bluuebunny/crossref_metadata_2025 huggingface dataset:
The L3 Flexion Angle Predicts Failure of Non-Operative Management in Patients with Tandem Spondylolithesis
Authors: Dalton Jonathan F. , Fourman Mitchell S. , Rynearson Bryan , Wawrose Rick , Cluts Landon , Shaw Jeremy D. , Lee Joon Y.
Published: March 2023

Study Design

Retrospective cohort study.

Objective

Determine impact of standard/novel spinopelvic parameters on global sagittal imbalance, health-related quality of life (HRQoL) scores, and clinical outcomes in patients with multi-level, tandem degenerative spondylolisthesis (TDS).

Methods

Single institution analysis; 49 patients with TDS. Demographics, PROMIS and ODI scores collected. Radiographic measurements—sagittal vertical axis (SVA), pelvic incidence (PI), lumbar lordosis (LL), PI-LL mismatch, sagittal L3 flexion angle (L3FA) and L3 sagittal distance (L3SD). Stepwise linear multivariate regression performed using full length cassettes to identify demographic and radiographic factors predictive of aberrant SVA (≥5 cm). Receiver operative curve (ROC) analysis used to identify cutoffs for lumbar radiographic values independently predictive of SVA ≥5 cm. Univariate comparisons of patient demographics, (HRQoL) scores and surgical indication were performed around this cutoff using two-way Student’s t-tests and Fisher’s exact test for continuous and categorical variables, respectively.

Results

Patients with increased L3FA had worse ODI (P = .006) and increased rate of failing non-operative management (P = .02). L3FA (OR 1.4, 95% CI) independently predicted of SVA ≥5 cm (sensitivity and specifity of 93% and 92%). Patients with SVA ≥5 cm had lower LL (48.7 ± 19.5 vs 63.3 ± 6.9 mm, P < .021), higher L3SD (49.3 ± 12.9 vs 28.8 ± 9.2, P < .001) and L3FA (11.6 ± 7.9 vs −3.2 ± 6.1, P < .001) compared to patients with SVA ≤5 cm.

Conclusions

Increased flexion of L3, which is easily measured by the novel lumbar parameter L3FA, predicts global sagittal imbalance in TDS patients. Increased L3FA is associated with worse performance on ODI, and failure of non-operative management in patients with TDS.
Annual Report Readability and Agency Cost: The Influence of Firm Size
Authors: Goswami Rishabh , Maji Santi Gopal , Hussain Farah
Published: March 2023

This study examines whether the impact of annual report readability on agency cost varies with firm size among listed Indian non-financial firms. For this study, we have selected two cross-sectional samples comprising 360 non-financial firms listed on National Stock Exchange (NSE)—divided into 183 small firms and 177 large firms—for the financial year 2019–2020 and 2020–2021. The classification between large and small firms is drawn based on the respective quartile values of total assets and market capitalization taken together. The proxy for agency cost is the natural logarithm of selling and distribution expenses. We have developed an index using the count of characters, words, lines, and pages of the annual report to measure readability. To investigate the association between the annual report readability, agency cost, and firm size, we use the OLS methodology. In our model, we control for fixed assets, leverage, ownership concentration, institutional ownership, the board size, and board independence. Our findings reflect an inverse relationship between readability and agency cost. Additionally, we find that the effect of annual report readability on agency cost is higher for large firms than for smaller firms. We further checked our findings’ robustness using a logistic regression model and found similar results.
Acute triage of childhood stroke in Denmark
Authors: Bindslev Julie Brix , Hansen Klaus , Laugesen Nicolaj Groenbaek , Benndorf Goetz , Hoei-Hansen Christina Engel , Truelsen Thomas
Published: March 2023

Objective:

This 2-year observational study aimed to test the feasibility of implementing a pediatric stroke triage-setup that connected frontline providers with vascular neurologists and to examine final diagnoses in children triaged for suspected stroke.

Methods:

Prospective, consecutive registration of children with suspected stroke triaged by a team of vascular neurologists from Jan 1st, 2020 and through Dec 2021, Eastern Denmark (census 530,000 children). Based on the provided clinical information, the children were triaged to either assessment at the Comprehensive Stroke Center (CSC) in Copenhagen or to a pediatric department. All included children were retrospectively followed-up for clinical presentations and final diagnosis.

Results:

A total of 163 children with 166 suspected stroke events were triaged by the vascular neurologists. Cerebrovascular disease was present in 15 (9.0%) suspected stroke events; one child had intracerebral hemorrhage, one had subarachnoid hemorrhage, two children presented with three TIA events and nine children presented with 10 ischemic stroke events. Two children with ischemic stroke were eligible for acute revascularization treatment of which both were triaged to the CSC. The sensitivity of the triage by acute revascularization indication was 1.00 (95% confidence interval (95% CI): 0.15–1.00) and specificity 0.65 (95% CI: 0.57–0.73). Non-stroke neurological emergencies were present in 34 (20.5%) children, including seizures in 18 (10.8%) and acute demyelinating disorders in 7 (4.2%).

