Brant
Published: August 2023

Background

The occurrence of zoonotic infections following an animal exposure continues to be an important consideration for all patients, especially those within agricultural communities. Streptococcus equi subspecies equi (S. equi subsp. equi) is a bacteria known to cause a common infection called ‘Strangles’ in horses. This article highlights a new case of pneumonia and bacteremia in a patient caused by S. equi subsp. equi following strangles exposure in a horse. Rarely has there been reported horse to human transmission of subsp. equi.

Case Presentation

A 70-year-old woman attended a rural emergency department with complaints of dry heaving, fever, chills, shakes, and nausea and presented with a cough. She had undergone a screening colonoscopy two days prior with no other significant medical history. The patient had computed tomography (CT) evidence of a pneumonia and positive blood cultures growing S. equi subsp. equi consistent with bacteremia. The patient later disclosed the recent passing of her horse following its sudden illness six days prior to her emergency department presentation. She had cuddled and kissed the horse prior to its death. The patient was treated with IV lactated ringers during the initial evaluation and admission and also received IV piperacillin-tazobactam 4.5 g every eight hours intravenously during her hospital stay. She was transitioned to an oral antibiotic on discharge. Subsequent blood cultures drawn the day after discharge were negative for S. equi subsp. equi, indicating successful treatment of her bacteremia.

Conclusions

This report discusses an atypical presentation of S. equi subsp. equi infection in an otherwise healthy individual, manifesting as early sepsis, pneumonia, and bacteremia. The patient likely developed this infection following direct contact exposure to her horse who had died from presumed strangles a few days prior to her symptom onset. This case highlights the importance of investigating potential exposures to S. equi subsp. equi in rural areas, areas where farming and ranching are prevalent, particularly among individuals working with horses. It is especially important to acknowledge high risk populations such as immunocompromised individuals with signs and symptoms of meningitis or bacteremia.
Multifunctional nanocarriers for targeted drug delivery and diagnostic applications of lymph nodes metastasis: a review of recent trends and future perspectives
Authors: Lan Huan-Rong , Zhang You-Ni , Han Yue-Jun , Yao Shi-Ya , Yang Meng-Xiang , Xu Xiao-Gang , Mou Xiao-Zhou , Jin Ke-Tao
Published: August 2023

Lymph node metastasis is a frequent occurrence in a variety of tumour forms and poses an enormous challenge to cancer treatment. This process is critical to the development of the disease and is frequently linked to a poor prognosis. Over 90% of cancerous cells move through lymph nodes, making them important entry routes for the spread of cancer cells. The prognosis of cancer patients is significantly impacted by lymph node metastases, which also affects treatment choices. Targeting lymph node metastases presents numerous difficulties for conventional medication delivery techniques. It is still very difficult to selectively target cancer cells in lymph nodes without risking injury to healthy organs and unforeseen consequences. Additionally, systemic delivery of drugs is hampered by the slow flow rate of lymphatic vessels. Chemotherapeutic medicines’ poor solubility and stability further reduce their effectiveness when taken orally. Additionally, the extracellular matrix that surrounds lymph node tumours is extensive, which makes it difficult for conventional pharmaceutical delivery systems to reach cancer cells. The development of nanocarriers for precise drug delivery to LNs has attracted a lot of interest to overcome these obstacles. Most solid tumours first spread through the lymphatic system, hence effective drug administration to these tissues is essential for better therapeutic results. Nanocarriers have several benefits, including the capacity to pass through barriers like blood-brain barriers and membranes to reach the lymphatic system. High medication dosages can be enclosed thanks to the physicochemical characteristics of nanocarriers, such as their higher surface-to-volume ratio. Additionally, ligands, antibodies, polymers, or biological molecules can be attached to nanocarrier surfaces to change their properties, allowing for the targeted delivery of lymph node epithelial cells. This use of nanocarriers for drug delivery maximizes on-target effects and related adverse effects while improving the effectiveness of medication delivery to target locations. More research and development in this field is needed to optimize nanocarrier design, increase targeting capabilities, and expand clinical applications for better cancer care.
Integrative medicine utilization among infertility patients
Authors: Sehgal Shruti , Dyer Ashley , Warren Christopher , Galic Isabel , Jain Tarun
Published: August 2023

