bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying strategies to support implementation of interprofessional primary care teams in Nova Scotia: Results of a survey and knowledge sharing event
Authors: Grant Amy , Giacomantonio Rachel , Lackie Kelly , MacKenzie Adrian , Jeffers Elizabeth , Kontak Julia , Marshall Emily Gard , Philpott Susan , Sheppard-LeMoine Debbie , Lappin Elizabeth , Bruce Alice , Mireault Amy , Beck Deanna , Cormier Lindsay , Martin-Misener Ruth
Published: May 2024

Background

Interprofessional primary care teams (IPCTs) work together to enhance care. Despite evidence on the benefits of IPCTs, implementation remains challenging. This research aims to 1) identify and prioritize barriers and enablers, and 2) co-develop team-level strategies to support IPCT implementation in Nova Scotia, Canada.

Methods

Healthcare providers and staff of IPCTs were invited to complete an online survey to identify barriers and enablers, and the degree to which each item impacted the functioning of their team. Top ranked items were identified using the sum of frequency x impact for each response. A virtual knowledge sharing event was held to identify strategies to address local barriers and enablers that impact team functioning.

Results

IPCT members (n = 117), with a mix of clinic roles and experience, completed the survey. The top three enablers identified were access to technological tools to support their role, standardized processes for using the technological tools, and having a team manager to coordinate collaboration. The top three barriers were limited opportunity for daily team communication, lack of conflict resolution strategies, and lack of capacity building opportunities. IPCT members, administrators, and patients attended the knowledge sharing event (n = 33). Five strategies were identified including: 1) balancing patient needs and provider scope of practice, 2) holding regular and accessible meetings, 3) supporting team development opportunities, 4) supporting professional development, and 5) supporting involvement in non-clinical activities.

Interpretation

This research contextualized evidence to further understand local perspectives and experiences of barriers and enablers to the implementation of IPCTs. The knowledge exchange event identified actionable strategies that IPCTs and healthcare administrators can tailor to support teams and care for patients.
Dependency and frailty in the older haemodialysis patient
Authors: Pereira M , Tocino M L Sanchez , Mas-Fontao Sebastian , Manso P , Burgos M , Carneiro D , Ortiz A , Arenas M D , González-Parra E
Published: May 2024

Background

Frailty among older adults undergoing hemodialysis is increasingly prevalent, significantly impacting cognitive function, mobility, and social engagement. This study focuses on the clinical profiles of very older adults in hemodialysis, particularly examining the interplay of dependency and frailty, and their influence on dialysis regimens.

Methods

In this observational, descriptive study, 107 patients aged over 75 from four outpatient centers and one hospital unit were examined over a year. Patient data encompassed sociodemographic factors, dialysis specifics, analytical outcomes, lifestyle elements, and self-reported post-treatment fatigue. Malnutrition-inflammation scale was used to measure the Nutritional status; MIS scale for malnutrition-inflammation, Barthel index for dependency, Charlson comorbidity index; FRIED scale for frailty and the SF12 quality of life measure.

Results

The study unveiled that a substantial number of older adults on hemodialysis faced malnutrition (55%), dependency (21%), frailty (46%), and diminished quality of life (57%). Patients with dependency were distinctively marked by higher comorbidity, severe malnutrition, enhanced frailty, nursing home residency, dependency on ambulance transportation, and significantly limited mobility, with 77% unable to walk. Notably, 56% of participants experienced considerable post-dialysis fatigue, correlating with higher comorbidity, increased dependency, and poorer quality of life. Despite varying clinical conditions, dialysis patterns were consistent across the patient cohort.

Conclusions

The older adult cohort, averaging over four years on hemodialysis, exhibited high rates of comorbidity, frailty, and dependency, necessitating substantial support in transport and living arrangements. A third of these patients lacked residual urine output, yet their dialysis regimen mirrored those with preserved output. The study underscores the imperative for tailored therapeutic strategies to mitigate dependency, preserve residual renal function, and alleviate post-dialysis fatigue, ultimately enhancing the physical quality of life for these patients.
Association between diet quality and malnutrition: pooled results from two population-based studies in older adults
Authors: Marcos-Delgado Alba , Yévenes-Briones Humberto , Fernández-Villa Tania , Martín-Sánchez Vicente , Guallar-Castillón Pilar , Rodríguez-Artalejo Fernando , Lopez-Garcia Esther
Published: May 2024

Background

The role of diet quality on malnutrition in older adults is uncertain, due the paucity of the research conducted and the use of use of screening tools that did not consider phenotypic criteria of malnutrition.

Objective

To evaluate the association of two indices of diet quality, namely the Mediterranean Diet Adherence Screener (MEDAS) and the Alternative Healthy Eating Index (AHEI-2010), with malnutrition among community-dwelling older adults in Spain.

Methods

Cross-sectional analysis of data from 1921 adults aged ≥ 60 years from the Seniors-ENRICA-1 (SE-1) study, and 2652 adults aged ≥ 65 years from the Seniors-ENRICA-2 (SE-2) study. Habitual food consumption was assessed through a validated diet history. Malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM) phenotypic criteria. Statistical analyses were performed with logistic regression with adjustment for socioeconomic and lifestyle variables as well as for total energy and protein intake.