Conclusion:

Implementing regional triage-setup that connected frontline providers to vascular neurologists was feasible; this system was activated for the majority of children with ischemic stroke according to an expected incidence and led to identification of children eligible for revascularization treatments.
Hypercalcemia of malignancy with simultaneous production of parathyroid hormone-related peptide and 1,25-Dihydroxyvitamin D by non-Hodgkin lymphoma: Case report & brief review
Authors: Carias Eduarda , Ferreira Hugo , Chuva Teresa , Paiva Ana , Maximino José
Published: March 2023

We report the case of a 63-year-old man with severe hypercalcemia, acute kidney injury, and concomitant diagnosis of germinal center diffuse large B-cell lymphoma (nHL). Hypercalcemia is a common finding in patients with cancer. Multiple mechanisms can lead to hypercalcemia of malignancy, and different malignancies are often associated with a specific mechanism of hypercalcemia. Parathyroid hormone-related protein (PTHrP) and excessive production of 1,25-dihydroxyvitamin D can independently (and rarely, concomitantly) lead to development of hypercalcemia in patients with a variety of malignancies. Literature review of hypercalcemia related with PTHrP and 1,25-dihydroxyvitamin D co-secretion shows that most reported cases are associated with solid tumors and responded to tumor directed therapy. Our case of nHL was associated with increased PTHrP and 1,25-dihydroxyvitamin D making this an unusual presentation.
Retinal Arterial Macroaneurysm in a Patient With Lynch Syndrome
Authors: Sood Shefali , Friedman Scott
Published: March 2023

Purpose: To describe a case of retinal arterial macroaneurysm (RAM) in a patient with hereditary nonpolyposis colon cancer (HNPCC)/Lynch syndrome. Methods: A case and its findings were analyzed. Results: A 68-year-old woman presented with a recent history of decreased near vision in the left eye. Both eyes had a visual acuity of 20/20 with normal intraocular pressure. The right retina was normal. The left retina had a focal dilation of the retinal arteriole with a surrounding hemorrhage and lipid in the inferonasal quadrant. The patient was diagnosed with RAM and was subsequently treated with focal laser photocoagulation. The patient had a medical history of stage 1 colon cancer associated with HNPCC/Lynch syndrome. Conclusions: Increased vascular network complexity has been reported in HNPCC/Lynch syndrome. This is the first report of a RAM in a patient with this genetic profile. Given the atypical presentation, there may be an association between HNPCC/Lynch syndrome and RAMs.
Expected Risk as basis for assessment of safe use of chemicals
Authors: van de Meent Dik , de Zwart Dick , Struijs Jaap , Hermens Joop L. M. , van Straalen Nico M. , den Haan Klaas H. , Parsons John R. , de Voogt Pim , van Leeuwen Kees
Published: March 2023

This paper describes a straightforward modeling procedure to derive ‘expected risk’ (ER) of chemical substances. Starting from proposed use volumes, intended uses, physical and chemical substance properties and toxicity information, the procedure combines multimedia environmental fate modeling with species sensitivity modeling to derive the probability that exposure concentrations exceed critical effect concentrations. The procedure was tested on 1977 so-called mono-constituent organic chemicals that had been registered to be marketed in the EU, after ‘possibility to be used safely’ had been demonstrated by showing that the possible Risk Quotients (RQ) defined as PEC/PNEC ratios (Predicted Exposure Concentration & Predicted No Effect Concentration) were expected to remain below the value of 1, as required by REACH. It appears from this study that (i) RQ and ER of chemicals can be calculated readily, reliably, transparently and reproducibly, that (ii) both RQ and ER can be used to assess whether a new chemical may exceed a chosen acceptability level, but that (iii) in addition ER can be straightforwardly used to rank chemicals according to expected environmental safety. In conclusion, the paper states that modeling ER of chemicals (instead of estimating RQ values), could strengthen the scientific basis of environmental risk assessment for use in REACH. The paper further recommends that more robust environmental risk calculation can be done by using acute EC50, instead of chronic NOEC as critical effect concentration.
Doxorubicin-loaded liposomes surface engineered with the matrix metalloproteinase-2 cleavable polyethylene glycol conjugate for cancer therapy
Authors: Askarizadeh Anis , Mashreghi Mohammad , Mirhadi Elaheh , Mirzavi Farshad , Shargh Vahid Heravi , Badiee Ali , Alavizadeh Seyedeh Hoda , Arabi Leila , Jaafari Mahmoud Reza
Published: March 2023

Background

Colorectal cancer is one of the prominent leading causes of fatality worldwide. Despite recent advancements within the field of cancer therapy, the cure rates and long-term survivals of patients suffering from colorectal cancer have changed little. The application of conventional chemotherapeutic agents like doxorubicin is limited by some drawbacks such as cardiotoxicity and hematotoxicity. Therefore, nanotechnology has been exploited as a promising solution to address these problems. In this study, we synthesized and compared the anticancer efficacy of doxorubicin-loaded liposomes that were surface engineered with the 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-matrix metalloproteinase-2 (MMP-2) cleavable peptide-polyethylene glycol (PEG) conjugate. The peptide linker was used to cleave in response to the upregulated MMP-2 in the tumor microenvironment, thus exposing a positive charge via PEG-deshielding and enhancing liposomal uptake by tumor cells/vasculature. Liposomal formulations were characterized in terms of size, surface charge and morphology, drug loading, release properties, cell binding and uptake, and cytotoxicity.

Results

The formulations had particle sizes of ~ 100–170 nm, narrow distribution (PDI ˂ 0.2), and various surface charges (− 10.2 mV to + 17.6 mV). MMP-2 overexpression was shown in several cancer cell lines (C26, 4T1, and B16F10) as compared to the normal NIH-3T3 fibroblast cells by gelatin zymography and qRT-PCR. In vitro results demonstrated enhanced antitumor efficacy of the PEG-cleavable cationic liposomes (CLs) as compared to the commercial Caelyx® (up to fivefold) and the chick chorioallantoic membrane assay showed their great antiangiogenesis potential to target and suppress tumor neovascularization. The pharmacokinetics and efficacy studies also indicated higher tumor accumulation and extended survival rates in C26 tumor-bearing mice treated with the MMP-2 cleavable CLs as compared to the non-cleavable CLs with no remarkable sign of toxicity in healthy tissues.