Background

Previous research suggests that some women are using integrative and complementary holistic approaches to optimize their own health and treat infertility. We aimed to determine patterns of integrative medicine use among those seeking fertility optimization by 1) Characterizing patterns of integrative medicine use to increase fertility; 2) Identifying demographic predictors associated with such integrative medicine use; and 3) Exploring cultural and religious influences on use of integrative medicine.

Methods

Cross-sectional self-reported survey data were collected from 1460 patients presenting to an academic fertility center in Chicago, Illinois. Variables were described with univariate frequencies and proportions, unadjusted bivariate comparisons were made between patient-level factors and reported integrative modality use, and multivariable logistic regression evaluated the strength of covariate-adjusted predictors of reported integrative medicine utilization.

Results

80.4% of respondents reported using at least one integrative medicine modality to treat infertility (Acupuncture: 38.5%, Yoga: 27.6%, Massage: 25.8%, Meditation: 16.7%, and Herbal supplements: 18.5%). Diet therapy was the most frequently utilized modality (74.0%) followed by body therapy (45.2%), traditional alternative medicine (42.0%), mind therapy (32.1%), and senses therapy (23.0%). Any integrative medicine modality use was 4.03 times more likely among Hindu respondents compared to participants that identified as not religious (95% CI 1.2–13.7, p < 0.026). Significant differences in specific modality use were observed by race, religious affiliation, age, income, and insurance coverage.

Conclusion

Most infertility patients in our study reported using at least one integrative medicine modality to help them conceive. Utilization was associated with age of participant, religious affiliation, annual income, and insurance coverage. Further research is needed to assess the impact of integrative medicine utilization on patient quality of life and outcomes.
Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease
Authors: Yan Qian , Liu Shasha , Sun Yang , Chen Chen , Yang Songwei , Lin Meiyu , Long Junpeng , Yao Jiao , Lin Yuting , Yi Fan , Meng Lei , Tan Yong , Ai Qidi , Chen Naihong , Yang Yantao
Published: August 2023

Cardiovascular diseases (CVDs) continue to exert a significant impact on global mortality rates, encompassing conditions like pulmonary arterial hypertension (PAH), atherosclerosis (AS), and myocardial infarction (MI). Oxidative stress (OS) plays a crucial role in the pathogenesis and advancement of CVDs, highlighting its significance as a contributing factor. Maintaining an equilibrium between reactive oxygen species (ROS) and antioxidant systems not only aids in mitigating oxidative stress but also confers protective benefits on cardiac health. Herbal monomers can inhibit OS in CVDs by activating multiple signaling pathways, such as increasing the activity of endogenous antioxidant systems and decreasing the level of ROS expression. Given the actions of herbal monomers to significantly protect the normal function of the heart and reduce the damage caused by OS to the organism. Hence, it is imperative to recognize the significance of herbal monomers as prospective therapeutic interventions for mitigating oxidative damage in CVDs. This paper aims to comprehensively review the origins and mechanisms underlying OS, elucidate the intricate association between CVDs and OS, and explore the therapeutic potential of antioxidant treatment utilizing herbal monomers. Furthermore, particular emphasis will be placed on examining the cardioprotective effects of herbal monomers by evaluating their impact on cardiac signaling pathways subsequent to treatment.

Graphical Abstract
Transcriptome alterations in peripheral blood B cells of patients with multiple sclerosis receiving immune reconstitution therapy
Authors: Hecker Michael , Fitzner Brit , Boxberger Nina , Putscher Elena , Engelmann Robby , Bergmann Wendy , Müller Michael , Ludwig-Portugall Isis , Schwartz Margit , Meister Stefanie , Dudesek Ales , Winkelmann Alexander , Koczan Dirk , Zettl Uwe Klaus
Published: August 2023

Background

Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease that leads to irreversible damage to the brain and spinal cord. The goal of so-called "immune reconstitution therapies" (IRTs) is to achieve long-term disease remission by eliminating a pathogenic immune repertoire through intense short-term immune cell depletion. B cells are major targets for effective immunotherapy in MS.

