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Long Noncoding RNAs MEG3, TUG1, and hsa-miR-21-3p Are Potential Diagnostic Biomarkers for Coronary Artery Disease

Mol Biol (Mosk). 2023 Nov-Dec;57(6):1-10.

ABSTRACT

Peripheral blood biomarkers are of particular importance to diagnose certain diseases including coronary artery disease (CAD) due to their non-invasiveness. Investigating the expression of noncoding RNAs (ncRNAs) paves the way to early disease diagnosis, prognosis, and treatment. Consequently, in this research, we aimed to investigate a panel of ncRNAs as potential biomarkers in patients with coronary artery disease. Two different groups have been designed (control and CAD). All participants were subjected to interviews and clinical examinations. Peripheral blood samples were collected, and plasma was extracted. At the same time, target ncRNAs have been selected based on literature review and bioinformatic analysis, and later they underwent investigation using quantitative real-time PCR. The selected panel encompassed the long non-coding RNAs (lncRNAs) MEG3, TUG1, and SRA1, and one related microRNA (miRNA): hsa-miR-21-3p. We observed statistically significant upregulation in MEG3, TUG1, and hsa-miR21-3p in CAD patients compared to control participants (p-value < 0.01). Nevertheless, SRA1 exhibited downregulation with no statistical significance (p-value > 0.05). All ncRNAs under study displayed a significantly strong correlation with disease incidence, age, and smoking. Network construction revealed a strong relationship between MEG3 and TUG1. ROC analysis indicated high potentiality for hsa-miR-21-3p to be a promising biomarker for CAD. Moreover, MEG3 and TUG1 displayed distinguished diagnostic discrimination but less than hsa-miR-21-3p, all of them exhibited strong statistical significance differences between CAD and control groups. Conclusively, this research pinpointed that MEG3, TUG1, and hsa-miR-21-3p are potential biomarkers of CAD incidence and diagnosis.

PMID:38062969

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Anesthesia and intensive care unit care in pediatric kidney transplantation: An international survey

Paediatr Anaesth. 2023 Dec 8. doi: 10.1111/pan.14810. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the high perioperative risk profile, international guidelines for anesthesia and intensive care unit (ICU) care in pediatric kidney transplantation do not exist. Optimizing hemodynamics can be challenging in these patients, while scientific data to guide decisions in hemodynamic monitoring, hemodynamic targets, and perioperative fluid management are lacking. The limited annual number of pediatric kidney transplantations, even in reference centers, necessitates the urge for international collaboration to share knowledge and develop research and guidelines. The aim of this study was to collect data on current perioperative anesthesia and ICU care practices in pediatric kidney transplantation.

METHODS: An international survey with an anonymized link was sent from a validated electronic data capture system (Castor). Inclusion criteria were: medical doctor in anesthesia, (ICU), or pediatric nephrology working in a pediatric kidney transplantation specialized center; and signed informed consent. Data were analyzed using descriptive statistics.

RESULTS: Thirty-three records were analyzed. Responders were anesthesiologists (58%), pediatric nephrologists (30%), and pediatric intensivists (12%), representing 13 countries worldwide. About half of the centers (48%) performed more than 10 pediatric kidney transplantations a year. Perioperative hemodynamic support was guided by intra-arterial blood pressure (88%), central venous pressure (CVP; 88%), and cardiac output (CO; 39%). The most variation was seen in the hemodynamic targets CVP and CO, fluid administration, and inotrope/vasopressor use. The protocolized use of furosemide (46%) and mannitol (61%) also varied between centers. Postoperative care for the youngest recipients occurred in the pediatric intensive care unit at all centers.

CONCLUSION: The results of this survey reveal a large variation in anesthesia and ICU care in pediatric kidney transplantation centers worldwide, particularly in CVP and CO targets, hemodynamic therapy, and the use of furosemide and mannitol. These data identify areas for further research and can be a starting point for international research collaboration and guideline development.

