bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of asymmetric zeta-potential on natural convection flow in a vertical microannulus with electroosmotic and Joule heating effects
Authors: Oni Michael O , Jha Basant K
Published: June 2022

Analytical solutions of temperature distributions and flow formation of joint buoyancy and electroosmotic flow in a vertical microtube formed by two concentric microcylinders are presented. The central equations describing flow formations and thermal energy are offered and solved in closed-form in terms of modified Bessel’s function of first and second kinds. These solutions have significant application in predicting and analyzing flow formation and thermal behavior of Newtonian fluids in micropumps and microchips. Based on the exact solutions obtained, the effects of flow parameters are clearly explained with the use of line graphs. Based on the simulation of results using MATLAB, it is found that fluid temperature distributions and fluid velocity in the vertical microannulus could be enhanced by increasing the radius ratio of the concentric microcylinders.
TMJ Arthroscopy: A Review Article & Recent Advances
Authors: Khan Shahla , Hashmi G. S.
Published: June 2022

The temporomandibular joint is the joint formed by the glenoid fossa of the temporal bone and the condylar process of the mandible. It is covered by dense fibrocartilage called the capsule. Each mandibular condyle has a wide motion range, consisting of both rotation and translation. Temporomandibular joint arthroscopy is a technique for direct visual inspection of internal joint structures, including biopsy and other surgical procedures performed under visual control with the help of an arthroscope. In this review article, the authors try to address the techniques of arthroscopy and its recent advances.
Quercetin ameliorates XIAP deficiency–associated hyperinflammation
Authors: Chiang Samuel C. C. , Owsley Erika , Panchal Neelam , Chaturvedi Vijaya , Terrell Catherine E. , Jordan Michael B. , Mehta Parinda A. , Davies Stella M. , Akeno Nagako , Booth Claire , Marsh Rebecca A.
Published: June 2022

XIAP (X-linked inhibitor of apoptosis) deficiency is a rare inborn error of immunity. XIAP deficiency causes hyperinflammatory disease manifestations due to dysregulated TNF (tumor necrosis factor)-receptor signaling and NLRP3 (NOD- [nucleotide-binding oligomerization domain], LRR- [leucine-rich repeat] and pyrin domain-containing protein 3) inflammasome function. Safe and effective long-term treatments are needed and are especially important to help prevent the need for high-risk allogeneic hematopoietic cell transplantation. Here we evaluated inflammasome inhibitors as potential therapeutics with a focus on the natural flavonoid antioxidant quercetin. Bone marrow (BM)-derived macrophages were derived from XIAP-deficient or wild-type (WT) mice. Human monocytes were obtained from control or XIAP-deficient patients. Cells were stimulated with TLR (Toll-like receptor) agonists or TNF-α ± inhibitors or quercetin. For in vivo lipopolysaccharide (LPS) challenge experiments, XIAP-deficient or WT mice were fed mouse chow ± supplemental quercetin (50 mg/kg per day exposure) for 7 days followed by a challenge with 10 ng/kg LPS. IL-1β (interleukin-1β) and IL-18 were measured by ELISA (enzyme-linked immunosorbent assay). In murine studies, quercetin prevented IL-1β secretion from XIAP knockout cells following TLR agonists or TNF-α stimulation (P < .05) and strongly reduced constitutive production of IL-18 by both WT and XIAP-deficient cells (P < .05). At 4 hours after in vivo LPS challenge, blood levels of IL-1β and IL-18 were significantly decreased in mice that had received quercetin-supplemented chow (P < .05). In experiments using human cells, quercetin greatly reduced IL-1β secretion by monocytes following TNF-α stimulation (P < .05). Our data suggest that quercetin may be an effective natural therapeutic for the prevention of XIAP deficiency-associated hyperinflammation. Clinical trials, including careful pharmacokinetic and pharmacodynamic studies to ensure that effective levels of quercetin can be obtained, are warranted.
Global, highly specific and fast filtering of alignment seeds
Authors: Ebel Matthis , Migliorelli Giovanna , Stanke Mario
Published: June 2022

Background

An important initial phase of arguably most homology search and alignment methods such as required for genome alignments is seed finding. The seed finding step is crucial to curb the runtime as potential alignments are restricted to and anchored at the sequence position pairs that constitute the seed. To identify seeds, it is good practice to use sets of spaced seed patterns, a method that locally compares two sequences and requires exact matches at certain positions only.

Results

We introduce a new method for filtering alignment seeds that we call geometric hashing. Geometric hashing achieves a high specificity by combining non-local information from different seeds using a simple hash function that only requires a constant and small amount of additional time per spaced seed. Geometric hashing was tested on the task of finding homologous positions in the coding regions of human and mouse genome sequences. Thereby, the number of false positives was decreased about million-fold over sets of spaced seeds while maintaining a very high sensitivity.

