Assessment of Vitamin D Status in Primary Hyperparathyroidism Patients: A Retrospective Study.

BACKGROUND: Primary hyperparathyroidism (PHPT), a condition that manifests in various clinical forms, is a significant health concern. Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by normal calcemia despite elevated parathyroid hormone (PTH) levels. Vitamin D deficiency can contribute to the clinical spectrum and complexity of NPHPT. Low vitamin D levels can elevate PTH, making it difficult to distinguish between NPHPT and secondary hyperparathyroidism. Additionally, it might mask hypercalcemia, leading to an underestimation of the disease severity. Our study aims to shed light on these complexities by investigating normocalcemic and hypercalcemic PHPT patient's clinical, hormonal, and biochemical patterns, including their vitamin D status.    Materials: In this retrospective study, we enrolled 60 PHPT patients with autonomous parathyroid function confirmed using a combination of ultrasonography, radionuclide scan, and parathyroid function index calculation. We evaluated the albumin-corrected calcemia, calciuria, PTH, 25(OH)D level, serum phosphate, bone mineral density, and major clinical symptoms (fracture, nephrolithiasis). A comparative analysis and a correlation study were performed between normo- and hypercalcemic and vitamin D-deficient and vitamin D-non-deficient groups. RESULTS:  The median age was 62 years, 51.66% (31/60) being normocalcemic and 46.66% (29/60) presenting a deficient 25(OH)D level. In the group with 25(OH)D below 20 ng/mL, we observed a reduced level of albumin-corrected calcemia, without a significant increase of PTH compared to the adequate 25(OH)D level group. The frequency of the NPHPT and the risk of fracture were significantly higher in the deficient 25(OH)D group (20/60, 33.33% and 8/60, 13.33%) than in the adequate one (11/60, 18.33% and 1/60, 1.66%) with OR=4.7 (p<0.004) and OR=9.7 (p<0.027), respectively. We also found a positive correlation between PTH and adenoma size, the parathyroid function index and adenoma size, as well as PTH and phosphate levels. However, the correlation between 25(OH)D and phosphate levels was negative and moderate (rho=-0.504, p<0.001), adding a new layer of complexity to our understanding of these relationships. CONCLUSION: Our study provided significant insight into the link between vitamin D status and normocalcemic PHPT. We found that vitamin D-deficient patients with normocalcemic PHPT have an increased fracture risk, which requires meticulous monitoring and possible supplementation with vitamin D. This should be done carefully to avoid exacerbating hypercalcemia or hypercalciuria. Further research is needed to refine these management strategies and deepen our understanding of the complex relationships between the analyzed parameters.

Adrenal Mass and Hypokalaemia: The Zebra Among Horses.

Pheochromocytoma rarely presents with unexplained hypokalaemia, although there are some case reports in the literature. The mechanism behind this could be the increased cellular potassium uptake promoted by beta-2-adrenoreceptor hyperactivation and insulin resistance. We present the case of a 68-year-old hypertensive female patient with a unilateral adrenal mass discovered on angio-CT and typical signs of adrenergic hyperstimulation (hypertensive crisis, headache, and sweating) associated with multiple arrhythmic episodes but with normal plasma and urinary catecholamine levels. During the work-up for hormonal hypersecretion and the cessation of anti-aldosterone medication, the patient presented resistant hypokalaemia. Due to uncorrectable hypokalaemia, we were unable to perform hormonal investigations for primary hyperaldosteronism and referred the patient for laparoscopic adrenalectomy. The histological diagnosis revealed left pheochromocytoma. Postoperatively, the patient experienced rebound hyperkalaemia. In a patient with a unilateral adrenal mass and hypokalaemia, besides primary hyperaldosteronism and adrenocorticotropic hormone-independent hypercortisolism, a possible pheochromocytoma should be ruled out as well by the clinician before surgery.