Conclusion

Altogether, the MMP-2-cleavable CLs have great potency to improve tumor-targeted drug delivery and cellular/tumor-vasculature uptake which merits further investigation.
Propensity scores as a novel method to guide sample allocation and minimize batch effects during the design of high throughput experiments
Authors: Carry Patrick M. , Vigers Tim , Vanderlinden Lauren A. , Keeter Carson , Dong Fran , Buckner Teresa , Litkowski Elizabeth , Yang Ivana , Norris Jill M. , Kechris Katerina
Published: March 2023

Background

We developed a novel approach to minimize batch effects when assigning samples to batches. Our algorithm selects a batch allocation, among all possible ways of assigning samples to batches, that minimizes differences in average propensity score between batches. This strategy was compared to randomization and stratified randomization in a case–control study (30 per group) with a covariate (case vs control, represented as β1, set to be null) and two biologically relevant confounding variables (age, represented as β2, and hemoglobin A1c (HbA1c), represented as β3). Gene expression values were obtained from a publicly available dataset of expression data obtained from pancreas islet cells. Batch effects were simulated as twice the median biological variation across the gene expression dataset and were added to the publicly available dataset to simulate a batch effect condition. Bias was calculated as the absolute difference between observed betas under the batch allocation strategies and the true beta (no batch effects). Bias was also evaluated after adjustment for batch effects using ComBat as well as a linear regression model. In order to understand performance of our optimal allocation strategy under the alternative hypothesis, we also evaluated bias at a single gene associated with both age and HbA1c levels in the ‘true’ dataset (CAPN13 gene).

Results

Pre-batch correction, under the null hypothesis (β1), maximum absolute bias and root mean square (RMS) of maximum absolute bias, were minimized using the optimal allocation strategy. Under the alternative hypothesis (β2 and β3 for the CAPN13 gene), maximum absolute bias and RMS of maximum absolute bias were also consistently lower using the optimal allocation strategy. ComBat and the regression batch adjustment methods performed well as the bias estimates moved towards the true values in all conditions under both the null and alternative hypotheses. Although the differences between methods were less pronounced following batch correction, estimates of bias (average and RMS) were consistently lower using the optimal allocation strategy under both the null and alternative hypotheses.

Conclusions

Our algorithm provides an extremely flexible and effective method for assigning samples to batches by exploiting knowledge of covariates prior to sample allocation.
Urine-derived mesenchymal stem cells-derived exosomes enhances survival and proliferation of aging retinal ganglion cells
Authors: Dan Qi-Qin , Chen Li , shi Lan-Lan , Zhou Xiu , Wang Ting-Hua , Liu Hua
Published: March 2023

Objectives

This study was designed to investigate to test the effect of exosomes from urine-derived mesenchymal stem cells (USCs) on the survival and viability of aging retinal ganglion cells (RGCs), and explored the preliminary related mechanisms.

Methods

Primary USCs were cultured and identified by immunofluorescence staining. Aging RGCs models were established by D-galactose treatment and identified by β-Galactosidase staining. After treatment with USCs conditioned medium (with USCs removal), flow cytometry was performed to examine the apoptosis and cell cycle of RGCs. Cell viability of RGCs was detected by Cell-counting Kit 8 (CCK8) assay. Moreover, gene sequencing and bioinformatics analysis were applied to analyze the genetic variation after medium treatment in RGCs along with the biological functions of differentially expressed genes (DEGs).

Results

The number of apoptotic aging RGCs was significantly reduced in USCs medium-treated RGCs. Besides, USCs-derived exosomes exert significant promotion on the cell viability and proliferation of aging RGCs. Further, sequencing data analyzed and identified DEGs expressed in aging RGCs and aging RGCs treated with USCs conditioned medium. The sequencing outcomes demonstrated 117 upregulated genes and 186 downregulated genes in normal RGCs group vs aging RGCs group, 137 upregulated ones and 517 downregulated ones in aging RGCs group vs aging RGCs + USCs medium group. These DEGs involves in numerous positive molecular activities to promote the recovery of RGCs function.

Conclusions

Collectively, the therapeutic potentials of USCs-derived exosomes include suppression on cell apoptosis, enhancement on cell viability and proliferation of aging RGCs. The underlying mechanism involves multiple genetic variation and changes of transduction signaling pathways.
Factors affecting the microbiological quality and contamination of farm bulk milk by Staphylococcus aureus in dairy farms in Asella, Ethiopia
Authors: Deddefo Abiot , Mamo Gezahegne , Asfaw Minda , Amenu Kebede
Published: March 2023

Background

The determination of the microbiological quality and safety of raw milk and the associated influencing factors at the farm level is very critical given that the quality or safety of subsequent products that are further produced depends on this. Therefore, this study aimed to determine the microbiological quality and safety of bulk milk and identify associated risk factors, and assess the presence/absence ofS. aureusin bulk milk with potential contaminating sources in dairy farms in Asella, Ethiopia.