Conclusions

An additional geometric hashing filtering phase could improve the run-time, accuracy or both of programs for various homology-search-and-align tasks.
Investigation of fluconazole susceptibility to Candida albicans by MALDI-TOF MS and real-time PCR for CDR1, CDR2, MDR1 and ERG11
Authors: Maenchantrarath Chanika , Khumdee Pradchama , Samosornsuk Seksun , Mungkornkaew Narissara , Samosornsuk Worada
Published: June 2022

Background

C. albicans is a pathogenic yeast that is the most common cause of fungal infections in humans. Unfortunately, the yeast’s resistance to the antifungal medication fluconazole (FLC) is increasing; furthermore, testing its susceptibility to FLC by conventional methods takes time, resulting in treatment failure. The susceptibility of C. albicans to FLC was investigated using MALDI-TOF Mass Spectrometry and Real-time PCR tests for CDR1, CDR2, MDR1 and ERG11. Overall, 32 C. albicans strains made up of four reference strains (three FLC susceptible [S] and one FLC resistant [R], one spontaneous mutant strain [FLC susceptible-dose-dependent (SDD)] and 27 clinical strains obtained from two Thai University Hospitals) were tested for susceptibility to FLC. The following tests were performed: SensititreYeastOne and broth microdilution method, FLC resistant expression mechanism by Real-time PCR, and the major peak determination by MALDI-TOF MS.

Results

The change of CDR1 and CDR2 mRNA expression was only significantly observed in SDD and R strains. MALDI-TOF MS was performed after incubation for six hours; the change of mass spectral intensity at range 3376–3382 m/z (major peak) was significantly related to FLC susceptibility as SDD (decreased at 4 µg/mL and increased at 8 µg/mL), S (all increased), and R (all slightly decreased or no change). All 27 clinical strains showed FLC minimum inhibitory concentrations (MIC range 0.25-2 µg/mL), no change in CDR1 and CDR2 expression and S major peak type. The FLC resistant C. albicans with CDR1and CDR2 expression may possibly affect the change of mass spectral intensity at range 3376–3382 m/z.

Conclusions

The MALDI-TOF MS may be used to simultaneously classify and predict FLC resistant C. albicans strains associated with CDR1 and CDR2 expression. Further studies are essential to clarify the methodology and improve the reliability of this assay for routine diagnosis.
Fun and a meaningful routine: the experience of physical activity in people with dementia
Authors: Telenius Elisabeth Wiken , Tangen Gro Gujord , Eriksen Siren , Rokstad Anne Marie Mork
Published: June 2022

Background

Physical activity is important to health and wellbeing. People with dementia are less physically active than their cognitively healthy counterparts. Reasons for this are multifaceted, and are thought to be social, psychological, and physiological. People with dementia often use services such as home care, day care centres and nursing home, and according to the stage of disease they are less or more dependent on other people to take part in activities. To develop appropriate services to this patient group, their needs and preferences regarding physical activity must be recognized. The aim of the study was therefore to provide insight into experiences with physical activity in people with dementia.

Methods

The current study is part of a larger research project on needs in people with dementia. The main project included qualitative semi-structured interviews with 35 persons with dementia. 27 of the participants talked about their experience with physical activity. In the current study, the relevant findings on this theme were analysed separately. A phenomenological hermeneutic research design was applied.

Results

The analysis revealed three main categories regarding experiences with physical activity. To be physically active providedpositive experiencessuch as feelings of mastering and post-exercise euphoria. To be physically active wasmeaningful. The daily walk was an important routine to many, and it gave meaningful content to the day. Keeping up with activities confirmed identity. Lastly, to be active was perceived aschallenging. Participants described different barriers to being physically active such as a decline of physical function, lack of motivation and being dependent on others to go out.

Conclusions

Many of the participants expressed that being physically active was important to them. It is essential that informal and formal carers are aware of the role physical activity plays in the lives of many people with dementia, so that appropriate measures can be taken to assure continued active living in order to preserve health and quality of life.
Decreased survival in children inpatients with COVID-19 and antibiotic prescription
Authors: Murillo-Zamora Efrén , Trujillo Xóchitl , Huerta Miguel , Ríos-Silva Mónica , Lugo-Radillo Agustin , Mendoza-Cano Oliver
Published: June 2022

Background

The empirical prescription of antibiotics to inpatients with Coronavirus Disease 2019 (COVID-19) is frequent despite uncommon bacterial coinfections. Current knowledge of the effect of antibiotics on the survival of hospitalized children with COVID-19 is limited.

Objective

To characterize the survival experience of children with laboratory-positive COVID-19 in whom antibiotics were prescribed at hospital admission.

Methods

A retrospective cohort study was conducted in Mexico, with children hospitalized due to COVID-19 from March 2020 to December 2021. Data from 1601 patients were analyzed using the Kaplan–Meier method and the log-rank test. We computed hazard ratios (HR) and 95% confidence intervals (CI) to evaluate the effect of the analyzed exposures on disease outcomes.

Results

Antibiotics were prescribed to 13.2% ($$n$$
n
= 211) of enrolled children and a higher mortality rate [14.9 (95% CI 10.1–19.8) vs. 8.3 (95% CI 6.8–9.8)] per 1000 person-days, $$p$$
p
< 0.001) was found among them. At any given cut-off, survival functions were lower in antibiotic-positive inpatients ($$p$$
p
< 0.001). In the multiple model, antibiotic prescription was associated with a 50% increase in the risk of fatal outcome (HR = 1.50, 95% CI 1.01–2.22). A longer interval between illness onset and healthcare-seeking and pneumonia at hospital admission was associated with a poorer prognosis.