The Effect of Preoperative Administration of Glucocorticoids on the Postoperative Complication Rate in Liver Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Glucocorticoids may grant a protective effect against postoperative complications. The evidence on their efficacy, however, has been inconclusive thus far. We investigated the effects of preoperatively administered glucocorticoids on the overall postoperative complication rate, and on liver function recovery in patients undergoing major liver surgery. Methods: We performed a systematic literature search on PubMed, Embase, and CENTRAL in October 2021, and repeated the search in April 2023. Pre-study protocol was registered on PROSPERO (ID: CRD42021284559). Studies investigating patients undergoing liver resections or transplantation who were administered glucocorticoids preoperatively and reported postoperative complications were eligible. Meta-analyses were performed using META and DMETAR packages in R with a random effects model. Risk of bias was assessed using RoB2. Results: The selection yielded 11 eligible randomized controlled trials (RCTs) with 964 patients. Data from nine RCTs (n = 837) revealed a tendency toward a lower overall complication rate with glucocorticoid administration (odds ratio: 0.71; 95% confidence interval: 0.38-1.31, p = 0.23), but it was not statistically significant. Data pooled from seven RCTs showed a significant reduction in wound infections with glucocorticoid administration [odds ratio: 0.64; 95% confidence interval: 0.45-0.92 p = 0.02]. Due to limited data availability, meta-analysis of liver function recovery parameters was not possible. Conclusions: The preoperative administration of glucocorticoids did not significantly reduce the overall postoperative complication rate. Future clinical trials should investigate homogenous patient populations with a specific focus on postoperative liver recovery.

Outcomes of Exeter cemented total hip arthroplasty in a county hospital: survivorship of eight hundred and ninety four hips with a minimum ten-year follow up.

PURPOSE: A total of 894 hips were evaluated to describe the survivorship of Exeter cemented femoral stems and report the outcomes and complications of our 'Exeter- era', and there is no study from Central or Eastern Europe demonstrating similar results. METHODS: Between January 2000 and December 2009, a total of 894 hips were included who underwent Exeter universal and V40 femoral stems with a mean follow up of 13 years. Cemented Exeter low profile polyethylene cups were used in 889 patients (99.4%) cups. Harris hip score (HHS) was used and statistical outcome measures were calculated with revision as an endpoint for aseptic loosening of the stem, aseptic loosening of any component, all-cause revision of the stem, and all-cause revision of the hip. RESULTS: A total of 103 patients died and 129 (14.4%) operated hips were lost to follow-up before ten years. Out of the 662, ten stems (1.5%) were revised for aseptic loosening. Aseptic loosening of any component was the reason for revision in 43 cases (6.5%), consisting of 40 cup revisions and ten stem exchanges. Periprosthetic fracture occurred in 17 cases (1.9%) Periprosthetic joint infection occurred in 18 cases (2.01%). Three cups were exchanged for recurrent dislocation, and two stems had broken. CONCLUSION: Exeter hip system has provided reproducible results across different centres worldwide, as it did in our series. Thorough surgical and cementing technique is of utmost importance for achieving these results. The cup is the weak point of the system and use of a hybrid system is worth considering.

Evidence for gait improvement with robotic-assisted gait training of children with cerebral palsy remains uncertain.

BACKGROUND: Cerebral palsy (CP) is a group of neuromotor diseases that develops as a result of damage to the developing central nervous system during the perinatal period. The condition is usually accompanied by musculoskeletal problems resulting in movement disorders. Gait improvement therefore, is an important part of its treatment. Roboticassisted gait training (RAGT) is a new potential rehabilitation tool for CP patients, however there is no clear evidence for the effectiveness of this method. RESEARCH QUESTION: Can robotic-assisted gait training improve walking function in children with CP? METHODS: A systematic search was performed in five databases: MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Scopus, and Web of Science. Eligible studies were randomized controlled trials (RCT) with CP patients under the age of 18. Gross motor function and kinematic gait parameters of patients were the main outcomes. Two authors determined the risk of bias of the RCTs independently using the revised Risk of Bias 2 (ROB 2) tool. Mean Differences (MDs) along with their 95% Confidence Interval (CI) were calculated when at least three studies were present for an outcome, subgroup analysis was performed based on the treatment of the control group. RESULTS: Of the 7363 screened articles, 13 papers met our inclusion criteria and among them, 7 studies could be used in our meta-analyses. The results related to RAGT suggest nonsignificant improvement in standing and walking function (Gross Motor Function Measure D, E), moreover changes in gait speed, step length, and in cadence were also only comparable to controls. SIGNIFICANCE: The results indicate that there is a trend in some gait parameters where the improvement was higher in the intervention group than in control group. The therapeutic effect of RAGT was probably not superior to physiotherapy combined with treadmill training.

