bluuebunny/crossref_metadata_2025 huggingface dataset:
Syndesmosis Instability
Authors: Sintong Langga
Published: March 2023

The syndesmosis is one of important stabilizer of the ankle joint and consists of a complex ligamentous structure: the anterior inferior tibiofibular ligament; the interosseous ligament; the posterior inferior tibiofibular and the transverse ligaments. The posterior syndesmosis plays the most important role providing 40–45% of the resistance to diastasis, while the AITFL provides around 35%. Major injuries of two of the syndesmosis components represent a loss of more than 50% of resistance to diastasis and may result in instability. Syndesmosis injury or a high ankle sprain, is a frequent athletic trauma accounting for 1% to 18% of all ankle sprains, 17 to 84% of all sport injuries, and 10% of all ankle fractures. Most of the mechanism injury is external rotation injury. A radiographic study suggested that about 20.3% of ankle sprains were combined with a syndesmosis injury. Without proper treatment, the chronic syndesmosis injury remains symptomatic for more than 6 months after the initial trauma, with persistent pain, functional disability, and early-stage ankle arthritis. Normally, syndesmosis widens 1 mm during normal gait. Widening of syndesmosis more than 1 mm can reduce tibiotalar contact surface about 42%. The degenerative changes can occur if the lateral talar shift more than 2 mm. Clinical tests for syndesmosis injuries are external rotation stress test, Cotton test, dorsiflexion-compression test, squeeze test, crossed-leg test, fibular translation and AITFL palpation. Standard radiographs are part of ankle trauma evaluation, especially for fracture exclusion, applying the Ottawa criteria. Computerized tomography (CT) scan is a useful tool to assess tibiofibular diastasis, fibular rotation and joint asymmetry, but shows low sensitivity. MRI is showing very high sensitivity and specificity in identification of syndesmotic injuries. For stable lesion can be treated with conservative means, including non weight bearing or protected weight bearing with a cast or walking boot and a rehabilitation protocol. An unstable lesion requires a surgical procedure to avoid long-term disability and chronic instability. Ankle arthroscopy remains essential for diagnosis and treatment. With accessory tools that measure the syndesmosis gap (e.g. 3.5 mm shaver canula or a metallic tools). Passage of a 3 mm spherical probe during external rotation indicates very high likelihood of rupture of both the AITFL and the IOL. Also, concomitant intra-articular pathologies (osteochondral lesions, other ligamentous rupture or loose bodies) can be presented, with 19% needs to be addressed, reinforcing the role of arthroscopy not only for diagnosis but also for treatment. It is also an excellent tool to evaluate anatomic reduction and residual diastasis.
Return to Play and Pattern of Injury After ACL Rupture in a Consecutive Series of Elite UEFA Soccer Players
Authors: Farinelli Luca , Abermann Elisabeth , Meena Amit , Ueblacker Peter , Hahne Jochen , Fink Christian
Published: March 2023

Background:

Anterior cruciate ligament rupture represents a career-threatening injury for professional soccer players.

Purpose:

To analyze the pattern of injury, return to play (RTP), and performance of a consecutive series of elite professional soccer players after anterior cruciate ligament reconstruction (ACLR).

Study Design:

Case series; Level of evidence, 4.

Methods:

We evaluated the medical records of 40 consecutive elite soccer players who underwent ACLR by a single surgeon between September 2018 and May 2022. Patient age, height, weight, body mass index, position, injury history, affected side, RTP time, minutes played per season (MPS), and MPS as a percentage of playable minutes before and after ACLR were retrieved from medical records and from publicly available media-based platforms.

Results:

Included were 27 male patients (mean ± SD age at surgery, 23.2 ± 4.3 years; range, 18-34 years). The injury occurred during matches in 24 players (88.9%), with a noncontact mechanism in 22 (91.7%). Meniscal pathology was found in 21 patients (77.8%). Lateral meniscectomy and meniscal repair were performed in 2 (7.4%) and 14 (51.9%) patients, respectively, and medial meniscectomy and meniscal repair were performed in 3 (11.1%) and 13 (48.1%) patients, respectively. A total of 17 players (63.0%) underwent ACLR with bone–patellar tendon–bone autograft and 10 (37.0%) with soft tissue quadriceps tendon. Lateral extra-articular tenodesis was added in 5 patients (18.5%). The overall RTP rate was 92.6% (25 of 27). Two athletes moved to a lower league after surgery. The mean MPS% during the last preinjury season was 56.69% ± 21.71%; this decreased significantly to 29.18% ± 20.6% ( P < .001) in the first postoperative season and then increased to 57.76% ± 22.89% and 55.89% ± 25.8% in the second and third postoperative seasons. Two (7.4%) reruptures and 2 (7.4%) failed meniscal repairs were reported.

Conclusion:

ACLR in elite UEFA soccer players was associated with a 92.6% rate of RTP and 7.4% rate of reinjury within 6 months after primary surgery. Moreover, 7.4% of soccer players moved to a lower league during the first season after surgery. Age, graft selection, concomitant treatments, and lateral extra-articular tenodesis were not significantly associated with prolonged RTP.
Local Injection for Treating Mood Disorders (LIFT-MOOD): A Pilot Feasibility RCT of Stellate Ganglion Block for Treatment-Resistant Depression
Authors: Sussman David , Tassone Vanessa K , Gholamali Nezhad Fatemeh , Wu Michelle , Adamsahib Fathima , Mattina Gabriella F , Pazmino-Canizares Janneth , Demchenko Ilya , Jung Hyejung , Lou Wendy , Ladha Karim S , Bhat Venkat
Published: March 2023

Background

With nearly one-third of patients with major depressive disorder being resistant to available antidepressants, there is a need to develop new treatments for this population. Stellate ganglion block (SGB) is a procedure used to block sympathetic input to the central autonomic system; it has been administered to treat several conditions, including pain. Recently, indications for SGB have extended and the potential benefits for psychiatric disorders are under investigation.