Results

The geometric means of bacterial counts in farm bulk milk were 5.25 log cfu/ml, 3.1 log cfu/ml and 2.97 log cfu/ml for total bacterial count (TBC), coliform count (CC) and coagulase-positive staphylococci count (CPS), respectively. Of the 50 dairy farms, 66, 88, and 32% had TBC, CC and CPS counts, respectively, that exceeded the standard international limits for raw cow’s milk intended for direct human consumption. TBC tended to increase as CC increased in bulk milk (r = 0.5). In the final regression model, increased TBC, CC and the contamination of farm bulk milk byS. aureuswere significantly associated with dirty barns, dirty cows and soiled udder and teats. TBC was higher during the rainy season than during the dry season. The reported practice of washing teats with warm water significantly decreased CC and CPS. The occurrence ofS. aureuswas significantly (p < 0.05) higher in bulk farm milk (42%) than in pooled udder milk (37.3%), teat swabs (22.5%), milkers’ hand swabs (18%), bulking bucket swabs (16.7%), milking container swabs (14%), and water for cleaning of udder and milkers’ hands (10%). The questionnaire survey result showed widespred raw milk consumption habits, low level of training and poor hygienic milking practices.

Conclusions

This study revealed low-quality bulk farm milk with high bacterial counts and a high occurrence ofS. aureus. This indicates the potential food safety risks due to consumption of raw milk or its products. This study suggests awareness creation to dairy farmers and the public on hygienic milk production and heat treatment of milk before consumption.
Controlling taxa abundance improves metatranscriptomics differential analysis
Authors: Ji Zhicheng , Ma Li
Published: March 2023

Background

A common task in analyzing metatranscriptomics data is to identify microbial metabolic pathways with differential RNA abundances across multiple sample groups. With information from paired metagenomics data, some differential methods control for either DNA or taxa abundances to address their strong correlation with RNA abundance. However, it remains unknown if both factors need to be controlled for simultaneously.

Results

We discovered that when either DNA or taxa abundance is controlled for, RNA abundance still has a strong partial correlation with the other factor. In both simulation studies and a real data analysis, we demonstrated that controlling for both DNA and taxa abundances leads to superior performance compared to only controlling for one factor.

Conclusions

To fully address the confounding effects in analyzing metatranscriptomics data, both DNA and taxa abundances need to be controlled for in the differential analysis.
Clonal transmission of polymyxin B-resistant hypervirulent Klebsiella pneumoniae isolates coharboring blaNDM-1 and blaKPC-2 in a tertiary hospital in China
Authors: Tang Mengli , Li Jun , Liu Zhaojun , Xia Fengjun , Min Changhang , Hu Yongmei , Wang Haichen , Zou Mingxiang
Published: March 2023

Background

The prevalence of multidrug-resistant hypervirulent K. pneumoniae (MDR-hvKP) has gradually increased. It poses a severe threat to human health. However, polymyxin-resistant hvKP is rare. Here, we collected eight polymyxin B-resistant K. pneumoniae isolates from a Chinese teaching hospital as a suspected outbreak.

Results

The minimum inhibitory concentrations (MICs) were determined by the broth microdilution method. HvKP was identified by detecting virulence-related genes and using a Galleria mellonella infection model. Their resistance to serum, growth, biofilm formation, and plasmid conjugation were analyzed in this study. Molecular characteristics were analyzed using whole-genome sequencing (WGS) and mutations of chromosome-mediated two-component systems pmrAB and phoPQ, and the negative phoPQ regulator mgrB to cause polymyxin B (PB) resistance were screened. All isolates were resistant to polymyxin B and sensitive to tigecycline; four were resistant to ceftazidime/avibactam. Except for KP16 (a newly discovered ST5254), all were of the K64 capsular serotype and belonged to ST11. Four strains co-harbored blaKPC-2, blaNDM-1, and the virulence-related genes prmpA, prmpA2, iucA, and peg344, and were confirmed to be hypervirulent by the G. mellonella infection model. According to WGS analysis, three hvKP strains showed evidence of clonal transmission (8–20 single nucleotide polymorphisms) and had a highly transferable pKOX_NDM1-like plasmid. KP25 had multiple plasmids carrying blaKPC-2, blaNDM-1, blaSHV-12, blaLAP-2, tet(A), fosA5, and a pLVPK-like virulence plasmid. Tn1722 and multiple additional insert sequence-mediated transpositions were observed. Mutations in chromosomal genes phoQ and pmrB, and insertion mutations in mgrB were major causes of PB resistance.

Conclusions

Polymyxin-resistant hvKP has become an essential new superbug prevalent in China, posing a serious challenge to public health. Its epidemic transmission characteristics and mechanisms of resistance and virulence deserve attention.
Tree peony transcription factor PrWRI1 enhances seed oil accumulation
Authors: Xie Lihang , Hu Jiayuan , Yan Zhenguo , Li Xinyao , Wei Sailong , Xu Ruilin , Yang Weizong , Gu Huihui , Zhang Qingyu
Published: March 2023

Background

WRINKLED1 (WRI1) encodes a transcription factor, belonging to the APETALA2 (AP2) family, and plays a key role in regulating plant oil biosynthesis. As a newly woody oil crop, tree peony (Paeonia rockii) was notable for the abundant unsaturated fatty acids in its seed oil. However, the role of WRI1 during the accumulation of P. rockii seeds oil remains largely unknown.

Results

In this study, a new member of the WRI1 family was isolated from P. rockii and was named PrWRI1. The ORF of PrWRI1 consisted of 1269 nucleotides, encoding a putative protein of 422 amino acids, and was highly expressed in immature seeds. Subcellular localization analysis in onion inner epidermal cells showed that PrWRI1 was located at the nucleolus. Ectopic overexpression of PrWRI1 could significantly increase the total fatty acid content in Nicotiana benthamiana leaf tissue and even PUFAs in transgenic Arabidopsis thaliana seeds. Furthermore, the transcript levels of most genes related to fatty acids (FA) synthesis and triacylglycerol (TAG) assembly were also up-regulated in transgenic Arabidopsis seeds.