Conclusions

Our results suggest that antibiotic prescription in children hospitalized due to COVID-19 is associated with decreased survival. If later replicated, these findings highlight the need for rational antibiotics in these patients.
Emotion regulation and drunkorexia behaviors among Lebanese adults: the indirect effects of positive and negative metacognition
Authors: Azzi Vanessa , Bianchi Dora , Pompili Sara , Laghi Fiorenzo , Gerges Sarah , Akel Marwan , Malaeb Diana , Obeid Sahar , Hallit Souheil
Published: June 2022

Background

Although metacognition processes are a core feature of restrictive eating and alcohol cravings and entail an individual to control both of his/her emotions and thoughts, yet, to our knowledge, a scarcity of research has examined their potential role in drunkorexia as cognitive and emotional predictors. The following study investigates the different associations between two emotion regulation strategies (i.e. emotional suppression and cognitive reappraisal) and drunkorexia behaviors in a sample of Lebanese adults, exploring the possible indirect effects of positive and negative alcohol-related metacognitions.

Methods

This was a cross-sectional study that enrolled 335 participants (March-July 2021).

Results

Higher problematic alcohol use (beta = 5.56), higher physical activity index (beta = 0.08), higher expressive suppression (beta = 0.23), higher negative metacognitive beliefs about cognitive harm due to drinking (beta = 0.75) and higher cognitive reappraisal (beta = 0.20) were significantly associated with more drunkorexic behaviors. The positive metacognitive beliefs about cognitive self-regulation significantly mediated the association between cognitive reappraisal and drunkorexia behaviors. Both the positive metacognitive beliefs about cognitive self-regulation and the negative metacognitive beliefs about the uncontrollability of drinking significantly mediated the association between expressive suppression and drunkorexia behaviors.

Conclusion

This study demonstrated that emotional and metacognitive processes are associated with drunkorexia, addressing as well the mediating effect between deficient emotional regulation and risky behavioral patterns. Overall, our results would speculate that the lack of emotional and cognitive assets might enhance internal distress perceived out of control, leading individuals to indulge in maladaptive behavioral patterns for managing the underlying impairment.
Clinical evaluation of usefulness and effectiveness of sitting type continuous passive motion machines in patients with total knee arthroplasty: a study protocol for a single-blinded randomized controlled trial
Authors: Lee Byung Chan , Moon Chang Won , Choi Woo Sung , Kim Young Mo , Joo Yong Bum , Lee Da Gyo , Lee Sook Joung , Choi Eun Seok , Ji Jong Hun , Suh Dong Whan , Cho Kang Hee
Published: June 2022

Background

Total knee arthroplasty (TKA) is an important management strategy for patients with knee osteoarthritis (OA) refractory to conservative management. Postoperative range of motion (ROM) exercise is important to recover patients’ activities of daily living. Continuous passive motion (CPM) is a machine that provides passive ROM exercises of the knee joint in a pre-defined arc of motion. The short- and long-term effects of CPM exercise are controversial. We hypothesized that the inconsistent results of the CPM exercise are due to poor fitting of CPM machines and measurement errors. This study aims to present a protocol for investigating a new type of CPM machine that could be applied in a sitting position in comparison with the conventional type of CPM machine for patients with unilateral TKAs.

Methods

This study presents the protocol of a prospective, multicenter, single-blinded, three-armed randomized controlled trial (RCT). One hundred and twenty-six patients receiving unilateral TKAs will be recruited at the physical medicine and rehabilitation clinics of two urban tertiary medical hospitals. The patients were randomly divided into three groups with a 1:1:1 allocation. The intervention group will receive two weeks of post-operative rehabilitation using a new type of CPM machine. The control group will receive 2 weeks of post-operative rehabilitation using conventional CPM machines. The third group will receive post-operative rehabilitation with both types of CPM machines. The primary outcome will be the change in the passive ROM of the affected knee joint from baseline to 2 weeks after baseline assessment. The secondary outcomes will be pain and functional measurements, and will include patient-reported outcomes and performance tests surveyed at multiple time points up to 3 months after TKA.

Discussion

This is the first RCT to investigate the effect of a new type of CPM machine. The results of this RCT will determine whether the position of the patients during CPM exercise is important in post-operative rehabilitation protocols after TKAs and will provide evidence for the development of proper rehabilitation guidelines after TKAs.

Trial registration

Clinical Research Information Service of Republic of Korea, KCT0005520, Registered on 21 October 2020, https://cris.nih.go.kr/cris/search/detailSearch.do/21750
An evaluation of the efficacy of percutaneous reduction and screw fixation without bone grafting in Sanders Type-II and Type-III displaced intra-articular calcaneal fractures
Authors: Luo Gang , Fan Chongyin , Gao Peili , Huang Wei , Ni Weidong
Published: June 2022

Background

The aim of this retrospective monocentric study was to investigate the clinical efficacy of percutaneous reduction and screw fixation without bone grafting in Sanders Type-II and Type-III displaced intra-articular calcaneal fractures (DIACFs).