Results

The prevalence of malnutrition in the SE-1 study was 9.5% (95% confidence interval: 8.2 to 10.9) and 11.7% (10.5 to 13.9) in the SE-2. Adherence to the MEDAS score was associated with lower prevalence of malnutrition [pooled odds ratio for high (≥ 9 points) vs. low adherence (< 7 points): 0.64 (0.48–0.84); p-trend < 0.001]. Higher adherence to the AHEI-2010 also showed an inverse association with malnutrition (pooled odds ratio for quartile 4 vs. 1: 0.65 (0.49–0.86); p-trend 0.006). Among the individual components, higher consumption of fish and long-chain n-3 fatty acids in MEDAS and AHEI-2010, and of vegetables and nuts and legumes in AHEI-2010, and lower intake of trans-fat and sugar-sweetened beverages and fruit juice in AHEI-2010 were independently associated with lower odds of malnutrition.

Conclusion

Adherence to high diet-quality patterns was associated with lower frequency of malnutrition among older adults.

Clinical trial registry

ClinicalTrials.gov identifier: NCT02804672. June 17, 2016.; ClinicalTrials.gov NCT03541135. May 30, 2018.
Characterization of linezolid- and methicillin-resistant coagulase-negative staphylococci in a tertiary hospital in China
Authors: Liu Cailin , Yu Jing , Chen Chunguang , Li Xiaogai , Ye Yafei , Dong Yani , Ying Xinxin , Li Haijun , Wang Wanhai
Published: May 2024

Background

Recently, linezolid-resistant staphylococci have become an emerging problem worldwide. Understanding the mechanisms of resistance, molecular epidemiology and transmission of linezolid-resistant CoNS in hospitals is very important.

Methods

The antimicrobial susceptibilities of all isolates were determined by the microdilution method. The resistance mechanisms and molecular characteristics of the strains were determined using whole-genome sequencing and PCR.

Results

All the strains were resistant to oxacillin and carried the mecA gene; 13 patients (36.1%) had prior linezolid exposure. Most S. epidermidis and S. hominis isolates were ST22 and ST1, respectively. MLST typing and evolutionary analysis indicated most linezolid-resistant CoNS strains were genetically related. In this study, we revealed that distinct CoNS strains have different mechanisms of linezolid resistance. Among ST22-type S. epidermidis, acquisition of the T2504A and C2534T mutations in the V domain of the 23 S rRNA gene, as well as mutations in the ribosomal proteins L3 (L101V, G152D, and D159Y) and L4 (N158S), were linked to the development of linezolid resistance. In S. cohnii isolates, cfr, S158Y and D159Y mutations in the ribosomal protein L3 were detected. Additionally, emergence of the G2576T mutation and the cfr gene were major causes of linezolid resistance in S. hominis isolates. The cfr gene, G2576T and C2104T mutations, M156T change in L3 protein, and I188S change in L4 protein were found in S. capitis isolates.

Conclusion

The emergence of linezolid-resistant CoNS in the environment is concerning because it involves clonal dissemination and frequently coexists with various drug resistance mechanisms.
Associations of systemic inflammatory regulators with CKD and kidney function: evidence from the bidirectional mendelian randomization study
Authors: Liu Hailang , Xiang Wei , Wu Wei , Zhou Gaofeng , Yuan Jingdong
Published: May 2024

Background

Previous observational studies have reported that systemic inflammatory regulators are related to the development of chronic kidney disease (CKD); however, whether these associations are causal remains unclear. The current study aimed to investigate the potential causal relationships between systemic inflammatory regulators and CKD and kidney function.

Method

We performed bidirectional two-sample Mendelian randomization (MR) analyses to infer the underlying causal associations between 41 systemic inflammatory regulators and CKD and kidney function. The inverse-variance weighting (IVW) test was used as the primary analysis method. In addition, sensitivity analyses were executed via the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test and the weighted median test.

Results

The findings revealed 12 suggestive associations between 11 genetically predicted systemic inflammatory regulators and CKD or kidney function in the forward analyses, including 4 for CKD, 3 for blood urea nitrogen (BUN), 4 for eGFRcrea and 1 for eGFRcys. In the other direction, we identified 6 significant causal associations, including CKD with granulocyte-colony stimulating factor (GCSF) (IVW β = 0.145; 95% CI, 0.042 to 0.248; P = 0.006), CKD with stem cell factor (SCF) (IVW β = 0.228; 95% CI, 0.133 to 0.323; P = 2.40 × 10− 6), eGFRcrea with SCF (IVW β =-2.90; 95% CI, -3.934 to -1.867; P = 3.76 × 10− 8), eGFRcys with GCSF (IVW β =-1.382; 95% CI, -2.404 to -0.361; P = 0.008), eGFRcys with interferon gamma (IFNg) (IVW β =-1.339; 95% CI, -2.313 to -0.366; P = 0.007) and eGFRcys with vascular endothelial growth factor (VEGF) (IVW β =-1.709; 95% CI, -2.720 to -0.699; P = 9.13 × 10− 4).

