bluuebunny/crossref_metadata_2025 huggingface dataset:
Within-person fluctuations of fatigue in patients with a clinical diagnosis of systemic sclerosis and its relationship with mood, pain, sleep and physical activity
Authors: Velauthapillai Arthiha , Vonk Madelon C , van den Ende Cornelia HM , Vriezekolk Johanna E
Published: May 2024

Objectives:

To explore the within-person fluctuations of fatigue in systemic sclerosis and its association with negative affect, positive affect, pain, perceived exertion of physical activity and quality of sleep.

Methods:

We performed an ecological momentary assessment study in adult patients with a clinical diagnosis of systemic sclerosis. During 14 days, patients completed daily assessments of fatigue severity, negative affect, positive affect, pain, quality of sleep and perceived exertion of physical activity at four fixed time points. The day-to-day fluctuations in fatigue were quantified by the intra-individual variance and probability of acute change, capturing the magnitude and frequency of clinical relevant within-person day-to-day fluctuations, respectively. Using multilevel models, the within-person association between fatigue and the daily assessments were analysed.

Results:

Fifty-seven patients with systemic sclerosis participated. The mean (standard deviation) intra-individual variance was 1.08 (0.42) and the probability of acute change was mean (standard deviation) 0.40 (0.14), ranging from 0.08 to 0.77. For fatigue, a within-person variation of 51% was observed. Multilevel analyses showed that higher average levels and daily increases in negative affect, pain and perceived exertion of physical activity were associated with more fatigue, while the opposite was observed for positive affect and quality of sleep. Positive affect demonstrated the strongest association with fatigue fluctuations.

Conclusion:

This is the first quantitative study showing that fatigue in systemic sclerosis is characterized by a dynamic course and that approximately half of the day-to-day fluctuations within persons are clinically meaningful. Furthermore, our results indicate that integrating activities with positive impact on mood into fatigue treatment strategies might reduce the frequency of fatigue fluctuations.
Integrin αVβ3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis
Authors: Geng Xiangwu , Tang Yifan , Gu Changjiang , Zeng Junkai , Zhao Yin , Zhou Quanwei , Jia Lianshun , Zhou Shengyuan , Chen Xiongsheng
Published: May 2024

Background

Ossification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVβ3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVβ3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVβ3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL.

Methods

OPLL or control ligament samples were collected in surgery. For OPLL samples, RNA-sequencing results revealed activation of the integrin family, particularly integrin αVβ3. Integrin αVβ3 expression was detected by qPCR, Western blotting, and immunohistochemical analysis. Fluorescence microscopy was used to observe the targeted inhibition of integrin αVβ3 by the c(RGDyk) peptide on ligaments fibroblasts (LFs) derived from patients with OPLL and endothelial cells (ECs). The effect of c(RGDyk) peptide on the ossification of pathogenic LFs was detected using qPCR, Western blotting. Alkaline phosphatase staining or alizarin red staining were used to test the osteogenic capability. The effect of the c(RGDyk) peptide on angiogenesis was determined by EC migration and tube formation assays. The effects of the c(RGDyk) peptide on heterotopic bone formation were evaluated by micro-CT, histological, immunohistochemical, and immunofluorescence analysis in vivo.

Results

The results indicated that after being treated with c(RGDyk), the osteogenic differentiation of LFs was significantly decreased. Moreover, the c(RGDyk) peptide inhibited the migration of ECs and thus prevented the nutritional support required for osteogenesis. Furthermore, the c(RGDyk) peptide inhibited ectopic bone formation in mice. Mechanistic analysis revealed that c(RGDyk) peptide could inhibit osteogenesis and angiogenesis in OPLL by targeting integrin αVβ3 and regulating the FAK/ERK pathway.

Conclusions

Therefore, the integrin αVβ3 appears to be an emerging therapeutic target for OPLL, and the c(RGDyk) peptide has dual inhibitory effects that may be valuable for the new therapeutic strategy of OPLL.
Genetic legacy and adaptive signatures: investigating the history, diversity, and selection signatures in Rendena cattle resilient to eighteenth century rinderpest epidemics
Authors: Somenzi Elisa , Partel Erika , Barbato Mario , Chero Osorio Ana María , Colli Licia , Franceschi Niccolò , Mantovani Roberto , Pilla Fabio , Komjanc Matteo , Achilli Alessandro , Hauffe Heidi Christine , Ajmone Marsan Paolo
Published: May 2024

Background

Rendena is a dual-purpose cattle breed, which is primarily found in the Italian Alps and the eastern areas of the Po valley, and recognized for its longevity, fertility, disease resistance and adaptability to steep Alpine pastures. It is categorized as 'vulnerable to extinction' with only 6057 registered animals in 2022, yet no comprehensive analyses of its molecular diversity have been performed to date. The aim of this study was to analyse the origin, genetic diversity, and genomic signatures of selection in Rendena cattle using data from samples collected in 2000 and 2018, and shed light on the breed's evolution and conservation needs.