Objectives

The aim of this study was to analyze the gene expression pattern of B cells before and during IRT (i.e., before B-cell depletion and after B-cell repopulation) to better understand the therapeutic effects and to identify biomarker candidates of the clinical response to therapy.

Methods

B cells were obtained from blood samples of patients with relapsing–remitting MS (n = 50), patients with primary progressive MS (n = 13) as well as healthy controls (n = 28). The patients with relapsing MS received either monthly infusions of natalizumab (n = 29) or a pulsed IRT with alemtuzumab (n = 15) or cladribine (n = 6). B-cell subpopulation frequencies were determined by flow cytometry, and transcriptome profiling was performed using Clariom D arrays. Differentially expressed genes (DEGs) between the patient groups and controls were examined with regard to their functions and interactions. We also tested for differences in gene expression between patients with and without relapse following alemtuzumab administration.

Results

Patients treated with alemtuzumab or cladribine showed on average a > 20% lower proportion of memory B cells as compared to before IRT. This was paralleled by profound transcriptome shifts, with > 6000 significant DEGs after adjustment for multiple comparisons. The top DEGs were found to regulate apoptosis, cell adhesion and RNA processing, and the most highly connected nodes in the network of encoded proteins were ESR2, PHB and RC3H1. Higher mRNA levels ofBCL2,IL13RA1andSLC38A11were seen in patients with relapse despite IRT, though these differences did not pass the false discovery rate correction.

Conclusions

We show that B cells circulating in the blood of patients with MS undergoing IRT present a distinct gene expression signature, and we delineated the associated biological processes and gene interactions. Moreover, we identified genes whose expression may be an indicator of relapse risk, but further studies are needed to verify their potential value as biomarkers.
Topographic distribution of inflammation factors in a healing aneurysm
Authors: Grüter Basil E. , Canzanella Gwendoline , Hägler Joshua , Rey Jeannine , Wanderer Stefan , von Gunten Michael , Galvan José A. , Grobholz Rainer , Widmer Hans-Rudolf , Remonda Luca , Andereggen Lukas , Marbacher Serge
Published: August 2023

Background

Healing of intracranial aneurysms following endovascular treatment relies on the organization of early thrombus into mature scar tissue and neointima formation. Activation and deactivation of the inflammation cascade plays an important role in this process. In addition to timely evolution, its topographic distribution is hypothesized to be crucial for successful aneurysm healing.

Methods

Decellularized saccular sidewall aneurysms were created in Lewis rats and coiled. At follow-up (after 3 days (n = 16); 7 days (n = 19); 21 days (n = 8)), aneurysms were harvested and assessed for healing status. In situ hybridization was performed for soluble inflammatory markers (IL6, MMP2, MMP9, TNF-α, FGF23, VEGF), and immunohistochemical analysis to visualize inflammatory cells (CD45, CD3, CD20, CD31, CD163, HLA-DR). These markers were specifically documented for five regions of interest: aneurysm neck, dome, neointima, thrombus, and adjacent vessel wall.

Results

Coiled aneurysms showed enhanced patterns of thrombus organization and neointima formation, whereas those without treatment demonstrated heterogeneous patterns of thrombosis, thrombus recanalization, and aneurysm growth (p = 0.02). In coiled aneurysms, inflammation markers tended to accumulate inside the thrombus and in the neointima (p < 0.001). Endothelial cells accumulated directly in the neointima (p < 0.0001), and their presence was associated with complete aneurysm healing.