Methods

The medical records of calcaneal fractures patients who were admitted to our department from January 2018 to January 2020 were retrospectively reviewed, and those meeting the inclusion criteria were fnally included for analysis. All patients were treated with percutaneous reduction and screw fixation, and no patients received bone grafting. The radiologic parameters evaluated included the BÖhler angle and the calcaneal height. In addition, the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, Maryland Foot Score (MFS), and visual analog scale (VAS) score were determined.

Results

Thirty-eight patients with Sanders Type-II and Type-III DIACFs were finally included, including 30 males and 8 females aged 21 to 61 years [(42.6 ± 9.6) years]. According to the Essex-Lopresti classification, 27 of the fractures were the tongue type, and 11 were the joint compression type. According to the Sanders classification, 27 of the fractures were type II, and 11 were type III. Immediately postoperatively, the calcaneal height had recovered to 39.8 ± 2.1 mm, the BÖhler angle had recovered from 4.2° ± 13.6° preoperatively to 27.2° ± 3.4° (P = 0.000). All patients were followed up for 18–42 months [(25.2 ± 9.5) months]. All fractures healed. No differences were found in the outcome measures six-months postoperatively (BÖhler angle, p = 0.24; calcaneal height, p = 0.82) or at final follow-up (BÖhler angle, p = 0.33; calcaneal height, p = 0.28) compared to the immediately postoperative values. At the final follow-up, the AOFAS score was 91.7 ± 7.4 points, with an excellent and good rate of 92.1%; the MFS was 90.3 ± 7.8 points, with an excellent and good rate of 92.1%; and the VAS score was 2.2 ± 1.5 points. None of the patients had incision complications, and one patient developed traumatic arthritis.

Conclusion

Percutaneous reduction and screw fixation without bone grafting in Sanders Type-II and Type-III DIACFs can achieve good recovery and maintenance of the BÖhler angle and calcaneal height. Moreover, it has the advantage of a low complication rate.
Critical shoulder angle and failure of conservative treatment in patients with atraumatic full thickness rotator cuff tears
Authors: Meissner-Haecker Arturo , Contreras Julio , Valenzuela Alfonso , Delgado Byron , Taglioni Angelinni , De Marinis Rodrigo , Calvo Claudio , Soza Francisco , Liendo Rodrigo
Published: June 2022

Background

Atraumatic full thickness rotator cuff tears (AFTRCT) are common lesions whose incidence increases with age. Physical therapy is an effective conservative treatment in these patients with a reported success rate near 85% within 12 weeks of treatment. The critical shoulder angle (CSA) is a radiographic metric that relates the glenoid inclination with the lateral extension of the acromion in the coronal plane. A larger CSA has been associated with higher incidence of AFTRCT and a higher re-tear rate after surgical treatment. However, no study has yet described an association between a larger CSA and failure of conservatory treatment in ARCT. The main objective of this study is to determine whether there is an association between CSA and failure of physical therapy in patients with AFTRCT.

Methods

We reviewed the imaging and clinical records of 48 patients (53 shoulders), 60% female, with a mean age of 63.2 years (95% CI ± 10.4 years); treated for AFTRCT who also underwent a true anteroposterior radiograph of the shoulder within a year of diagnosis of the tear. We recorded demographic (age, sex, type of work), clinical (comorbidities), and imaging data (CSA, size and location of the tear). We divided the patients into two groups according to success or failure of conservative treatment (indication for surgery), so 21 shoulders (39.6%) required surgery and were classified as failure of conservative treatment.

Univariate and multivariate analysis was performed to detect predictors of failure of conservative treatment.

Results

The median CSA was 35.5º with no differences between those with failure (median 35.5º, range 29º to 48.2º) and success of conservative treatment (median 35.45º, range 30.2º to 40.3º), p = 0.978.

The multivariate analysis showed a younger age in patients with failure of conservative treatment (56.14 ± 9.2 vs 67.8 ± 8.4, p < 0.001) and that male gender was also associated with failure of conservative treatment (57% of men required surgery vs 28% of women, p = 0.035).

Conclusions

It is still unclear if CSA does predict failure of conservative treatment. A lower age and male gender both could predicted failure of conservative treatment in AFTRCT. Further research is needed to better address this subject.
Human resource management in Ethiopian public hospitals
Authors: Gile Philipos Petros , van de Klundert Joris , Buljac-Samardzic Martina
Published: June 2022

Background

In Ethiopia, public hospitals deal with a persistent human resource crisis, even by Sub-Saharan Africa (SSA) standards. Policy and hospital reforms, however, have thus far resulted in limited progress towards addressing the strategic human resource management (SHRM) challenges Ethiopia’s public hospitals face.

Methods

To explore the contextual factors influencing these SHRM challenges of Ethiopian public hospitals, we conducted a qualitative study based on the Contextual SHRM framework of Paauwe. A total of 19 structured interviews were conducted with Chief Executive Officers (CEOs) and HR managers from a purposive sample of 15 hospitals across Ethiopia. An additional four focus groups were held with professionals and managers.