Conclusions

Together, PrWRI1 could push carbon flow to FA biosynthesis and further enhance the TAG amount in seeds with a high proportion of PUFAs.
Comprehensive analysis of the laccase gene family in tea plant highlights its roles in development and stress responses
Authors: Zhu Jiaxin , Zhang Hongxiu , Huang Kelin , Guo Rui , Zhao Jingjuan , Xie Hui , Zhu Junyan , Gu Honglian , Chen Hongrong , Li Guoqiang , Wei Chaoling , Liu Shengrui
Published: March 2023

Background

Laccase (LAC) is the pivotal enzyme responsible for the polymerization of monolignols and stress responses in plants. However, the roles of LAC genes in plant development and tolerance to diverse stresses are still largely unknown, especially in tea plant (Camellia sinensis), one of the most economically important crops worldwide.

Results

In total, 51 CsLAC genes were identified, they were unevenly distributed on different chromosomes and classified into six groups based on phylogenetic analysis. The CsLAC gene family had diverse intron–exon patterns and a highly conserved motif distribution. Cis-acting elements in the promoter demonstrated that promoter regions of CsLACs encode various elements associated with light, phytohormones, development and stresses. Collinearity analysis identified some orthologous gene pairs in C. sinensis and many paralogous gene pairs among C. sinensis, Arabidopsis and Populus. Tissue-specific expression profiles revealed that the majority of CsLACs had high expression in roots and stems and some members had specific expression patterns in other tissues, and the expression patterns of six genes by qRT‒PCR were highly consistent with the transcriptome data. Most CsLACs showed significant variation in their expression level under abiotic (cold and drought) and biotic (insect and fungus) stresses via transcriptome data. Among them, CsLAC3 was localized in the plasma membrane and its expression level increased significantly at 13 d under gray blight treatment. We found that 12 CsLACs were predicted to be targets of cs-miR397a, and most CsLACs showed opposite expression patterns compared to cs-miR397a under gray blight infection. Additionally, 18 highly polymorphic SSR markers were developed, these markers can be widely used for diverse genetic studies of tea plants.

Conclusions

This study provides a comprehensive understanding of the classification, evolution, structure, tissue-specific profiles, and (a)biotic stress responses of CsLAC genes. It also provides valuable genetic resources for functional characterization towards enhancing tea plant tolerance to multiple (a)biotic stresses.
Effect of isotemporal substitution of sedentary behavior with different intensities of physical activity on the muscle function of older adults in the context of a medical center
Authors: Lai Ting-Fu , Liao Yung , Hsueh Ming-Chun , Lin Kun-Pei , Chan Ding-Cheng , Chen Yung-Ming , Wen Chiung-Jung
Published: March 2023

Background

Engaging in physical activity and reducing sedentary time in daily life may enable older individuals to maintain muscle mass. This study aimed to investigate the effects of replacing sedentary behavior with light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on the muscle function of older adults at a medical center in Taiwan.

Methods

We recruited 141 older adults (51.1% men; 81.1 ± 6.9 years old) and asked them to wear a triaxial accelerometer on the waist to measure their sedentary behavior and physical activity. Functional performance was assessed based on handgrip strength, Timed Up and Go (TUG) test, gait speed, and five-times-sit-to-stand test (5XSST). Isotemporal substitution analysis was performed to examine the effect of substituting 60 min of sedentary time with 60 min of LPA, MVPA, and combined LPA and MVPA in different proportions.

Results

Reallocating 60 min of sedentary behavior per day to LPA was associated with better handgrip strength (Beta [B] = 1.587, 95% confidence interval [CI] = 0.706, 2.468), TUG test findings (B = -1.415, 95% CI = -2.186, -0.643), and gait speed (B = 0.042, 95% CI = 0.007, 0.078). Reallocating 60 min of sedentary behavior per day to MVPA was associated with better gait speed (B = 0.105, 95% CI = 0.018, 0.193) and 5XSST findings (B = -0.060, 95% CI = -0.117, -0.003). In addition, each 5-min increment in MVPA in the total physical activity replacing 60 min of sedentary behavior per day resulted in greater gait speed. Replacing 60 min of sedentary behavior with 30-min of LPA and 30-min of MVPA per day significantly decreased the 5XSST test time.

Conclusion

Our study indicates that introducing LPA and a combination of LPA and MVPA to specifically replace sedentary behavior may help maintain muscle function in older adults.
Re-examination of successful agers with lower biological than chronological age still after a 20-year follow-up period
Authors: Viljanen Anna , Salminen Marika , Irjala Kerttu , Korhonen Päivi , Vahlberg Tero , Viitanen Matti , Löppönen Minna , Viikari Laura
Published: March 2023

Background

Successful ageing is the term often used for depicting exceptional ageing but a uniform definition is lacking. The aim was to re-examine and describe the successful agers living at home at the age of 84 years or over after a 20-year follow-up. The purpose was also to identify possible factors leading to their successful ageing.

Methods

Successful ageing was defined as the ability to live at home without daily care. Data on the participants’ functional ability, objective health, self-rated health and satisfaction with life were gathered at baseline and after a 20-year follow-up period. A measurement of personal biological age (PBA) was established and the difference between the PBA and the chronological age (CA) was counted.