Conclusion

The presence of proinflammatory cells plays a crucial role in aneurysm remodeling after coiling. Whereas thrombus organization is hallmarked by a pronounced intra-thrombotic inflammatory reaction, neointima maturation is characterized by direct invasion of endothelial cells. Knowledge concerning topographic distribution of regenerative inflammatory processes may pave the way for future treatment modalities which enhance aneurysm healing after endovascular therapy.
Epidemiological characterization of viral etiological agents of the central nervous system infections among hospitalized patients in Egypt between 2016 and 2019
Authors: Roshdy Wael H. , Kandeil Ahmed , Fahim Manal , Naguib Nourhan Y. , Mohsen Gehad , Shawky Shaymaa , Abd El-Fattah Marwa M. , Naguib Amel , Salamony Azza , Shamikh Yara I. , Moawad Mahmoud , Guindy Nancy El , Khalifa Mohamed K. , Abbas Eman , Galal Ramy , Hassany Mohamed , Ibrahem Mohamed , El-Shesheny Rabeh , Asem Noha , Kandeel Amr
Published: August 2023

Viral infections of the central nervous system (CNS) are common worldwide and result in considerable morbidity and mortality associated with neurologic illness. Until now, there have been no epidemiologic data regarding viruses causing aseptic meningitis, encephalitis, and CNS infections in Egypt. We investigated 1735 archived cerebrospinal fluid samples collected from Egyptian patients between 2016 and 2019 and performed molecular characterization for infection for12 different viruses: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), human herpesviruses 6 and 7 (HHV-6 and HHV-7), human enteroviruses (HEVs), human parechovirus (HPeV), parvovirus B19 (B19V), adenovirus (AdV), and mumps virus (MuV). All included samples were negative for bacterial infection. Our results indicated a relatively high prevalence of viral infection, with HEVs being the most prevalent viruses, followed by HSV-1, EBV, and then HSV-2. The highest prevalence was among male patients, peaking during the summer. Data obtained from this study will contribute to improving the clinical management of viral infections of the CNS in Egypt.
Neutrophils in COVID-19: recent insights and advances
Authors: Li Jiayu , Zhang Kegong , Zhang ye , Gu Ziyang , Huang Changxing
Published: August 2023

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can lead to acute respiratory distress syndrome (ARDS), multi-organ failure and death, posing significant threat to human health. Studies have found that pathological mechanisms, such as cytokine storms caused by uncontrolled innate immune system activation, release of damage-associated molecular patterns during tissue injury and a high incidence of thrombotic events, are associated with the function and dysfunction of neutrophils. Specifically, the increased formation of low-density neutrophils (LDNs) and neutrophil extracellular traps (NETs) has been shown to be closely linked with the severity and poor prognosis in patients with COVID-19. Our work focuses on understanding the increased number, abnormal activation, lung tissue infiltration, and elevated neutrophil-to-lymphocyte ratio in the pathogenesis of COVID-19. We also explore the involvement of NETs and LDNs in disease progression and thrombosis formation, along with potential therapeutic strategies targeting neutrophil and NETs formation.
Effect of a 3-month L-carnitine supplementation and resistance training program on circulating markers and bone mineral density in postmenopausal women: a randomized controlled trial
Authors: Olek Robert A. , Samborowska Emilia , Wisniewski Piotr , Wojtkiewicz Pawel , Wochna Krystian , Zielinski Jacek
Published: August 2023

Background

Higher circulating levels of trimethylamine N-oxide (TMAO), which is a metabolite that can be produced by the gut microbiota from L-carnitine (LC), have been associated with bone mineral density (BMD). Because LC supplementation can improve bone density and microstructural properties in animal models, this study aimed to examine the effects of 12 weeks of LC supplementation on BMD and selected blood markers involved in bone metabolism of postmenopausal women participating in a resistance training (RT) program.

Methods

Twenty-seven postmenopausal women, who had not been treated for osteoporosis, with a total T-score above − 3.0 and no diet differences completed 12 weeks of RT. The participants’ diets were supplemented with either 1 g of LC-L-tartrate and 3 g of leucine per day (LC group) or 4 g of leucine per day as a placebo (PLA group), in a double-blind fashion.