Methods

The Local Injection For Treating Mood Disorders (LIFT-MOOD) study investigated the feasibility of a trial of 2 right-sided injections of bupivacaine 0.5% (7 mL) at the stellate ganglion in participants with treatment-resistant depression (TRD) using a randomized, placebo-controlled, pilot trial. Ten participants were randomized in a 1:1 allocation to receive active treatment or placebo (saline). Primary feasibility outcomes included recruitment rate, withdrawal, adherence, missing data, and adverse events. As a secondary, exploratory objective, we explored the efficacy of SGB in improving symptoms of depression by calculating the change in scores from baseline to follow-up on day 42 for each treatment group.

Results

The recruitment rate was reasonable and sufficient, retention and adherence were high, missing data were low, and adverse events were mild and temporary. Both treatment groups demonstrated decreases in Montgomery-Åsberg Depression Rating Scale scores, compared to baseline, by the end of the study.

Conclusion

This study supports the feasibility of a confirmatory trial of SGB in participants with TRD. Conclusions regarding efficacy cannot be made based on this preliminary study due to the small number of participants who completed active treatment. Larger-scale randomized controlled trials with long-term follow-ups and alternate sham procedures are needed to assess the efficacy and duration of symptom improvement with the use of SGB in TRD.
Does a bicycle accident as the cause of proximal femur fracture indicate that geriatric co-management is superfluous? A retrospective cohort study
Authors: Spies Petra E. , Fix Malene , Emmink Benjamin L. , Schermer Tjard R.
Published: March 2023

Background

Deployment of geriatric care would be more sustainable if we could limit geriatric co-management to older hip fracture patients who benefit most from it. We assumed that riding a bicycle is a proxy of good health and hypothesized that older patients with a hip fracture due to a bicycle accident have a more favorable prognosis than patients whose hip fracture was caused by another type of accident.

Methods

Retrospective cohort study of hip fracture patients ≥ 70 years admitted to hospital. Nursing home residents were excluded. Primary outcome was length of hospital stay (LOS). Secondary outcomes were delirium, infection, blood transfusion, intensive care unit stay and death during hospitalization. The group with a bicycle accident (BA) was compared to the non-bicycle accident (NBA) group using linear and logistic regression  models, with correction for age and sex.

Results

Of the 875 patients included, 102 (11.7%) had a bicycle accident. BA patients were younger (79.8 versus 83.9 years, p < 0.001), less often female (54.9 versus 71.2%, p = 0.001) and lived independently more often (100 versus 85.1%, p < 0.001). Median LOS in the BA group was 0.91 times the median LOS in the NBA group (p = 0.125). For none of the secondary outcomes the odds ratio favored the BA group, except for infection during hospital stay (OR = 0.53, 95%CI 0.28–0.99; p = 0.048).

Conclusions

Although older hip fracture patients who had a bicycle accident appeared more healthy than other older hip fracture patients, their clinical course was not more favorable. Based on this study, a bicycle accident is not an indicator that geriatric co-management can be omitted.
Synaptic retrograde regulation of the PKA-induced SNAP-25 and Synapsin-1 phosphorylation
Authors: Polishchuk Aleksandra , Cilleros-Mañé Víctor , Just-Borràs Laia , Balanyà-Segura Marta , Vandellòs Pont Genís , Silvera Simón Carolina , Tomàs Marta , Garcia Neus , Tomàs Josep , Lanuza Maria A.
Published: March 2023

Background

Bidirectional communication between presynaptic and postsynaptic components contribute to the homeostasis of the synapse. In the neuromuscular synapse, the arrival of the nerve impulse at the presynaptic terminal triggers the molecular mechanisms associated with ACh release, which can be retrogradely regulated by the resulting muscle contraction. This retrograde regulation, however, has been poorly studied. At the neuromuscular junction (NMJ), protein kinase A (PKA) enhances neurotransmitter release, and the phosphorylation of the molecules of the release machinery including synaptosomal associated protein of 25 kDa (SNAP-25) and Synapsin-1 could be involved.

Methods

Accordingly, to study the effect of synaptic retrograde regulation of the PKA subunits and its activity, we stimulated the rat phrenic nerve (1 Hz, 30 min) resulting or not in contraction (abolished by µ-conotoxin GIIIB). Changes in protein levels and phosphorylation were detected by western blotting and cytosol/membrane translocation by subcellular fractionation. Synapsin-1 was localized in the levator auris longus (LAL) muscle by immunohistochemistry.

Results

Here we show that synaptic PKA Cβ subunit regulated by RIIβ or RIIα subunits controls activity-dependent phosphorylation of SNAP-25 and Synapsin-1, respectively. Muscle contraction retrogradely downregulates presynaptic activity-induced pSynapsin-1 S9 while that enhances pSNAP-25 T138. Both actions could coordinately contribute to decreasing the neurotransmitter release at the NMJ.