Results

Genetic analysis revealed that the Rendena breed shares genetic components with various Alpine and Po valley breeds, with a marked genetic proximity to the Original Braunvieh breed, reflecting historical restocking efforts across the region. The breed shows signatures of selection related to both milk and meat production, environmental adaptation and immune response, the latter being possibly the result of multiple rinderpest epidemics that swept across the Alps in the eighteenth century. An analysis of the Rendena cattle population spanning 18 years showed an increase in the mean level of inbreeding over time, which is confirmed by the mean number of runs of homozygosity per individual, which was larger in the 2018 sample.

Conclusions

The Rendena breed, while sharing a common origin with Brown Swiss, has developed distinct traits that enable it to thrive in the Alpine environment and make it highly valued by local farmers. Preserving these adaptive features is essential, not only for maintaining genetic diversity and enhancing the ability of this traditional animal husbandry to adapt to changing environments, but also for guaranteeing the resilience and sustainability of both this livestock system and the livelihoods within the Rendena valley.
Equivalence of variance components between standard and recursive genetic models using LDL′ transformations
Authors: Varona Luis , López-Carbonell David , Srihi Houssemeddine , Hervás-Rivero Carlos , González-Recio Óscar , Altarriba Juan
Published: May 2024

Background

Recursive models are a category of structural equation models that propose a causal relationship between traits. These models are more parameterized than multiple trait models, and they require imposing restrictions on the parameter space to ensure statistical identification. Nevertheless, in certain situations, the likelihood of recursive models and multiple trait models are equivalent. Consequently, the estimates of variance components derived from the multiple trait mixed model can be converted into estimates under several recursive models through LDL′ or block-LDL′ transformations.

Results

The procedure was employed on a dataset comprising five traits (birth weight—BW, weight at 90 days—W90, weight at 210 days—W210, cold carcass weight—CCW and conformation—CON) from the Pirenaica beef cattle breed. These phenotypic records were unequally distributed among 149,029 individuals and had a high percentage of missing data. The pedigree used consisted of 343,753 individuals. A Bayesian approach involving a multiple-trait mixed model was applied using a Gibbs sampler. The variance components obtained at each iteration of the Gibbs sampler were subsequently used to estimate the variance components within three distinct recursive models.

Conclusions

The LDL′ or block-LDL′ transformations applied to the variance component estimates achieved from a multiple trait mixed model enabled inference across multiple sets of recursive models, with the sole prerequisite of being likelihood equivalent. Furthermore, the aforementioned transformations simplify the handling of missing data when conducting inference within the realm of recursive models.
Comparative transcriptomics analysis reveals defense mechanisms of Manihot esculenta Crantz against Sri Lanka Cassava MosaicVirus
Authors: Chaowongdee Somruthai , Vannatim Nattachai , Malichan Srihunsa , Kuncharoen Nattakorn , Tongyoo Pumipat , Siriwan Wanwisa
Published: May 2024

Background

Cassava mosaic disease (CMD), caused by Sri Lankan cassava mosaic virus (SLCMV) infection, has been identified as a major pernicious disease in Manihot esculenta Crantz (cassava) plantations. It is widespread in Southeast Asia, especially in Thailand, which is one of the main cassava supplier countries. With the aim of restricting the spread of SLCMV, we explored the gene expression of a tolerant cassava cultivar vs. a susceptible cassava cultivar from the perspective of transcriptional regulation and the mechanisms underlying plant immunity and adaptation.

Results

Transcriptomic analysis of SLCMV-infected tolerant (Kasetsart 50 [KU 50]) and susceptible (Rayong 11 [R 11]) cultivars at three infection stages—that is, at 21 days post-inoculation (dpi) (early/asymptomatic), 32 dpi (middle/recovery), and 67 dpi (late infection/late recovery)—identified 55,699 expressed genes. Differentially expressed genes (DEGs) between SLCMV-infected KU 50 and R 11 cultivars at (i) 21 dpi to 32 dpi (the early to middle stage), and (ii) 32 dpi to 67 dpi (the middle stage to late stage) were then identified and validated by real-time quantitative PCR (RT-qPCR). DEGs among different infection stages represent genes that respond to and regulate the viral infection during specific stages. The transcriptomic comparison between the tolerant and susceptible cultivars highlighted the role of gene expression regulation in tolerant and susceptible phenotypes.

Conclusions

This study identified genes involved in epigenetic modification, transcription and transcription factor activities, plant defense and oxidative stress response, gene expression, hormone- and metabolite-related pathways, and translation and translational initiation activities, particularly in KU 50 which represented the tolerant cultivar in this study.
Vitamin B6 ameliorates acute pancreatitis by suppressing the caspase3 signaling pathway
Authors: Xu Heling , Yue Hongqin , Ge Haijue , Wang Fusheng
Published: May 2024

Background

Acute pancreatitis (AP) is a prevalent exocrine inflammatory disorder of the pancreas characterized by pancreatic inflammation and injury to acinar cells. Vitamin B6 (VB6) is a vital nutrient that plays a significant role in preserving human health and has anti-inflammatory and anti-apoptotic effects.