Results

After the intervention in the LC group, plasma total carnitine and serum decorin levels were higher than the corresponding preintervention values (p = 0.040 and p = 0.042, respectively). Moreover, plasma TMAO and serum SPARC levels were higher in the LC group than the corresponding postintervention values in the PLA group (p < 0.001 and p = 0.030, respectively). No changes in the BMD were observed after 3 months of the intervention.

Conclusions

Twelve weeks of LC supplementation during RT program increased plasma TMAO levels and appeared to affect signaling molecules, as indicated by the increase in the resting SPARC and decorin levels, with no significant modification in the BMD.

Trial registration

Retrospectively registered at the ClinicalTrials.gov (NCT05120011).
Influence of head-over-body and body-over-head posture on craniospinal, vascular, and abdominal pressures in an acute ovine in-vivo model
Authors: Podgoršak Anthony , Trimmel Nina Eva , Flürenbrock Fabian , Oertel Markus Florian , Arras Margarete , Weisskopf Miriam , Schmid Daners Marianne
Published: August 2023

Introduction

Optimal shunt-based hydrocephalus treatments are heavily influenced by dynamic pressure behaviors between proximal and distal ends of shunt catheters. Posture-dependent craniospinal, arterial, venous, and abdominal dynamics thereby play an essential role.

Methods

An in-vivo ovine trial (n = 6) was conducted to evaluate communication between craniospinal, arterial, venous, and abdominal dynamics. Tilt-testing was performed between –13° and + 13° at 10-min intervals starting and ending at 0° prone position. Mean pressure, pulse pressure, and Pearson correlation (r) to the respective angle were calculated. Correlations are defined as strong: |r|≥ 0.7, mild: 0.3 <|r|< 0.7, and weak: |r|≤ 0.3. Transfer functions (TFs) between the arterial and adjacent compartments were derived.

Results

Strong correlations were observed between posture and: mean carotid/femoral arterial (r = − 0.97, r = − 0.87), intracranial, intrathecal (r = − 0.98, r = 0.94), jugular (r = − 0.95), abdominal cranial, dorsal, caudal, and intravesical pressure (r = − 0.83, r = 0.84, r = − 0.73, r = 0.99) while mildly positive correlation exists between tilt and central venous pressure (r = 0.65). Only dorsal abdominal pulse pressure yielded a significant correlation to tilt (r = 0.21). TFs followed general lowpass behaviors with resonant peaks at 4.2 ± 0.4 and 11.5 ± 1.5 Hz followed by a mean roll-off of − 15.9 ± 6.0 dB/decade.

Conclusions

Tilt-tests with multi-compartmental recordings help elucidate craniospinal, arterial, venous, and abdominal dynamics, which is essential to optimize shunt-based therapy. Results motivate hydrostatic influences on mean pressure, with all pressures correlating to posture, with little influence on pulse pressure. TF results quantify the craniospinal, arterial, venous, and abdominal compartments as compliant systems and help pave the road for better quantitative models of the interaction between the craniospinal and adjacent spaces.
Factors influencing successful bone union of isolated subtalar arthrodesis for posttraumatic subtalar arthritis: a multicenter case series
Authors: Kim Hyong Nyun , Choi Young Rak , Kim Bom Soo , Kim Yu Mi , Lee Jaehyung , Cho Jae Ho , Cha Sunho , Park Jae Yong
Published: August 2023

Background

The purpose of this study was to find the factors influencing successful bone union for isolated subtalar arthrodesis in posttraumatic subtalar arthritis following calcaneal fracture.

Material and methods

We retrospectively analyzed the rate of successful bone union of 119 cases of isolated subtalar arthrodesis for posttraumatic subtalar arthritis performed at five university hospitals between January 2010 and December 2019. Multivariate logistic regression analysis was used to find the factors associated with successful bone union. Successful bone union was defined as resolution of hindfoot pain with the presence of osseous trabecular bridging involving more than 50% of the posterior facet within 6 months postoperatively.