PMID:38062930 | DOI:10.1111/pan.14810

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General dental practitioners’ fees for root canal treatment, coronal restoration and follow-on treatment in the adult population in Sweden: A 10-year follow-up of data from the Swedish Dental Register

Clin Exp Dent Res. 2023 Dec 7:e826. doi: 10.1002/cre2.826. Online ahead of print.

ABSTRACT

OBJECTIVES: To analyze the accumulated fees connected with root filling, permanent coronal restoration and follow-on treatment charged by Swedish dentists over a 10-11-year follow-up period. Furthermore, analyzing these fees with reference to the type of restoration, tooth group, and the root-filled teeth which survived compared to those requiring extraction.

MATERIAL AND METHODS: In 2009, the data register of the Swedish Social Insurance Agency recorded a total of 215,611 teeth as root-filled. The accumulated fees for each tooth encompassed the following interventions: initial root filling, coronal restorations, and follow-up treatments during the designated period. The outcomes were analyzed using descriptive and analytic statistics, including t tests and one-way analysis of variance. The fees are presented in Euros (€1 = SEK 8.94).

RESULTS: The total accumulated fees for root fillings amounted to 72 million Euros: the mean fee per root filled tooth was €333.6. The total mean fee over a 10-11-year period, comprising root canal treatment, coronal restorations, and any follow-up treatments, was €923.4. Root-filled teeth with indirect restorations presented a higher mean fee (€1 279.3) compared to those with direct restorations (€829.4) or those without specified restorations (€832.7; p < .001). Moreover, molars presented a significantly higher mean fee (€966.4) compared to premolars (€882.8) and anterior teeth (€891.3; p < .001). Lastly, the mean fee for extracted teeth was €1225.3, which was higher compared to those who survived the follow-up period (€848.0; p < .001).

CONCLUSIONS: Fees charged by general dental practitioners for root-filled teeth accumulate over time, probably due to the need for further treatment of the tooth. The total mean fee was significantly higher for molars and root-filled teeth with indirect restorations. However, an analysis of the total costs would require prospective clinical cost-effectiveness studies.

PMID:38062924 | DOI:10.1002/cre2.826

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Transcriptional changes are tightly coupled to chromatin reorganization during cellular aging

Aging Cell. 2023 Dec 7:e14056. doi: 10.1111/acel.14056. Online ahead of print.

ABSTRACT

Human life expectancy is constantly increasing and aging has become a major risk factor for many diseases, although the underlying gene regulatory mechanisms are still unclear. Using transcriptomic and chromosomal conformation capture (Hi-C) data from human skin fibroblasts from individuals across different age groups, we identified a tight coupling between the changes in co-regulation and co-localization of genes. We obtained transcription factors, cofactors, and chromatin regulators that could drive the cellular aging process by developing a time-course prize-collecting Steiner tree algorithm. In particular, by combining RNA-Seq data from different age groups and protein-protein interaction data we determined the key transcription regulators and gene regulatory changes at different life stage transitions. We then mapped these transcription regulators to the 3D reorganization of chromatin in young and old skin fibroblasts. Collectively, we identified key transcription regulators whose target genes are spatially rearranged and correlate with changes in their expression, thereby providing potential targets for reverting cellular aging.

PMID:38062919 | DOI:10.1111/acel.14056

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Loss of subcutaneous fat in 20 patients, both sexes, using a second-generation TECAR device of 1.240 Watts and results analyzed with magnetic resonance

J Cosmet Dermatol. 2023 Dec 7. doi: 10.1111/jocd.16078. Online ahead of print.

ABSTRACT

BACKGROUND: Body contouring and abdominal fat loss without surgery are increasingly used technique. In a study in pigs, it is noted that both capacitive and resistive radiofrequency stimulation reduced subcutaneous fat. One human study demonstrated a loss of 2.90 cm in waist diameter. Second-generation TECAR (Acronym for Transfer Electric Capacitive and Resistive) device with 4 channels, 200 cm2 work area per channel, and high power (1240 W), regulates body energy input by measuring absorption in the body and adjusting the power for 80 min at 50°C.

