-
Frontiers in Endocrinology 2024Proliferative diabetic retinopathy (PDR) is a common diabetes complication, significantly impacting vision and quality of life. Previous studies have suggested a...
Levels of asymmetric dimethylarginine in plasma and aqueous humor: a key risk factor for the severity of fibrovascular proliferation in proliferative diabetic retinopathy.
INTRODUCTION
Proliferative diabetic retinopathy (PDR) is a common diabetes complication, significantly impacting vision and quality of life. Previous studies have suggested a potential link between arginine pathway metabolites and diabetic retinopathy (DR). Connective tissue growth factor (CTGF) plays a role in the occurrence and development of fibrovascular proliferation (FVP) in PDR patients. However, the relationship between arginine pathway metabolites and FVP in PDR remains undefined. This study aimed to explore the correlation between four arginine pathway metabolites (arginine, asymmetric dimethylarginine[ADMA], ornithine, and citrulline) and the severity of FVP in PDR patients.
METHODS
In this study, plasma and aqueous humor samples were respectively collected from 30 patients with age-related cataracts without diabetes mellitus (DM) and from 85 PDR patients. The PDR patients were categorized as mild-to-moderate or severe based on the severity of fundal FVP. The study used Kruskal-Wallis test to compare arginine, ADMA, ornithine, and citrulline levels across three groups. Binary logistic regression identified risk factors for severe PDR. Spearman correlation analysis assessed associations between plasma and aqueous humor metabolite levels, and between ADMA and CTGF levels in aqueous humor among PDR patients.
RESULTS
ADMA levels in the aqueous humor were significantly greater in patients with severe PDR than in those with mild-to-moderate PDR(0.0004). However, the plasma and aqueous humor levels of arginine, ornithine, and citrulline did not significantly differ between mild-to-moderate PDR patients and severe PDR patients (0.05). Binary logistic regression analysis indicated that the plasma (0.01) and aqueous humor (0.006) ADMA levels in PDR patients were risk factors for severe PDR. Furthermore, significant correlations were found between plasma and aqueous humor ADMA levels (0.263, =0.015) and between aqueous humor ADMA and CTGF levels (0.837, <0.001).
CONCLUSION
Elevated ADMA levels in plasma and aqueous humor positively correlate with the severity of FVP in PDR, indicating ADMA as a risk factor for severe PDR.
Topics: Humans; Arginine; Male; Female; Diabetic Retinopathy; Middle Aged; Aqueous Humor; Risk Factors; Aged; Severity of Illness Index; Ornithine; Citrulline; Biomarkers; Connective Tissue Growth Factor
PubMed: 38933824
DOI: 10.3389/fendo.2024.1364609 -
Frontiers in Veterinary Science 2024Feline chronic enteropathies (FCE) are common causes of chronic gastrointestinal signs in cats and include different diseases such as food-responsive enteropathy (FRE),...
Feline chronic enteropathies (FCE) are common causes of chronic gastrointestinal signs in cats and include different diseases such as food-responsive enteropathy (FRE), inflammatory bowel diseases (IBD), and low-grade intestinal T-cell lymphoma (LGITL). Although changes in intestinal microbiota and fecal metabolites have been reported in dogs and humans with chronic enteropathy, research in cats has been limited. Therefore, this study aimed to evaluate the fecal microbiota and lipid-related fecal metabolites in cats with FCE to a clinically healthy comparison group (CG). A total of 34 cats with FCE (13 FRE, 15 IBD, and 6 LGITL) and 27 cats in the CG were enrolled in this study. The fecal microbiota was evaluated by the qPCR-based feline Dysbiosis Index (DI). The feline DI in cats with CE (median: 1.3, range: -2.4 to 3.8) was significantly higher ( < 0.0001) compared to CG (median: - 2.3, Range: -4.3 to 2.3), with no difference found among the FCE subgroups. The fecal abundances of Faecalibacterium ( < 0.0001), ( < 0.0001), ( = 0.0398), Bifidobacterium ( = 0.0004), and total bacteria ( = 0.0337) significantly decreased in cats with FCE. Twenty-seven targeted metabolites were measured by gas chromatography-mass spectrometry, including long-chain fatty acids (LCFAs), sterols, and bile acids (BAs). Fecal concentrations of 5 of 12 LCFAs were significantly increased in cats with FCE compared to CG. Fecal concentrations of zoosterol ( = 0.0109), such as cholesterol ( < 0.001) were also significantly increased in cats with FCE, but those of phytosterols were significantly decreased in this group. No differences in fecal BAs were found between the groups. Although no differences were found between the four groups, the fecal metabolomic pattern of cats with FRE was more similar to that of the CG than to those with IBD or LGITL. This could be explained by the mild changes associated with FRE compared to IBD and LGITL. The study showed changes in intestinal microbiota and alteration of fecal metabolites in FCE cats compared to the CG. Changes in fecal lipids metabolites suggest a dysmetabolism of lipids, including LCFAs, sterols, and unconjugated BAs in cats with CE.