Conclusion

This provides a molecular mechanism of the bidirectional communication between nerve terminals and muscle cells to balance the accurate process of ACh release, which could be important to characterize molecules as a therapy for neuromuscular diseases in which neuromuscular crosstalk is impaired.
Relationships between feeding behaviors and emotions: an electroencephalogram (EEG) frequency analysis study
Authors: Kusunoki Shintaro , Fukuda Takako , Maeda Saori , Yao Chenjuan , Hasegawa Takahiro , Akamatsu Tetsuya , Yoshimura Hiroshi
Published: March 2023

Feeding behaviors may be easily affected by emotions, both being based on brain activity; however, the relationships between them have not been explicitly defined. In this study, we investigated how emotional environments modulate subjective feelings, brain activity, and feeding behaviors. Electroencephalogram (EEG) recordings were obtained from healthy participants in conditions of virtual comfortable space (CS) and uncomfortable space (UCS) while eating chocolate, and the times required for eating it were measured. We found that the more participants tended to feel comfortable under the CS, the more it took time to eat in the UCS. However, the EEG emergence patterns in the two virtual spaces varied across the individuals. Upon focusing on the theta and low-beta bands, the strength of the mental condition and eating times were found to be guided by these frequency bands. The results determined that the theta and low-beta bands are likely important and relevant waves for feeding behaviors under emotional circumstances, following alterations in mental conditions.
Processing genome-wide association studies within a repository of heterogeneous genomic datasets
Authors: Bernasconi Anna , Canakoglu Arif , Comolli Federico
Published: March 2023

Background

Genome Wide Association Studies (GWAS) are based on the observation of genome-wide sets of genetic variants – typically single-nucleotide polymorphisms (SNPs) – in different individuals that are associated with phenotypic traits. Research efforts have so far been directed to improving GWAS techniques rather than on making the results of GWAS interoperable with other genomic signals; this is currently hindered by the use of heterogeneous formats and uncoordinated experiment descriptions.

Results

To practically facilitate integrative use, we propose to include GWAS datasets within the META-BASE repository, exploiting an integration pipeline previously studied for other genomic datasets that includes several heterogeneous data types in the same format, queryable from the same systems. We represent GWAS SNPs and metadata by means of the Genomic Data Model and include metadata within a relational representation by extending the Genomic Conceptual Model with a dedicated view. To further reduce the gap with the descriptions of other signals in the repository of genomic datasets, we perform a semantic annotation of phenotypic traits. Our pipeline is demonstrated using two important data sources, initially organized according to different data models: the NHGRI-EBI GWAS Catalog and FinnGen (University of Helsinki). The integration effort finally allows us to use these datasets within multi-sample processing queries that respond to important biological questions. These are then made usable for multi-omic studies together with, e.g., somatic and reference mutation data, genomic annotations, epigenetic signals.

Conclusions

As a result of the our work on GWAS datasets, we enable 1) their interoperable use with several other homogenized and processed genomic datasets in the context of the META-BASE repository; 2) their big data processing by means of the GenoMetric Query Language and associated system. Future large-scale tertiary data analysis may extensively benefit from the addition of GWAS results to inform several different downstream analysis workflows.
KDM4A, involved in the inflammatory and oxidative stress caused by traumatic brain injury-hemorrhagic shock, partly through the regulation of the microglia M1 polarization
Authors: Cai Jimin , Yang Yang , Han Jiahui , Gao Yu , Li Xin , Ge Xin
Published: March 2023

Background

Microglial polarization and the subsequent neuroinflammatory response and oxidative stress are contributing factors for traumatic brain injury (TBI) plus hemorrhagic shock (HS) induced brain injury. In the present work, we have explored whether Lysine (K)-specific demethylase 4 A (KDM4A) modulates microglia M1 polarization in the TBI and HS mice.

Results

Male C57BL/6J mice were used to investigate the microglia polarization in the TBI + HS model in vivo. Lipopolysaccharide (LPS)-induced BV2 cells were used to examine the mechanism of KDM4A in regulating microglia polarization in vitro. We found that TBI + HS resulted in neuronal loss and microglia M1 polarization in vivo, reflected by the increased level of Iba1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, malondialdehyde (MDA) and the decreased level of reduced glutathione (GSH). Additionally, KDM4A was upregulated in response to TBI + HS and microglia were among the cell types showing the increased level of KDM4A. Similar to the results in vivo, KDM4A also highly expressed in LPS-induced BV2 cells. LPS-induced BV2 cells exhibited enhanced microglia M1 polarization, and enhanced level of pro-inflammatory cytokines, oxidative stress and reactive oxygen species (ROS), while this enhancement was abolished by the suppression of KDM4A.

Conclusion

Accordingly, our findings indicated that KDM4A was upregulated in response to TBI + HS and microglia were among the cell types showing the increased level of KDM4A. The important role of KDM4A in TBI + HS-induced inflammatory response and oxidative stress was at least partially realized through regulating microglia M1 polarization.
Surgery-related anxiety on geriatric patients undergoing total knee arthroplasty: a retrospective observational study
Authors: Jung Kwang-Hwan , Park Jang-Ho , Ahn Jae-Woo , Park Ki-Bong
Published: March 2023

Background

The prevalence of anxiety in patients undergoing total knee arthroplasty (TKA) and its association with postoperative functions are well known; however, the levels of anxiety or anxiety-related characteristics are unknown. This study aimed to investigate the prevalence of clinically significant state anxiety in geriatric patients undergoing TKA for osteoarthritis (OA) of the knee and to evaluate the anxiety-related characteristics experienced by these patients pre- and post-operatively.

