bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of diagnosis to treatment interval in patients with newly diagnosed mantle cell lymphoma
Authors: Epperla Narendranath , Switchenko Jeffrey , Bachanova Veronika , Gerson James N. , Barta Stefan K. , Gordon Max J. , Danilov Alexey V. , Grover Natalie S. , Mathews Stephanie , Burkart Madelyn , Karmali Reem , Sawalha Yazeed , Hill Brian T. , Ghosh Nilanjan , Park Steven I. , Bond David A. , Hamadani Mehdi , Fenske Timothy S. , Martin Peter , Malecek Mary-Kate , Kahl Brad S. , Flowers Christopher R. , Link Brian K. , Kaplan Lawrence D. , Inwards David J. , Feldman Andrew L. , Hsi Eric D. , Maddocks Kami , Blum Kristie A. , Bartlett Nancy L. , Cerhan James R. , Leonard John P. , Habermann Thomas M. , Maurer Matthew J. , Cohen Jonathon B.
Published: December 2022

The prognostic relevance of diagnosis to treatment interval (DTI) in patients with newly diagnosed mantle cell lymphoma (MCL) is unknown. Hence, we sought to evaluate the impact of DTI on outcomes in MCL using 3 large datasets (1) the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource, (2) patients enrolled in the ALL Age Asthma Cohort/CALGB 50403, and (3) a multisitecohort of patients with MCL. Patients were a priori divided into 2 groups, 0 to 14 days (short DTI) and 15 to 60 days (long DTI). The patients in whom observation was deemed appropriate were excluded. One thousand ninety-seven patients newly diagnosed with MCL and available DTI were included in the study. The majority (73%) had long DTI (n=797). Patients with short DTI had worse eastern cooperative oncology group performance status (ECOG PS ≥2), higher lactate dehydrogenase, bone marrow involvement, more frequent B symptoms, higher MCL International Prognostic Index (MIPI ≥6.2), and were less likely to receive intensive induction therapy than long DTI group. The median progression-free survival (2.5 years vs 4.8 years, p<0.0001) and overall survival (7.8 years vs. 11.8 years, p<0.0001) were significantly inferior in the short DTI group than the long DTI cohort and remained significant for progression-free survival and overall survival in multivariable analysis. We show that the DTI is an important prognostic factor in patients newly diagnosed with MCL and is strongly associated with adverse clinical factors and poor outcomes. DTI should be reported in all the patients newly diagnosed with MCL who are enrolling in clinical trials and steps must be taken to ensure selection bias is avoided.
Progressive pulmonary fibrosis: an expert group consensus statement
Authors: Rajan Sujeet K. , Cottin Vincent , Dhar Raja , Danoff Sonye , Flaherty Kevin R. , Brown Kevin K. , Mohan Anant , Renzoni Elizabeth , Mohan Murali , Udwadia Zarir , Shenoy Padmanabha , Currow David , Devraj Anand , Jankharia Bhavin , Kulshrestha Ritu , Jones Steve , Ravaglia Claudia , Quadrelli Silvia , Iyer Rajam , Dhooria Sahajal , Kolb Martin , Wells Athol U.
Published: December 2022

This expert group consensus statement emphasises the need for standardising the definition of progressive fibrosing interstitial lung diseases (F-ILDs), with an accurate initial diagnosis being of paramount importance in ensuring appropriate initial management. Equally, case-by-case decisions on monitoring and management are essential, given the varying presentations of F-ILDs and the varying rates of progression. The value of diagnostic tests in risk stratification at presentation and, separately, the importance of a logical monitoring strategy, tailored to manage the risk of progression, are also stressed. The term “progressive pulmonary fibrosis” (PPF) exactly describes the entity that clinicians often face in practice. The importance of using antifibrotic therapy early in PPF (once initial management has failed to prevent progression) is increasingly supported by evidence. Artificial intelligence software for high-resolution computed tomography analysis, although an exciting tool for the future, awaits validation. Guidance is provided on pulmonary rehabilitation, oxygen and the use of non-invasive ventilation focused specifically on the needs of ILD patients with progressive disease. PPF should be differentiated from acute deterioration due to drug-induced lung toxicity or other forms of acute exacerbations. Referral criteria for a lung transplant are discussed and applied to patient needs in severe diseases where transplantation is not realistic, either due to access limitations or transplantation contraindications. In conclusion, expert group consensus guidance is provided on the diagnosis, treatment and monitoring of F-ILDs with specific focus on the recognition of PPF and the management of pulmonary fibrosis progressing despite initial management.
Virtual consultations for patients with obstructive sleep apnoea: a systematic review and meta-analysis
Authors: Alsaif Sulaiman S. , Kelly Julia L. , Little Stuart , Pinnock Hilary , Morrell Mary J. , Polkey Michael I. , Murphie Phyllis
Published: December 2022

Background

The coronavirus disease 2019 pandemic has accelerated the adoption of virtual care strategies for the management of patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS).

Research question

What is the effectiveness of virtual consultations compared to in-person consultations for the management of continuous positive airway pressure (CPAP) therapy in adult patients with OSAHS?

Methods

A systematic review and meta-analysis (PROSPERO; CRD42022297532) based on six electronic databases plus manually selected journals was conducted in January 2022. Two researchers independently selected, quality appraised and extracted data. The co-primary outcomes were patient-reported sleepiness, assessed by the Epworth Sleepiness Scale (ESS), and reported cost-effectiveness.