PubMed: 38933703
DOI: 10.3389/fvets.2024.1401592 -
Frontiers in Pharmacology 2024Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and...
Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial.
Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (C) and the area under the concentration-time curve (AUC) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3',5'-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension. http://www.chinadrugtrials.org.cn, identifier CTR20210064.
PubMed: 38933676
DOI: 10.3389/fphar.2024.1359939 -
AJPM Focus Aug 2024This study aimed to clarify the relationship between psychological factors (goal orientation and desire for approval from others) and the severity of sports injuries...
INTRODUCTION
This study aimed to clarify the relationship between psychological factors (goal orientation and desire for approval from others) and the severity of sports injuries experienced by young Japanese athletes.
METHODS
A total of 560 young Japanese athletes (328 males and 232 females) aged 18-24 years completed an online survey in 2022-2023. A web questionnaire was used to investigate participants' task and ego orientations, desire for approval from others (e.g., coaches and friends/families), and history of injury. The samples were then split into 3 groups on the basis of the rest duration due to the injury: noninjury group (0 days), mild-to-moderate injury group (1-27 days), and severe injury group (>28 days). Spearman's test examined a correlation between task and ego orientation scores among all samples. The Mann-Whitney test was used to compare the scores between the severe injury and noninjury groups.
RESULT
A significant positive correlation was found between task and ego orientation scores from all samples (ρ=0.27, <0.001). The severe injury group had significantly higher task orientation scores and desire for approval scores than the noninjury group (ρ=0.001, <0.001).
CONCLUSIONS
Japanese young athletes with high task orientation and approval desire may be at risk of severe sports injuries requiring >4 weeks to return to sports. The goal orientation profiles should be interpreted with caution. Future research should examine contextual effects such as the perceived motivational climate, in addition to the goal orientation profiles.
PubMed: 38933529
DOI: 10.1016/j.focus.2024.100236 -
Frontiers in Pediatrics 2024The COVID-19 pandemic has disproportionately affected marginalized groups in the United States. Although most children have mild or asymptomatic COVID-19, some...
BACKGROUND
The COVID-19 pandemic has disproportionately affected marginalized groups in the United States. Although most children have mild or asymptomatic COVID-19, some experience severe disease and long-term complications. However, few studies have examined health disparities in severe COVID-19 outcomes among US children.
OBJECTIVE
To examine disparities in the clinical outcomes of infants and children aged <5 years hospitalized with COVID-19 by race/ethnicity and payer status.
METHODS
Children aged <5 years hospitalized with an admission diagnosis of COVID-19 (April 2021-February 2023) were selected from the PINC AI™ Healthcare Database. Hospital outcomes included length of stay (LOS), intensive care unit (ICU) admission, oxygen supplementation, invasive mechanical ventilation (IMV), and prolonged duration of each outcome. Multivariable logistic regression models compared hospitalization outcomes by race/ethnicity and payer status.
RESULTS
Among 10,190 children (mean age: 0.9 years, 56.5% male, 66.7% Medicaid-insured), race/ethnicity was distributed as follows: White non-Hispanic (35.1%), Hispanic (any or Unknown race; 28.3%), Black non-Hispanic (15.2%), Other race/ethnicity (8.9%) and Unknown (12.5%). Payer status varied by race/ethnicity. White non-Hispanic children had the highest proportion with commercial insurance (42.9%) while other racial/ethnic groups ranged between 13.8% to 26.1%. Black non-Hispanic children had the highest proportion with Medicaid (82.3%) followed by Hispanic children (76.9%). Black non-Hispanic children had higher odds of prolonged outcomes: LOS (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI]:1.05-1.38), ICU days (aOR = 1.44, 95% CI: 1.07-1.93), and IMV days (aOR = 1.80, 95% CI: 1.09-2.97) compared to White non-Hispanic children. Similar patterns were observed for Hispanic and children of Other race/ethnicity. Medicaid-insured and children with other insurance had higher odds of prolonged LOS and oxygen days than commercially insured patients.
CONCLUSION
There were disparities in clinical outcomes of COVID-19 by race/ethnicity and insurance type, particularly for prolonged-duration outcomes. Further research is required to fully comprehend the causes and consequences of these disparities and develop strategies to reduce them while ensuring equitable healthcare delivery.