Methods

This retrospective observational study recruited patients who had undergone TKA for knee OA using general anesthesia between February 2020 and August 2021. The study participants were geriatric patients older than 65 years who had moderate or severe OA. We evaluated patient characteristics including age, sex, body mass index, smoking status, hypertension, diabetes, and cancer. We assessed their levels of anxiety status using the STAI-X which comprises 20-item scales. Clinically meaningful state anxiety was defined as a total score of 52 or higher. An independent Student’s t-test was used to determine differences of STAI score between subgroups in terms of patient characteristics. And patients were asked to complete questionnaires, which assessed four areas: (1) the main cause of anxiety; (2) the most helpful factor in overcoming anxiety before surgery; (3) the most helpful factor in reducing anxiety after surgery; and (4) the most anxious moment during the entire process.

Results

The mean STAI score of patients who underwent TKA was 43.0 points and 16.4% of patients experienced clinically significant state anxiety. The current smoking status affect STAI score and the proportion of patients with clinically meaningful state anxiety. The most common cause of preoperative anxiety was the surgery itself. Overall, 38% of patients reported that they experienced the greatest level of anxiety when the surgeon had recommended TKA in the outpatient clinic. The trust in the medical staff before surgery and the surgeon’s explanations after surgery helped the most in reducing anxiety.

Conclusions

One in six patients before TKA experience clinically meaningful state anxiety, and about 40% of patients experience anxiety from the time they are recommended for surgery. Patients tended to overcome anxiety before TKA through trust in the medical staff, and the surgeon’s explanations after surgery was found to be helpful in reducing anxiety.
A fully human connective tissue growth factor blocking monoclonal antibody ameliorates experimental rheumatoid arthritis through inhibiting angiogenesis
Authors: Qin Yang , Wu Gan , Jin Jiayi , Wang Hao , Zhang Jiani , Liu Li , Zhao Heping , Wang Jianguang , Yang Xinyu
Published: March 2023

Background

Connective tissue growth factor (CTGF) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) by facilitating angiogenesis and is a promising therapeutic target for RA treatment. Herein, we generated a fully human CTGF blocking monoclonal antibody (mAb) through phage display technology.

Results

A single-chain fragment variable (scFv) with a high affinity to human CTGF was isolated through screening a fully human phage display library. We carried out affinity maturation to elevate its affinity for CTGF and reconstructed it into a full-length IgG1 format for further optimization. Surface plasmon resonance (SPR) data showed that full-length antibody IgG mut-B2 bound to CTGF with a dissociation constant (KD) as low as 0.782 nM. In the collagen-induced arthritis (CIA) mice, IgG mut-B2 alleviated arthritis and decreased the level of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, we confirmed that the TSP-1 domain of CTGF is essential for the interaction. Additionally, the results of Transwell assays, tube formation experiments, and chorioallantoic membrane (CAM) assays showed that IgG mut-B2 could effectively inhibit angiogenesis.

Conclusion

The fully human mAb that antagonizes CTGF could effectively alleviate arthritis in CIA mice, and its mechanism is tightly associated with the TSP-1 domain of CTGF.
Dietary selenium intake in relation to non-alcoholic fatty liver disease assessed by fatty liver index and hepatic steatosis index; a cross-sectional study on the baseline data of prospective PERSIAN Kavar cohort study.
Authors: Shojaei Zarghani Sara , Rahimi Kashkooli Nima , Bagheri Zahra , Tabatabaei Mahdy , Fattahi Mohammad Reza , Safarpour Ali Reza
Published: March 2023

Background

There is limited and conflicting evidence on the association between selenium and non-alcoholic fatty liver disease (NAFLD). Therefore, the present population-based cross-sectional study aimed to explore the relationship between dietary selenium intake and the risk of NAFLD.

Methods

A total of 3026 subjects from the PERSIAN (Prospective Epidemiological Research Studies in IrAN) Kavar cohort study were included in the analysis. The daily selenium intake was evaluated using a semi-quantitative food frequency questionnaire, and energy-adjusted quintiles of selenium intake (µg/day) were calculated. NAFLD was defined as the fatty liver index (FLI) ≥ 60 or the hepatic steatosis index (HSI) > 36. The association between dietary selenium intake and NAFLD was evaluated using logistic regression analysis.

Results

The prevalence rates of NAFLD were 56.4% and 51.9%, based on the FLI and HSI markers, respectively. The odds ratios (ORs) for FLI-defined NAFLD were 1.31 (95% confidence interval (CI): 1.01–1.70) and 1.50 (95% CI: 1.13–1.99) for the fourth and fifth quintiles of selenium intake, respectively, after adjustment for sociodemographic variables, smoking status, alcohol drinking, physical activity, and dietary factors (P trend = 0.002). There was also a similar association between selenium intakes and HSI-defined NAFLD (OR = 1.34 (95% CI: 1.03–1.75) for the fourth quintile and OR = 1.50 (95% CI: 1.12–2.01) for the fifth quintile of selenium intake) (P trend = 0.006).