Ancient chicken remains reveal the origins of virulence in Marek's disease virus.

The pronounced growth in livestock populations since the 1950s has altered the epidemiological and evolutionary trajectory of their associated pathogens. For example, Marek's disease virus (MDV), which causes lymphoid tumors in chickens, has experienced a marked increase in virulence over the past century. Today, MDV infections kill >90% of unvaccinated birds, and controlling it costs more than US$1 billion annually. By sequencing MDV genomes derived from archeological chickens, we demonstrate that it has been circulating for at least 1000 years. We functionally tested the Meq oncogene, one of 49 viral genes positively selected in modern strains, demonstrating that ancient MDV was likely incapable of driving tumor formation. Our results demonstrate the power of ancient DNA approaches to trace the molecular basis of virulence in economically relevant pathogens.

Medium-Term Results of Staged Laparoscopic Traction Orchiopexy for Intra-abdominal Testes: A Multicenter Analysis.

BACKGROUND: Staged laparoscopic traction orchiopexy (SLTO) is a novel technique for the intra-abdominal testis (IAT) based on elongation of the testicular vessels without separating them. This multicenter study evaluated the medium-term results of this technique. METHODS: Data of SLTO performed in three pediatric surgical centers between 2013 and 2020 were analyzed retrospectively. In 2021, physical and Doppler ultrasound examinations were performed to determine the position and viability of testes. Success was defined as an intra-scrotal testicle without atrophy. RESULTS: SLTO was performed on 48 cases (55 testes, 7 bilateral). Mean age at first stage was 2.9 (0.8-12.6) years. High intra-abdominal testes were found in 16.4% and in 60% morphological abnormalities were observed. To fix the testes to the abdominal wall monofilament suture was used in 67.3%, braided in 29.1%. Mean time between the two stages was 16.4 weeks; three testes required redo traction. Perioperative complications occurred in 21 patients (38.2%) including insufficient fixation (11), testicular atrophy (4), wound complications (4), adhesion of the spermatic cords (1) and hydrocele (1). In case of insufficient fixation monofilament sutures were used in 90.9%. In 2021 38 patients (43 testes) had physical and 36 patients (41 testes) had ultrasound examinations. Mean follow-up was 2.7 (0.34-7.9) years. Altogether five atrophies were identified, and three testicular ascents (7.0%) occurred. The overall success rate was 82.2%. CONCLUSIONS: SLTO may be a feasible alternative to conventional treatments of IATs. Additionally, braided suture seems to be a better option to fix the testicle to the abdominal wall. LEVEL OF EVIDENCE: LEVEL IV.

Fruit Extract, Rich in Polyphenols and Flavonoids, Modifies the Expression of DNMT and HDAC Genes Involved in Epigenetic Processes.

Recently, the field of epigenetics has been intensively studied in relation to nutrition. In our study, the gene expression patterns of histone deacetylases (HDACs), which regulate the stability of histone proteins, and DNA methyltransferases (DNMTs), which regulate DNA methylation, were determined in mice. The animals were fed a human-equivalent dose of the aqueous extract of fruit seeds and peels, which is rich in flavonoids and polyphenols, for 28 days and then exposed to the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The concentrations of trans-resveratrol and trans-piceid were determined in the consumed extract by HPLC and were 1.74 mg/L (SD 0.13 mg/L) and 2.37 mg/L (SD 0.32 mg/L), respectively, which corresponds to the consumption of 0.2-1 L of red wine, the main dietary source of resveratrol, in humans daily. Subsequently, 24 h after DMBA exposure, the expression patterns of the HDAC and DNMT genes in the liver and kidneys were determined by qRT-PCR. The DMBA-induced expression of the tested genes HDAC1, HDAC2, DNMT1, DNMT3A and DNMT3B was reduced in most cases by the extract. It has already been shown that inhibition of the DNMT and HDAC genes may delay cancer development and tumour progression. We hypothesise that the extract studied may exert chemopreventive effects.

Recruitment into randomised trials of arteriovenous grafts: A systematic review.