PubMed: 38933493
DOI: 10.3389/fped.2024.1373444 -
Frontiers in Physiology 2024Oleuropein, a phenolic compound derived from olives, has known glucoregulatory effects in mammalian models but effects in birds are unknown. We investigated effects of...
Oleuropein, a phenolic compound derived from olives, has known glucoregulatory effects in mammalian models but effects in birds are unknown. We investigated effects of dietary supplementation and exogenous administration of oleuropein on broiler chick feed intake and glucose homeostasis during the first 7 days post-hatch. One hundred and forty-eight day-of-hatch broiler chicks were randomly allocated to one of four dietary treatments with varying oleuropein concentrations (0, 250, 500, or 1,000 mg/kg). Body weight and breast muscle and liver weights were recorded on day 7. In the next experiment, chicks received intraperitoneal (IP) injections of oleuropein at doses of 0 (vehicle), 50, 100, or 200 mg/kg on day 4 post-hatch, with feed intake and blood glucose levels measured thereafter. Lastly, chicks fed a control diet were fasted and administered intracerebroventricular (ICV) injections of oleuropein at doses of 0, 50, 100, or 200 μg, after which feed intake was recorded. Results indicated that IP and ICV injections led to decreased feed intake, primarily at 60 min post-injection, with effects diminishing by 90 min in the IP study. Blood glucose levels decreased 1-h post-IP injection at higher oleuropein doses. These findings suggest that oleuropein acts as a mild appetite suppressant and influences energy metabolism in broiler chickens.
PubMed: 38933363
DOI: 10.3389/fphys.2024.1409211 -
Frontiers in Neurology 2024Traumatic brain injury (TBI) is one of the leading causes of all injury-related deaths and disabilities in the world, especially in low to middle-income countries...
INTRODUCTION
Traumatic brain injury (TBI) is one of the leading causes of all injury-related deaths and disabilities in the world, especially in low to middle-income countries (LMICs) which also suffer from lower levels of funding for all levels of the health care system for patients suffering from TBI. These patients do not generally get comprehensive diagnostic workup, monitoring, or treatment, and return to work too quickly, often with undiagnosed post-traumatic deficits which in turn can lead to subsequent incidents of physical harm.
METHODS
Here, we share methods and results from our research project to establish innovative, simple, and scientifically based practices that dramatically leverage technology and validated testing strategies to identify post-TBI deficits quickly and accurately, to circumvent economic realities on the ground in LMICs. We utilized paper tests such as the Montreal cognitive assessment (MoCA), line-bisection, and Bell's test. Furthermore, we combined modifications of neuroscience computer tasks to aid in assessing peripheral vision, memory, and analytical accuracies. Data from seventy-one subjects (51 patients and 20 controls, 15 females and 56 males) from 4 hospitals in Ethiopia are presented. The traumatic brain injury group consists of 17 mild, 28 moderate, and 8 severe patients (based on the initial Glasgow Comma Score). Controls are age and education-matched subjects (no known history of TBI, brain lesions, or spatial neglect symptoms).
RESULTS
We found these neurophysiological methods can: 1) be implemented in LMICs and 2) test impairments caused by TBI, which generally affect brain processing speed, memory, and both executive and cognitive controls.
DISCUSSION
The main findings indicate that these examinations can identify several deficits, especially the MoCA test. These tests show great promise to assist in the evaluation of TBI patients and support the establishment of dedicated rehabilitation centers. Our next steps will be expansion of the cohort size and application of the tests to other settings.
PubMed: 38933324
DOI: 10.3389/fneur.2024.1397625 -
Frontiers in Medicine 2024Despite the need, measuring glomerular filtration rate (mGFR) is not routinely performed for adults with cerebral palsy (CP), possibly due to unknown feasibility given...
OBJECTIVE
Despite the need, measuring glomerular filtration rate (mGFR) is not routinely performed for adults with cerebral palsy (CP), possibly due to unknown feasibility given the secondary complications of CP. This study aimed to assess the feasibility and reliability of mGFR and explore factors associated with eGFR-mGFR discordance among young adults with mild-to-moderate CP.
METHODS
This single-center, cross-sectional study included 18- to 40-year-olds with CP gross motor function classification system (GMFCS) I-III. The participants were excluded if they were pregnant/lactating, had cognitive impairments, or had contraindications to mGFR. A routine clinical protocol for mGFR and eGFR was used. mGFR feasibility was assessed based on the number of participants who completed testing. mGFR reliability was assessed using the coefficient of variation (CV) across the four 30 min intervals. The association between age, sex, and GMFCS and the percentage of eGFR-mGFR discordance was assessed.