Results

12 studies (n=1823 adults) were included in the review. Seven studies (n=1089) were included in the meta-analysis which showed no difference in the magnitude of improvement in patient-reported sleepiness scores between virtual and in-person consultations (mean difference −0.39, 95% CI −1.38–0.60; p=0.4), although ESS scores improved in both groups. Virtual care strategies modestly increased CPAP therapy adherence and were found to be less costly than in-person care strategies in the three Spanish trials that reported cost-effectiveness.

Conclusion

The findings of this review suggest that virtual care delivered by telephone or video consultations is as effective as in-person consultations for improving subjective sleepiness in patients with OSAHS treated with CPAP. This clinical management strategy may also improve CPAP adherence without increasing the costs, supporting its potential as a follow-up management strategy, where patients prefer this approach.
Pleural effusion due to nonmalignant gastrointestinal disease
Authors: Ferreiro Lucía , Casal Ana , Toubes María Elena , Suárez-Antelo Juan , Golpe Antonio , Abelleira-París Romina , Riveiro Vanessa , Álvarez-Dobaño José Manuel , Valdés Luis
Published: December 2022

Although pleural effusion is a frequent finding in clinical practice, determining its aetiology may be challenging, and up to 20% of cases remain undiagnosed. Pleural effusion may occur secondary to a nonmalignant gastrointestinal disease. A gastrointestinal origin is confirmed based on a review of the medical history of the patient, thorough physical examination and abdominal ultrasonography. In this process, it is crucial to correctly interpret findings on pleural fluid obtained by thoracentesis. In the absence of high clinical suspicion, identifying the aetiology of this type of effusion may be difficult. Clinical symptoms will be determined by the gastrointestinal process causing pleural effusion. In this setting, correct diagnosis relies on the specialist's ability to evaluate pleural fluid appearance, test for the appropriate biochemical parameters and determine whether it is necessary or not to send a specimen for culture. The established diagnosis will determine how pleural effusion is approached. Although this clinical condition is self-limited, many cases will require a multidisciplinary approach because some effusions can only be resolved with specific therapies.
Validation of volatile metabolites of pulmonary oxidative injury: a bench to bedside study
Authors: Fenn Dominic , Lilien Thijs A. , Hagens Laura A. , Smit Marry R. , Heijnen Nanon F.L. , Tuip-de Boer Anita M. , Neerincx Anne H. , Golebski Korneliusz , Bergmans Dennis C.J.J. , Schnabel Ronny M. , Schultz Marcus J. , Maitland-van der Zee Anke H. , Brinkman Paul , Bos Lieuwe D.J.
Published: December 2022

Background

Changes in exhaled volatile organic compounds (VOCs) can be used to discriminate between respiratory diseases, and increased concentrations of hydrocarbons are commonly linked to oxidative stress. However, the VOCs identified are inconsistent between studies, and translational studies are lacking.

Methods

In this bench to bedside study, we captured VOCs in the headspace of A549 epithelial cells after exposure to hydrogen peroxide (H2O2), to induce oxidative stress, using high-capacity polydimethylsiloxane sorbent fibres. Exposed and unexposed cells were compared using targeted and untargeted analysis. Breath samples of invasively ventilated intensive care unit patients (n=489) were collected on sorbent tubes and associated with the inspiratory oxygen fraction (FIO2) to reflect pulmonary oxidative stress. Headspace samples and breath samples were analysed using gas chromatography and mass spectrometry.

Results

In the cell, headspace octane concentration was decreased after oxidative stress (p=0.0013), while the other VOCs were not affected. 2-ethyl-1-hexanol showed an increased concentration in the headspace of cells undergoing oxidative stress in untargeted analysis (p=0.00014). None of the VOCs that were linked to oxidative stress showed a significant correlation withFIO2(Rsrange: −0.015 to −0.065) or discriminated between patients withFIO2≥0.6 or below (area under the curve range: 0.48 to 0.55).

Conclusion

Despite a comprehensive translational approach, validation of known and novel volatile biomarkers of oxidative stress was not possible in patients at risk of pulmonary oxidative injury. The inconsistencies observed highlight the difficulties faced in VOC biomarker validation, and that caution is warranted in the interpretation of the pathophysiological origin of discovered exhaled breath biomarkers.
Exogenous 8-hydroxydeoxyguanosine attenuates doxorubicin-induced cardiotoxicity by decreasing pyroptosis in H9c2 cardiomyocytes
Authors: Hwang Soyoung , Kim Se-Hee , Yoo Kwai Han , Chung Myung-Hee , Lee Jin Woo , Son Kuk Hui
Published: December 2022