Conclusion

In this large sample study, we observed a weak positive association between dietary selenium intake and NAFLD risk.
Leveraging the vantage point – exploring nurses’ perception of residents’ communication skills: a mixed-methods study
Authors: Rahim Komal Abdul , Lakhdir Maryam Pyar Ali , Afzal Noreen , Merchant Asma Altaf Hussain , Shaikh Namra Qadeer , Noorali Ali Aahil , Tariq Umar , Ahmad Rida , Bakhshi Saqib Kamran , Mahmood Saad bin Zafar , Khan Muhammad Rizwan , Tariq Muhammed , Haider Adil H.
Published: March 2023

Introduction

Effective communication is key to a successful patient-doctor interaction and improved healthcare outcomes. However, communication skills training in residency is often subpar, leading to inadequate patient-physician communication. There is a dearth of studies exploring the observations of nurses – key members of healthcare teams with a special vantage point to observe the impact of residents’ communication with patients. Thus, we aimed to gauge the perceptions of nurses regarding residents’ communication skills expertise.

Methods

This study employed a sequential mixed-methods design, and was conducted at an academic medical center in South Asia. Quantitative data was collected via a REDCap survey using a structured validated questionnaire. Ordinal logistic regression was applied. For qualitative data, In-depth interviews were conducted with nurses using a semi-structured interview guide.

Results

A total of 193 survey responses were obtained from nurses hailing from various specialties including Family Medicine (n = 16), Surgery (n = 27), Internal Medicine (n = 22), Pediatrics (n = 27), and Obstetrics/Gynecology (n = 93). Nurses rated long working hours, infrastructural deficits, and human failings as the main barriers to effective patient-resident communication. Residents working in in-patient settings were more likely to have inadequate communication skills (P-value = 0.160). Qualitative data analysis of nine in-depth interviews revealed two major themes: existing status-quo of residents’ communication skills (including deficient verbal and non-verbal communication, bias in patient counselling and challenging patients) and recommendations for improving patient-resident communication.

Conclusion

The findings from this study highlight significant gaps in patient-resident communication from the perception of nurses and identify the need for creating a holistic curriculum for residents to improve patient-physician interaction.
Construct validity of advanced practice nurse core competence scale: an exploratory factor analysis
Authors: Chair Sek Ying , Wong Frances Kam Yuet , Bryant-Lukosius Denise , Liu Ting , Jokiniemi Krista
Published: March 2023

Background

Determining the core competence of advanced practice nurses is foundational for promoting optimal design and implementation of advanced practice nursing roles. Core competencies specific to the contexts of the advanced practice nurse in Hong Kong have been developed, but not yet validated. Thus, this study aims to assess the construct validity of advanced practice nurse core competence scale in Hong Kong.

Methods

We performed a cross-sectional study using an online self-report survey. Exploratory factor analysis was used to examine the factor structure of a 54-item advanced practice nurse core competence scale through principal axis factoring with direct oblique oblimin rotation. A parallel analysis was conducted to determine the number of factors to be extracted. The Cronbach’s α was computed to evaluate the internal consistency of the confirmed scale. The STROBE checklist was used as reporting guideline.

Results

A total of 192 advanced practice nurse responses were obtained. Exploratory factor analysis led to the final 51-item scale with a three-factor structure, which accounted for 69.27% of the total variance. The factor loadings of all items ranged from 0.412 to 0.917. The Cronbach’s alpha of the total scale and three factors ranged from 0.945 to 0.980, indicating robust internal consistency.

Conclusion

This study identified a three-factor structure of the advanced practice nurse core competency scale: client-related competencies, advanced leadership competencies, and professional development and system-related competencies. Future studies are recommended to validate the core competence content and construct in different contexts. Moreover, the validated scale could provide a cornerstone framework for advanced practice nursing roles development, education, and practice, and inform future competency research nationally and internationally.
Resilience in keeping the balance between demand and capacity in the COVID-19 pandemic, a case study at a Swedish middle-sized hospital
Authors: Rosenbäck Ritva Gisela , Svensson Ann
Published: March 2023

Background

In pandemics, it is critical to find a balance between healthcare demand, and capacity, taking into consideration the demands of the patients affected by the pandemic, as well as other patients (in elective or emergency care). The purpose of this paper is to suggest conceptual models for the capacity requirements at the emergency department, the inpatient care, and intensive care unit as well as a model for building staff capacity in pandemics.

Methods

This paper is based on a qualitative single case study at a middle-sized hospital in Sweden. The primary data are collected from 27 interviewees and inductively analyzed.

Results

The interviewees described a large difference between the immediate catastrophe scenario described in the emergency plan (which they had trained for), and the reality during the COVID-19 pandemic. The pandemic had a much slower onset and lasted longer compared to, for example, an accident, and the healthcare demand fluctuated with the societal infection. The emergency department and inpatient care could create surge capacity by reducing elective care. Lower inflow of other emergency patients also helped to create surge capacity. The number of intensive care beds increased by 350% at the case hospital. At the same time, the capacity of the employees decreased due to infection, exhaustion, and fear. The study contributes to knowledge of conceptional models and key factors affecting the balance between demand and capacity.

Conclusion

The framework suggests conceptual models for balancing surge capacity during a pandemic Health care practitioners need to provide assumptions of the key factors to find the balance between the demand and capacity corresponding to the reality and maintain the delivery of high-quality healthcare services.
Molecular investigation of Feline Panleukopenia in an endangered leopard (Panthera pardus) – a case report
Authors: Kolangath S. M. , Upadhye S. V. , Dhoot V. M. , Pawshe M. D. , Bhadane B. K. , Gawande A. P. , Kolangath R. M.
Published: March 2023

Background

Feline Panleukopenia is an important disease of cats and has been reported worldwide. The disease is caused by a non-enveloped, single-stranded DNA virus; Feline Panleukopenia Virus (FPLV), belonging to the Parvoviridae family. The disease causes significant mortality in unvaccinated kittens. The disease has been well documented in companion animals. However, only a few reports have surfaced from the wild.