Results

The study found that hospitals compete on the supply side for scarce resources, including skilled professionals. There was little reporting on demand-side competition for health services provided, service quality, and service innovation. Governmental regulations were the main institutional mechanism in place. These regulations also emphasized human resources and were perceived to tightly regulate employee numbers, salaries, and employment arrangements at detailed levels. These regulations were perceived to restrict the autonomy of hospitals regarding SHRM. Regulation-induced differences in allowances and external employment arrangements were among the concerns that decreased motivation and job satisfaction and caused employees to leave. The mismatch between regulation and workforce demands posed challenges for leadership and caused leaders to be perceived as incompetent and unable when they could not successfully address workforce needs.

Conclusions

Bottom-up involvement in SHRM may help resolve the aforementioned persistent problems. The Ethiopian government might better loosen regulations and provide more autonomy to hospitals to develop SHRM and implement mechanisms that emphasize the quality of the health services demanded rather than the quantity of human resources supplied.
Donor notification of permanent deferral: a qualitative study on the perceptions and practices of notifier and blood donor in Mexico
Authors: Serrano-Delgado V Moisés , Valdez-Martínez Edith , Márquez-González Horacio
Published: June 2022

Background

Informing about permanent deferral requires a process that links the notifier with the donor in a particular way. Little is known about the type of information and how it is disclosed to the donors. The current study aimed to examine perceptions and practices of notifier and blood donor within the framework of the notification process of permanent deferral and from the perspective of the notifier―blood donor relationship.

Methods

A qualitative study with in-depth interviews. The participants were 13 notifiers and 25 permanently deferred donors. Participants were recruited from a national blood bank and a state’s blood bank. The entire dataset/narratives were analysed using the method of thematic analysis.

Results

The disclosure of permanent deferral was understood as a matter of disclosing the serological test results and their medical meaning along with a concise explanation of the deferral status with regard to future blood donation and the plan to be followed. The notifiers preferred to act in accordance with the standard protocol despite acknowledging the adverse psychological and social effects to which donors are exposed when they are informed of the possible disease and the consequent permanent deferral. Donors described a variety of psychological and social affectations. They valued honesty in the communication, the clarity of the information provided and a greater involvement of the notifier.

Conclusion

Even though the notification process does not imply that medical care is being offered to donors, the notifier is the administrator of the well-being of the donor. Notification must not be considered as something apart from care, since it is intimately related to the health of each of the donors and their medical care.
Chinese adult segmentation according to health skills and analysis of their use for smart home: a cross-sectional national survey
Authors: He Feiying , Wu Yibo , Yang Jiao , Chen Keer , Xie Jingyu , Tuersun Yusupujiang , Li Lehuan , Wu Fangjing , Kan Yifan , Deng Yuqian , Zhao Liping , Chen Jingxi , Sun Xinying , Liao Shengwu , Chen JiangYun
Published: June 2022

Background

Digital health has become a heated topic today and smart homes have received much attention as an important area of digital health. Smart home is a device that enables automation and remote control in a home environment via the internet. However, most of the existing studies have focused on discussing the impact of smart home on people. Only few studies have focused on relationship between health skills and use of smart home.

Aims

To analyze the health skills of Chinese adults and segment them to compare and analyze the use of smart home for each group.

Methods

We used data from 11,031 participants aged 18 and above. The population was clustered based on five health skills factors: perceived social support, family health, health literacy, media use, and chronic diseases self-behavioral management. A total of 23 smart homes were categorized into three sub-categories based on their functions: entertainment smart home, functional smart home, and health smart home. We analyzed demographic characteristics and utilization rate of smart home across different cluster. Each groups’ features and the differences in their needs for smart home functions were compared and analyzed.

Results

As a result of the survey on health skills, three groups with different characteristics were clustered: good health skills, middle health skills, and poor health skills. The utilization rate of smart home was the highest was good health skills group (total smart home: 92.7%; entertainment smart home: 61.1%, functional smart home: 77.4%, and health smart home: 75.3%;P< 0.001). For entertainment smart home, smart TV had the highest utilization rate (good health skills: 45.7%; middle health skills: 43.5%, poor health skills: 33.4%, P < 0.001). For functional smart home, smart washing machine (good health skills: 37.7%, middle health skills: 35.11%, poor health skills: 26.5%;P < 0.001) and smart air conditioner (good health skills: 36.0%, middle health skills: 29.1%, poor health skills: 24.6%) were higher than other of this category. For health smart home, sports bracelet has the highest utilization rate (good health skills: 37.3%, middle health skills: 24.5%, poor health skills: 22.8%).

Conclusion

People can be divided into different categories based on health skill profiles, those with good health skills had a better utilization rate of smart home. The government and smart home companies need to focus on people with poor smart home use in various ways to promote their use of smart homes for personal health management.
Topical applications of allogeneic adipose-derived mesenchymal stem cells ameliorate the canine keratoconjunctivitis sicca
Authors: Wei Li-Ning , Wu Ching-Ho , Lin Chung-Tien , Liu I-Hsuan
Published: June 2022

Background

Canine keratoconjunctivitis sicca (KCS) is predominantly an immune-mediated disease. Current therapy of canine KCS is mainly by immunosuppressant, but the effectiveness was limited in some patients. In the past few years, some studies showed the results of the use of mesenchymal stem cells in treating canine KCS via periocular injections. However, the periocular injection procedure requires sedation or general anesthesia, and may lead to iatrogenic or incidental injury during the injection process. The aim of this study was to investigate the efficacy of topical allogenic canine adipose-derived mesenchymal stem cells (cAD-MSCs) in clinical patients of canine KCS.