Methods

This study aimed to explore the potential pancreatic protective effects of VB6 in mitigating pancreatic inflammation and apoptosis induced by taurocholate sodium (TLCS) in an AP model and to assess the underlying mechanism of action. AP was induced in Sprague‒Dawley (SD) rats through TLCS administration and lipopolysaccharide (LPS)-treated AR42J cells, followed by treatment with VB6.

Results

Various parameters associated with AP were assessed in both plasma and pancreatic tissues. VB6 has been shown to ameliorate the severity of AP through various mechanisms. It effectively reduces the levels of serum amylase, lipase, and inflammatory factors, thereby mitigating histological injury to the pancreas. Moreover, VB6 inhibited pancreatic apoptosis by downregulating bax expression and up-regulating Bcl2 expression in TLCS-treated rats. Additionally, VB6 suppressed the expression of caspase3. The anti-inflammatory and anti-apoptotic effects of VB6 observed in LPS-treated AR42J cells are consistent with those observed in a rat model of AP.

Conclusions

These results suggest that VB6 exerts anti-inflammatory and anti-apoptotic effects through inhibition of the caspase3 signaling pathway and has a protective effect against AP.
Effect of vitamin D, calcium, or combined supplementation on fall prevention: a systematic review and updated network meta-analysis
Authors: Tan Long , He Ruiqian , Zheng Xiaoxue
Published: May 2024

Background

The association between vitamin D supplementation and the risk of falls in older adults has been controversial. This systematic review and network meta-analysis aims to assess the efficacy of vitamin D, calcium, and combined supplementation in the prevention of falls.

Methods

Randomized controlled trials (RCTs) on the efficacy of vitamin D in fall prevention were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science from inception to May 9, 2023. The network meta-analysis was performed using a random effects model in R4.1.3 and Stata15.0. Heterogeneity was evaluated by the I2 statistic, and publication bias was assessed using funnel plots, Begg’s test, and Egger’s tests. Data were pooled and expressed as relative risk (RR) and 95% confidence interval (CI).

Results

A total of 35 RCTs involving 58,937 participants were included in this study, among which 11 RCTs (31.4%) applied calcium combined with vitamin D. There was low heterogeneity (I2 = 11%) among the included studies. Vitamin D supplementation at 800–1000 International Unit (IU)/d resulted in a lower risk of falls than placebo or no treatment (RR = 0.85, 95%CI: 0.74–0.95). In addition, 800–1000 IU/d of vitamin D with or without calcium were more effective in preventing falls than calcium alone. High-dose vitamin D (> 1000 IU/day) increased the risk of falls compared with 800–1000 IU/d of vitamin D. According to the subgroup analysis, daily administration of 800–1000 IU/d vitamin D was associated with a 22% reduction in the risk of falls (RR = 0.78, 95%CI:0.64–0.92), whereas intermittent vitamin D administration had no preventive effect. Furthermore, 800–1000 IU/d of vitamin D also significantly decreased the risk of falls in old adults with ≤ 50 nmol/L 25-hydroxyvitamin D [25(OH)D] (RR = 0.69, 95%CI:0.52–0.86) but not in individuals with > 50 nmol/L 25(OH)D.

Conclusion

Vitamin D supplementation at 800–1000 IU/d is associated with a lower risk of falls among older adults. 800-1000IU/d of vitamin D has a benefit on prevention of falls in population received daily dose regimens and in population with vitamin D deficiency.
Pregnancy outcomes of monochorionic diamniotic and dichorionic diamniotic twin pregnancies conceived by assisted reproductive technology and conceived naturally: a study based on chorionic comparison
Authors: Liu Shuhua , Xu Qianhua , Qian Jingyu , Liu Dehong , Zhang Bin , Chen Xianxia , Zheng Mingming
Published: May 2024

Objective

To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally.

Methods

We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally.

Result

MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p < 0.05). Women with DCDA pregnancies conceived naturally had lower rates of preterm birth, higher neonatal weights, and higher twin survival rates than women with DCDA pregnancies conceived by ART and those with DCT and TCT pregnancies reduced to DCDA pregnancies (all p < 0.05).

Conclusion

Our study confirms that the pregnancy outcomes of MCDA pregnancies conceived by ART are worse than those of MCDA pregnancies conceived naturally. Similarly, the pregnancy outcomes of naturally-conceived DCDA pregnancies are better than those of DCDA pregnancies conceived by ART and DCT and TCT pregnancies reduced to DCDA pregnancies.
Understanding referral of patients with cancer in rural Ethiopia: a qualitative study
Authors: Trabitzsch Josephin , Marquardt Morena , Negash Sarah , Belay Winini , Abebe Yonas , Seife Edom , Abdella Kunuz , Gizaw Muluken , Getachew Sefonias , Addissie Adamu , Kantelhardt Eva Johanna , Wondimagegnehu Abigiya
Published: May 2024

Background

Cancer incidence is increasing in Ethiopia mainly due to increased life expectancy, while oncological capacities remain limited. Strong referral linkages between different levels of the healthcare system are key to provide timely access to cancer care. In this qualitative study, we assessed limitations and potential of cancer patient referral in the rural Southwest of Ethiopia.