Conclusions

Our findings support causal links between systemic inflammatory regulators and CKD or kidney function both in the forward and reverse MR analyses.
Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report
Authors: Shao Yan , Chen Yi , Wang Shichang , Li Chaowei , Sun Hongqiang , Sun Xinyu
Published: May 2024

Background

Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects.

Case presentation

A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge.

Discussion and conclusions

This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.
Association between physical activity and thyroid function in American adults: a survey from the NHANES database
Authors: Tian Lijun , Lu Cihang , Teng Weiping
Published: May 2024

Objective

Physical activity (PA) is closely related to our lives, and the effects of PA on thyroid function have not been elucidated.

Methods

Using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2012, we included 5877 participants and analyzed the associations of thyroid function with weekly physical activity (PAM, expressed in metabolic equivalents of task) and physical activity time (PAT) in American adults. Univariate and multivariate logistic analyses were used to demonstrate the associations of PAM and PAT with the primary outcome. Linear regression analysis was performed to determine the associations between thyroid biochemical indicators/diseases and PAM/PAT.

Results

Our study revealed noticeable sex differences in daily PA among the participants. The odds ratio of the fourth versus the first quartile of PAM was 3.07 (confidence interval, CI [1.24, 7.58], p = 0.02) for overt hypothyroidism, 3.25 (CI [1.12, 9.45], p = 0.03) for subclinical hyperthyroidism in adult men. PAT in the range of 633–1520 min/week was found to be associated with the occurrence of subclinical hyperthyroidism [p < 0.001, OR (95% CI) = 5.89 (1.85, 18.80)], PAT of the range of > 1520 min/week was found to be associated with the occurrence of overt hypothyroidism [p < 0.001, OR (95% CI) = 8.70 (2.80, 27.07)] and autoimmune thyroiditis (AIT) [p = 0.03, OR (95% CI) = 1.42 (1.03, 1.97)] in adult men. When PAM < 5000 MET*minutes/week or PAT < 1000 min/week, RCS showed an L-shaped curve for TSH and an inverted U-shaped curve for FT4. The changes in FT3 and TT3 in men were linearly positively correlated with PAM and PAT, while TT4 is linearly negatively correlated.

Conclusion

The amount of daily physical activity of American adults is strongly associated with changes in thyroid function, including thyroid hormone levels and thyroid diseases. Thyroid hormone levels were varied to a certain extent with changes in PAM and PAT.
Unilateral biportal endoscopy via two different approaches for upper lumbar disc herniation: a technical note
Authors: Shao Rongxue , Du Weibin , Zhang Wei , Cheng Wei , Zhu Chengyue , Liang Jiaming , Yue Jun , Pan Hao
Published: May 2024

Background

The traditional surgical procedures for upper lumbar disc herniation (ULDH) usually lead to frequent complications. We aim to investigate the clinical efficacy of the unilateral biportal endoscopy (UBE) technique in treating upper lumbar disc herniation (ULDH).

Methods

From January 2020 to December 2021, the clinical data of 28 patients with ULDH treated with the UBE technique were collected and analyzed for surgery time under UBE, postsurgical drainage, postsurgical hospital stay, and complications. The clinical efficacy was evaluated according to the modified MacNab score, Oswestry disability index (ODI), and visual analogue scale (VAS) of low back pain and lower limb pain before the surgery; one week, one month, and three months after the surgery; and at the last follow-up.

Results

All patients underwent the UBE surgery successfully. The surgery time under UBE for non-fusion cases was 47.50 ± 11.84 min (monosegment) and 75.00 ± 20.66 min (two segments), while that for fusion cases was 77.50 ± 21.02 min. The postsurgical drainage for non-fusion cases was 25.00 ± 13.94 mL (monosegment) and 38.00 ± 11.83 mL (two segments), while that for fusion cases was 71.25 ± 31.72 mL. The postsurgical hospital stay was 8.28 ± 4.22 days. The follow-up time was 15.82 ± 4.54 months. The VAS score for each time period after the surgery was significantly lower (P < 0.05), while the ODI was significantly higher than that before the surgery (P < 0.05). According to the modified MacNab scoring standard, the ratio of excellent to good was 96.43% at the last follow-up. Two patients experienced transient numbness and pain in their lower limbs and no activity disorder after the surgery, and they recovered after conservative treatment.

Conclusions

The clinical effect of UBE technique in treating ULDH was reliable. According to the needs of the disease, the interlaminar approach or paraspinal approach of the UBE technique was selected. This technique took into account the effect of treatment, achieved the purpose of minimal invasiveness, and did not require special instruments. Therefore, it has the potential for clinical application.
Cross-cultural adaption, validity, and reliability of the Japanese version of the Central Aspects of Pain in the Knee (CAP-Knee-J) questionnaire in patients with knee pain: a validation study
Authors: Oka Tomohiro , Wada Osamu , Matsuda Shun , Tanaka Katsuyoshi , Mizuno Kiyonori
Published: May 2024

Background

Knee pain is a prominent concern among older individuals, influenced by the central nervous system. This study aimed to translate the Central Aspects of Pain in the Knee (CAP-Knee) questionnaire into Japanese and investigate its reliability and validity in older Japanese individuals with knee pain.