Results

The cAD-MSCs used in this study were characterized for their capability of tri-lineage differentiation and immunomodulatory properties. In addition, preparation methods for eye drops of cAD-MSCs was developed and its optimal preservation was tested. The canine KCS patients were recruited for clinical trial and divided into two groups based on their history of previous treatment. All patients received topical cAD-MSCs treatment once per week for 6 consecutive weeks and complete ophthalmic examinations were performed 1 week before treatment (week 0) and at 3rd, 6th, 9th weeks, respectively. The results showed that the quantity and quality of tears have improved significantly following topical cAD-MSCs treatment based on Schirmers tear test-1 and tear break-up time. More than half of all patients were found improved in the tear quantity. In particular, 56.5% of the patients that were unresponsive to prior immunosuppressant therapy had an effective increase in tear volume. The severity of clinical signs was also ameliorated according to the numeric rating scale score from both patient owners and the clinician.

Conclusion

To sum up, topical cAD-MSCs may be beneficial especially in KCS patients with poor owner compliance for frequent daily use of eye drops or those who are unresponsive to immunosuppressant therapy.
Antibacterial treatment for exotic species, backyard ruminants and small flocks: a narrative review highlighting barriers to effective and appropriate antimicrobial treatment
Authors: Jelinski Dana C. , Orsel Karin , Weese J. Scott , Conly John M. , Julien Danielle A.
Published: June 2022

Antimicrobial resistance is a complex One Health issue that exists in both human and veterinary medicine. To mitigate this ever-growing problem, efforts have been made to develop guidelines for appropriate antimicrobial use (AMU) across sectors. In veterinary medicine, there are notable literature gaps for proper AMU in minor species. We conducted a structured narrative review covering the years of July 2006 – July 2021 to find antimicrobial treatments for common bacterial infections in exotic (birds, rodents, reptiles, and others), small flock (chickens, turkeys, and other fowl), and backyard small ruminant (sheep and goats) species. We retrieved a total of 4728 articles, of which 21 articles met the criteria for our review. Studies were grouped according to species, syndrome, and body system affected. Other data extracted included the bacterial pathogen(s), treatment (active ingredient), and geographical origin. Body systems reported included: intra-oral (n = 4), gastrointestinal (n = 1), respiratory (n = 2), reproductive (n = 1), skin (n = 3), aural (n = 1), ocular (n = 4), and other/multisystem (n = 5). By species, our search resulted in: rabbit (n = 5), rat (n = 2), guinea pig (n = 1), chinchilla (n = 1), guinea pig and chinchilla (n = 1), avian species (n = 1), psittacine birds (n = 2), loris and lorikeets (n = 1), turtles (n = 2), lizards (n = 1), goats (n = 2) and sheep (n = 2). The results of our findings identified a distinct gap in consistent antimicrobial treatment information for commonly encountered bacterial conditions within these species. There is a persisting need for clinical trials that focus on antibacterial treatment to strengthen the evidence base for AMU within exotic, small flock, and backyard small ruminant species.
Triglyceride-glucose index variability and incident cardiovascular disease: a prospective cohort study
Authors: Li Haibin , Zuo Yingting , Qian Frank , Chen Shuohua , Tian Xue , Wang Penglian , Li Xia , Guo Xiuhua , Wu Shouling , Wang Anxin
Published: June 2022

Background

Recent studies have suggested that triglyceride-glucose (TyG) index is an independent predictor of cardiovascular disease (CVD). However, the impact of long-term visit-to-visit variability in TyG index on the risk of CVD is not known. We aimed to investigate the longitudinal association between baseline and mean TyG index as well as TyG index variability and incident CVD in a Chinese population.

Methods

We included 49,579 participants without previous history of CVD in the Kailuan study who underwent three health examinations (2006, 2008, and 2010) and were followed up for clinical events until 2019. TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. We measured TyG index variability as the SD of the residuals obtained from a linear regression on the three TyG index measurements for each individual. Multivariate-adjusted Cox models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) with incident CVD.

Results

During a median follow-up time of 9.0 years, 2404 developed CVD. The highest tertile (T3) of baseline and mean TyG index were each associated with higher CVD incidence as compared with the lowest tertile (T1): aHR, 1.25; 95% CI 1.11–1.42; and aHR 1.40; 95% CI 1.24–1.58, respectively. Tertile 3 of TyG index variability was associated with increased CVD incidence compared to T1 group (aHR, 1.12; 95% CI 1.01–1.24). Similar findings were observed in a series of sensitivity analyses.