RESULTS
Of the 19 participants enrolled, 18 completed the testing [mean age (SD), 29.9 (7.4) years, = 10 female participants, = 10/3/5 for GMFCS I/II/III] and most ( = 15) of the participants had an mGFR >90 mL/min; 14 participants (77.8%) had a CV <20%, 2 had a CV between 20 and 25%, and 2 had a CV >50%. eGFR overestimated mGFR by a median (interquartile range) of approximately 17.5% (2-38%); the full range of mis-estimation was -20.5 to 174.3%. Increasing age and GMFCS levels exhibited notable, but weak-to-modest, associations with a larger eGFR-mGFR discordance.
DISCUSSION
Obtaining mGFR was feasible and reasonably reliable within this small sample. eGFR overestimated mGFR by a notable amount, which may be associated with patient-level factors.
PubMed: 38933110
DOI: 10.3389/fmed.2024.1295104 -
Endocrinology, Diabetes & Metabolism Jul 2024Iatrogenic hypoparathyroidism is a common cause of postthyroidectomy hypocalcaemia. It has varying incidence rates after neck surgery in Saudi Arabia, ranging from 0.07%...
BACKGROUND
Iatrogenic hypoparathyroidism is a common cause of postthyroidectomy hypocalcaemia. It has varying incidence rates after neck surgery in Saudi Arabia, ranging from 0.07% to 65.30%. Hypoparathyroidism can manifest with a spectrum of symptoms, ranging from mild to severe and life-threatening. This study aimed to assess the rate and predictors of iatrogenic hypoparathyroidism after thyroid surgery and its natural course.
METHODS
This retrospective cohort study used a data collection form to extract patient information from the electronic healthcare system (Best-Care) for patients treated from 2017 to 2022. Patients' demographics, surgical specifics and biochemical profiles were recorded for subsequent analysis.
RESULTS
Among the 343 patients who underwent thyroidectomy, 130 (37.9%) developed hypoparathyroidism, primarily within the first day after surgery. Calcium or vitamin D supplementation before surgery did not significantly influence hypoparathyroidism development. Notably, extensive combined lymph node dissection was significantly associated with postoperative hypoparathyroidism development (p = 0.0004). More patients who underwent central and lateral lymph node dissection (n = 19, 79.17%) developed hypoparathyroidism than patients who underwent central (n = 18, 40.91%) or lateral (n = 8, 38.10%) dissection alone. Permanent hypoparathyroidism was observed in 40 patients (11.66%).
CONCLUSION
This study revealed a high incidence of iatrogenic hypoparathyroidism and high rates of permanent hypoparathyroidism. Further research is warranted to better comprehend the risk factors and optimise management strategies for iatrogenic hypoparathyroidism. Overall, our findings emphasise the need for vigilant monitoring and effective management of patients undergoing thyroidectomy and the significance of postoperative replacement therapies.
Topics: Humans; Thyroidectomy; Hypoparathyroidism; Retrospective Studies; Female; Male; Iatrogenic Disease; Middle Aged; Adult; Postoperative Complications; Hypocalcemia; Aged; Saudi Arabia; Incidence; Cohort Studies; Risk Factors
PubMed: 38932435
DOI: 10.1002/edm2.506 -
Vaccines Jun 2024Novel mechanisms of COVID-19 vaccines raised concern about their potential immunogenicity in patients with rheumatoid arthritis (RA) undergoing immunomodulatory...
Novel mechanisms of COVID-19 vaccines raised concern about their potential immunogenicity in patients with rheumatoid arthritis (RA) undergoing immunomodulatory treatments. We designed a retrospective single-center study to investigate their effectiveness and safety in this population, analyzing data from the first vaccination program (December 2020-October 2021). Inclusion criteria were availability of post-vaccination serology and a minimum subsequent follow-up of 6 months. Binding antibody units (BAU/mL) ≥ 7.1 defined an adequate serological response. Post-vaccine COVID-19 incidence and its timing since vaccination, adverse events (AEs), and RA flares were recorded. Adjusted logistic and linear multivariate regression analyses were carried out to identify factors associated with vaccine response. We included 118 patients (87.2% women, age 65.4 ± 11.6 years, evolution 12.0 ± 9.6 years), of whom 95.8% had a complete vaccination schedule. Adequate humoral immunogenicity was achieved in 88.1% of patients and was associated with previous COVID-19 and mRNA vaccines, whereas smoking, aCCP, age, and DMARDs exerted a negative impact. Post-vaccine COVID-19 occurred in 18.6% of patients, a median of 6.5 months after vaccination. Vaccine AE (19.5%) and RA flares (1.7%) were mostly mild and inversely associated with age. Our results suggest that COVID-19 vaccines induce adequate humoral immunogenicity, with an acceptable safety profile in RA patients.
PubMed: 38932401
DOI: 10.3390/vaccines12060672