Results

There were 77 (64.7%) cases of successful bone union, 11 (9.2%) cases of delayed union, 8 (6.7%) cases of questionable union, and 23 (19.3%) cases of nonunion. Use of fully threaded screws was 5.90 times [odds ratio (OR) = 5.90, 95% confidence interval (CI) = 1.42–24.49,p = 0.02] more likely to achieve successful bone union compared to the use of partially threaded screws. Use of two parallel screws or the two divergent screws were 3.71 times (OR = 3.71, 95% CI = 1.05–13.14,p = 0.04) and 4.65 times (OR = 4.65, 95% CI = 1.23–17.53,p = 0.02) more likely to achieve successful bone union compared to the use of a single screw. Use of cancellous autograft or structural autograft was 4.72 times (OR = 4.72, 95% CI = 1.17–19.06,p = 0.03) and 7.12 times (OR = 7.12, 95% CI = 1.46–34.68,p = 0.02) more likely to achieve successful bone union compared to no graft use.

Conclusion

Use of fully threaded screws, autograft, and two screws compared to a single screw were the factors associated with successful bone union within six postoperative months after subtalar arthrodesis for the posttraumatic arthritis.
Comparative transcriptome findings reveal the neuroinflammatory network and potential biomarkers to early detection of ischemic stroke
Authors: Luo Jiefeng , Chen Dingzhi , Mei Yujia , Li Hepeng , Qin Biyun , Lin Xiao , Chan Ting Fung , Lai Keng Po , Kong Deyan
Published: August 2023

Introduction

Ischemic stroke accounts for 70–80% of all stroke cases, leading to over two million people dying every year. Poor diagnosis and late detection are the major causes of the high death and disability rate.

Methods

In the present study, we used the middle cerebral artery occlusion (MCAO) rat model and applied comparative transcriptomic analysis, followed by a systematic advanced bioinformatic analysis, including gene ontology enrichment analysis and Ingenuity Pathway Analysis (IPA). We aimed to identify novel biomarkers for the early detection of ischemic stroke. In addition, we aimed to delineate the molecular mechanisms underlying the development of ischemic stroke, in which we hoped to identify novel therapeutic targets for treating ischemic stroke.

Results

In the comparative transcriptomic analysis, we identified 2657 differentially expressed genes (DEGs) in the brain tissue of the MCAO model. The gene enrichment analysis highlighted the importance of these DEGs in oxygen regulation, neural functions, and inflammatory and immune responses. We identified the elevation of angiopoietin-2 and leptin receptor as potential novel biomarkers for early detection of ischemic stroke. Furthermore, the result of IPA suggested targeting the inflammasome pathway, integrin-linked kinase signaling pathway, and Th1 signaling pathway for treating ischemic stroke.

Conclusion

The results of the present study provide novel insight into the biomarkers and therapeutic targets as potential treatments of ischemic stroke.
Novel mutations in CYBB Gene Cause X-linked chronic Granulomatous Disease in Pakistani patients
Authors: Gul Irum , Khan Taj Ali , Akbar Noor ul , Gul Naila , Ali Rehman , Khan Shahid Niaz
Published: August 2023

Background

Chronic Granulomatous Disease (CGD) is a primary immunodeficiency that causes susceptibility to recurrent fungal and bacterial infections. The CYBB gene encodes gp91phox component of the Phagocytic Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and specifically, X-linked CGD is caused by mutations in the CYBB gene, located on the X chromosome. The aim of the study was to characterize functional and genetic mutations in X-linked CGD.

Methods

Functional analysis was conducted on the whole blood of seventeen male individuals who were suspected to have X-linked chronic granulomatous disease (CGD). Flow cytometry was employed to assess the capacity of NADPH oxidase, measuring both H2O2 production and gp91phox protein expression in neutrophils. Additionally, DNA Sanger sequencing was performed for genetic analysis. The pathogenicity of novel mutations was assessed by pathogenicity prediction tools.