Methods

We held four focus group discussions (FGD) with health professionals at one primary and three secondary hospitals and conducted eight in-depth interviews (IDI) with the hospitals´ medical executives and local health bureau representatives. Data was analysed inductively using thematic analysis and emerging themes were categorized within the revised concept of access by Penchansky and Saurman.

Results

The inevitable referral of patients with cancer in the rural Southwest of Ethiopia is characterized by the absence of clear communication protocols and the lack of formal referral linkages. The newly implemented hub-system has improved emergency referrals and could be expanded to non-emergency referrals, sensitive to the needs of advanced oncological care. Liaison officers can pave the way but need to be trained and equipped adequately. Referred patients struggle with inadequate transportation systems, the lack of accommodation close to specialized facilities as well as the inability to navigate at those sites due to language barriers, illiteracy, and stigmatization. Few Non-Governmental Organizations (NGOs) help but cannot compensate the limited governmental support. The shortage of medications at public hospitals leads to patients being directed to costly private pharmacies. In the light of those challenges, cancer remains to be perceived as a “death sentence” within the rural communities.

Conclusions

Standardized referral linkages and a multi-faceted support network throughout the cancer care continuum are necessary to make oncology care accessible to Ethiopia´s large rural population.
Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia
Authors: Guo Fengtao , Jing Lin , Xu Yunfan , Zhang Kun , Li Ying , Sun Ning , Liu Penghong , Zhang Huanhu
Published: May 2024

Background

This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores.

Methods

46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman’s correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia.

Results

1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The β-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97.

Conclusion

This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP.
Diet quality as assessed by the healthy eating index-2020 among different smoking status: an analysis of national health and nutrition examination survey (NHANES) data from 2005 to 2018
Authors: Luo Ting , Tseng Tung-Sung
Published: May 2024

Background

Combining smoking with poor eating habits significantly elevates the risk of chronic illnesses and early death. Understanding of how dietary quality shifts post-smoking cessation remains limited. The objective of this study is to examine dietary quality – using Healthy Eating Index (HEI – 2020) and its 13 components, among current, former, and never smokers, and particularly the impact of quitting and the duration of cessation on dietary habits.

Methods

A cross-sectional analysis of 31,569 adults from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 was conducted. Dietary quality was assessed using HEI-2020 scores, which were determined by NIH developed - simple HEI scoring algorithm per person. Smoking status was categorized into current, former, and never smokers, with further subdivisions for current (heavy/light smokers) and former smokers (duration post-cessation). Descriptive analysis and multiple regression models weighted to represent the US population were performed.

Results

The current smoking rate was 19.4%, with a higher prevalence in males (22.5%) than females (17.5%). Current smokers reported statistically significantly lower HEI total score than both former and never smokers. Former smokers exhibited HEI scores similar to those of never smokers. The adjusted HEI total scores for current, former, and never smokers were 49.2, 54.0, and 53.3, respectively, with a statistically significant difference (p < 0.001). Moreover, light smokers had better total HEI score than heavy smokers (46.8 vs. 50.8, p < 0.001, respectively), but former and never smokers scored even higher. Quitting smoking immediately improved dietary quality, with former smokers reaching the dietary levels of never smokers within 5–10 years (53.8 vs. 53.3, p > 0.05, respectively). Compared to current smokers, former smokers tended to consume more beneficial foods (e.g., fruits, vegetables, greens and beans, whole grains, proteins, and fatty acids), while also consuming more sodium and less added sugar.

Conclusions

Current smokers, particularly heavy smokers, exhibit poorer dietary habits than former and never smokers. The dietary quality of former smokers aligns with never smokers over time, highlighting the positive impact of smoking cessation on diet. This has implications for reducing chronic disease risks associated with poor diet and smoking.
Prevalence of Parkinson’s disease among adults aged 45 years and older in China: a cross-sectional study based on the China health and retirement longitudinal study
Authors: Meng Detao , Wu Jiayu , Huang Xinyu , Liang Xiaoxiao , Fang Boyan
Published: May 2024

Background

In recent decades, China has experienced a rapid increase in the number of elderly individuals and life expectancy, as well as industrialization, which is associated with an increased prevalence of Parkinson's disease (PD). However, inconsistent results have recently been reported. Therefore, this study aimed to investigate the prevalence and distribution characteristics of PD among individuals aged 45 years and older.

Methods

Using data from the China Health and Retirement Longitudinal Study (CHARLS), we attempted to estimate the prevalence of PD and its distribution characteristics among 19,034 individuals aged 45 years and older residing in 446 communities/villages within 27 provinces/autonomous regions/municipalities in mainland China. Cases were established based on a doctor's previous diagnosis. Crude and age-adjusted prevalence rates were calculated and stratified by age, sex, area of residence, education level, marital status, and geographic region. Logistic regression models were used to identify risk factors associated with PD.