Methods

Using a forward–backward method, CAP-Knee was translated into Japanese, and data from 110 patients at an orthopedic clinic were analyzed. The Japanese version (CAP-Knee-J) was evaluated regarding pain intensity during walking, central sensitization inventory, and pain catastrophizing scale. Statistical analyses confirmed internal validity and test–retest reliability. Concurrent validity was assessed through a single correlation analysis between CAP-Knee-J and the aforementioned measures. Exploratory factor analysis was employed on each CAP-Knee-J item to examine structural validity.

Results

CAP-Knee-J showed good internal consistency (Cronbach’s α = 0.86) and excellent test–retest reliability (intraclass correlation coefficient = 0.77). It correlated significantly with pain intensity while walking, central sensitization inventory scores, and pain catastrophizing scale scores. Exploratory factor analysis produced a three-factor model.

Conclusions

CAP-Knee-J is a reliable and valid questionnaire for assessing central pain mechanisms specific to knee pain in older Japanese individuals, with moderate correlations with the CSI and weak with the PCS, thus indicating construct validity. This study supports the development of effective knee pain treatments and prognosis predictions.
Evaluating flexure properties, hardness, roughness and microleakage of high-strength injectable dental composite: an in vitro study
Authors: Basheer Rasha R. , Hasanain Fatin A. , Abuelenain Dalia A.
Published: May 2024

Background

Recently, a new generation of high-strength flowable dental composites has been introduced by manufacturers. The manufacturers claim that these materials have enhanced mechanical and physical properties and are suitable for use in a wide range of direct anterior and posterior restorations, even in high-stress bearing areas.

Aim

The objective of this study was to assess certain physical and mechanical properties of these recently introduced high-strength flowable composites in comparison to conventional multipurpose dental composites.

Methods

Four types of high-strength flowable composites (Genial Universal FLO, Gaenial Universal Injectable, Beautifil Injectable, and Beautifil Flow Plus) were tested in experimental groups, while a nanohybrid conventional composite (Filtek Z350 XT) was used as the control. For flexure properties, ten rectangular samples (2 × 2 × 25 mm) were prepared from each composite material and subjected to 5000 cycles of thermocycling. Samples were then subjected to flexural strength testing using the universal testing machine. Another twenty disc-shaped specimens of dimensions (5 mm diameter × 2 mm thickness) were fabricated from each composite material for surface roughness (Ra) (n = 10) and hardness (VHN) test (n = 10). All samples underwent 5000 cycles of thermocycling before testing. Additionally, microleakage testing was conducted on 60 standardized class V cavities prepared on molar teeth and divided randomly into five groups (n = 12). Cavities were then filled with composite according to the manufacturer’s instructions and subjected to thermocycling for 1000 cycles before testing using methylene blue solution and a stereomicroscope.

Results

All tested materials were comparable to the control group in terms of flexural strength and surface roughness (p > 0.05), with Gaenial Universal FLO exhibiting significantly higher flexural strength compared to the other flowable composite materials tested. However, all tested materials demonstrated significantly lower elastic modulus and surface hardness than the control group (p < 0.05). The control group exhibited higher microleakage scores, while the lowest scores were observed in the Gaenial Universal FLO material (p < 0.05)

Conclusion

The physical and mechanical behaviors of the different high-strength flowable composites investigated in this study varied. Some of these materials may serve as suitable alternatives to conventional composites in specific applications, emphasizing the importance of dentists being familiar with material properties before making material selections.
Effects of on-site Supportive Communication Training (On-site SCT) on doctor-patient communication in oncology: Study protocol of a randomized, controlled mixed-methods trial
Authors: KK Antonsen , AT Johnsen , LØ Poulsen , JD Lyhne , L Lund , S Eßer-Naumann , S Timm , LH Jensen
Published: May 2024

Background

The quality of communication in oncology significantly impacts patients' health outcomes, as poor communication increases the risk of unnecessary treatment, inadequate pain relief, higher anxiety levels, and acute hospitalizations. Additionally, ineffective communication skills training (CST) is associated with stress, low job satisfaction, and burnout among doctors working in oncology. While acknowledging the importance of effective communication, the specific features of successful CST remain uncertain. Role-play and recorded consultations with direct feedback appear promising for CST but may be time-consuming and face challenges in transferring acquired skills to clinical contexts. Our aim is to bridge this gap by proposing a novel approach: On-site Supportive Communication Training (On-site SCT). The concept integrates knowledge from previous studies but represents the first randomized controlled trial employing actual doctor-patient interactions during CST.