Results

The participants’ mean age was 87.6 years (Standard deviation 2.5, range 84–96). All analyzed variables depicted poorer physical ability and subjective health at re-examination than at baseline. Still, 99% of the participants were at least moderately satisfied with their lives. The PBA at baseline was 6.5 years younger than CA, and at re-examination, the difference was even more pronounced at 10.5 years.

Discussion

Even though the participants were chronologically older, had poorer physical ability and subjective health, they were still satisfied with their lives indicating possible psychological resilience. The difference between the PBA and CA was greater at re-examination than at baseline indicating that they were also biologically successful agers.

Conclusions

Successful agers were satisfied with life despite hardships and had a lower biological than chronological age. Further research is needed to evaluate causality.
Implementation of an antimicrobial stewardship program in the Vascular Surgery ward of a university tertiary care hospital in Pavia, Northern Italy
Authors: Vecchia Marco , Colaneri Marta , Sacchi Paolo , Marvulli Lea Nadia , Salvaderi Andrea , Lanza Jessica , Boschini Stefano , Ragni Franco , Marone Piero , Cutti Sara , Muzzi Alba , Marena Carlo , Calvi Monica , Scudeller Luigia , Marone Enrico Maria , Bruno Raffaele
Published: March 2023

Purpose

The commitment of multidisciplinary teams in antimicrobial stewardship programs (ASPs) is often inadequately considered, especially in surgical wards. We wanted to evaluate clinical, microbiological, and pharmacological outcomes before and after the implementation of an ASP in the Vascular Surgery ward of Fondazione IRCCS Policlinico San Matteo, a tertiary care hospital in Pavia, Italy.

Methods

This was a quasi-experimental quality-improvement study. The antimicrobial stewardship activity was conducted twice a week for 12 months and consisted of both prospective audit and feedback of all the ongoing antimicrobial prescriptions by the infectious diseases’ consultants and educational meetings for the healthcare workers of the Vascular Surgery ward. For comparison between the study periods, Student t test (Mann–Whitney test for skewed distributions) was used for quantitative variables (ANOVA or Kruskall-Wallis for > 2 groups respectively), and Pearson’s chi-squared test (Fisher exact test where appropriate) for categorical variables. 2-tailed tests were used. P-value significance cut-off was 0.05.

Results

During the 12-month intervention period, among a total number of 698 patients, 186 prescriptions were revised, mostly leading to de-escalating an ongoing antimicrobial therapy (39, 20.97%). A statistically significant reduction in isolates of carbapenem-resistant Pseudomonas aeruginosa (p-value 0.003) and the absence of Clostridioides difficile infections were reported. No statistically significant changes were observed in terms of length of stay and all-cause in-hospital mortality. A significant decrease in the administration of carbapenems (p-value 0.01), daptomycin (p-value < 0.01) and linezolid (p-value 0.43) was registered. A significant reduction in antimicrobial costs was also observed.

Conclusions

The implementation of a 12-month ASP brought significant clinical and economic results, highlighting the benefits of a multidisciplinary teamwork.
Ocular Mycobacterium haemophilum infection originating in the cornea: a case report
Authors: Zhang Yu-Qiang , Xu Ting-Ting , Wang Fu-Yan , Wang Shuang , Cheng Jun
Published: March 2023

Background

Mycobacterium haemophilum is a slow-growing non-chromogenic nontuberculous Mycobacterium species that can cause skin infection or arthritis in an immunocompromised population or in children. Primary infection of the healthy adult cornea is rare. The special requirements for culture make this pathogen difficult to diagnose. The study aims to report the clinical manifestation and treatment process of corneal infection and notify the awareness of M. Haemophilus keratitis among clinicians. This is the first case report of primary M. haemophilum infection in the cornea of healthy adults reported in the literature.

Case presentation

A 53-year-old healthy goldminer presented with left eye redness and a history of vision loss for four months. The patient was misdiagnosed with herpes simplex keratitis until M. haemophilum was detected using high-throughput sequencing. Penetrating keratoplasty was performed, and a large number of mycobacteria were detected by Ziehl-Neelsen staining of the infected tissue. Three months later, the patient developed conjunctival and eyelid skin infections that manifested as caseous necrosis of the conjunctiva and skin nodules. After excision and debridement of the conjunctival lesions and systemic antituberculosis drug treatment for 10 months, the patient was cured.

Conclusion

M. haemophilum could cause primary corneal infection in healthy adults, which is an infrequent or rare infection. Owing to the need for special bacterial culture conditions, conventional culture methods do not provide positive results. High-throughput sequencing can rapidly identify the presence of bacteria, which aids in early diagnosis and timely treatment. Prompt surgical intervention is an effective treatment option for severe keratitis. Long-term systemic antimicrobial therapy is crucial.
Time to diagnosis and treatment of pulmonary tuberculosis in indigenous peoples: a systematic review
Authors: Varughese Marie , Heffernan Courtney , Li Michael Y. , Long Richard
Published: March 2023

Background

Time to diagnosis and treatment is a major factor in determining the likelihood of tuberculosis (TB) transmission and is an important area of intervention to reduce the reservoir of TB infection and prevent disease and mortality. Although Indigenous peoples experience an elevated incidence of TB, prior systematic reviews have not focused on this group. We summarize and report findings related to time to diagnosis and treatment of pulmonary TB (PTB) among Indigenous peoples, globally.