Results

We identified 178 patients with PD among 19,034 residents aged 45 years and older. The crude prevalence was 0.94%, and the age-adjusted prevalence was 0.82% for individuals aged 45 years and older. The prevalence of PD increased with age (P < 0.001). No significant differences were found in terms of sex, area of residence, or education level. Stratified by geographic region, the prevalence of PD was greater in North and Northwest China and lower in southern China (p < 0.001). Multiple regression analyses showed that age was a significant risk factor for PD.

Conclusion

The prevalence of PD increased with age in the Chinese population.
The facilitators of and barriers to antimicrobial use and misuse in Lalitpur, Nepal: a qualitative study
Authors: Udas Summita , Chand Obindra Bahadur , Shrestha Babin , Pathak Sushmita , Syantang Sarita , Dahal Ashata , Karkey Abhilasha , Giri Abhishek , Shilpakar Olita , Basnyat Buddha , Salami Olawale , Nkeramahame Juvenal , Olliaro Piero , Horgan Philip
Published: May 2024

Background

Antimicrobial resistance (AMR) is a pressing global health concern driven by inappropriate antibiotic use, which is in turn influenced by various social, systemic, and individual factors. This study, nested within FIND’s AMR Diagnostic Use Accelerator clinical trial in Nepal, aimed to (i) explore the perspectives of patients, caregivers, and healthcare workers (HCWs) on antibiotic prescription adherence and (ii) assess the impact of a training and communication (T&C) intervention on adherence to antibiotic prescriptions.

Methods

Using qualitative, semi-structured interviews, pre-intervention and Day 7 follow-up components, and the Behaviour Change Wheel process, we investigated the facilitators of and barriers to the use and misuse of antibiotic prescriptions.

Results

Results of the study revealed that adherence to antibiotic prescriptions is influenced by a complex interplay of factors, including knowledge and understanding, forgetfulness, effective communication, expectations, beliefs and habits, attitudes and behaviours, convenience of purchasing, trust in medical effectiveness, and issues of child preferences. The T&C package was also shown to play a role in addressing specific barriers to treatment adherence.

Conclusions

Overall, the results of this study provide a nuanced understanding of the challenges associated with antibiotic use and suggest that tailored interventions, informed by behaviour frameworks, can enhance prescription adherence, may be applicable in diverse settings and can contribute to the global effort to mitigate the rising threat of AMR.
Respiratory Rate Oxygenation (ROX) index as predictor of high flow nasal cannula in pediatric patients in pediatric intensive care unit
Authors: Yuniar Irene , Pudjiadi Antonius Hocky , Dewi Rismala , Prawira Yogi , Puspaningtyas Niken Wahyu , Tartila Tartila , Fulki Sharfina
Published: May 2024

Background

High-flow nasal cannula (HFNC) is often used in pediatric populations with respiratory distress. In adults, the respiratory-rate oxygenation (ROX) index is used as a predictor of HFNC therapy; however, children have age-associated differences in respiratory rate, thus may not be applicable to children. This study aims to find the reliability of ROX index and modified P-ROX index as predictors of HFNC therapy failure in pediatric patients.

Methods

Subjects in this analytical cross-sectional study were taken from January 2023 until November 2023 in Cipto Mangunkusumo Hospital. Inclusion criteria are children aged 1 month to 18 years with respiratory distress and got HFNC therapy. Receiver operating characteristics (ROC) analysis was used to find mP-ROX index cutoff value as a predictor of HFNC failure. The area under curve (AUC) score of mP-ROX index was assessed at different time point.

Results

A total of 102 patients, with 70% of the population with pneumonia, were included in this study. There are significant differences in the ROX index between the successful and failed HFNC group therapy (p < 0.05). This study suggests that mP-ROX index is not useful as predictor of HFNC therapy in pediatrics. While ROX index < 5.52 at 60 min and < 5.68 at 90 min after HFNC initiation have a sensitivity of 90% and specificity of 71%, sensitivity of 78% and specificity of 76%, respectively.

Conclusion

mP-ROX index is not useful as a predictor of HFNC therapy in pediatrics. Meanwhile, ROX index at 60 min and 90 min after initiation of HFNC is useful as a predictor of HFNC failure.
Assessing the reproducibility and predictive value of objective cough measurement for successful withdrawal of invasive ventilatory support in adult patients
Authors: Varón-Vega Fabio , Rincón Adriana , Giraldo-Cadavid Luis F. , Tuta-Quintero Eduardo , Palacios Jonathan , Crevoisier Stephanie , Duarte Diana C. , Poveda Marcela , Cucunubo Laura , Monedero Pablo
Published: May 2024

Background

Utilizing clinical tests, such as objective cough measurement, can assist in predicting the success of the weaning process in critically ill patients.

Methods

A multicenter observational analytical study was conducted within a prospective cohort of patients recruited to participate in COBRE-US. We assessed the capability of objective cough measurement to predict the success of the spontaneous breathing trial (SBT) and extubation. Intra- and inter-observer reproducibility of the cough test and was evaluated using the intraclass correlation coefficient (ICC) and Cohen’s weighted kappa. We used receiver operating characteristic curves (ROC-curve) to evaluate the predictive ability of objective cough measurement.