Result

Among the seventeen patients evaluated, five patients (P1, P2, P3, P4, and P5) displayed impaired H2O2 production by their neutrophils upon stimulation with Phorbol myristate acetate (PMA), accompanied by abnormal gp91phox expression. DNA sequencing of the CYBB gene identified specific mutations in each patient. In P1 and P2 (previously reported cases), a hemizygous missense mutation, c.925G > A/p.E309K was identified. In P3 and P4 (novel cases), hemizygous nonsense mutations, c.216T > A/p.C72X were found. Lastly, in P5 (also a novel case), a hemizygous missense mutation, c.732T > G/p.C244W was detected. These mutations reside in exons 9,3 and 7 of the CYBB gene, respectively.

Conclusions

The current study contributes to the understanding of the clinical and genetic spectrum associated with X-linked chronic granulomatous disease (CGD). It highlights the significance of early diagnosis in CGD and emphasizes the importance of lifelong prophylaxis to prevent severe infections.
RNAi-mediated CHS-2 silencing affects the synthesis of chitin and the formation of the peritrophic membrane in the midgut of Aedes albopictus larvae
Authors: Zhang Chen , Ding Yanjuan , Zhou Min , Tang Ya , Chen Rufei , Chen Yanrong , Wen Yating , Wang Shigui
Published: August 2023

Background

Mosquitoes are an important vector of viral transmission, and due to the complexity of the pathogens they transmit, vector control may be the most effective strategy to control mosquito-borne diseases. Chitin is required for insect growth and development and is absent in higher animals and plants, so regulating the chitin synthesis pathway can serve as a potentially effective means to control vector insects. Most of the current research on the chitin synthase (CHS) gene is focused on chitin synthase-1 (CHS-1), while relatively little is known about chitin synthase-2 (CHS-2).

Results

The CHS-2 gene of Ae. albopictus is highly conserved and closely related to that of Aedes aegypti. The expression of CHS-2 in the third-instar larvae and pupal stage of Ae. albopictus was relatively high, and CHS-2 expression in adult mosquitoes reached the highest value 24 h after blood-feeding. In the fourth-instar larvae of Ae. albopictus, CHS-2 expression was significantly higher in the midgut than in the epidermis. Silencing CHS-2 in Ae. albopictus larvae had no effect on larval survival and emergence. The expression of four genes related to chitin synthesis enzymes was significantly upregulated, the expression level of three genes was unchanged, and only the expression level of GFAT was significantly downregulated. The expression of chitin metabolism-related genes was also upregulated after silencing. The level of chitin in the midgut of Ae. albopictus larvae was significantly decreased, while the chitinase activity was unchanged. The epithelium of the midgut showed vacuolization, cell invagination and partial cell rupture, and the structure of the peritrophic membrane was destroyed or even absent.

Methods

The expression of CHS-2 in different developmental stages and tissues of Aedes albopictus was detected by real-time fluorescence quantitative PCR (qPCR). After silencing CHS-2 of the fourth-instar larvae of Ae. albopictus by RNA interference (RNAi), the expression levels of genes related to chitin metabolism, chitin content and chitinase
activity in the larvae were detected. The structure of peritrophic membrane in the midgut of the fourth-instar larvae
after silencing was observed by paraffin section and hematoxylin–eosin (HE) staining.

Conclusion

CHS-2 can affect midgut chitin synthesis and breakdown by regulating chitin metabolic pathway-related genes and is involved in the formation of the midgut peritrophic membrane in Ae. albopictus, playing an important role in growth and development. It may be a potential target for enhancing other control methods.

Graphical Abstract
High level of serum complement 3 is a risk factor for vascular stenosis progression in TA patients receiving tocilizumab: a prospective observational study
Authors: Rongyi Chen , Xiaojuan Dai , Jinghua Wang , Lingying Ma , Xiaomin Dai , Lili Ma , Huiyong Chen , Lindi Jiang , Ying Sun
Published: August 2023

Background

The IL-6R antibody tocilizumab has been proven effective in treating Takayasu arteritis (TA). However, some patients show silent vascular stenosis progression (VSP) despite treatment with tocilizumab. The aim of the study was to explore the related risk factors of VSP in patients treated with tocilizumab.