Case presentation

An orphan leopard cub was presented to Wildlife Rescue Centre, Nagpur, for further care; the leopard was kept under quarantine. On day 22 of the quarantine, the leopard showed inappetence, lethargy and depression and did not consume the offered carabeef (Day 0 of treatment). The leopard was examined clinically and was found to have a temperature of 102°F; blood was collected and analysed. On day one, the leopard exhibited bloody diarrhoea, inappetence, fever and depression. The leopard was rationally treated with fluids, antibiotics, multi-vitamins, haemostatics and haematinics. To gain qualitative insights into the epidemiological aspect of the disease, molecular investigation, including Polymerase Chain Reaction (PCR) and qPCR (Quantitative Polymerase Chain Reaction), were utilized to confirm the infection. The amplicon was sequenced and was found to be similar to sequences of FPLV reported domestic cats and other wild felids from India and abroad. Phylogenetic analysis was performed to understand the evolutionary relationship of the virus with previously reported sequences of FPLV. Sequences were submitted to National Center for Biotechnology Information (NCBI) and were allotted accession numbers.

Conclusion

The infection in endangered leopard cubs could be managed with prompt fluid therapy, antibiotics and support treatment, ensuring an uneventful recovery. Molecular investigation and sequencing efforts can provide valuable data on epidemiology and the evolutionary relationship of the virus with the circulating strains in the field. The study has implications in the preventive management of FPLV in captivity and the selection of strains for inclusion in vaccines meant for the wild felids.
Low carbohydrate high fat-diet in real life assessed by diet history interviews
Authors: Hagström Henrik , Hagfors Linda Nyström , Tellström Anna , Hedelin Rikard , Lindmark Krister
Published: March 2023

Background

Low carbohydrate high fat (LCHF) diet has been a popular low carbohydrate diet in Sweden for 15 years. Many people choose LCHF to lose weight or control diabetes, but there are concerns about the effect on long-term cardiovascular risks. There is little data on how a LCHF diet is composed in real-life. The aim of this study was to evaluate the dietary intake in a population with self-reported adherence to a LCHF diet.

Methods

A cross-sectional study of 100 volunteers that considered themselves eating LCHF was conducted. Diet history interviews (DHIs) and physical activity monitoring for validation of the DHIs were performed.

Results

The validation shows acceptable agreement of measured energy expenditure and reported energy intake. Median carbohydrate intake was 8.7 E% and 63% reported carbohydrate intake at potentially ketogenic levels. Median protein intake was 16.9 E%. The main source of energy was dietary fats (72.0 E%). Intake of saturated fat was 32 E% and cholesterol was 700 mg per day, both of which exceeded the recommended upper limits according to nutritional guidelines. Intake of dietary fiber was very low in our population. The use of dietary supplements was high, and it was more common to exceed the recommended upper limits of micronutrients than to have an intake below the lower limits.

Conclusions

Our study indicates that in a well-motivated population, a diet with very low carbohydrate intake can be sustained over time and without apparent risk of deficiencies. High intake of saturated fats and cholesterol as well as low intake of dietary fiber remains a concern.
Recent advances of CREKA peptide-based nanoplatforms in biomedical applications
Authors: Zhang Nannan , Ru Bin , Hu Jiaqi , Xu Langhai , Wan Quan , Liu Wenlong , Cai WenJun , Zhu Tingli , Ji Zhongwei , Guo Ran , Zhang Lin , Li Shun , Tong Xiangmin
Published: March 2023

Nanomedicine technology is a rapidly developing field of research and application that uses nanoparticles as a platform to facilitate the diagnosis and treatment of diseases. Nanoparticles loaded with drugs and imaging contrast agents have already been used in clinically, but they are essentially passive delivery carriers. To make nanoparticles smarter, an important function is the ability to actively locate target tissues. It enables nanoparticles to accumulate in target tissues at higher concentrations, thereby improving therapeutic efficacy and reducing side effects. Among the different ligands, the CREKA peptide (Cys-Arg-Glu-Lys-Ala) is a desirable targeting ligand and has a good targeting ability for overexpressed fibrin in different models, such as cancers, myocardial ischemia-reperfusion, and atherosclerosis. In this review, the characteristic of the CREKA peptide and the latest reports regarding the application of CREKA-based nanoplatforms in different biological tissues are described. In addition, the existing problems and future application perspectives of CREKA-based nanoplatforms are also addressed.
Valproic acid inhibits cell growth in both MCF-7 and MDA-MB231 cells by triggering different responses in a cell type-specific manner
Authors: Giordano Francesca , Paolì Alessandro , Forastiero Martina , Marsico Stefania , De Amicis Francesca , Marrelli Mariangela , Naimo Giuseppina Daniela , Mauro Loredana , Panno Maria Luisa
Published: March 2023

Background

Breast cancer is the second leading cause of death among women after lung cancer. Despite the improvement in prevention and in therapy, breast cancer still remains a threat, both for pre- and postmenopausal women, due to the development of drug resistance. To counteract that, novel agents regulating gene expression have been studied in both hematologic and solid tumors. The Histone Deacetylase (HDAC) inhibitor Valproic Acid (VA), used for epilepsy and other neuropsychiatric diseases, has been demonstrated a strong antitumoral and cytostatic activity. In this study, we tested the effects of Valproic Acid on the signaling pathways involved in breast cancer cells viability, apoptosis and in Reactive Oxygen Species (ROS) production using ER-α positive MCF-7 and triple negative MDA-MB-231 cells.