Results

We recruited 367 subjects who were receiving invasive mechanical ventilation. A total of 451 objective cough measurements and 456 SBTs were conducted. A significant association was found between objective cough measurement and successful SBT (OR: 1.68; 95% CI 1.48–1.90; p = 0.001). The predictive capability of the objective cough test for SBT success had a ROC-curve of 0.58 (95% CI: 0.56–0.61). Objective cough measurement to predict successful extubation had a ROC-curve of 0.61 (95% CI: 0.56–0.66). The intraobserver reproducibility exhibited an ICC of 0.94 (95% CI: 0.89–0.96; p < 0.001), while the interobserver reproducibility demonstrated an ICC of 0.72 (95% CI: 0.51–0.85; p < 0.001). The intraobserver agreement, assessed using Cohen’s weighted kappa was 0.94 (95% CI: 0.93–0.99; p < 0.001), whereas the interobserver agreement was 0.84 (95% CI: 0.67 − 0.10; p < 0.001).

Conclusions

The objective measurement of cough using the method employed in our study demonstrates nearly perfect intra-observer reproducibility and agreement. However, its ability to predict success or failure in the weaning process is limited.
Effects of high-flow nasal cannula oxygen therapy in bronchiectasis and hypercapnia: a retrospective observational study
Authors: Yang Jing , Chen Lei , Yu Hang , Hu Jingjing , Qiu Feng
Published: May 2024

Background

The effectiveness of high-flow nasal cannula (HFNC) therapy in patients with bronchiectasis experiencing hypercapnia remains unclear. Our aim was to retrospectively analyze the short-term outcomes of HFNC therapy in such patients, and to further explore the predictors of HFNC treatment failure in this particular patient population.

Methods

A retrospective review was conducted on patients with bronchiectasis who received HFNC (n = 70) for hypercapnia (arterial partial pressure of carbon dioxide, PaCO2 ≥ 45 mmHg) between September 2019 and September 2023.

Results

In the study population, 30% of patients presented with acidemia (arterial pH < 7.35) at baseline. Within 24 h of HFNC treatment, there was a significant reduction in PaCO2 levels by a mean of 4.0 ± 12.7 mmHg (95% CI -7.0 to -1.0 mmHg). Concurrently, arterial pH showed a statistically significant increase with a mean change of 0.03 ± 0.06 (95% CI 0.01 to 0.04). The overall hospital mortality rate in our study was 17.5%. The median length of hospital stay was 11.0 days (interquartile range [IQR] 8.0 to 16.0 days). Sub-analysis revealed no statistically significant differences in hospital mortality (19.0% vs. 20.4%, p = 0.896), length of hospital stay (median 14.0 days [IQR 9.0 to 18.0 days] vs. 10.0 days [IQR 7.0 to 16.0 days], p = 0.117) and duration of HFNC application (median 5.0 days [IQR 2.0 to 8.5 days] vs. 6.0 days [IQR 4.9 to 9.5 days], p = 0.076) between the acidemia group and the non-acidemia group (arterial pH ≥ 7.35). However, more patients in the non-acidemia group had do-not-intubate orders. The overall treatment failure rate for HFNC was 28.6%. Logistic regression analysis identified the APACHE II score (OR 1.24 per point) as the independent predictor of HFNC failure.

Conclusions

In patients with bronchiectasis and hypercapnia, HFNC as an initial respiratory support can effectively reduce PaCO2 level within 24 h of treatment. A high APACHE II score has emerged as a prognostic indicator for HFNC treatment failure. These observations highlight randomized controlled trials to meticulously evaluate the efficacy of HFNC in this specific population.
Full life cycle changes of low impacted mandibular third molar associated cystic lesions and adjacent tooth root resorption: a retrospective study
Authors: Zhang Jiankang , Zhang Kun , Zhou Xueer , Ye Li , Liu Yuanyuan , Peng Yiran , Pan Jian
Published: May 2024

Objective

Low impacted third molars are usually asymptomatic and are often found by X-ray examination. The removal of asymptomatic low impacted third molars is one of the most controversial clinical issues in oral and maxillofacial surgery.

Methods

In this study, 806 patients with low impacted mandibular third molars (LIMTMs) (full bony impaction) were analyzed to determine the prevalence and risk factors for cystic lesions and adjacent tooth root resorption throughout the patients’ entire life cycle.

Results

The results showed that the prevalence of adjacent tooth root resorption and cystic lesions was age-related, exhibiting a trend of first increasing and then decreasing; prevalence peaked at the age of 41 to 45 years old, the prevalence rates were 12.50% and 11.11% respectively. And the lowest prevalence rate was 2.86% and 2.44% in ≥ 61 group and 56- to 60-year age group respectively. Age was an independent risk factor for adjacent tooth root resorption of LIMTMs, whereas age and impaction type (especially inverted impaction) were independent risk factors for cystic lesions.