Conclusion

Higher TyG index level and greater TyGindex variability were each independently associated with a higher incidence of CVD.
KCNN4 may weaken anti-tumor immune response via raising Tregs and diminishing resting mast cells in clear cell renal cell carcinoma
Authors: Cui Yankang , Shen Tianyi , Xu Feng , Zhang Jing , Wang Yuhao , Wu Jiajin , Bu Hengtao , Fu Dian , Fang Bo , Lv Huichen , Wang Suchun , Shi Changjie , Liu Bianjiang , He Haowei , Tang Hao , Ge Jingping
Published: June 2022

Background

Studies over the past decade have shown that competitive endogenous RNA (ceRNA) plays an essential role in the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). Meanwhile, immune checkpoint blocker is gradually moving towards the first-line treatment of ccRCC. Hence, it’s urgent to develop a new prediction model for the efficiency of immunotherapy. At present, there is no study to reveal the effect of ceRNA network on the efficiency of immunotherapy for ccRCC.

Methods

To systematically analyze the effect of ceRNA hub genes in ccRCCon immune response, we constructed prognosis models based on ceRNAs and immune cells, respectively. We constructed ceRNA network using hypergeometric distribution test and correlation analysis with R script based on The Cancer Genome Atlas (TCGA) database. We then applied the Cibersort algorithm to simulate the infiltration overview of immune cells in kidney renal clear carcinoma (KIRC) samples. Prognosis-related immune cells were screened and a predictive model of these cells was constructed. Prognosis-related immune cells and ceRNA hub genes were performed with co-expression analysis. Finally, qRT-PCR and immunofluorescence assays were performed to validate the results.

Results

The construction of ceRNA related prognosis model contained 8 hub genes, including RELT, MYO9B, KCNN4, SIX1, OTOGL, MALAT1, hsa-miR-130b-3p, and hsa-miR-21-5p. The area under the receiver operating characteristic curve (AUC) was 0.77 at 5 years. For the construction of immune cells prognosis model, 3 immune cells (T cells regulatory, Macrophages, Mast cells resting) were adopted, and the AUC was 0.65 at 5 years. We then merged the two models by correlation analysis and co-expression analysis. Finally, we found that KCNN4 positively correlates with T cells regulatory (Tregs) and negatively correlates with mast cells resting significantly. Furthermore, higher expression of KCNN4 may lead to a higher potential for immune evasion and lower efficiency for immune checkpoint inhibitors (ICIs).

Conclusions

Generally, this is the first study to assess the prognostic value of immune related ceRNA hub genes in ccRCC, and KCNN4 was finally demonstrated to be a key regulatory factor with strong correlation with Tregs and mast cells resting.
Cattle-related risk factors for malaria in southwest Ethiopia: a cross-sectional study
Authors: Chan Kallista , Cano Jorge , Massebo Fekadu , Messenger Louisa A.
Published: June 2022

Background

Despite the low to moderate intensity of malaria transmission present in Ethiopia, malaria is still a leading public health problem. Current vector control interventions, principally long-lasting insecticidal nets and indoor residual spraying, when deployed alone or in combination, are insufficient to control the dominant vector species due to their exophagic and exophilic tendencies. Zooprophylaxis presents a potential supplementary vector control method for malaria; however, supporting evidence for its efficacy has been mixed.

Methods

To identify risk factors of malaria and to estimate the association between cattle and Anopheles vector abundance as well as malaria risk, a cross-sectional study was conducted in a village near Arba Minch, Ethiopia. Epidemiological surveys (households = 95, individuals = 463), mosquito collections using CDC light traps and a census of cattle and human populations were conducted. To capture environmental conditions, land cover and water bodies were mapped using satellite imagery. Risk factor analyses were performed through logistic, Poisson, negative binomial, and spatial weighted regression models.

Results

The only risk factor associated with self-reported malaria illness at an individual level was being a child aged 5 or under, where they had three times higher odds than adults. At the household level, variables associated with malaria vector abundance, especially those indoors, included socioeconomic status, the proportion of children in a household and cattle population density.

Conclusions

Study results are limited by the low abundance of malaria vectors found and use of self-reported malaria incidence. Environmental factors together with a household’s socioeconomic status and host availability played important roles in the risk of malaria infection in southwest Ethiopia. Cattle abundance in the form of higher cattle to human ratios may act as a protective factor against mosquito infestation and malaria risk. Humans should remain indoors to maximize potential protection against vectors and cattle kept outside of homes.
Application of the deep learning algorithm in nutrition research – using serum pyridoxal 5′-phosphate as an example
Authors: Ma Chaoran , Chen Qipin , Mitchell Diane C. , Na Muzi , Tucker Katherine L. , Gao Xiang
Published: June 2022

Background

Multivariable linear regression (MLR) models were previously used to predict serum pyridoxal 5′-phosphate (PLP) concentration, the active coenzyme form of vitamin B6, but with low predictability. We developed a deep learning algorithm (DLA) to predict serum PLP based on dietary intake, dietary supplements, and other potential predictors.