Methods

Cell proliferation assay was performed by MTT Cell cycle, ROS levels and apoptosis were analyzed by flow cytometry, protein levels were detected by Western Blotting.

Results

Cell treatment with Valproic Acid reduced cell proliferation and induced G0/G1 cell cycle arrest in MCF-7 and G2/M block in MDA-MB-231 cells. In addition, in both cells the drug enhanced the generation of ROS by the mitochondria. In MCF-7 treated cells, it has been observed a reduction in mitochondrial membrane potential, a down regulation of the anti-apoptotic marker Bcl-2 and an increase of Bax and Bad, leading to release of cytochrome C and PARP cleavage. Less consistent effects are recorded in MDA-MB-231 cells, in which the greater production of ROS, compared to MCF-7cells, involves an inflammatory response (activation of p-STAT3, increased levels of COX2).

Conclusions

Our results have demonstrated that in MCF-7 cells the Valproic Acid is a suitable drug to arrest cell growth, to address apoptosis and mitochondrial perturbations, all factors that are important in determining cell fate and health. In a triple negative MDA-MB 231 cells, valproate directs the cells towards the inflammatory response with a sustained expression of antioxidant enzymes. Overall, the not always unequivocal data between the two cellular phenotypes indicate that further studies are needed to better define the use of the drug, also in combination with other chemotherapy, in the treatment of breast tumors.
Immunogenic cell death in cancer: concept and therapeutic implications
Authors: Galluzzi Lorenzo , Kepp Oliver , Hett Erik , Kroemer Guido , Marincola Francesco M.
Published: March 2023

Mammalian cells responding to specific perturbations of homeostasis can undergo a regulated variant of cell death that elicits adaptive immune responses. As immunogenic cell death (ICD) can only occur in a precise cellular and organismal context, it should be conceptually differentiated from instances of immunostimulation or inflammatory responses that do not mechanistically depend on cellular demise. Here, we critically discuss key conceptual and mechanistic aspects of ICD and its implications for cancer (immuno)therapy.
Outcome of adalimumab monotherapy in paediatric non-infectious uveitis
Authors: Al-Julandani DA , Bagri NK , Tsang N , Clarke S , Upadhyay A , Guly C , Ramanan AV
Published: March 2023

Background

Adalimumab in combination with other disease-modifying antirheumatic drugs (DMARD) such as methotrexate has a proven efficacy in the management of paediatric non-infectious uveitis. However, many children experience significant intolerance to methotrexate while on this combination, leaving a dilemma for clinicians for choosing the subsequent therapeutic roadmap. Continuation of adalimumab monotherapy might be an alternative feasible option under such settings. This study aims to investigate the efficacy of adalimumab monotherapy in paediatric non-infectious uveitis.

Methods

Children with non-infectious uveitis on adalimumab monotherapy (from August 2015 to June 2022) following intolerance to accompanying methotrexate or mycophenolate mofetil were included in this retrospective study. Data were collected at the initiation of adalimumab monotherapy and at three monthly intervals until the last visit. The primary outcome was to evaluate disease control on adalimumab monotherapy as determined by the proportion of patients who had less than a 2-step worsening in uveitis (as per SUN score) and no additional systemic immunosuppression during follow-up. Secondary outcome measures were visual outcome, complications and side-effect profile of adalimumab monotherapy.

Results

Data was collected for 28 patients (56 eyes). The most common uveitis type and course were anterior and chronic uveitis respectively. Juvenile idiopathic arthritis-associated uveitis was the most common underlying diagnosis. During the study period, 23 (82.14%) of the study subjects met the primary outcome. On Kaplan–Meier survival analysis 81.25% (95% CI; 60.6–91.7%) children maintained remission at 12 months on adalimumab monotherapy.

Conclusion

Continuation of adalimumab monotherapy is an effective therapeutic option for the treatment of non-infectious uveitis in children who are intolerant to the combination of adalimumab and methotrexate or mycophenolate mofetil.
Opposing effects of β-2 and β-1 adrenergic receptor signaling on neuroinflammation and dopaminergic neuron survival in α-synuclein-mediated neurotoxicity
Authors: Torrente Daniel , Su Enming J. , Schielke Gerald P. , Warnock Mark , Mann Kris , Lawrence Daniel A.
Published: March 2023

Background

Noradrenergic neurons in the locus coeruleus (LC) are the primary source of norepinephrine (NE) in the brain and degeneration of these neurons is reported in the early stages of Parkinson’s disease (PD), even prior to dopaminergic neuron degeneration in the substantia nigra (SN), which is a hallmark of PD pathology. NE depletion is generally associated with increased PD pathology in neurotoxin-based PD models. The effect of NE depletion in other models of PD-like α-synuclein-based models is largely unexplored. In PD models and in human patients, β-adrenergic receptors’ (AR) signaling is associated with a reduction of neuroinflammation and PD pathology. However, the effect of NE depletion in the brain and the extent of NE and β-ARs signaling involvement in neuroinflammation, and dopaminergic neuron survival is poorly understood.