Conclusions

The full life cycle management strategy for LIMTMs may need to be individualized. Surgical removal is recommended for LIMTMs in patients younger than 41 to 45 years, especially for inverted, mesioangular, and horizontally impacted LIMTMs. LIMTMs in patients older than 41 to 45 years may be treated conservatively with regular follow-up, but surgical removal of inverted impacted LIMTMs is still recommended to avoid cyst formation.
End of life decision making when home mechanical ventilation is used to sustain breathing in Motor Neurone Disease: patient and family perspectives
Authors: Wilson Eleanor , Palmer Jonathan , Armstrong Alison , Messer Ben , Presswood Edward , Faull Christina
Published: May 2024

Background

Motor Neurone Disease (MND) leads to muscle weakening, affecting movement, speech, and breathing. Home mechanical ventilation, particularly non-invasive ventilation (NIV), is used to alleviate symptoms and support breathing in people living with MND. While home mechanical ventilation can alleviate symptoms and improve survival, it does not slow the progression of MND. This study addresses gaps in understanding end-of-life decision-making in those dependent on home mechanical ventilation, considering the perspectives of patients, family members, and bereaved families.

Methods

A UK-wide qualitative study using flexible interviews to explore the experiences of people living with MND (n = 16), their family members (n = 10), and bereaved family members (n = 36) about the use of home mechanical ventilation at the end of life.

Results

Some participants expressed a reluctance to discuss end-of-life decisions, often framed as a desire to “live for the day” due to the considerable uncertainty faced by those with MND. Participants who avoided end-of-life discussions often engaged in ‘selective decision-making’ related to personal planning, involving practical and emotional preparations. Many faced challenges in hypothesising about future decisions given the unpredictability of the disease, opting to make ‘timely decisions’ as and when needed. For those who became dependent on ventilation and did not want to discuss end of life, decisions were often ‘defaulted’ to others, especially once capacity was lost. ‘Proactive decisions’, including advance care planning and withdrawal of treatment, were found to empower some patients, providing a sense of control over the timing of their death. A significant proportion lacked a clear understanding of the dying process and available options.

Conclusions

The study highlights the complexity and evolution of decision-making, often influenced by the dynamic and uncertain nature of MND. The study emphasises the need for a nuanced understanding of decision-making in the context of MND.
Teaching foundational language equity concepts in the pre-clinical curriculum
Authors: Valle Coto Maria Gabriela , Iñiguez Reniell X. , Lentskevich Marina A. , Ally Syeda Akila , Farfan Julia F. , Park Yoon Soo , Gangopadhyaya Ananya G. , Ortega Pilar
Published: May 2024

Background

Despite the prevalence of non-English languages in the US population, existing medical training to teach communication with linguistically diverse communities is limited to electives or solely focuses on medical interpreting. Language-appropriate communication skills are seldom comprehensively integrated in medical education. This study describes the development and evaluation of an intervention to teach foundational language equity concepts.

Methods

The authors implemented a pre-clinical language equity course at three medical school campuses between August 2020 and March 2022. Sessions focused on the impact of language in health, physician language proficiency standards, and working with medical interpreters. The study sought to (1) understand students’ language skills and prior clinical experiences with patients with non-English language preference and (2) evaluate the curriculum’s impact. Students self-reported their language skills and experiences as part of a voluntary pre-questionnaire. Pre and post-questionnaires evaluated knowledge, attitudes, and intent to apply language equity concepts. Descriptive statistics and chi-squared tests were used to examine trends; themes were identified from free-text responses.

Results

Overall, 301 students completed the course, 252 (83%) completed at least one questionnaire; for each session, between 35% and 46% of learners completed both pre and post-questionnaires. Three quarters (189/252) reported non-English languages. Over half (138/252) reported previous non-English language patient care, and 28% (62/224) had served as ad hoc (untrained) interpreters. Only two students (< 1%) had ever been assessed for medical language abilities. Students demonstrated improved post-course language equity knowledge, strategies for interpreter-mediated encounters, and likelihood to report a plan for language skills assessment (all p < .001). Most plans were multifaceted (61%, 38/62), involving goals like completing a language course, taking a proficiency exam, openly discussing skills and uncertainties with team members, and increasing professional interpreter utilization.

Conclusions

A longitudinal language equity curriculum can be feasibly integrated in pre-clinical education, highlight the linguistic diversity of the student body, and serve as a first step in ensuring that all students have a strong language equity foundation prior to clinical rotations. Future steps include evaluating the intervention’s potential long-term effects on professional interpreter utilization, student clinical performance, and institutional culture that promotes multilingualism.
Development of a prototypic, field-usable diagnostic tool for the detection of gram-positive cocci-induced mastitis in cattle
Authors: Dobrut Anna , Skibiński Jakub , Bekier Adrian , Drożdż Kamil , Rudnicka Karolina , Płociński Przemysław , Siemińska Izabela , Brzychczy-Włoch Monika
Published: May 2024

Background

Bovine mastitis is one of the most widespread diseases affecting cattle, leading to significant losses for the dairy industry. Currently, the so-called gold standard in mastitis diagnosis involves determining the somatic cell count (SCC). Apart from a number of advantages, this method has one serious flaw: It does not identify the etiological factor causing a particular infection, making it impossible to introduce targeted antimicrobial therapy. This can contribute to multidrug-resistance in bacterial species. The diagnostic market lacks a test that has the advantages of SCC and also recognizes the species of pathogen causing the inflammation. Therefore, the aim of our study was to develop a lateral flow immunoassay (LFIA) based on elongation factor Tu for identifying most prevalent Gram-positive cocci responsible for causing mastitis including Streptococcus uberis, Streptococcus agalactiae and Staphylococcus aureus.