Methods

This cross-sectional analysis included 3778 participants aged ≥20 years in the National Health and Nutrition Examination Survey (NHANES) 2007-2010, with completed information on studied variables. Dietary intake and supplement use were assessed with two 24-hour dietary recalls. We included potential predictors for serum PLP concentration in the models, including dietary intake and supplement use, sociodemographic variables (age, sex, race-ethnicity, income, and education), lifestyle variables (smoking status and physical activity level), body mass index, medication use, blood pressure, blood lipids, glucose, and C-reactive protein. We used a 4-hidden-layer deep neural network to predict PLP concentration, with 3401 (90%) participants for training and 377 (10%) participants for test using random sampling. We obtained outputs after sending the features of the training set and conducting forward propagation. We then constructed a loss function based on the distances between outputs and labels and optimized it to find good parameters to fit the training set. We also developed a prediction model using MLR.

Results

After training for 105steps with the Adam optimization method, the highestR2was 0.47 for the DLA and 0.18 for the MLR model in the test dataset. Similar results were observed in the sensitivity analyses after we excluded supplement-users or included only variables identified by stepwise regression models.

Conclusions

DLA achieved superior performance in predicting serum PLP concentration, relative to the traditional MLR model, using a nationally representative sample. As preliminary data analyses, the current study shed light on the use of DLA to understand a modifiable lifestyle factor.
Activating cGAS–STING axis contributes to neuroinflammation in CVST mouse model and induces inflammasome activation and microglia pyroptosis
Authors: Ding Rui , Li Haiyan , Liu Yaqi , Ou Weiyang , Zhang Xifang , Chai Huihui , Huang Xiaofei , Yang Weijie , Wang Qiujing
Published: June 2022

Background

Neuroinflammation-induced injury is intimately associated with poor prognosis in patients with cerebral venous sinus thrombosis (CVST). The cyclic GMP-AMP synthase–stimulator of interferon gene (cGAS–STING) axis is a cytoplasmic double-stranded DNA (dsDNA) sensing pathway has recently emerged as a crucial mediator of neuroinflammation in ischemic stroke. However, the role of the cGAS–STING pathway in modulating post-CVST inflammation and the underlying mechanisms involved remain unclear.

Methods

A CVST model was induced by ferric chloride in male C57BL/6J mice. The selective cGAS inhibitor RU.521, STING agonist 2′3′-cGAMP, and STING siRNA were delivered by intranasal administration or intraventricular injection. Post-CVST assessments included rotarod test, TUNEL staining, Fluoro-Jade C staining, dihydroethidium staining, western blotting, qPCR, immunofluorescence, immunohistochemistry, ELISA and flow cytometry.

Results

cGAS, STING, NLRP3 and GSDMD were significantly upregulated after CVST and mostly in the microglia of the mouse brain. CVST triggered the release of dsDNA into the cytoplasm and elicited an inflammatory response via activating the cGAS–STING axis. RU.521 decreased the levels of 2′3′-cGAMP, STING and downstream inflammatory cytokines, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-pertinent components containing cleaved caspase-1, GSDMD, GSDMD-C, pro- and cleaved IL-1β, and cleaved IL-1β/pro-IL-1β. Besides, RU.521 treatment also reduced oxidative stress, lessened the numbers of microglia and neutrophils, and ameliorated neuronal apoptosis, degeneration along with neurological deficits post-CVST. 2′3'-cGAMP delivery enhanced the expressions of STING and related inflammatory mediators, NLRP3 inflammasome and pyroptosis-relevant proteins, whereas these alterations were significantly abrogated by the silencing of STING by siRNA.

Conclusions

Our data demonstrate that repression of the cGAS–STING pathway diminishes the neuroinflammatory burden of CVST and highlight this approach as a potential therapeutic tactic in CVST-mediated pathologies.
Regulation of brain iron uptake by apo- and holo-transferrin is dependent on sex and delivery protein
Authors: Baringer Stephanie L. , Neely Elizabeth B. , Palsa Kondaiah , Simpson Ian A. , Connor James R.
Published: June 2022

Background

The brain requires iron for a number of processes, including energy production. Inadequate or excessive amounts of iron can be detrimental and lead to a number of neurological disorders. As such, regulation of brain iron uptake is required for proper functioning. Understanding both the movement of iron into the brain and how this process is regulated is crucial to both address dysfunctions with brain iron uptake in disease and successfully use the transferrin receptor uptake system for drug delivery.

Methods

Using in vivo steady state infusions of apo- and holo-transferrin into the lateral ventricle, we demonstrate the regulatory effects of brain apo- and holo-transferrin ratios on the delivery of radioactive 55Fe bound to transferrin or H-ferritin in male and female mice. In discovering sex differences in the response to apo- and holo-transferrin infusions, ovariectomies were performed on female mice to interrogate the influence of circulating estrogen on regulation of iron uptake.

Results

Our model reveals that apo- and holo-transferrin significantly regulate iron uptake into the microvasculature and subsequent release into the brain parenchyma and their ability to regulate iron uptake is significantly influenced by both sex and type of iron delivery protein. Furthermore, we show that cells of the microvasculature act as reservoirs of iron and release the iron in response to cues from the interstitial fluid of the brain.

Conclusions

These findings extend our previous work to demonstrate that the regulation of brain iron uptake is influenced by both the mode in which iron is delivered and sex. These findings further emphasize the role of the microvasculature in regulating brain iron uptake and the importance of cues regarding iron status in the extracellular fluid.