Methods

Two mouse models of PD, a 6OHDA neurotoxin-based model and a human α-synuclein (hα-SYN) virus-based model of PD, were used. DSP-4 was used to deplete NE levels in the brain and its effect was confirmed by HPLC with electrochemical detection. A pharmacological approach was used to mechanistically understand the impact of DSP-4 in the hα-SYN model of PD using a norepinephrine transporter (NET) and a β-AR blocker. Epifluorescence and confocal imaging were used to study changes in microglia activation and T-cell infiltration after β1-AR and β2-AR agonist treatment in the hα-SYN virus-based model of PD.

Results

Consistent with previous studies, we found that DSP-4 pretreatment increased dopaminergic neuron loss after 6OHDA injection. In contrast, DSP-4 pretreatment protected dopaminergic neurons after hα-SYN overexpression. DSP-4-mediated protection of dopaminergic neurons after hα-SYN overexpression was dependent on β-AR signaling since using a β-AR blocker prevented DSP-4-mediated dopaminergic neuron protection in this model of PD. Finally, we found that the β-2AR agonist, clenbuterol, reduced microglia activation, T-cell infiltration, and dopaminergic neuron degeneration, whereas xamoterol a β-1AR agonist showed increased neuroinflammation, blood brain barrier permeability (BBB), and dopaminergic neuron degeneration in the context of hα-SYN-mediated neurotoxicity.

Conclusions

Our data demonstrate that the effects of DSP-4 on dopaminergic neuron degeneration are model specific, and suggest that in the context of α-SYN-driven neuropathology, β2-AR specific agonists may have therapeutic benefit in PD.
Practical approaches of PULSE Racing in training their athlete for the Cybathlon Global Edition Functional Electrical Stimulation bike race: a case report
Authors: Docter Heleen , Podvinšek Katja , Koomen Sander ,   PULSE Racing III, Kaman Birgit E , Visser Ilona , Klunder Niek , van den Berg Anneloes , Bellens Laurien , Wijnbelt Chrétine , Groot Sterre
Published: March 2023

During the Cybathlon Global Edition 2020, athletes compete in a Functional Electrical Stimulation (FES) bike race. In this event, athletes with a spinal cord injury cover a distance of 1200 m on an adapted bike by using electrostimulation to activate their leg muscles in order to evoke a pedalling movement. This report reviews the training regimen, as designed by the PULSE Racing team, and the experience of one athlete in preparation for the Cybathlon Global Edition 2020. The training plan was designed to vary exercise modes in order to optimize physiological adaptations and minimize monotony for the athlete. Additional constraints due to coronavirus pandemic, e.g., postponement of the Cybathon Global Edition and modification from a live cycling track to a virtual stationary race, along with the health concerns of the athlete, e.g. unwanted effects from the FES and bladder infection, required creativity to ensure an effective and safe training protocol. The individual needs of the athlete and task requirements for the FES bike race made the design of a suitable training programme challenging, emphasizing the importance of monitoring. Several objective and subjective measures to assess the athlete’s health and progress are presented, all with their own advantages and disadvantages. Despite these limitations, the athlete achieved a gold medal in the FES bike race Cybathlon Global Edition 2020 through discipline, team collaboration and the athlete’s own motivation.
Virtual reality-based interventions for the rehabilitation of vestibular and balance impairments post-concussion: a scoping review
Authors: LeMarshall Soraya J. , Stevens Lachlan M. , Ragg Nicholas P. , Barnes Leia , Foster Jacinta , Canetti Elisa F. D.
Published: March 2023

Background

Concussions and mild traumatic brain injuries are the most common causes of physical and cognitive disability worldwide. Concussion can result in post-injury vestibular and balance impairments that can present up to five years post initial concussion event, ultimately affecting many daily and functional activities. While current clinical treatment aims to reduce symptoms, the developing use of technology in everyday life has seen the emergence of virtual reality. Current literature has failed to identify substantial evidence regarding the use of virtual reality in rehabilitation. The primary aim of this scoping review is to identify, synthesise, and assess the quality of studies reporting on the effectiveness of virtual reality for the rehabilitation of vestibular and balance impairments post-concussion. Additionally, this review aims to summarise the volume of scientific literature and identify the knowledge gaps in current research pertaining to this topic.

Methods

A scoping review of six databases (PubMed, Embase, CINAHL, ProQuest, SportDiscus, Scopus) and a grey literature (Google Scholar) was conducted using three key concepts (virtual reality, vestibular symptoms, and post-concussion). Data was charted from studies and outcomes were categorised into one of three categories: (1) balance; (2) gait; or (3) functional outcome measures. Critical appraisal of each study was conducted using the Joanna Briggs Institute checklists. A critical appraisal of each outcome measure was also completed utilising a modified GRADE appraisal tool to summarise the quality of evidence. Effectiveness was assessed using calculations of change in performance and change per exposure time.

Results

Three randomised controlled trials, three quasi-experimental studies, three case studies, and one retrospective cohort study were ultimately included, using a thorough eligibility criteria. All studies were inclusive of different virtual reality interventions. The ten studies had a 10-year range and identified 19 different outcome measures.

Conclusion

The findings from this review suggests that virtual reality is an effective tool for the rehabilitation of vestibular and balance impairments post-concussion. Current literature shows sufficient but low level of evidence, and more research is necessary to develop a quantitative standard and to better understand appropriate dosage of virtual reality intervention.