Doxorubicin (DOX), which is widely used in cancer treatment, can induce cardiomyopathy. One of the main mechanisms whereby DOX induces cardiotoxicity involves pyroptosis through the NLR family pyrin domain containing 3 (NLRP3) inflammasome and gasdermin D (GSDMD). Increased NAPDH oxidase (NOX) and oxidative stress trigger pyroptosis. Exogenous 8-hydroxydeoxyguanosine (8-OHdG) decreases reactive oxygen species (ROS) production by inactivating NOX. Here, we examined whether 8-OHdG treatment can attenuate DOX-induced pyroptosis in H9c2 cardiomyocytes. Exposure to DOX increased the peroxidative glutathione redox status and NOX1/2/4, toll-like receptor (TLR)2/4, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, while an additional 8-OHdG treatment attenuated these effects. Furthermore, DOX induced higher expression of NLRP3 inflammasome components, including NLRP3, apoptosis-associated speck-like protein containing a c-terminal caspase recruitment domain (ASC), and pro-caspase-1. Moreover, it increased caspase-1 activity, a marker of pyroptosis, and interleukin (IL)-1β expression. All these effects were attenuated by 8-OHdG treatment. In addition, the expression of the cardiotoxicity markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was increased by DOX, whereas the increase of ANP and BNP induced by DOX treatment was reversed by 8-OHdG. In conclusion, exogenous 8-OHdG attenuated DOX-induced pyroptosis by decreasing the expression of NOX1/2/3, TLR2/4, and NF-κB. Thus, 8-OHdG may attenuate DOX-induced cardiotoxicity through the inhibition of pyroptosis.
Initial treatment is associated with improved survival and end-of-life outcomes for patients with pancreatic cancer: a cohort study
Authors: Khan Rishad , Salim Misbah , Tanuseputro Peter , Hsu Amy T. , Coburn Natalie , Hallet Julie , Talarico Robert , James Paul D.
Published: December 2022

Background

We describe the association between initial treatment and end-of-life (EOL) outcomes among patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

This population-based cohort study included patients with PDAC who died from April 2010–December 2017 in Ontario, Canada using administrative databases. We used multivariable models to explore the association between index cancer treatment (no cancer-directed therapy, radiation, chemotherapy, surgery alone, and surgery and chemotherapy), and primary (mortality, healthcare encounters and palliative care) and secondary outcomes (location of death, hospitalizations, and receipt of chemotherapy within the last 30 days of life).

Results

In our cohort (N = 9950), 56% received no cancer-directed therapy, 5% underwent radiation, 27% underwent chemotherapy, 7% underwent surgery alone, and 6% underwent surgery and chemotherapy. Compared to no cancer-directed therapy, radiation therapy (HR = 0.63), chemotherapy (HR = 0.43) surgery alone (HR = 0.32), and surgery and chemotherapy (HR = 0.23) were all associated with decreased mortality. Radiation (AMD = − 3.64), chemotherapy (AMD = -6.35), surgery alone (AMD = -6.91), and surgery and chemotherapy (AMD = -6.74) were all associated with fewer healthcare encounters per 30 days in the last 6 months of life. Chemotherapy (AMD = -1.57), surgery alone (AMD = -1.65), and surgery and chemotherapy (AMD = -1.67) were associated with fewer palliative care visits (all p-values for estimates above < 0.05). Treatment groups were associated with lower odds of institutional death and hospitalization at EOL, and higher odds of chemotherapy at EOL.

Conclusions

Receiving cancer-directed therapies was associated with higher survival, fewer healthcare visits, lower odds of dying in an institution and hospitalization at EOL, fewer palliative care visits, and higher odds of receiving chemotherapy at EOL.
Roles of Toric intraocular Lens implantation on visual acuity and astigmatism in glaucomatous eyes treated with iStent and cataract surgery
Authors: Ichioka Sho , Ishida Akiko , Takayanagi Yuji , Manabe Kaoru , Matsuo Masato , Tanito Masaki , Tanito Masaki
Published: December 2022

Background

To assess the efficacy of toric intraocular lenses (IOLs) in combined cataract and minimally invasive glaucoma surgery (MIGS), visual and refractive outcomes were compared between eyes implanted with non-toric and toric IOLs during iStent triple procedures.

Methods

In this retrospective study, open angle glaucoma eyes with preexisting corneal astigmatism of -1.5 diopter (D) or more and implanted with non-toric (n = 9) or toric (n = 9) IOLs were included. The main outcome measures were the intergroup difference in the uncorrected visual acuity (UCVA) and refractive astigmatism at 3 months postoperatively.

Results

Preoperatively, the logarithm of the minimum angle of resolution (logMAR) UCVAs and refractive astigmatism were equivalent between the groups. Postoperatively, the logMAR UCVA (non-toric, 0.45 ± 0.31; toric, 0.14 ± 0.15;P = 0.021) was significantly better and the refractive astigmatism (non-toric, -2.03 ± 0.63 D; toric, -0.67 ± 0.53 D;P = 0.0014) significantly less in the toric group. The toric group had postoperative improvements in the logMAR UCVA (-0.21,P = 0.020) and refractive astigmatism (+ 1.72 D,P = 0.0039). Vector analyses showed the postoperative centroid magnitude and confidence eclipses of refractive astigmatism was less in the toric group (0.47 D at 173°±0.73D) than the non-toric group (1.10 D at 2°±1.91D). Postoperatively, 78% of eyes in the toric group had 1.0 D or less refractive astigmatism compared with 11% in the non-toric group. Surgically induced astigmatism (non-toric, 0.18 D at 65°; toric, 0.29 D at 137°) did not differ between groups.

Conclusion

Use of toric IOLs is a reasonable option for better visual outcomes when the combined cataract and iStent surgery is performed in glaucomatous eyes with corneal astigmatism.
Association of lifestyle and sociodemographic factors on multimorbidity: a cross-sectional study in Portugal
Authors: Páscoa Rosália , Teixeira Andreia , Monteiro Hugo , Prazeres Filipe , Martins Carlos
Published: December 2022

Background

Lifestyle factors are widely recognized as modifiers and major risk factors for non-communicable diseases. Previous studies on the prevalence of multimorbidity in Portugal predict an unfavourable reality. The aim of the present study was to analyse 1) the prevalence of multimorbidity in Portugal and 2) the association of individuals’ lifestyles and sociodemographic factors with multimorbidity.

