Evaluation of the therapeutic potential of infrapatellar fat pad adipose-derived stem cells and their secretome for regenerating knee articular cartilage in a rat model of osteoarthritis.

Background: Mesenchymal stem cell (MSC) therapy has ameliorative effects for treating knee osteoarthritis (KOA) disease. Moreover, there is a growing interest in using MSCs-derived secretome (Sec) containing trophic factors secreted by MSCs for KOA treatment. Recently, some studies have suggested that the combination of MSCs and Sec has the potential to treat the diseases. Aims: This study aimed to evaluate the ameliorative effects of combined administration of infrapatellar fat pad (IPFP)-derived MSCs, a type of adipose-derived stem cells (ASCs), for treating degenerated cartilage in a rat model of KOA. Methods: IPFP-ASCs were isolated from the IPFP of male rats. Sec was obtained from IPFP-ASCs in the fourth passage. Eight weeks after the induction of KOA by collagenase II, the rats were divided into 5 groups (n=5), including a control group with no treatment, and four experimental groups that received sodium hyaluronate (Hyalgan®, Hya), ASCs, Sec, and IPFP-ASCs+Sec, respectively by an infrapatellar injection. To perform the pathological and radiological evaluations, the animals were sacrificed 8 weeks later. Results: Our findings indicated that combined administration of the IPFP-ASCs and Sec statistically (P<0.05) improved scores of medial tibial and femoral condyles and medial fabella osteophytes. Also, it statistically (P<0.05) enhances the cartilage surface, matrix, cell distribution and population viability, and subchondral bone indices. No statistical difference was observed between IPFP-ASCs+Sec and IPFP-ASCs. Conclusion: Administration of IPFP-ASCs+Sec has a therapeutic potential to treat KOA in rats. However, there is no difference in the combined administration of IPFP-ASCs and Sec with IPFP-ASCs alone.

The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population.

PURPOSE: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. PARTICIPANTS: Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data. METHODS: Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. MAIN OUTCOME MEASURES: Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. RESULTS: In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12-0.17; P < 0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07-1.14; P < 0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36-0.53, P < 0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17-1.45; P < 0.001). Stronger associations with glaucoma (P interaction = 0.001) were noted in participants with a higher glaucoma polygenic risk score. CONCLUSIONS: Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Laparoscopic Versus Open Gastrectomy for Advanced Gastric Cancer: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) is a well-established surgical technique in treating patients with early gastric cancer. However, the efficacy and safety of LAG versus open gastrectomy (OG) in patients with advanced gastric cancer (AGC) remains unclear. METHODS: We systematically searched PubMed, Embase, and Cochrane Library in June 2023 for RCTs comparing LAG versus OG in patients with AGC. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for binary and continuous endpoints, respectively. We performed all statistical analyses using R software version 4.3.1 and a random-effects model. RESULTS: Nine RCTs comprising 3827 patients were included. There were no differences in terms of intraoperative complications (RR 1.14; 95% CI 0.72 to 1.82), number of retrieved lymph nodes (MD -0.54 lymph nodes; 95% CI -1.18 to 0.09), or mortality (RR 0.91; 95% CI 0.30 to 2.83). LAG was associated with a longer operative time (MD 49.28 minutes; 95% CI 30.88 to 67.69), lower intraoperative blood loss (MD -51.24 milliliters; 95% CI -81.41 to -21.06), shorter length of stay (MD -0.83 days; 95% CI -1.60 to -0.06), and higher incidence of pancreatic fistula (RR 2.44; 95% CI 1.08 to 5.50). Postoperatively, LAG was also superior to OG in reducing bleeding rates (RR 0.44; 95% CI 0.22 to 0.86) and time to first flatus (MD -0.27 days; 95% CI -0.47 to -0.07), with comparable results in anastomotic leakage, wound healing issues, major complications, time to ambulation, or time to first liquid intake. In the long-term analyses at 3 and 5 years, there were no significant differences between LAG and OG in terms of overall survival (RR 0.99; 95% CI 0.96 to 1.03) or relapse-free survival (RR 0.99; 95% CI 0.94 to 1.04). CONCLUSION: This meta-analysis of RCTs suggests that LAG may be an effective and safe alternative to OG for treating AGC; albeit, it may be associated with an increased risk for pancreatic fistula.

Smoking, Corneal Biomechanics, and Glaucoma: Results From Two Large Population-Based Cohorts.