Methods

This randomized multicenter trial is conducted at three departments of oncology in Denmark. Doctors are randomized 1:1 to the intervention and control groups. The intervention group involves participation in three full days of On-site SCT facilitated by a trained psychologist. On-site SCT focuses on imparting communication techniques, establishing a reflective learning environment, and offering emotional support with a compassionate mindset. The primary endpoint is the change in percentage of items rated “excellent” by the patients in the validated 15-item questionnaire Communication Assessment Tool. The secondary endpoints are changes in doctors’ ratings of self-efficacy in health communication, burnout, and job satisfaction measured by validated questionnaires. Qualitative interviews will be conducted with the doctors after the intervention to evaluate its relevance, feasibility, and working mechanisms. Doctors have been actively recruited during summer/autumn 2023. Baseline questionnaires from patients have been collected. Recruitment of new patients for evaluation questionnaires is scheduled for Q1-Q2 2024.

Discussion

This trial aims to quantify On-site SCT efficacy. If it significantly impacts patients/doctors, it can be a scalable CST concept for clinical practice. Additionally, qualitative interviews will reveal doctors' insight into the most comprehensible curriculum parts.

Trial registration

April 2023 – ClinicalTrials.gov (NCT05842083). April 2023 – The Research Ethics Committee at the University of Southern Denmark (23/19397).
Analysis of onset-to-door time and its influencing factors in Chinese patients with acute ischemic stroke during the 2020 COVID-19 epidemic: a preliminary, prospective, multicenter study
Authors: Liao Yuqi , Qi Wenwei , Li Shuting , Shi Xin , Wu Xiaohong , Chi Feng , Xia Runyu , Qin Limin , Cao Liming , Ren Lijie
Published: May 2024

Background

Pre-hospital delay in China is a serious issue with unclear relevant reasons, seriously impeding the adoption of appropriate measures. Herein, we analyzed the onset-to-door time (ODT) in Chinese patients with acute ischemic stroke (AIS) and its influencing factors.

Methods

We prospectively recruited 3,459 patients with AIS from nine representative tertiary general hospitals in China between January and June 2022. Patients were divided into ODT ≤ 3 h and ODT > 3 h groups. Following single-factor analysis, binary logistic regression analysis was performed to evaluate the risk factors leading to pre-hospital delay.

Results

In total, 763 (21.83%) patients arrived at the hospital within 3 h of onset. After adjusting for confounding factors, the risk factors for ODT were residence in rural areas (odds ratio [OR]: 1.478, 95% credibility interval [CI]: 1.024–2.146) and hospital transfer (OR: 7.479, 95% CI: 2.548–32.337). The protective factors for ODT were location of onset ≤ 20 km from the first-visit hospital (OR: 0.355, 95% CI: 0.236–0.530), transportation by emergency medical services (OR: 0.346, 95% CI: 0.216–0.555), history of atrial fibrillation (OR: 0.375, 95% CI: 0.207–0.679), moderate stroke (OR: 0.644, 95% CI: 0.462–0.901), and severe stroke (OR: 0.506, 95% CI: 0.285–0.908).

Conclusions

Most patients with AIS fail to reach a hospital within the critical 3-h window. The following measures are recommended to reduce pre-hospital delays: reasonable distribution of hospitals accessible to nearby residents, minimizing interhospital transfer, paying attention to patients with mild stroke, and encouraging patients to use ambulance services. Pre-hospital delays for patients can be reduced by implementing these measures, ultimately improving the timeliness of treatment and enhancing patient prognosis. This study was carried out amid the COVID-19 pandemic, which presented challenges and constraints.
Contribution of extracellular vesicles for the pathogenesis of retinal diseases: shedding light on blood-retinal barrier dysfunction
Authors: Martins Beatriz , Pires Maria , Ambrósio António Francisco , Girão Henrique , Fernandes Rosa
Published: May 2024

Retinal degenerative diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), loom as threats to vision, causing detrimental effects on the structure and function of the retina. Central to understanding these diseases, is the compromised state of the blood-retinal barrier (BRB), an effective barrier that regulates the influx of immune and inflammatory components. Whether BRB breakdown initiates retinal distress, or is a consequence of disease progression, remains enigmatic. Nevertheless, it is an indication of retinal dysfunction and potential vision loss.

The intricate intercellular dialogues among retinal cell populations remain unintelligible in the complex retinal milieu, under conditions of inflammation and oxidative stress. The retina, a specialized neural tissue, sustains a ceaseless demand for oxygen and nutrients from two vascular networks. The BRB orchestrates the exchange of molecules and fluids within this specialized region, comprising the inner BRB (iBRB) and the outer BRB (oBRB). Extracellular vesicles (EVs) are small membranous structures, and act as messengers facilitating intercellular communication in this milieu.

EVs, both from retinal and peripheral immune cells, increase complexity to BRB dysfunction in DR and AMD. Laden with bioactive cargoes, these EVs can modulate the retinal microenvironment, influencing disease progression. Our review delves into the multifaceted role of EVs in retinal degenerative diseases, elucidating the molecular crosstalk they orchestrate, and their microRNA (miRNA) content. By shedding light on these nanoscale messengers, from their biogenesis, release, to interaction and uptake by target cells, we aim to deepen the comprehension of BRB dysfunction and explore their therapeutic potential, therefore increasing our understanding of DR and AMD pathophysiology.
Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies
Authors: Rolver Monica G , Emanuelsson Frida , Nordestgaard Børge G , Benn Marianne
Published: May 2024

Objective

To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related.