Methods

A cross-sectional, population-wide study was conducted on a representative sample of the general population of Portuguese adults aged ≥ 20 years. Categorical variables were described by their respective absolute and relative frequencies (n (%)). All variables with a p-value < 20% were included in the multiple logistic regression model. The variables were removed one by one in descending order of p-value (p) until the model contained only significant variables. The results are presented using the odds ratio and 95% confidence intervals. P-values ​​ < 5% were considered significant.

Results

The prevalence of multimorbidity was 48.9% (n = 436), and the odds of multimorbidity increased 4% (p < 0.001) for each year of increase in age. Participants with reasonable general health status had higher odds of multimorbidity (Odds ratio (OR) = 3.04; p < 0.001), and those with poor or very poor general health status had even higher odds (OR = 9.14; p < 0.001). Compared to those who never smoked, participants who quit smoking ≥ 1 year presented an increase of 91% (p = 0.005) in the odds of multimorbidity. Individuals with no good-quality sleep, non-moderate screen time, or non-moderate stress level had higher odds of multimorbidity (OR = 1.98; OR = 1.88; OR = 2.22, respectively. p < 0.001).

Conclusions

This study presented a new approach to multimorbidity in Portugal. Population-based, multidimensional lifestyle interventions are needed. It seems necessary to optimize and adjust measures to prevent non-communicable diseases to improve health in Portugal. In the future, longitudinal studies will be an asset to reinforce and clarify these conclusions.
The effect of posture on airflow distribution, airway geometry and air velocity in healthy subjects
Authors: Ides Kris M. , De Backer Wilfried A. , Lanclus Maarten , Leemans Glenn , Dierckx Wendel , Lauwers Eline , Vissers Dirk , Steckel Jan , De Backer Jan W.
Published: December 2022

Background

Gravity, and thus body position, can affect the regional distribution of lung ventilation and blood flow. Therefore, body positioning is a potential tool to improve regional ventilation, thereby possibly enhancing the effect of respiratory physiotherapy interventions. In this proof-of-concept study, functional respiratory imaging (FRI) was used to objectively assess effects of body position on regional airflow distribution in the lungs.

Methods

Five healthy volunteers were recruited. The participants were asked during FRI first to lie in supine position, afterwards in standardized right lateral position.

Results

In right lateral position there was significantly more regional ventilation also described as Imaging Airflow Distribution in the right lung than in the left lung (P < 0.001). Air velocity was significantly higher in the left lung (P < 0.05). In right lateral position there was significantly more airflow distribution in the right lung than in the left lung (P < 0.001). Significant changes were observed in airway geometry resulting in a decrease in imaged airway volume (P = 0.024) and a higher imaged airway resistance (P = 0.029) in the dependent lung. In general, the effect of right lateral position caused a significant increase in regional ventilation (P < 0.001) in the dependent lung when compared with the supine position.

Conclusions

Changing body position leads to significant changes in regional lung ventilation, objectively assessed by FRI The volume based on the imaging parameters in the dependent lung is smaller in the lateral position than in the supine position. In right lateral decubitus position, airflow distribution is greater in dependent lung compared to the nondependent lung.

Trial registration: The trial has been submitted to www.clinicaltrials.gov with identification number NCT01893697 on 07/02/2013.
Effect of percutaneous and arthroscopically assisted osteosynthesis of talar body fractures
Authors: Hu Yong , Li Zhengxun , Wang Yang , Zhang Ning , Xu Wenpeng , Li Xiucun
Published: December 2022

Background

Talar fractures are relatively uncommon, and the complex anatomy of the talus impedes their visualization, reduction, and fixation without performing an arthrotomy or osteotomy. To date, few studies have evaluated the complications of arthroscopically assisted percutaneous talar osteosynthesis. This clinical retrospective study aimed to investigate the effectiveness of this procedure according to the complications and functional outcomes.

Methods

Arthroscopically assisted percutaneous talar osteosynthesis was performed in 15 patients (10 men and 5 women) with 16 fractures (one bilateral). The mean patient age was 31 years (range, 14–52 years). The Sneppen classification of the fractures was type II in 14 cases and type III in 2 cases.

Results

Fifteen patients were followed up for 36 months on average (range, 18–65 months). No skin infection, osteomyelitis, or skin necrosis was observed in any patient. During the follow-up, no bony non-union or delayed union was found. At the final follow-up, 2 out of the 15 patients (13.3%) had peri-talar osteoarthritis. The ankle–hindfoot pain was absent in 11 patients (12 ankles) and mild in 4 patients. Based on the American Orthopaedic Foot and Ankle Society (AOFAS) ankle–hindfoot scale, functional results were excellent in 7 ankles and good in 9 ankles. The mean AOFAS ankle–hindoot score of the patients was 85.7 (range, 79–93).

Conclusion

Arthroscopically assisted percutaneous talar osteosynthesis is a reliable and feasible technique that yields good clinical outcomes.
Oral health and quality of life: findings from the Survey of Health, Ageing and Retirement in Europe
Authors: Block Celina , König Hans-Helmut , Hajek André
Published: December 2022

Background

The aim of this study was to clarify the link between oral health and quality of life among older adults in Europe.