Methods

A Systematic review was performed using Ovid and PubMed databases. Articles or abstracts estimating time to diagnosis, or treatment of PTB among Indigenous peoples were included with no restriction on sample size with publication dates restricted up to 2019. Studies that focused on outbreaks, solely extrapulmonary TB alone in non-Indigenous populations were excluded. Literature was assessed using the Hawker checklist. Registration Protocol (PROSPERO): CRD42018102463.

Results

Twenty-four studies were selected after initial assessment of 2021 records. These included Indigenous groups from five of six geographical regions outlined by the World Health Organization (all except the European Region). The range of time to treatment (24–240 days), and patient delay (20 days–2.5 years) were highly variable across studies and, in at least 60% of the studies, longer in Indigenous compared to non-Indigenous peoples. Risk factors associated with longer patient delays included poor awareness of TB, type of health provider first seen, and self-treatment.

Conclusion

Time to diagnosis and treatment estimates for Indigenous peoples are generally within previously reported ranges from other systematic reviews focusing on the general population. However among literature examined in this systematic review that stratified by Indigenous and non-Indigenous peoples, patient delay and time to treatment were longer compared to non-Indigenous populations in over half of the studies. Studies included were sparse and highlight an overall gap in literature important to interrupting transmission and preventing new TB cases among Indigenous peoples. Although, risk factors unique to Indigenous populations were not identified, further investigation is needed as social determinants of health among studies conducted in medium and high incidence countries may be shared across both population groups.

Trial registration N/a.
Epidemiology and molecular characteristics of respiratory syncytial virus (RSV) among italian community-dwelling adults, 2021/22 season
Authors: Panatto Donatella , Domnich Alexander , Lai Piero Luigi , Ogliastro Matilde , Bruzzone Bianca , Galli Cristina , Stefanelli Federica , Pariani Elena , Orsi Andrea , Icardi Giancarlo
Published: March 2023

Background

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections worldwide. While historically RSV research has been focused on children, data on RSV infection in adults are limited. The goal of this study was to establish the prevalence of RSV in community-dwelling Italian adults and analyze its genetic variability during the 2021/22 winter season.

Methods

In this cross-sectional study, a random sample of naso-/oropharyngeal specimens from symptomatic adults seeking for SARS-CoV-2 molecular testing between December 2021 and March 2022 were tested for RSV and other respiratory pathogens by means of reverse-transcription polymerase chain reaction. RSV-positive samples were further molecularly characterized by sequence analysis.

Results

Of 1,213 samples tested, 1.6% (95% CI: 0.9–2.4%) were positive for RSV and subgroups A (44.4%) and B (55.6%) were identified in similar proportions. The epidemic peak occurred in December 2021, when the RSV prevalence was as high as 4.6% (95% CI: 2.2–8.3%). The prevalence of RSV detection was similar (p = 0.64) to that of influenza virus (1.9%). All RSV A and B strains belonged to the ON1 and BA genotypes, respectively. Most (72.2%) RSV-positive samples were also positive for other pathogens being SARS-CoV-2, Streptococcus pneumoniae and rhinovirus the most frequent. RSV load was significantly higher among mono-detections than co-detections.

Conclusion

During the 2021/22 winter season, characterized by the predominant circulation of SARS-CoV-2 and some non-pharmaceutical containment measures still in place, a substantial proportion of Italian adults tested positive for genetically diversified strains of both RSV subtypes. In view of the upcoming registration of vaccines, establishment of the National RSV surveillance system is urgently needed.
A case of SARS-CoV-2 Omicron reinfection resulting in a significant immunity boost in a paediatric patient affected by B-cell acute lymphoblastic leukemia
Authors: Scutari Rossana , Fox Valeria , De Ioris Maria Antonietta , Fini Vanessa , Granaglia Annarita , Costabile Valentino , Colagrossi Luna , Russo Cristina , Mastronuzzi Angela , Locatelli Franco , Perno Carlo Federico , Alteri Claudia
Published: March 2023

Background

Since its emergence in November 2021, SARS-CoV-2 Omicron clade has quickly become dominant, due to its increased transmissibility and immune evasion. Different sublineages are currently circulating, which differ in mutations and deletions in regions of the SARS-CoV-2 genome implicated in the immune response. In May 2022, BA.1 and BA.2 were the most prevalent sublineages in Europe, both characterized by ability of evading natural acquired and vaccine-induced immunity and of escaping monoclonal antibodies neutralization.

Case presentation

A 5-years old male affected by B-cell acute lymphoblastic leukemia in reinduction was tested positive for SARS-CoV-2 by RT-PCR at the Bambino Gesù Children Hospital in Rome in December 2021. He experienced a mild COVID-19 manifestation, and a peak of nasopharyngeal viral load corresponding to 15.5 Ct. Whole genome sequencing identified the clade 21 K (Omicron), sublineage BA.1.1. The patient was monitored over time and tested negative for SARS-CoV-2 after 30 days. Anti-S antibodies were detected positive with modest titre (3.86 BAU/mL), while anti-N antibodies were negative. 74 days after the onset of the first infection and 23 days after the last negative test, the patient was readmitted to hospital with fever, and tested positive for SARS-CoV-2 by RT-PCR (peak of viral load corresponding to 23.3 Ct). Again, he experienced a mild COVID-19. Whole genome sequencing revealed an infection with the Omicron lineage BA.2 (21L clade). Sotrovimab administration was started at the fifth day of positivity, and RT-PCR negativity occurred 10 days later. Surveillance SARS-CoV-2 RT-PCR were persistently negative, and in May 2022, anti-N antibodies were found positive and anti-S antibodies reached titres > 5000 BAU/mL.