Research design and methods

Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC.

Results

Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (β-coefficient: 0.02 (0.02, 0.03), p = 3 × 10− 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (−0.04 (−0.12, 0.32) and − 0.03 (−0.13, 0.06)), nor of glucose on CRP (−0.01 (−0.08, 0.07) and − 0.00 (−0.14, 0.13)).

Conclusions

Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.
Persistent inequities in maternal mortality in Latin America and the Caribbean, 1990–2019
Authors: Sáenz Rocío , Nigenda Gustavo , Gómez-Duarte Ingrid , Rojas Karol , Castro Arachu , Serván-Mori Edson
Published: May 2024

Background

Despite the resources and personnel mobilized in Latin America and the Caribbean to reduce the maternal mortality ratio (MMR, maternal deaths per 100 000 live births) in women aged 10–54 years by 75% between 2000 and 2015, the region failed to meet the Millenium Development Goals (MDGs) due to persistent barriers to access quality reproductive, maternal, and neonatal health services.

Methods

Using 1990–2019 data from the Global Burden of Disease project, we carried out a two-stepwise analysis to (a) identify the differences in the MMR temporal patterns and (b) assess its relationship with selected indicators: government health expenditure (GHE), the GHE as percentage of gross domestic product (GDP), the availability of human resources for health (HRH), the coverage of effective interventions to reduce maternal mortality, and the level of economic development of each country.

Findings

In the descriptive analysis, we observed a heterogeneous overall reduction of MMR in the region between 1990 and 2019 and heterogeneous overall increases in the GHE, GHE/GDP, and HRH availability. The correlation analysis showed a close, negative, and dependent association of the economic development level between the MMR and GHE per capita, the percentage of GHE to GDP, the availability of HRH, and the coverage of SBA. We observed the lowest MMRs when GHE as a percentage of GDP was close to 3% or about US$400 GHE per capita, HRH availability of 6 doctors, nurses, and midwives per 1,000 inhabitants, and skilled birth attendance levels above 90%.

Conclusions

Within the framework of the Sustainable Development Goals (SDGs) agenda, health policies aimed at the effective reduction of maternal mortality should consider allocating more resources as a necessary but not sufficient condition to achieve the goals and should prioritize the implementation of new forms of care with a gender and rights approach, as well as strengthening actions focused on vulnerable groups.
Left knee septic monoarthritis in a pediatric patient due to shewanella putrefaciens: case report and literature review
Authors: Madrid Nathalie Yepes , Mejia Luis Fernando , Urrego José Fernando Gomez
Published: May 2024

Background

Shewanella putrefaciens is a gram-negative, nonfermenting, oxidase-positive, hydrogen sulfide-producing bacillus and a halophilic bacterium, known for causing unusual infections in humans and often regarded as an opportunistic pathogen. Its diverse symptoms have a significant impact on human health, with 260 documented disorders reported in the literature over the last 40 years, highlighting its potential danger.

Case presentation

We present the case of a previously healthy 15-year-old male patient who sustained a self-inflicted sharp-object injury while working in the field, resulting in secondary septic monoarthritis due to Shewanella putrefaciens.

Conclusions

This case highlights the bacteriological and clinical characteristics, as well as the antibiogram, of Shewanella spp. Given the recent increase in notifications of Shewanella infections, predominantly by S. algae and S. putrefaciens, it is essential to consider these pathogens in patients with a history of contact with bodies of water. Special attention must be paid to their resistance patterns in patient management to prevent the development of intrinsic antimicrobial resistance.
The landscape of transcriptional profiles in human oocytes with different chromatin configurations
Authors: Zhang Yi-Ran , Yin Ying , Guo Shi-Meng , Wang Yu-Fan , Zhao Guang-Nian , Ji Dong-Mei , Zhou Li-Quan
Published: May 2024

With increasingly used assisted reproductive technology (ART), the acquisition of high-quality oocytes and early embryos has become the focus of much attention. Studies in mice have found that the transition of chromatin conformation from non-surrounded nucleolus (NSN) to surrounded nucleolus (SN) is essential for oocyte maturation and early embryo development, and similar chromatin transition also exists in human oocytes. In this study, we collected human NSN and SN oocytes and investigated their transcriptome. The analysis of differentially expressed genes showed that epigenetic functions, cyclin-dependent kinases and transposable elements may play important roles in chromatin transition during human oocyte maturation. Our findings provide new insights into the molecular mechanism of NSN-to-SN transition of human oocyte and obtained new clues for improvement of oocyte in vitro maturation technique.
Aftermath Türkiye’s double earthquake: detailed analysis of fracture characteristics and acute management from a level I trauma center
Authors: Gökmen Mehmet Yiğit , Uluöz Mesut , Pazarcı Özhan , Çiloğlu Osman , Varmış Hasan Orkun
Published: May 2024

Background

This research investigated surgical interventions for the treatment of extremity and pelvic fractures and aimed to provide an analysis of management challenges under crisis conditions in a Level I Trauma Center after Türkiye’s February 6, 2023, earthquakes.