AIMS: To evaluate the loss of subcutaneous fat, this magnitude was measured in grams and centimeters throughout the abdomen by MRI before and after each treatment.

SUBJECT AND METHODS: We have studied 25 patients, 13 women and 12 men with a mean age of 49 years. All patients had their waist diameter measured and an MRI performed before and after 10 continuous sessions except Saturday and Sunday, over 2 weeks. Additionally, a lipid profile was performed on the same day of the study and at the end of it. The study was approved by the Ethics Committee.

RESULTS: Waist diameter decreased by 5.5 cm, these differences being statistically significant (p = 0.000). Subcutaneous fat measured by MRI in cm decreased by 784 cm (p = 0.000). In grams, it decreased 808.7 g (p = 0.000). In the lipid profile, all the values decreased, but they were not statistically significant.

CONCLUSIONS: The use of this second generation of TECAR equipment at 1 MHz decreases the waist diameter by more than 5 cm and leads to the loss of more than 800 grams of subcutaneous fat in 12 days. It is a method without risks or side effects, well tolerated, and an alternative for those patients who do not want to go to the operating room.

PMID:38062900 | DOI:10.1111/jocd.16078

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Small and Large Bowel Anatomy is Associated with Enteral Autonomy in Infants with Short Bowel Syndrome: A retrospective cohort study

JPEN J Parenter Enteral Nutr. 2023 Dec 7. doi: 10.1002/jpen.2587. Online ahead of print.

ABSTRACT

BACKGROUND: Achievement of enteral autonomy (EA) is the ultimate treatment goal in pediatric intestinal failure. We aimed to assess predictors of EA in pediatric short bowel syndrome (SBS) and explore the impact of residual small bowel (SB) and large bowel (LB) length on EA.

METHODS: A retrospective cohort study was performed on infants <12 months (n=367, six centers) with SBS referred between 2010 and 2015. The cohort was stratified based on achievement of EA. Statistical testing completed using t test, Chi Square, Cox Proportional Hazards regression model and Kaplan-Meier analysis.

RESULTS: EA was achieved in 229 patients. In the multivariable analysis, percentage of residual LB (HR=1.02; 95% CI 1.01-1.02) and SB (HR= 1.01; 95% CI 1.01-1.02) length, presence of ICV (HR= 2.02; 95% CI 1.41-2.88), and not coming from a high-volume transplantation center (HR= 2.42; 95% CI 1.68-3.49) were positively associated with EA, while a negative association was seen with the presence of stoma at the time when shortest remnant was documented (HR= 0.72; 95% CI 0.52-1.00). EA achievement was significantly different between the anatomical subgroups (Log-rank test p<0.001) with EA rate of 80.4% in infants with ≥ 50% SB and LB (median time – 209 days); 62.5% with ≥ 50% SB and<50% LB (397 days); 58.3% with <50% SB and ≥ 50% LB (1192 days), 25.9% with < 50% SB and LB. NEC was not associated with a better achievement of EA (NEC vs. other etiologies; Log-rank test p = 0.33).

CONCLUSIONS: Overall 62% of infants with IF secondary to SBS achieved EA over a mean time of follow-up of 2.3 years. A colon length of >50% can compensate for the loss of small bowel (<50%) and account for similar EA rates as in children with residual SB>50%. This article is protected by copyright. All rights reserved.

PMID:38062898 | DOI:10.1002/jpen.2587

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SAFE technique to improve Nerve-Sparing in Robotic-Assisted Radical Prostatectomy

BJU Int. 2023 Dec 7. doi: 10.1111/bju.16238. Online ahead of print.

ABSTRACT

BACKGROUND: Radical Prostatectomy is the standard of care for localized prostate cancer. Despite the introduction of minimally invasive surgery and a better understanding of the anatomy, erectile dysfunction still represents a challenge.