Methods

Cross-sectional data from wave 5 (n = 59,048 observations) were used from the representative Survey of Health, Ageing and Retirement in Europe. Oral health was quantified by three questions: presence of all natural teeth (yes; no); among individuals with missing natural teeth, the number of missing teeth and the extent of replaced natural teeth were quantified. Quality of life was quantified using the widely used CASP-12. Multiple linear regressions were used to determine the association between oral health and quality of life, adjusting for various potential confounders.

Results

Multiple linear regressions showed that higher quality of life was associated with (1) the presence of all natural teeth and among individuals with missing natural teeth, with (2) a lower number of missing natural teeth and (3) completely replaced natural teeth. Additionally, quality of life was positively associated with younger age, being female, being married or in a partnership, higher income, higher educational level, not currently smoking, a lower number of functional impairments, better self-rated health, a lower number of depressive symptoms and a lower number of chronic diseases.

Conclusion

Study findings showed an association between oral health and quality of life among older adults in Europe. Thus, the importance of good oral health for successful ageing was stressed. Future research is required to clarify the underlying mechanisms. Moreover, longitudinal studies are required to confirm our current findings.
Use of complementary and alternative medicine in pregnancy and labour pain: a cross-sectional study from turkey
Authors: Öztürk Ruşen , Emi̇nov Ayşe , Ertem Gül
Published: December 2022

Background

This study aimed to determine the prevalence and pattern of complementary and alternative medicine (CAM) use by and attitudes towards CAM of Turkish women during pregnancy and birth.

Methods

This was a descriptive, cross-sectional study that included 260 women who gave birth in a university hospital. The Personal Information Form and Complementary, Alternative and Conventional Medicine Attitudes Scale (CACMAS) were used as data collection tools.

Results

A total of 71.5% of the pregnant women received CAM. Phytotherapy, spiritual meditation and therapeutic touch techniques were the most frequently used techniques. A total of 42.7% women used herbal products. The mean score of the women on the CACMAS scale was 108.37 ± 7.71; this result indicates that pregnant women had a positive attitude. There were significant differences in attitudes according to marital status, education level and place of residence. It was determined that there was a significant difference in the CACMAS scores of the women according to the symptoms experienced during pregnancy, CAM use during pregnancy and the concerns about triggering preterm birth by using CAM methods (p < 0.05).

Conclusion

Although the women commonly used CAM methods during pregnancy, the rate of using these methods during birth considerably decreased. Despite such widespread use, pregnant women have concerns about CAM methods. Therefore, health professionals must actively provide counselling on CAM methods for the protection of maternal and infant health.
Responsiveness of the healthcare system in the Kingdom of Saudi Arabia: evidence from a nationally representative survey
Authors: Nikoloski Zlatko , Alghaith Taghred , Herbst Christopher H. , Hamza Mariam , AlSaffer Quds , Alluhidan Mohammed , Dong Di , Alsukait Reem , Alqasem Latifah , Alazemi Nahar
Published: December 2022

Background

Responsiveness is one of the widely used metrics in assessing the performance of healthcare systems. An analysis of the determinants of health care demand and supply and how the Saudi health system responds to the needs of patients (inpatient and outpatient) is needed; hence the need for this study.

Methods

We analysed data from the Saudi Health Systems Responsiveness survey – a nationally representative survey of 10,000 households interviewed in 2017. Using this dataset, we descriptively analysed the level of responsiveness of inpatient and outpatient services (using the standard World Health Organization (WHO) responsiveness dimensions). Based on a logit modelling approach, the relationship between responsiveness and its key determinants was analysed in terms of healthcare demand and supply.

Results

Over four fifths of respondents are satisfied with the level of inpatient and outpatient responsiveness. Furthermore, we find that those in bad health tend to show lower levels of satisfaction with inpatient and outpatient care. We also find some evidence that age, gender, and to some extent nationality act as correlates of health system responsiveness. Specifically, we find evidence that Saudi nationals are less satisfied with health services compared to foreign nationals.

Conclusion

Based on these findings improving the responsiveness of public healthcare facilities would need to be prioritized. Focusing on patients in worse health and lower socio-economic status should also be one of the main priorities.
Regulation of mRNA and miRNA in the response to Salmonella enterica serovar Enteritidis infection in chicken cecum
Authors: Miao Xiuxiu , Liu Lewen , Liu Liying , Hu Geng , Wu Guixian , Wang Yuanmei , Zhao Yanan , Yang Jingchao , Li Xianyao
Published: December 2022

Background

Salmonella enterica, serovar Enteritidis (SE) is a food-borne pathogen, which can cause great threat to human health through consumption of the contaminated poultry products. Chicken is the main host of SE. The mRNA and microRNA (miRNA) expression profiles were analyzed on cecum of Shouguang chicken via next-generation sequencing and bioinformatics approaches. The treated group was inoculated SE, and the control group was inoculated with phosphate buffer saline (PBS).