Purpose: Smoking may influence measured IOP through an effect on corneal biomechanics, but it is unclear whether this factor translates into an increased risk for glaucoma. This study aimed to examine the association of cigarette smoking with corneal biomechanical properties and glaucoma-related traits, and to probe potential causal effects using Mendelian randomization (MR). Methods: Cross-sectional analyses within the UK Biobank (UKB) and Canadian Longitudinal Study on Aging (CLSA) cohorts. Multivariable linear and logistic regression models were used to assess associations of smoking (status, intensity, and duration) with corneal hysteresis (CH), corneal resistance factor, IOP, inner retinal thicknesses, and glaucoma. Two-sample MR analyses were performed. Results: Overall, 68,738 UKB (mean age, 56.7 years; 54.7% women) and 22 845 CLSA (mean age, 62.7 years; 49.1% women) participants were included. Compared with nonsmokers, smokers had a higher CH (UKB, +0.48 mm Hg; CLSA, +0.57 mm Hg; P < 0.001) and corneal resistance factor (UKB, +0.47 mm Hg; CLSA, +0.60 mm Hg; P < 0.001) with evidence of a dose-response effect in both studies. Differential associations with Goldmann-correlated IOP (UKB, +0.25 mm Hg; CLSA, +0.36 mm Hg; P < 0.001) and corneal-compensated IOP (UKB, -0.28 mm Hg; CLSA, -0.32 mm Hg; P ≤ 0.001) were observed. Smoking was not associated with inner retinal thicknesses or glaucoma status in either study. MR provided evidence for a causal effect of smoking on corneal biomechanics, especially higher CH. Conclusions: Cigarette smoking seems to increase corneal biomechanical resistance to deformation, but there was little evidence to support a relationship with glaucoma. This outcome may result in an artefactual association with measured IOP and could account for discordant results with glaucoma in previous epidemiological studies.

A Comprehensive Review of Identification Methods for Pathogenic Yeasts: Challenges and Approaches.

Given the increasing incidence of yeast infections and the presence of drug-resistant isolates, accurate identification of the pathogenic yeasts is essential for the management of yeast infections. In this review, we tried to introduce the routine and novel techniques applied for yeast identification. Laboratory identification methods of pathogenic yeast are classified into three categories; I. conventional methods, including microscopical and culture-base methods II. biochemical/physiological-processes methods III. molecular methods. While conventional and biochemical methods require more precautions and are not specific in some cases, molecular diagnostic methods are the optimum tools for diagnosing pathogenic yeasts in a short time with high accuracy and specificity, and having various methods that cover different purposes, and affordable costs for researchers. Nucleotide sequencing is a reference or gold standard for identifying pathogenic yeasts. Since it is an expensive method, it is not widely used in developing countries. However, novel identification techniques are constantly updated, and we recommend further studies in this field. The results of this study will guide researchers in finding more accurate diagnostic method(s) for their studies in a short period of time.

The Association of Physical Activity with Glaucoma and Related Traits in the UK Biobank.

PURPOSE: To examine the association of physical activity (PA) with glaucoma and related traits, to assess whether genetic predisposition to glaucoma modified these associations, and to probe causal relationships using Mendelian randomization (MR). DESIGN: Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. PARTICIPANTS: UK Biobank participants with data on self-reported or accelerometer-derived PA and intraocular pressure (IOP; n = 94 206 and n = 27 777, respectively), macular inner retinal OCT measurements (n = 36 274 and n = 9991, respectively), and glaucoma status (n = 86 803 and n = 23 556, respectively). METHODS: We evaluated multivariable-adjusted associations of self-reported (International Physical Activity Questionnaire) and accelerometer-derived PA with IOP and macular inner retinal OCT parameters using linear regression and with glaucoma status using logistic regression. For all outcomes, we examined gene-PA interactions using a polygenic risk score (PRS) that combined the effects of 2673 genetic variants associated with glaucoma. MAIN OUTCOME MEASURES: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and glaucoma status. RESULTS: In multivariable-adjusted regression models, we found no association of PA level or time spent in PA with glaucoma status. Higher overall levels and greater time spent in higher levels of both self-reported and accelerometer-derived PA were associated positively with thicker mGCIPL (P < 0.001 for trend for each). Compared with the lowest quartile of PA, participants in the highest quartiles of accelerometer-derived moderate- and vigorous-intensity PA showed a thicker mGCIPL by +0.57 µm (P < 0.001) and +0.42 µm (P = 0.005). No association was found with mRNFL thickness. High overall level of self-reported PA was associated with a modestly higher IOP of +0.08 mmHg (P = 0.01), but this was not replicated in the accelerometry data. No associations were modified by a glaucoma PRS, and MR analyses did not support a causal relationship between PA and any glaucoma-related outcome. CONCLUSIONS: Higher overall PA level and greater time spent in moderate and vigorous PA were not associated with glaucoma status but were associated with thicker mGCIPL. Associations with IOP were modest and inconsistent. Despite the well-documented acute reduction in IOP after PA, we found no evidence that high levels of habitual PA are associated with glaucoma status or IOP in the general population. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Psychometric evaluation of Oral Mucositis Daily Questionnaire: A cross-cultural adaptation of the Malay version in multiethnic adult autologous stem cell transplant.