Although randomised controlled trials (RCT) are considered the optimal form of evidence, there are relatively few in surgery. Surgical RCT are particularly likely to be discontinued with poor recruitment cited as a leading reason. Surgical RCT present challenges over and above those seen in drug trials as the treatment under study may vary between procedures, between surgeons in one unit, and between units in multi-centred RCT. The most contentious and debated area of vascular access remains the role of arteriovenous grafts, and thus the quality of the data that is used to support opinions, guidelines and recommendations is critical. The aim of this review was to determine the extent of variation in the planning and recruitment in all RCT involving AVG. The findings of this are stark: there have been only 31 RCT performed in 31 years, the vast majority of which exhibited major limitations severe enough to undermine the results. This underlines the need for better quality RCT and data, and further inform the design of future studies. Perhaps most fundamental is the planning for a RCT that accounts for the intended population, the uptake of a RCT and the attrition for the significant co-morbidity in this population.

Investigating the association between IL-6 antagonist therapy and blood coagulation in critically ill patients with COVID-19: a protocol for a prospective, observational, multicentre study.

INTRODUCTION: Hypercoagulation is one the main features of COVID-19. It is induced by the hyperinflammatory response that shifts the balance of haemostasis towards pro-coagulation. Interleukin-6 (IL-6) antagonist therapy has been recommended in certain subgroups of critically ill patients with COVID-19 to modulate inflammatory response. The interaction between immune response and haemostasis is well recognised. Therefore, our objective is to evaluate whether the modulation of the inflammatory response by IL-6 antagonist inflicts any changes in whole blood coagulation as assessed by viscoelastic methods in critically ill patients with COVID-19. METHODS AND ANALYSIS: In this prospective observational study, we are going to collect data on inflammatory parameters and blood coagulation using the ClotPro® device. The primary outcome is the change of the fibrinolytic system measured by the Lysis Time and Lysis onset time before and after immunomodulation therapy. Data will be collected before the IL-6 antagonist administration at baseline (T0) then after 24, 48 hours, then on day 5 and 7 (T1-4, respectively). Secondary outcomes include changes in other parameters related to inflammation, blood coagulation and biomarkers of endothelial injury. ETHICS AND DISSEMINATION: Ethical approval was given by the Medical Research Council of Hungary (1405-3/2022/EÜG). All participants provided written consent. The results of the study will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05218369; Clinicaltrials.gov.

The Utilization of Physiologically Active Molecular Components of Grape Seeds and Grape Marc.

Nutritional interventions may highly contribute to the maintenance or restoration of human health. Grapes (Vitis vinifera) are one of the oldest known beneficial nutritional components of the human diet. Their high polyphenol content has been proven to enhance human health beyond doubt in statistics-based public health studies, especially in the prevention of cardiovascular disease and cancer. The current review concentrates on presenting and classifying polyphenol bioactive molecules (resveratrol, quercetin, catechin/epicatechin, etc.) available in high quantities in Vitis vinifera grapes or their byproducts. The molecular pathways and cellular signaling cascades involved in the effects of these polyphenol molecules are also presented in this review, which summarizes currently available in vitro and in vivo experimental literature data on their biological activities mostly in easily accessible tabular form. New molecules for different therapeutic purposes can also be synthesized based on existing polyphenol compound classes available in high quantities in grape, wine, and grape marc. Therefore an overview of these molecular structures is provided. Novel possibilities as dendrimer nanobioconjugates are reviewed, too. Currently available in vitro and in vivo experimental literature data on polyphenol biological activities are presented in easily accessible tabular form. The scope of the review details the antidiabetic, anticarcinogenic, antiviral, vasoprotective, and neuroprotective roles of grape-origin flavonoids. The novelty of the study lies in the description of the processing of agricultural by-products (grape seeds and skins) of industrial relevance, and the detailed description of the molecular mechanisms of action. In addition, the review of the clinical therapeutic applications of polyphenols is unique as no summary study has yet been done.

Topical pharmacotherapy for ocular surface squamous neoplasia: systematic review and meta-analysis.

Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical pharmacotherapy agents such as 5-fluorouracil (5-FU), interferon alfa-2b (IFN) and mitomycin-C (MMC) are also commonly used. The protocol was registered (CRD42021224961). Comprehensive literature research was carried out to compare topical pharmacotherapy (5-FU or IFN or MMC) to surgical excision regarding clinical success (tumor resolution), recurrence and complications in patients undergoing treatment for OSSN. From 7859 records, 7 articles were included in the qualitative and 4 in the quantitative synthesis. The outcomes of surgical excision and topical pharmacotherapy were comparable in the included articles. There were no significant differences between surgical excision and topical pharmacotherapy regarding the clinical success [odds ratio (OR): 0.785; confidence interval (CI): 0.130-4.736, P = 0.792)] and tumor recurrence (OR: 0.746; CI: 0.213-2.609; P = 0.646). The most common side effect of the different therapeutic options was dry eye. The highest rate of dry eye symptoms was reported after surgical excision (in 59%). Topical pharmacotherapy with all the 3 agents is as effective and well-tolerable as surgical excision in terms of tumor resolution, recurrence rate and side effects in all OSSN patients suggesting similar long-term clinical benefits.

Urodynamics in Early Diagnosis of Diabetic Bladder Dysfunction in Women: A Systematic Review and Meta-Analysis.

BACKGROUND Urodynamics can detect subtle voiding changes before cystopathy symptoms manifest. The aim of the present study was to assess urodynamic changes in diabetic women. MATERIAL AND METHODS A systematic search was performed on 04 November 2021 to identify studies reporting urodynamic parameters in diabetic women. Data were analyzed in a single-arm meta-analysis due to lack of sufficient studies with direct comparisons to healthy women. For data synthesis, a random-effects model with restricted maximum-likelihood estimation was applied. The calculated effect sizes were visualized in forest plots. Statistical heterogeneity was assessed using the I² measure and the χ² test. The risk of bias was assessed using the QUIPS tool. PROSPERO ID: CRD42021256275. RESULTS Out of 1750 records, 10 studies were used in the analysis (n=2342 diabetic women). Pooled event rates showed that mean voided volume was 288.21 mL [95% confidence interval (CI): 217.35-359.06, I²=98%], mean postvoid residual volume was 93.67 mL [95% CI: 31.35-155.99, I²=100%], mean Qmax was 18.80 mL/sec [95% CI: 15.27-22.33, I²=99%], mean PdetQmax is 30.13 cmH2O [95% CI: 25.53-34.73, I²=90%], mean first sensation of bladder filling was 178.66 mL [95% CI: 150.59-206.72, I²=97%], and mean cystometric capacity was 480.41 mL [95% CI: 409.32-551.50, I²=98%] in diabetic women. CONCLUSIONS Pooled results indicate that diabetic women tend to have a smaller voided volume, slower Qmax and PdetQmax, larger postvoid residual, and higher first sensation of bladder filling and cystometric capacity compared to the general female population.

The Chemopreventive Effects of Polyphenols and Coffee, Based upon a DMBA Mouse Model with microRNA and mTOR Gene Expression Biomarkers.

Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea (Camellia sinensis) extract, polyphenol extract (a mixture of blackberry (Rubus fruticosus), blackcurrants (Ribes nigrum), and added resveratrol phytoalexin), Chinese bayberry (Myrica rubra) extract, and a coffee (Coffea arabica) extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and mTOR gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely RAS and MYC. The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced PTEN as well as SIRT tumor suppressor genes.

Polyphosphate nanoparticles enhance the fibrin stabilization by histones more efficiently than linear polyphosphates.