Results

There were 1760 differentially expressed mRNAs in the SE-infected group, of which 1046 were up-regulated mRNA, and 714 were down-regulated mRNA. In addition, a total of 821 miRNAs were identified, and 174 miRNAs were differentially expressed, of which 100 were up-regulated and 74 were down-regulated. Functional enrichment of differentially expressed mRNAs was similar to miRNA target genes. The functional analysis results of differentially expressed mRNAs and miRNAs were performed. Immune-related processes and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were enriched by up-regulated mRNA. The down-regulated mRNAs were enriched in tissue development and metabolic-related KEGG pathways. The functional analysis of up-regulated miRNA target genes was similar to the down-regulated mRNAs. The down-regulated miRNA target genes were enriched in metabolic-related GO (Gene Ontology) -BP (Biological process) terms and KEGG pathways. The overlap of the up-regulated mRNA and the up-regulated miRNA target genes (class I) was 325, and the overlap of the down-regulated miRNA target genes (class II) was 169. The class I enriched in the immune-related GO-BP terms and KEGG pathways. The class II mainly enriched in metabolic-related GO-BP terms and KEGG pathways. Then we detected the expression of mRNA and miRNA through qRT-PCR. The results shown that the expression of HHIP, PGM1, HTR2B, ITGB5, RELN, SFRP1, TCF7L2, SCNN1A, NEK7, miR-20b-5p, miR-1662, miR-15a, miR-16-1-3p was significantly different between two groups. Dual-luciferase reporter assay was used to detect the relationship between miR-20b-5p and SCNN1A. The result indicated that miR-20b-5p regulate immune or metabolic responses after SE infection in Shouguang chickens by directly targeting SCNN1A.

Conclusions

The findings here contribute to the further analysis of the mechanism of mRNA and miRNA defense against SE infection, and provide a theoretical foundation for the molecular disease-resistant breeding of chickens.
Can birth weight predict offspring’s lung function in adult age? Evidence from two Swedish birth cohorts
Authors: Sakic Aleksandra , Ekström Magnus , Sharma Shantanu , Nilsson Peter M.
Published: December 2022

Background

Associations between birth weight (BW) and adult lung function have been inconsistent and limited to early adulthood. We aimed to study this association in two population-based cohorts and explore if BW, adjusted for gestational age, predicts adult lung function. We also tested adult lung function impairment according to the mis-match hypothesis—small babies growing big as adults.

Methods

We included 3495 individuals (aged 46.4 ± 5.4 years) from the Malmo Preventive Project (MPP), Sweden, born between 1921 and 1949, and 1401 young to middle-aged individuals (aged 28.6 ± 6.7 years) from the Malmo Offspring Study (MOS) with complete data on BW and gestational age. Adult lung function (forced vital capacity [FVC], forced expiratory volume in one second [FEV1] and the FEV1/FVC-ratio) were analysed as level of impairment (z-score), using multiple linear and logistic regressions.

Results

BW (z-score) did not predict adult lung function in MPP, whereas BW was a significant (p = 0.003) predictor of FEV1 following full adjustment in MOS. For every additional unit increase in BW, children were 0.77 (95% CI 0.65–0.92) times less likely to have impaired adult lung function (FEV1). Moreover, adults born with lower BW (< 3510 g) showed improved lung function (FEV1 and FEV1/FVC in MOS and MPP, respectively) if they achieved higher adult body weight.

Conclusions

Adults born with lower birth weight, adjusted for gestational age, are more likely to have impaired lung function, seen in a younger birth cohort. Postnatal growth pattern may, however, compensate for low birth weight and contribute to better adult lung function.
Higher circulating Trimethylamine N-oxide levels are associated with worse severity and prognosis in pulmonary hypertension: a cohort study
Authors: Yang Yicheng , Yang Beilan , Li Xin , Xue Lin , Liu Bingyang , Liang Yanru , Zhao Zhihui , Luo Qin , Liu Zhihong , Zeng Qixian , Xiong Changming
Published: December 2022

Background

Trimethylamine N-oxide (TMAO), the gut microbiota-dependent metabolite, is a potential biomarker in several cardiovascular diseases. However, no study has investigated its value in pulmonary hypertension (PH). Therefore, this study aimed to explore the association between plasma TMAO levels and prognosis in patients with PH.

Methods

Inpatients with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH), PAH associated with congenital heart disease (CHD-PAH), and chronic thromboembolic pulmonary hypertension (CTEPH) at Fuwai Hospital were enrolled after excluding those with relative comorbidities. The endpoint was defined as a composite outcome including death, rehospitalisation due to heart failure, and at least 15% decreased 6-min walk distance from the baseline. Fasting blood samples were collected to measure plasma levels of TMAO and other clinical indicators. The associations between TMAO levels with disease severity and patients’ prognosis were investigated.

Results

In total, 163 patients with PH were included, with a mean follow-up duration of 1.3 years. After adjusting for confounding factors, elevated TMAO levels were still associated with severe disease conditions. TMAO levels dynamically decreased in stable and improved patients after treatment [ΔTMAO = − 0.2 (− 1.6, 0.7) μmol/L,P = 0.006]. Moreover, high plasma TMAO levels predicted a poor prognosis in the PH cohort (P < 0.001), and the association remained significant after adjusting the confounders, including treatment, risk stratification, and PH subtypes.

Conclusion

Elevated plasma TMAO levels were associated with severe disease conditions and poor prognosis in patients with PH, indicating its potential biomarker role in PH.
Mapping under-five child malaria risk that accounts for environmental and climatic factors to aid malaria preventive and control efforts in Ghana: Bayesian geospatial and interactive web-based mapping methods
Authors: Aheto Justice Moses K.
Published: December 2022

Background

Under-five child malaria is one of the leading causes of morbidity and mortality globally, especially among sub-Saharan African countries like Ghana. In Ghana, malaria is responsible for about 20,000 deaths in children annually of which 25% are those aged < 5 years. To provide opportunities for efficient malaria surveillance and targeted control efforts amidst limited public health resources, the study produced high resolution interactive web-based spatial maps that characterized geographical differences in malaria risk and identified high burden communities.