Conclusions

By this clinical case, we showed that SARS-CoV-2 reinfection within the Omicron clade can occur and can be correlated to inadequate immune responses to primary infection. We also showed that the infection’s length was shorter in the second respect to first episode, suggesting that pre-existing T cell-mediated immunity, though not preventing re-infection, might have limited the SARS-CoV-2 replication capacity. Lastly, Sotrovimab treatment retained activity against BA.2, probably accelerating the viral clearance in the second infectious episode, after which seroconversion and increase of anti-S antibodies titres were observed.
Stage or size? The identity of anatomical and visual outcomes in stage 3 and stage 4 idiopathic macular holes after vitrectomy
Authors: Yu Yanping , Liang Xida , Wang Zengyi , Wang Jing , Qi Biying , Liu Wu
Published: March 2023

Background

Several previous reports suggested that stage 4 idiopathic macular holes (IMHs) may exhibit lower rate of anatomical success and poorer functional results comparing with stage 3 IMHs, while some others showed no differences. Actually, few studies focused on comparison of prognosis between stage 3 and stage 4 IMHs. Our previous study found that IMHs of these two stages demonstrate similar preoperative characteristics, and this study aims to compare anatomical and visual outcomes of IMHs between stage 3 and stage 4, and tries to figure out the outcome-associated factors.

Methods

This retrospective consecutive case series reviewed 317 eyes with IMHs of stage 3 and stage 4 from 296 patients who underwent vitrectomy with internal limiting membrane peeling. Preoperative characteristics like age, gender, and hole size, and intraoperative interventions such as combined cataract surgery were evaluated. Outcome measures included the primary closure rate (type 1), best-corrected visual acuity (BCVA), foveal retinal thickness (FRT) and prevalence of outer retinal defect (ORD) at the last visit. The pre-, intra-, and post-operative information were respectively compared between stage 3 and stage 4.

Results

The preoperative characteristics and intraoperative interventions exhibited no significant differences between stages. With comparable follow-up durations (6.6 vs. 6.7 months, P = 0.79), IMHs of the two stages exhibited similar primary closure rate (91.2% vs. 91.8%, P = 0.85), BCVA (0.51 ± 0.12 vs. 0.53 ± 0.11, P = 0.78), FRT (134.8 ± 55.5 μm vs. 138.8 ± 60.7 μm, P = 0.58), and prevalence of ORD (55.1% vs. 52.6%, P = 0.39). IMHs, either < 650 μm or larger, exhibited no significant difference in outcomes between the two stages. However, smaller IMHs (< 650 μm) demonstrated higher rate of primary closure (97.6% vs. 80.8%, P < 0.001), better postoperative BCVA (0.58 ± 0.26 vs. 0.37 ± 0.24, P < 0.001), and thicker postoperative FRT (150.2 ± 54.0 vs. 104.3 ± 52.0, P < 0.001) comparing with larger ones regardless of stage.

Conclusion

IMHs of stage 3 and stage 4 exhibited considerable identity of anatomical and visual outcomes. In large IMHs, the hole size, instead of stage, may be more important for prediction of surgical outcomes and choice of surgical techniques.
Knowledge and attitude toward eye disorders in children among pediatricians and family physicians: a survey study
Authors: Hersi Reem M. , Naaman Nada K. , Alghamdi Amer M. , Alnahdi Wejdan A. , Bukhari Ziad M. , Almarzouki Hashem S.
Published: March 2023

Background

Vision-related disorders are common in children. Therefore, eye examination and thorough visual assessment by first-contact physicians are crucial in children. This study aimed to evaluate the knowledge of and attitude toward children’s eye disorders among pediatricians and family physicians in the Ministry of National Guard Health Affairs-Western Region (MNGHA-WR) of Saudi Arabia.

Methods

In this observational, cross-sectional study, we used a self-administered, web-based questionnaire. The sample size was calculated to be 148 pediatricians and family physicians (of 240 in total) currently working at MNGHA-WR. The first section of the questionnaire dwelled on demographics, while the second section addressed the physician’s knowledge of and attitude toward commonly encountered ophthalmological pathologies in children. Data collected were entered into Microsoft Excel and then transferred to IBM SPSS version 22 for statistical analysis.

Results

A total of 148 responses (92 family physicians and 56 pediatricians) were received. Most of the participants were residents or staff physicians (n = 105, 70.9%). The mean knowledge score of the respondents was 54.67% ± 14.5%. Participants’ knowledge was further subclassified using Bloom’s original cutoff points into high (n = 4, 2.7%), moderate (n = 53, 35.8%), and low (n = 91, 61.5%) levels of knowledge. Regarding practices, 120 (81%) participants performed ophthalmic examinations; however, only 39 (26.4%) conducted routine examinations as part of every child’s visit. Fundus examinations were performed by 25 (16.9%) physicians. A significant deficiency in knowledge was noted in those with < 1 year of work experience (P = 0.014). Although statistically not significant (P = 0.052), family physicians possessed better knowledge than pediatricians regarding children’s eye disorders. On the contrary, more pediatricians performed eye examinations than family physicians (P = 0.015). The male sex was also associated with higher rates of eye examination (P = 0.033).

Conclusion

An unsatisfactory level of knowledge of eye disease among participating doctors was reported. The proportion was significantly higher among residents and staff physicians. Therefore, awareness efforts should be incorporated in both family medicine and pediatrics residency programs to limit the number of cases of ocular disorders going undiagnosed in children.