Methods

The study was a retrospective examination of the medical records of 243 fracture cases associated with the earthquakes. The age, gender, time of admission, types of extremity and pelvic fractures, anatomical localizations, and surgical treatment methods for fractures were recorded. The results of these parameters were evaluated in detail, together with the results of other surgical treatments performed in the hospital in the first week after the disaster, such as fasciotomy, amputation, and wound debridement.

Results

Most of the 243 (119 males and 124 females) patients with extremity fractures and pelvic fractures receiving surgical treatment were adults (n = 182, 74.9%). The most common lower extremity fractures among all fracture cases were tibial shaft (30.8%) and femoral shaft (20.6%) fractures. A total of 33 patients had surgical procedures for the treatment of two or more significant bone fractures involving either the extremity or the pelvic ring. The analysis showed that the median age of patients who underwent surgery due to extremity and pelvic fractures was 36 years, with a range of 1 to 91 years, which was statistically increased compared to patients who received surgery for other musculoskeletal injuries such as fasciotomy, amputation and debridement (p < 0.001).

Conclusion

Fractures were one of the most common musculoskeletal injuries in the first days after earthquakes, and the management of fractures differs significantly from soft tissue injuries and amputation surgeries as they require implants, special instruments, and imaging devices. The delivery of healthcare is often critically impaired after a severe earthquake. Shortages of consumables such as orthopedic implants, power drills, fluoroscopy equipment, and the need for additional staff should be addressed immediately after the earthquake, ideally by the end of the first day.
Machine learning derived serum creatinine trajectories in acute kidney injury in critically ill patients with sepsis
Authors: Takkavatakarn Kullaya , Oh Wonsuk , Chan Lili , Hofer Ira , Shawwa Khaled , Kraft Monica , Shah Neomi , Kohli-Seth Roopa , Nadkarni Girish N. , Sakhuja Ankit
Published: May 2024

Background

Current classification for acute kidney injury (AKI) in critically ill patients with sepsis relies only on its severity-measured by maximum creatinine which overlooks inherent complexities and longitudinal evaluation of this heterogenous syndrome. The role of classification of AKI based on early creatinine trajectories is unclear.

Methods

This retrospective study identified patients with Sepsis-3 who developed AKI within 48-h of intensive care unit admission using Medical Information Mart for Intensive Care-IV database. We used latent class mixed modelling to identify early creatinine trajectory-based classes of AKI in critically ill patients with sepsis. Our primary outcome was development of acute kidney disease (AKD). Secondary outcomes were composite of AKD or all-cause in-hospital mortality by day 7, and AKD or all-cause in-hospital mortality by hospital discharge. We used multivariable regression to assess impact of creatinine trajectory-based classification on outcomes, and eICU database for external validation.

Results

Among 4197 patients with AKI in critically ill patients with sepsis, we identified eight creatinine trajectory-based classes with distinct characteristics. Compared to the class with transient AKI, the class that showed severe AKI with mild improvement but persistence had highest adjusted risks for developing AKD (OR 5.16; 95% CI 2.87–9.24) and composite 7-day outcome (HR 4.51; 95% CI 2.69–7.56). The class that demonstrated late mild AKI with persistence and worsening had highest risks for developing composite hospital discharge outcome (HR 2.04; 95% CI 1.41–2.94). These associations were similar on external validation.

Conclusions

These 8 classes of AKI in critically ill patients with sepsis, stratified by early creatinine trajectories, were good predictors for key outcomes in patients with AKI in critically ill patients with sepsis independent of their AKI staging.
Insertion of short L1 sequences generates inter-strain histone acetylation differences in the mouse
Authors: Boyboy Beverly Ann G. , Ichiyanagi Kenji
Published: May 2024

Background

Gene expression divergence between populations and between individuals can emerge from genetic variations within the genes and/or in the cis regulatory elements. Since epigenetic modifications regulate gene expression, it is conceivable that epigenetic variations in cis regulatory elements can also be a source of gene expression divergence.

Results

In this study, we compared histone acetylation (namely, H3K9ac) profiles in two mouse strains of different subspecies origin, C57BL/6 J (B6) and MSM/Ms (MSM), as well as their F1 hybrids. This identified 319 regions of strain-specific acetylation, about half of which were observed between the alleles of F1 hybrids. While the allele-specific presence of the interferon regulatory factor 3 (IRF3) binding sequence was associated with allele-specific histone acetylation, we also revealed that B6-specific insertions of a short 3′ fragment of LINE-1 (L1) retrotransposon occur within or proximal to MSM-specific acetylated regions. Furthermore, even in hyperacetylated domains, flanking regions of non-polymorphic 3′ L1 fragments were hypoacetylated, suggesting a general activity of the 3′ L1 fragment to induce hypoacetylation. Indeed, we confirmed the binding of the 3′ region of L1 by three Krüppel-associated box domain-containing zinc finger proteins (KZFPs), which interact with histone deacetylases. These results suggest that even a short insertion of L1 would be excluded from gene- and acetylation-rich regions by natural selection. Finally, mRNA-seq analysis for F1 hybrids was carried out, which disclosed a link between allele-specific promoter/enhancer acetylation and gene expression.