Methods

Patients receiving tocilizumab were enrolled from the prospective living ongoing East China Takayasu Arteritis cohort. Their medical information was uniformly recorded with a homogenized evaluation method. Magnetic resonant angiography or computed tomographic angiography was employed to monitor VSP during the follow-up period, and Cox regression analysis was performed to explore the related risk factors.

Results

Thirty-eight patients were enrolled, among whom 18 (47.4%) experienced VSP, and seven and three patients experienced new and worsened vascular ischemic symptoms and events (VISE) during follow-up, respectively. The median period for VSP occurrence was 6.9 months during follow-up. Patients with VSP showed higher levels of baseline complement 3 (C3) than those in the patients without VSP. Multivariate Cox regression analysis revealed baseline C3 level (hazard ratio [HR] = 7.05, 95% confidence interval: 1.50–33.07, p = 0.013) was independently associated with VSP, with a cut-off value of 1.22 g/L.

Conclusions

47.4% of TA patients treated with tocilizumab would suffer VSP. A high C3 level is a risk factor for VSP in TA patients receiving tocilizumab, which may facilitate the option of tocilizumab in the future.
Impact of COVID-19 on hospital visits for non-traumatic dental conditions in Ontario, Canada
Authors: Singhal Sonica , Dhar Badal , Ayoub Nardin , Quiñonez Carlos
Published: August 2023

Background and rationale

As general health care is publicly funded in Canada and oral health care is not, many people seek care from hospitals for their dental problems. This study assessed if the unprecedented times of Coronavirus disease (COVID-19) affected the hospital visits for dental emergencies, making disadvantaged populations further vulnerable for attendance of their dental problems.

Methods

Data from IntelliHealth Ontario for emergency department (ED) visits, day surgery visits, and hospitalizations associated with non-traumatic dental conditions (NTDCs) were retrieved for years 2016 to 2020 to assess trends before COVID-19 and changes, if any, for the year 2020. Trends by month, for the years 2019 and 2020, to make straight comparisons and understand the effects of lockdown in Ontario, was also analyzed.

Results

In the year 2020, there was a reduction of 40% in day surgeries, 21% in ED visits and 8% in hospitalizations compared to 2019. Stratified by month, largest reductions were observed in April 2020: 96% in day surgeries; 50% in ED visits; and 38% reductions in hospitalizations when compared to the same month of 2019. In May 2020, day surgeries and ED visits though remained reduced, hospitalization rates increased by 31%.

Conclusion

Hospital EDs are inefficient avenues for handling dental emergencies. Nevertheless, they do remain a care setting that is sought by many for dental problems, and if the need for hospitalization and day surgery is there, this care setting is an important avenue for dentally related medical care. Perhaps unsurprisingly, COVID-19 has lessened the opportunity and capacity for such care.

Practical implications

Administrators and policy makers can utilize this information to strategize on augmenting community infrastructure for building more effective, and cost-efficient avenues of care for timely management of dental problems.
Therapeutic application of regeneration-associated cells: a novel source of regenerative medicine
Authors: Salybekov Amankeldi A. , Hassanpour Mehdi , Kobayashi Shuzo , Asahara Takayuki
Published: August 2023

Chronic diseases with comorbidities or associated risk factors may impair the function of regenerative cells and the regenerative microenvironment. Following this consideration, the vasculogenic conditioning culture (VCC) method was developed to boost the regenerative microenvironment to achieve regeneration-associated cells (RACs), which contain vasculogenic endothelial progenitor cells (EPCs) and anti-inflammatory/anti-immunity cells. Preclinical and clinical studies demonstrate that RAC transplantation is a safe and convenient cell population for promoting ischemic tissue recovery based on its strong vasculogenicity and functionality. The outputs of the scientific reports reviewed in the present study shed light on the fact that RAC transplantation is efficient in curing various diseases. Here, we compactly highlight the universal features of RACs and the latest progress in their translation toward clinics.