OBJECTIVE: To provide a summary of our initial experience and assess the impact of the SAFE (Saline-Assisted Fascial Exposure) technique on erectile function, urinary continence, and oncologic outcomes after Robotic-Assisted Radical Prostatectomy SETTING, AND PARTICIPANTS: From January 2021 to July 2022, we included patients with a baseline SHIM ≥17 and a high probability of extracapsular extension, ranging from 21% to 73%, as per Martini et al’s. nomogram. A propensity score matching was carried out at a ratio of 1:2 between patients who underwent RALP + SAFE (33) and RALP alone (66). The descriptive statistical analysis is presented SURGICAL PROCEDURE: The SAFE technique was performed using two approaches, transrectal guided by microultrasound or transperitoneal. Its principle entails a low-pressure injection of saline solution in the periprostatic fascia to achieve an atraumatic dissection of the neural hammock.

MEASUREMENTS: Potency was defined as a SHIM score ≥ 17. Continence as 0 pads per day.

RESULTS AND LIMITATIONS: At follow-up intervals of 6, 13, 26, and 52 weeks, the SHIM score differed significantly between the two groups, favoring the RALP + SAFE (p 0.01, p<0.001, p<0.001, and 0.01, respectively). These results remained significant when the mean SHIM was assessed. As shown by the cumulative incidence curve, EF rates were higher in the RALP + SAFE compared to the RALP alone group (log-rank p<0.001). The baseline SHIM and use of the SAFE technique were independent predictors of EF recovery.

CONCLUSIONS: The use of the SAFE technique led to better SHIM scores at 6, 13, 26, and 52 weeks after RALP in patients at high risk of ECE who underwent a partial NS procedure.

PMID:38062880 | DOI:10.1111/bju.16238

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Skeletal muscle atrophy in clinical and preclinical models of chronic kidney disease: A systematic review and meta-analysis

J Cachexia Sarcopenia Muscle. 2023 Dec 7. doi: 10.1002/jcsm.13400. Online ahead of print.

ABSTRACT

Patients with chronic kidney disease (CKD) are often regarded as experiencing wasting of muscle mass and declining muscle strength and function, collectively termed sarcopenia. The extent of skeletal muscle wasting in clinical and preclinical CKD populations is unclear. We evaluated skeletal muscle atrophy in preclinical and clinical models of CKD, with multiple sub-analyses for muscle mass assessment methods, CKD severity, sex and across the different preclinical models of CKD. We performed a systematic literature review of clinical and preclinical studies that measured muscle mass/size using the following databases: Ovid Medline, Embase and Scopus. A random effects meta-analysis was utilized to determine standard mean difference (SMD; Hedges’ g) between healthy and CKD. Heterogeneity was evaluated using the I2 statistic. Preclinical study quality was assessed via the Systematic Review Centre for Laboratory Animal Experimentation and clinical studies quality was assessed via the Newcastle-Ottawa Scale. This study was registered in PROSPERO (CRD42020180737) prior to initiation of the search. A total of 111 studies were included in this analysis using the following subgroups: 106 studies in the primary CKD analysis, 18 studies that accounted for diabetes and 7 kidney transplant studies. Significant atrophy was demonstrated in 78% of the preclinical studies and 49% of the clinical studies. The random effects model demonstrated a medium overall SMD (SMD = 0.58, 95% CI = 0.52-0.64) when combining clinical and preclinical studies, a medium SMD for the clinical population (SMD = 0.48, 95% CI = 0.42-0.55; all stages) and a large SMD for preclinical CKD (SMD = 0.95, 95% CI = 0.76-1.14). Further sub-analyses were performed based upon assessment methods, disease status and animal model. Muscle atrophy was reported in 49% of the clinical studies, paired with small mean differences. Preclinical studies reported significant atrophy in 78% of studies, with large mean differences. Across multiple clinical sub-analyses such as severity of CKD, dialysis modality and diabetes, a medium mean difference was found. Sub-analyses in both clinical and preclinical studies found a large mean difference for males and medium for females suggesting sex-specific implications. Muscle atrophy differences varied based upon assessment method for clinical and preclinical studies. Limitations in study design prevented conclusions to be made about the extent of muscle loss with disease progression, or the impact of dialysis. Future work would benefit from the use of standardized measurement methods and consistent clinical staging to improve our understanding of atrophy changes in CKD progression, and analysis of biological sex differences.