Conclusions

This study disclosed a number of genetic changes that have changed the histone acetylation levels during the evolution of mouse subspecies, a part of which is associated with gene expression changes. Insertions of even a very short L1 fragment can decrease the acetylation level in their neighboring regions and thereby have been counter-selected in gene-rich regions, which may explain a long-standing mystery of discrete genomic distribution of LINEs and SINEs.
Hyper-physiologic mechanical cues, as an osteoarthritis disease-relevant environmental perturbation, cause a critical shift in set points of methylation at transcriptionally active CpG sites in neo-cartilage organoids
Authors: Bloks Niek G. C. , Dicks Amanda , Harissa Zainab , Nelissen Rob G. H. H. , Hajmousa Ghazaleh , Ramos Yolande F. M. , de Almeida Rodrigo Coutinho , Guilak Farshid , Meulenbelt Ingrid
Published: May 2024

Background

Osteoarthritis (OA) is a complex, age-related multifactorial degenerative disease of diarthrodial joints marked by impaired mobility, joint stiffness, pain, and a significant decrease in quality of life. Among other risk factors, such as genetics and age, hyper-physiological mechanical cues are known to play a critical role in the onset and progression of the disease (Guilak in Best Pract Res Clin Rheumatol 25:815–823, 2011). It has been shown that post-mitotic cells, such as articular chondrocytes, heavily rely on methylation at CpG sites to adapt to environmental cues and maintain phenotypic plasticity. However, these long-lasting adaptations may eventually have a negative impact on cellular performance. We hypothesize that hyper-physiologic mechanical loading leads to the accumulation of altered epigenetic markers in articular chondrocytes, resulting in a loss of the tightly regulated balance of gene expression that leads to a dysregulated state characteristic of the OA disease state.

Results

We showed that hyper-physiological loading evokes consistent changes in CpGs associated with expression changes (ML-tCpGs) in ITGA5, CAV1, and CD44, among other genes, which together act in pathways such as anatomical structure morphogenesis (GO:0009653) and response to wound healing (GO:0042060). Moreover, by comparing the ML-tCpGs and their associated pathways to tCpGs in OA pathophysiology (OA-tCpGs), we observed a modest but particular interconnected overlap with notable genes such as CD44 and ITGA5. These genes could indeed represent lasting detrimental changes to the phenotypic state of chondrocytes due to mechanical perturbations that occurred earlier in life. The latter is further suggested by the association between methylation levels of ML-tCpGs mapped to CD44 and OA severity.

Conclusion

Our findings confirm that hyper-physiological mechanical cues evoke changes to the methylome-wide landscape of chondrocytes, concomitant with detrimental changes in positional gene expression levels (ML-tCpGs). Since CAV1, ITGA5, and CD44 are subject to such changes and are central and overlapping with OA-tCpGs of primary chondrocytes, we propose that accumulation of hyper-physiological mechanical cues can evoke long-lasting, detrimental changes in set points of gene expression that influence the phenotypic healthy state of chondrocytes. Future studies are necessary to confirm this hypothesis.
A novel easy-to-desorb eluant contributes to address environmental contamination of African swine fever virus
Authors: Zhang Li , Zhao Pengfei , Xia Yingjun , Hu Yanli , Wang Chaofei , Fang Rui , Zhao Junlong
Published: May 2024

African swine fever virus (ASFV) is a highly pathogenic and rapidly disseminated virus with strong viability in the environment, suggesting the importance of environmental detection for prevention and control in all the pig industry. However, the detection results of environmental swabs cannot always reflect the accurate status of viral pollution, leading to persistent ASFV environmental contamination. In this study, we developed an ASFV eluant with higher environmental ASFV detection efficiency relative to 0.85% saline solution, which obtains the patent certificate issued by the China Intellectual Property Office (patent number:202010976050.9). qPCR analysis showed that in the environmental swab samples, the number of viral copies was 100 times higher for the ASFV eluant treatment than the traditional eluant treatment (0.85% saline solution). And besides, the high sensitivity of the ASFV eluant had be verified in a slaughterhouse environmental sampling detection. In soil samples, the ASFV eluent showed the same extraction effect as the TIANamp Soil DNA Kit, in contrast to no extraction effect for 0.85% saline solution. Simultaneously, this eluent could protect ASFV from degradation and allow the transportation of samples at ambient temperature without refrigeration. In clinical practice, we monitored the environmental contamination condition of the ASFV in a large-scale pig farm. The results shown that the ASFV load decreased after every disinfection in environment. This study provides an effective solution for surveilling the potential threat of ASFV in environment.