Methods

This modelling and web-based mapping study utilized data from the 2019 Malaria Indicators Survey (MIS) of the Demographic and Health Survey Program. A novel and advanced Bayesian geospatial modelling and mapping approaches were utilized to examine predictors and geographical differences in under-five malaria. The model was validated via a cross-validation approach. The study produced an interactive web-based visualization map of the malaria risk by mapping the predicted malaria prevalence at both sampled and unsampled locations.

Results

In 2019, 718 (25%) of 2867 under-five children surveyed had malaria. Substantial geographical differences in under-five malaria risk were observed. ITN coverage (log-odds 4.5643, 95% credible interval = 2.4086–6.8874), travel time (log-odds 0.0057, 95% credible interval = 0.0017–0.0099) and aridity (log-odds = 0.0600, credible interval = 0.0079–0.1167) were predictive of under-five malaria in the spatial model. The overall predicted national malaria prevalence was 16.3% (standard error (SE) 8.9%) with a range of 0.7% to 51.4% in the spatial model with covariates and prevalence of 28.0% (SE 13.9%) with a range of 2.4 to 67.2% in the spatial model without covariates. Residing in parts of Central and Bono East regions was associated with the highest risk of under-five malaria after adjusting for the selected covariates.

Conclusion

The high-resolution interactive web-based predictive maps can be used as an effective tool in the identification of communities that require urgent and targeted interventions by programme managers and implementers. This is key as part of an overall strategy in reducing the under-five malaria burden and its associated morbidity and mortality in a country with limited public health resources where universal intervention is practically impossible.
Multiplexed evaluation of immunity against SARS-CoV-2 variants using surface enhanced fluorescence from a nanostructured plasmonic chip
Authors: Hu Ruibin , Yang Yang , Liu Ying , Liao Tao , Liu Yiyi , Tang Jiahu , Wang Guanghui , Wang Guoxin , Liang Yongye , Yuan Jing , Zhang Bo
Published: December 2022

Generated by the immune system post-infection or through vaccination, the effectiveness of antibodies against emerging SARS-CoV-2 variants is crucial for protecting individuals from the COVID-19 pandemic. Herein, a platform for the multiplexed evaluation of SARS-CoV-2 neutralizing antibodies against various variants was designed on the basis of near-infrared (NIR) surface enhanced fluorescence by nano-plasmonic gold chip (pGOLD). Antibody level across variants (Wild-type, Alpha, Beta, Delta, Omicron) was confirmed by the sera from recovered-individuals who were unvaccinated and had infected with Wild-type, Delta, Omicron variants. However, the neutralizing activity against Omicron variant was markedly decreased for individuals infected by Wild-type (~ 5.6-fold) and Delta variant (~ 19.1-fold). To the opposite, neutralizing antibody from individuals recovered from Omicron variant infection showed weak binding strength against non-Omicron variants. Antibody evolution over time was studied with individuals 196–530 days post Wild-type infection. Decreasing IgG antibody titer accompanied by increasing IgG binding avidity with elongated post-infection period were observed for the sera from Wild-type recovered-individuals with different post-infection times, suggesting that after the primary infection, a great number of antibodies were generated and then gradually decreased, while the antibody matured over time. By comparing the IgG level of individuals vaccinated for 27–51 days with individual post-infection, we found that ca. 1 month after two doses of vaccination, the antibody level was comparable to that of 500 days post-infection, and vaccination could enhance IgG avidity more efficiently. This work demonstrated a platform for the multiplexed, high-throughput and rapid screening of acquired immunity against SARS-CoV-2 variants, providing a new approach for the analysis of vaccine effectiveness, immunity against emerging variants, and related serological study.

Graphical Abstract
Adherence to Canadian 24-Hour Movement Guidelines among infants and associations with development: a longitudinal study
Authors: Carson Valerie , Zhang Zhiguang , Predy Madison , Pritchard Lesley , Hesketh Kylie D.
Published: December 2022

Background

To examine: 1) longitudinal adherence to the Canadian 24-Hour Movement Guidelines in a sample of infants and 2) associations between adherence to the guidelines over time and development.

Methods

Participants were 250 parent-infant dyads from the Early Movers project in Edmonton, Alberta. At 2, 4, and 6 months of age, physical activity, sedentary behaviour, sleep, and development were measured with a parental questionnaire that included items from the Ages & Stages Questionnaire (ASQ-3). Parents also reported the dates six major gross motor milestones were acquired during the first 18 months of life according to World Health Organization criteria. In a sub-sample (n = 93), movement behaviours were also measured with a time-use diary at 2, 4, and 6 months and gross motor development was measured by a physiotherapist using the Alberta Infant Motor Scale (AIMS) at 6 months. Guideline adherence was defined as: 1) ≥ 30 min/day of tummy time, 2) no screen time, some reading time, no restrained bouts > 1 h (time-use diary only), and 3) 14–17 h (2 months) or 12–16 h (4 and 6 months) of sleep per 24-h period. Generalized estimating equations were conducted as well as linear mixed models and linear regression models that adjusted for demographic characteristics.