INTRODUCTION: Beyond the three-dimensional fibrin network, the mechanical and lytic stability of thrombi is supported by the matrix of neutrophil extracellular traps (NETs) composed of polyanionic DNA meshwork with attached proteins including polycationic histones. Polyphosphates represent another type of polyanions, which in their linear form are known to enhance the fibrin stabilizing effects of DNA and histones. However, in vivo polyphosphates are also present in the form of nanoparticles (PolyP-NP), the interference of which with the fibrin/NET matrix is poorly characterized. AIMS: To compare the effects of linear and nanoparticulate polyphosphates, and their combinations with relevant NET components (DNA, histone H3) on fibrin formation, structure, and lysis in in vitro assays focusing on histone-polyphosphate interactions. METHODS: Transmission electron microscopy and dynamic light scattering for stability of the PolyP-NP preparations. Turbidimetry for kinetics of fibrinogen clotting by thrombin and fibrin dissolution by tissue-type plasminogen activator/plasminogen. Scanning electron microscopy for fibrin structure. Surface plasmon resonance for strength of histone-PolyP interactions. RESULTS: Both linear PolyP and PolyP-NP accelerated the fibrin formation and slowed down its dissolution and these effects were strongly dependent on the number of individual PolyP particles and not on their size. Addition of DNA did not modify significantly the PolyP-NP effects on fibrin formation and lysis. Both linear and nanoparticulate PolyP counteracted the effect of histone in the acceleration of fibrinogen clotting by thrombin. PolyP-NP, but not linear PolyP enhanced the prolongation of lysis time in fibrin containing histone and caused more pronounced thickening of the fibrin fibers than the linear form. Finally, PolyP-NP bound weaker to histone than the linear form. CONCLUSIONS: The interaction of PolyP with histone was a stronger modulator of fibrin formation and lysis than its interaction with DNA. In addition, the PolyP nanoparticles enhanced the thrombus stabilizing effects of histone more effectively than linear PolyP.

Differential Diagnostic Challenges in the COVID-19 Pandemic: Renal Abscess After SARS-CoV-2 Infection in a Young Adolescent.

BACKGROUND Prolonged fever in pediatric patients is often a diagnostic challenge. Clinicians tend to associate prolonged fever with COVID-19-related diseases in patients with a history of SARS-CoV-2 infection. Here we present a patient who was admitted with a clinical suspicion of multi-inflammatory syndrome in children (MIS-C) and was finally diagnosed with a renal abscess. CASE REPORT A 16-year-old girl with prolonged fever, bilateral non-purulent conjunctivitis, weight loss, muscle pain, general malaise, cough, and yellow sputum was admitted to Heim Pál National Pediatric Institute, Budapest, Hungary. She had proven SARS-CoV-2 infection 3 weeks prior to admission. Although inflammatory markers were elevated, repeated urine analyses, aerobic and anaerobic urine cultures, hemoculture, chest X-ray, and otorhinolaryngology examinations were negative. Based on clinical and laboratory criteria, the diagnosis of MIS-C was eventually ruled out. Abdominal ultrasound revealed a 17×20×15 mm simplex cyst at the edge of the parenchyma in the upper third of the left kidney. Magnetic resonance imaging was performed, showing a multi-compartment, septated, thick-walled parenchymal lesion of 50×40×52 mm in the upper pole of the right kidney, which showed signal characteristics of an abscess, and 20×16 mm and 8 mm lesions in the upper pole of the left kidney, which appeared to be cysts. After being unresponsive to intravenous wide-spectrum antibiotic therapy (meropenem 2 g tid for 5 days), surgical intervention was needed to remove the abscess. CONCLUSIONS This case demonstrates that during the COVID-19 pandemic, besides the obvious post-COVID etiology, other life-threatening conditions should be investigated in the first line.

Changes in miR-124-1, miR-212, miR-132, miR-134, and miR-155 Expression Patterns after 7,12-Dimethylbenz(a)anthracene Treatment in CBA/Ca Mice.

Specific gene and miRNA expression patterns are potential early biomarkers of harmful environmental carcinogen exposures. The aim of our research was to develop an assay panel by using several miRNAs for the rapid screening of potential carcinogens. The expression changes of miR-124-1, miR-212, miR-132, miR-134, and miR-155 were examined in the spleen, liver, and kidneys of CBA/Ca mice, following the 20 mg/bwkg intraperitoneal 7,12-dimethylbenz(a)anthracene (DMBA) treatment. After 24 h RNA was isolated, the miRNA expressions were analyzed by a real-time polymerase chain reaction and compared to a non-treated control. DMBA induced significant changes in the expression of miR-134, miR-132, and miR-124-1 in all examined organs in female mice. Thus, miR-134, miR-132, and miR-124-1 were found to be suitable biomarkers for the rapid screening of potential chemical carcinogens and presumably to monitor the protective effects of chemopreventive agents.

Olive Oil Improves While Trans Fatty Acids Further Aggravate the Hypomethylation of LINE-1 Retrotransposon DNA in an Environmental Carcinogen Model.