Objective: Mucositis is one of the most feared side effects of cancer treatment. Psychometric analysis of a patient self-assessment score, the oral mucositis daily questionnaire in Malay (OMDQ-Mal) and its construct validity by means of confirmatory factor analysis (CFA) is lacking. This research aimed to test the validity and reliability of OMDQ-Mal. Methods: A total of 114 autologous stem-cell transplantation patients aged ≥ 18 years old at a national hematology center in Malaysia from April 2019 to December 2020 completed OMDQ-Mal concurrently with physician scores. Internal consistency and reproducibility were determined by Cronbach alpha and intraclass correlation coefficient, respectively. Correlations with physician scores were determined by Spearman correlation. Discriminative validity and construct validity were determined by Mann-Whitney U and CFA, respectively. Results: OMDQ-Mal demonstrated high internal consistency (α â€‹= â€‹0.874). Test-retest reliability between paired days were moderate to excellent (95% CI â€‹= â€‹0.676-0.953). Items in OMDQ-Mal had moderate to strong correlations with physician scores (ρ â€‹= â€‹0.503-0.721). Discriminative validity indicated that the scores of scales were significantly different between participants with severe and mild conditions. Construct validity results of loading factors 0.708-0.952; composite reliability 0.879-0.974; average variant extracted 0.710-0.841; and heterotrait-monotrait ratio 0.528 established the convergent and divergent validity. Conclusions: In conclusion, the OMDQ-Mal, which captured important quality of life responses, demonstrated adequate validity and reliability. This was supported by a two-component model CFA. The strong correlation of OMDQ-Mal with both physician scores indicated its potential as a comprehensive patient-reported outcome measure of mucositis of the entire alimentary tract.

The Association of Alcohol Consumption with Glaucoma and Related Traits: Findings from the UK Biobank.

PURPOSE: To examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. PARTICIPANTS: UK Biobank participants with data on intraocular pressure (IOP) (n = 109 097), OCT-derived macular inner retinal layer thickness measures (n = 46 236) and glaucoma status (n = 173 407). METHODS: Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses. MAIN OUTCOME MEASURES: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma. RESULTS: Compared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P < 0.001) and thinner mGCIPL (-0.17 µm; P = 0.049), whereas former drinkers had a higher prevalence of glaucoma (odds ratio, 1.53; P = 0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P < 0.001). Restricted cubic spline regression analyses suggested nonlinear associations, with apparent threshold effects at approximately 50 g (∼6 UK or 4 US alcoholic units)/week for mRNFL and mGCIPL thickness. Significantly stronger alcohol-IOP associations were observed in participants at higher genetic susceptibility to glaucoma (Pinteraction < 0.001). Mendelian randomization analyses provided evidence for a causal association with mGCIPL thickness. CONCLUSIONS: Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (< 112 g/week) and United States (women, < 98 g/week; men, < 196 g/week) guidelines. Although we cannot infer causality definitively, these results will be of interest to people with or at risk of glaucoma and their advising physicians. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The Association of Female Reproductive Factors with Glaucoma and Related Traits: A Systematic Review.

TOPIC: This systematic review summarizes evidence for associations between female reproductive factors (age at menarche, parity, oral contraceptive [OC] use, age at menopause, and postmenopausal hormone [PMH] use) and intraocular pressure (IOP) or open-angle glaucoma (OAG). CLINICAL RELEVANCE: Understanding the associations between female reproductive factors and glaucoma may shed light on the disease pathogenesis and aid clinical prediction and personalized treatment strategies. Importantly, some factors are modifiable, which may lead to new therapies. METHODS: Two reviewers independently extracted articles in MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases to identify relevant studies. Eligibility criteria included studies with human subjects aged > 18 years; a measured outcome of either IOP or OAG; a cohort, case-control, cross-sectional, or randomized controlled trial design; a reported measure of association, such as the hazard ratio, relative risk, odds ratio, or mean difference, with an associated confidence interval; and a measured exposure of at least 1 of the following variables: age at menarche, parity, OC use, age at menopause, or PMH use. RESULTS: We included a total of 27 studies. Substantial differences in study designs, exposure and treatment levels, treatment durations, and variable reporting precluded a meaningful quantitative synthesis of the identified studies. Overall, relatively consistent associations between PMH use and a lower IOP were identified. Estrogen-only PMH use may be associated with lower OAG risk, which may be modified by race. No significant associations were found with combined estrogen-and-progesterone PMH use. No strong associations between parity or age at menarche and glaucoma were found, but a younger age at menopause was associated with an increased glaucoma risk, and adverse associations were identified with a longer duration of OC use, though no overall association with OC use was found. CONCLUSIONS: The association between PMH use and lower IOP or OAG risk is a potentially clinically relevant and modifiable risk factor and should be investigated further, although this needs to be interpreted in the context of a high risk of bias across included studies. Future research should examine associations with IOP specifically and how the relationship between genetic factors and OAG risks may be influenced by female reproductive factors.

The Association between Serum Lipids and Intraocular Pressure in 2 Large United Kingdom Cohorts.

PURPOSE: Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP). DESIGN: Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts. PARTICIPANTS: We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and 2009. METHODS: Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc). MAIN OUTCOME MEASURES: Corneal-compensated IOP. RESULTS: Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06-0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08-0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05-0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07-0.31 mmHg; P = 0.001), 0.14 mmHg (95% CI, 0.03-0.25 mmHg; P = 0.016), and 0.17 mmHg (95% CI, 0.06-0.29 mmHg; P = 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (-0.05 mmHg; 95% CI, -0.08 to -0.03; P < 0.001) was not replicated in the EPIC-Norfolk cohort (P = 0.30). CONCLUSIONS: Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.