PMID:38062879 | DOI:10.1002/jcsm.13400

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A critical look at adjusted fetal weights in rats

Birth Defects Res. 2023 Dec 8. doi: 10.1002/bdr2.2278. Online ahead of print.

ABSTRACT

BACKGROUND: A new derived (i.e., calculated) endpoint of developmental toxicology has appeared in a very few studies since 1990. This endpoint is adjusted mean live fetal weight per litter or adjusted fetal weight. Given our lack of familiarity with the endpoint, we evaluated the basis, prevalence, methods, and usefulness in embryo-fetal developmental toxicity (EFDT) studies in rats.

METHODS: Literature searches were performed with key terms using PubMed and Google Scholar. Major textbooks were consulted but lack of any mention of the endpoint. Unpublished EFDT data, which are readily available online, were utilized to test adjustment methods.

RESULTS: Pertinent information on factors that influence fetal weight goes back a century. Four papers utilizing rats were found in which fetal weights were adjusted using either statistical or formula-based methods to adjust fetal weights. Only one study showed a clear benefit to the endpoint when there was a marked decrease in live litter size; this pointed to situations in which the new endpoint might be useful. The lone formula-based adjustment method was found to be lacking adequate testing and justifications. A new experimental alternative formula-based adjustment is shown to produce results very similar to statistical methods.

CONCLUSIONS: From this assessment, we recommend that adjusted fetal weight should not be a routine endpoint at this time. However, there are likely cases where this derived endpoint could aid interpretation. We encourage other investigators to examine previous EFDT study data to establish guidance on the use of adjusted mean live fetal weights.

PMID:38062877 | DOI:10.1002/bdr2.2278

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Development and validation of chemometric-assisted spectrophotometric models for efficient quantitation of a binary mixture of supportive treatments in COVID-19 in the presence of its toxic impurities: a comparative study for eco-friendly assessment

BMC Chem. 2023 Dec 7;17(1):177. doi: 10.1186/s13065-023-01089-9.

ABSTRACT

The use of sustainable solvents has increased significantly in recent years due to advancements in green analytical methods. The number of impurities in the drug substance determines how safe the finished product is. Therefore, during the whole medication planning process, contaminants need to be closely watched. Using chemometric models, the concentrations of hyoscine N-butyl bromide (HYO) and paracetamol (PAR) were determined in the presence of three PAR impurities [P-nitrophenol (PNP), P-aminophenol (PAP), and P-chloroacetanilide (PCA), as well as DL-tropic acid (TRO) as a HYO impurity]. It was possible to isolate and measure these dangerous impurities. Fever and spasms associated with COVID-19 are reported to be considerably reduced when PAR and HYO are taken together. Artificial neural networks, principal component regression, multivariate curve resolution-alternating least squares, and partial least squares are the four chemometric-assisted spectrophotometric models that were created and verified. All of the proposed methods’ quantitative analytical potency was assessed using recoveries%, root mean square error of prediction, and standard error of prediction. For PAR, HYO, PNP, PCA, TRO, and PAP, respectively, the indicated approaches were used in the ranges of 4.00-8.00, 16.00-24.00, 1.00-5.00, 0.40-0.80, 4.00-12.00, and 2.00-6.00 µg/mL. They are able to get around difficulties like collinearity and spectral overlaps. After statistical testing, there was no discernible difference between the recommended methods and the published one. The degree of greenness of the established models was evaluated using three different green assessment methods. In the presence of their harmful impurities, PAR and HYO could be identified using the recommended methods.

PMID:38062478 | DOI:10.1186/s13065-023-01089-9