DNA methylation is an epigenetic mechanism that is crucial for mammalian development and genomic stability. Aberrant DNA methylation changes have been detected not only in malignant tumor tissues; the decrease of global DNA methylation levels is also characteristic for aging. The consumption of extra virgin olive oil (EVOO) as part of a balanced diet shows preventive effects against age-related diseases and cancer. On the other hand, consuming trans fatty acids (TFA) increases the risk of cardiovascular diseases as well as cancer. The aim of the study was to investigate the LINE-1 retrotransposon (L1-RTP) DNA methylation pattern in liver, kidney, and spleen of mice as a marker of genetic instability. For that, mice were fed with EVOO or TFA and were pretreated with environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-a harmful substance known to cause L1-RTP DNA hypomethylation. Our results show that DMBA and its combination with TFA caused significant L1-RTP DNA hypomethylation compared to the control group via inhibition of DNA methyltransferase (DNMT) enzymes. EVOO had the opposite effect by significantly decreasing DMBA and DMBA + TFA-induced hypomethylation, thereby counteracting their effects.

Elimination of oxacillin, its toxicity and antibacterial activity by using ionizing radiation.

The chemical changes caused by electron beam and γ irradiations and the biochemical characteristics of degradation products of a frequently used antibiotic oxacillin were investigated and compared with those of cloxacillin by applying pulse radiolysis, chemical and biochemical oxygen demand, total organic carbon content, oxygen uptake rate, toxicity and antibacterial activity measurements. Oxacillin was found to be non-toxic, but poorly biodegradable by the mixed microbial population of the activated sludge of a wastewater treatment plant. Therefore, it can significantly contribute to the spread of ß-lactam antibiotic resistant bacteria. However, the products formed by γ-irradiation were more easily biodegradable as they were utilized as nutrient source by the microbes of the activated sludge and the products did not show antibacterial activity. During irradiation treatment of aerated aqueous solutions mainly hydroxyl radicals induce the elimination of antimicrobial activity by making alterations at the bicyclic ß-lactam part of these antibiotics. Since the ß-lactam part is the same in oxacillin and cloxacillin, the biochemical characteristics of products of the two antibiotics are similar. The attack of hydrated electron takes place on the carbonyl groups. When the irradiation is made under anoxic conditions these reactions may also contribute considerably to alterations at the ß-lactam part and thereby to the loss of antibacterial activity.

Characterization of technical skill progress in a standardized rabbit model for training in laparoscopic duodenal atresia repair.

BACKGROUND: Laboratory skills training is an essential step before conducting minimally invasive surgery in clinical practice. Our main aim was to develop an animal model for training in clinically highly challenging laparoscopic duodenal atresia repair that could be useful in establishing a minimum number of repetitions to indicate safe performance of similar interventions on humans. MATERIALS AND METHODS: A rabbit model of laparoscopic duodenum atresia surgery involving a diamond-shaped duodeno-duodenostomy was designed. This approach was tested in two groups of surgeons: in a beginner group without any previous clinical laparoscopic experience (but having undergone previous standardized dry-lab training, n = 8) and in an advanced group comprising pediatric surgery fellows with previous clinical experience of laparoscopy (n = 7). Each participant performed eight interventions. Surgical time, expert assessment using the Global Operative Assessment of Laparoscopic Skills (GOALS) score, anastomosis quality (leakage) and results from participant feedback questionnaires were analyzed. RESULTS: Participants in both groups successfully completed all eight surgeries. The surgical time gradually improved in both groups, but it was typically shorter in the advanced group than in the beginner group. The leakage rate was significantly lower in the advanced group in the first two interventions, and it reached its optimal level after five operations in both groups. The GOALS and participant feedback scores showed gradual increases, evident even after the fifth surgery. CONCLUSIONS: Our data confirm the feasibility of this advanced pediatric laparoscopic model. Surgical time, anastomosis quality, GOALS score and self-assessment parameters adequately quantify technical improvement among the participants. Anastomosis quality reaches its optimal value after the fifth operation even in novice, but uniformly trained surgeons. A minimum number of wet-lab operations can be determined before surgery can be safely conducted in a clinical setting, where the development of further non-technical skills is also required.