Results

As a result, we showed that the assay for S. uberis detection demonstrated a specificity of 89.02%, a sensitivity of 43.59%, and an accuracy of 80.3%. In turn, the second variant - assay for Gram-positive cocci reached a specificity of 95.59%, a sensitivity of 43.28%, and an accuracy of 78.33%.

Conclusions

Our study shows that EF-Tu is a promising target for LFIA and we have delivered evidence that further evaluation could improve test parameters and fill the gap in the mastitis diagnostics market.
High production of ectoine from methane in genetically engineered Methylomicrobium alcaliphilum 20Z by preventing ectoine degradation
Authors: Lim Sang Eun , Cho Sukhyeong , Choi Yejin , Na Jeong-Geol , Lee Jinwon
Published: May 2024

Background

Methane is a greenhouse gas with a significant potential to contribute to global warming. The biological conversion of methane to ectoine using methanotrophs represents an environmentally and economically beneficial technology, combining the reduction of methane that would otherwise be combusted and released into the atmosphere with the production of value-added products.

Results

In this study, high ectoine production was achieved using genetically engineered Methylomicrobium alcaliphilum 20Z, a methanotrophic ectoine-producing bacterium, by knocking out doeA, which encodes a putative ectoine hydrolase, resulting in complete inhibition of ectoine degradation. Ectoine was confirmed to be degraded by doeA to N-α-acetyl-L-2,4-diaminobutyrate under nitrogen depletion conditions. Optimal copper and nitrogen concentrations enhanced biomass and ectoine production, respectively. Under optimal fed-batch fermentation conditions, ectoine production proportionate with biomass production was achieved, resulting in 1.0 g/L of ectoine with 16 g/L of biomass. Upon applying a hyperosmotic shock after high–cell–density culture, 1.5 g/L of ectoine was obtained without further cell growth from methane.

Conclusions

This study suggests the optimization of a method for the high production of ectoine from methane by preventing ectoine degradation. To our knowledge, the final titer of ectoine obtained by M. alcaliphilum 20ZDP3 was the highest in the ectoine production from methane to date. This is the first study to propose ectoine production from methane applying high cell density culture by preventing ectoine degradation.
Coarse particulate matter (PM10) induce an inflammatory response through the NLRP3 activation
Authors: Marín-Palma Damariz , Tabares-Guevara Jorge H. , Taborda Natalia , Rugeles Maria T. , Hernandez Juan C.
Published: May 2024

Introduction

PM exposure can induce inflammatory and oxidative responses; however, differences in these adverse effects have been reported depending on the chemical composition and size. Moreover, inflammatory mechanisms such as NLRP3 activation by PM10 have yet to be explored.

Objective

To assess the impact of PM10 on cell cytotoxicity and the inflammatory response through in vitro and in vivo models.

Methodology

Peripheral blood mononuclear cells (PBMCs) from healthy donors were exposed to PM10. Cytotoxicity was determined using the LDH assay; the expression of inflammasome components and the production of pro-inflammatory cytokines were quantified through qPCR and ELISA, respectively; and the formation of ASC complexes was examined using confocal microscopy. For in vivo analysis, male C57BL6 mice were intranasally challenged with PM10 and bronchoalveolar lavage fluid was collected to determine cell counts and quantification of pro-inflammatory cytokines by ELISA. RNA was extracted from lung tissue, and the gene expression of inflammatory mediators was quantified.

Results

PM10 exposure induced significant cytotoxicity at concentrations over 100 µg/mL. Moreover, PM10 enhances the gene expression and release of pro-inflammatory cytokines in PBMCs, particularly IL-1β; and induces the formation of ASC complexes in a dose-dependent manner. In vivo, PM10 exposure led to cell recruitment to the lungs, which was characterized by a significant increase in polymorphonuclear cells compared to control animals. Furthermore, PM10 induces the expression of several inflammatory response-related genes, such as NLRP3, IL-1β and IL-18, within lung tissue.

Conclusion

Briefly, PM10 exposure reduced the viability of primary cells and triggered an inflammatory response, involving NLRP3 inflammasome activation and the subsequent production of IL-1β. Moreover, PM10 induces the recruitment of cells to the lung and the expression of multiple cytokines; this phenomenon could contribute to epithelial damage and, thus to the development and exacerbation of respiratory diseases such as viral infections.