Results

Few infants met the guidelines at all time-points (questionnaire: 2%; time-use diary: 0%). Infants that met a recommendation at 2 months, compared to those that did not, were 1.8–8.2 times more likely to meet that recommendation at subsequent time-points. Meeting more recommendations across time-points, according to both measures, was associated with a higher mean ASQ-3 gross motor score. Each additional time-point of tummy time recommendation adherence (questionnaire-measured) was associated with a 5–11-day earlier acquisition of independent sitting, crawling, and independent standing milestones. In the sub-sample, each additional time-point of guideline adherence was associated with a 16% higher AIMS score at 6 months.

Conclusions

Guideline adherence was low across the first 6 months of infancy. Overall, meeting more recommendations over this period appeared important for gross motor development. Parents and caregivers should be targeted as early as possible with guideline dissemination and activation strategies to promote healthy infant development.
Biomarkers of cell damage, neutrophil and macrophage activation associated with in-hospital mortality in geriatric COVID-19 patients
Authors: Cardelli M. , Pierpaoli E. , Marchegiani F. , Marcheselli F. , Piacenza F. , Giacconi R. , Recchioni R. , Casoli T. , Stripoli P. , Provinciali M. , Matacchione G. , Giuliani A. , Ramini D. , Sabbatinelli J. , Bonafè M. , Di Rosa M. , Cherubini A. , Di Pentima C. , Spannella F. , Antonicelli R. , Bonfigli A. R. , Olivieri F. , Lattanzio F.
Published: December 2022

Background

The risk for symptomatic COVID-19 requiring hospitalization is higher in the older population. The course of the disease in hospitalised older patients may show significant variation, from mild to severe illness, ultimately leading to death in the most critical cases. The analysis of circulating biomolecules involved in mechanisms of inflammation, cell damage and innate immunity could lead to identify new biomarkers of COVID-19 severity, aimed to improve the clinical management of subjects at higher risk of severe outcomes.

In a cohort of COVID-19 geriatric patients (n= 156) who required hospitalization we analysed, on-admission, a series of circulating biomarkers related to neutrophil activation (neutrophil elastase, LL-37), macrophage activation (sCD163) and cell damage (nuclear cfDNA, mithocondrial cfDNA and nuclear cfDNA integrity). The above reported biomarkers were tested for their association with in-hospital mortality and with clinical, inflammatory and routine hematological parameters. Aim of the study was to unravel prognostic parameters for risk stratification of COVID-19 patients.

Results

Lower n-cfDNA integrity, higher neutrophil elastase and higher sCD163 levels were significantly associated with an increased risk of in-hospital decease. Median (IQR) values observed in discharged vs. deceased patients were: 0.50 (0.30-0.72) vs. 0.33 (0.22-0.62) for n-cfDNA integrity; 94.0 (47.7-154.0) ng/ml vs. 115.7 (84.2-212.7) ng/ml for neutrophil elastase; 614.0 (370.0-821.0) ng/ml vs. 787.0 (560.0-1304.0) ng/ml for sCD163. The analysis of survival curves in patients stratified for tertiles of each biomarker showed that patients with n-cfDNA integrity < 0.32 or sCD163 in the range 492-811 ng/ml had higher risk of in-hospital decease than, respectively, patients with higher n-cfDNA integrity or lower sCD163. These associations were further confirmed in multivariate models adjusted for age, sex and outcome-related clinical variables. In these models also high levels of neutrophil elastase (>150 ng/ml) appeared to be independent predictor of in-hospital death. An additional analysis of neutrophil elastase in patients stratified for n-cfDNA integrity levels was conducted to better describe the association of the studied parameters with the outcome.

Conclusions

On the whole, biomarkers of cell-free DNA integrity, neutrophil and macrophage activation might provide a valuable contribution to identify geriatric patients with high risk of COVID-19 in-hospital mortality.
MicroRNAs: a crossroad that connects obesity to immunity and aging
Authors: Rakib Ahmed , Kiran Sonia , Mandal Mousumi , Singh Udai P.
Published: December 2022

Obesity is characterized by an elevated amount of fat and energy storage in the adipose tissue (AT) and is believed to be the root cause of many metabolic diseases (MDs). Obesity is associated with low-grade chronic inflammation in AT. Like obesity, chronic inflammation and MDs are prevalent in the elderly. The resident immune microenvironment is not only responsible for maintaining AT homeostasis but also plays a crucial role in stemming obesity and related MDs. Mounting evidence suggests that obesity promotes activation in resident T cells and macrophages. Additionally, inflammatory subsets of T cells and macrophages accumulated into the AT in combination with other immune cells maintain low-grade chronic inflammation. microRNAs (miRs) are small non-coding RNAs and a crucial contributing factor in maintaining immune response and obesity in AT. AT resident T cells, macrophages and adipocytes secrete various miRs and communicate with other cells to create a potential effect in metabolic organ crosstalk. AT resident macrophages and T cells-associated miRs have a prominent role in regulating obesity by targeting several signaling pathways. Further, miRs also emerged as important regulators of cellular senescence and aging. To this end, a clear link between miRs and longevity has been demonstrated that implicates their role in regulating lifespan and the aging process. Hence, AT and circulating miRs can be used as diagnostic and therapeutic tools for obesity and related disorders. In this review, we discuss how miRs function as biomarkers and impact obesity, chronic inflammation, and aging.

Graphical Abstract