Group A1 Research Articles

Accelerated Early Childhood Growth Is Associated With the Development of Earlier Adrenarche and Puberty.

Small birth size and increased postnatal growth have been associated with earlier timing of adrenarche and puberty, but it is not well known whether these factors alone or together lead to earlier maturation. This work aimed to search for different growth trajectories using a clustering approach to analyze the effects of birth size and postnatal growth on adrenarchal and pubertal development. Altogether 351 children (48% girls) were examined prospectively at ages 6 to 9 and 9 to 11 years. Birth and early-growth data were collected retrospectively. Main outcome measures included clinical signs of adrenarche and puberty, and serum androgen concentrations (dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone). We detected 4 clusters with different birth sizes and postnatal growth trajectories: 1) children with average birth size and increased postnatal growth (AI), 2) children with small birth size and increased postnatal growth (SI), 3) children with average birth size and postnatal growth (AA), and 4) children with small birth size and average postnatal growth (SA). Thelarche at age 9 to 11 was most common and serum androgens at ages 6 to 9 and 9 to 11 years were highest in girls belonging to the AI and SI groups. Similar patterns in the onset of puberty and in androgen levels were not seen in the SA group. Increased early growth and weight gain predict higher serum androgen concentrations and earlier onset of puberty in girls. Adrenarche and puberty do not appear to be shifted earlier in children with small birth size who do not have catch-up growth.

Comprehensive Insight into the Structure Contribution of A2‐A1‐D‐A1‐A2 Acceptor to Performance of P3HT Solar Cells

AbstractPoly(3‐hexylthiophene) (P3HT) acting as one of the most popular and low‐cost polymers is quite suitable for commercialization of organic solar cells but suffers from low power conversion efficiency (PCE) because of the limited matching non‐fullerene acceptors (NFAs). One important reason that restricts the enhancement but remains unresolved is the undisclosed contributions of the subtle structure modification to the obvious performance change. In combination with the previous reports and this work, herein A2‐A1‐D‐A1‐A2 type NFAs with single, dual, and triple modifications based on parent BTA3 is designed, including benzyl‐substitution on A2 group (namely Bn modification), fluorine‐substitution on A1 group (namely F modification), and thieno[3,2‐b]thiophene‐substitution on D group (namely TT modification). It is finally found that the binary devices of P3HT with these NFAs underwent unexpected variations in the aspect of molecular optoelectronic property, blend morphological feature and charge generation process. The triple modification (including Bn, F, and TT) gives full play to their unique advantages and consequently increases PCE by 60%. To the knowledge, the obtained optimal PCE is one of the highest values for A2‐A1‐D‐A1‐A2 type NFAs. This study provides clearer insights into the rational substitutions on the A2‐A1‐D‐A1‐A2 acceptors matched with P3HT for high‐performance organic photovoltaics.

Effect of Acrylamide and Mycotoxins in SH-SY5Y Cells: A Review.

Thermal processes induce the formation of undesired toxic components, such as acrylamide (AA), which has been shown to induce brain toxicity in humans and classified as Group 2A by the International Agency of Research in Cancer (IARC), as well as some mycotoxins. AA and mycotoxins' toxicity is studied in several in vitro models, including the neuroblastoma cell line model SH-SY5Y cells. Both AA and mycotoxins occur together in the same food matrix cereal base (bread, pasta, potatoes, coffee roasting, etc.). Therefore, the goal of this review is to deepen the knowledge about the neurological effects that AA and mycotoxins can induce on the in vitro model SH-SY5Y and its mechanism of action (MoA) focusing on the experimental assays reported in publications of the last 10 years. The analysis of the latest publications shows that most of them are focused on cytotoxicity, apoptosis, and alteration in protein expression, while others are interested in oxidative stress, axonopathy, and the disruption of neurite outgrowth. While both AA and mycotoxins have been studied in SH-SY5Y cells separately, the mixture of them is starting to draw the interest of the scientific community. This highlights a new and interesting field to explore due to the findings reported in several publications that can be compared and the implications in human health that both could cause. In relation to the assays used, the most employed were the MTT, axonopathy, and qPCR assays. The concentration dose range studied was 0.1-10 mM for AA and 2 fM to 200 µM depending on the toxicity and time of exposure for mycotoxins. A healthy and varied diet allows the incorporation of a large family of bioactive compounds that can mitigate the toxic effects associated with contaminants present in food. Although this has been reported in some publications for mycotoxins, there is still a big gap for AA which evidences that more investigations are needed to better explore the risks for human health when exposed to AA and mycotoxins.

Ultrasound-guided caudal anaesthesia combined with epidural anaesthesia for caesarean section: a randomized controlled clinical trial

BackgroundAlthough epidural anaesthesia and spinal anaesthesia are currently the general choices for patients undergoing caesarean section, these two neuraxial anaesthesia methods still have drawbacks. Caudal anaesthesia has been considered to be more appropriate for gynaecological surgery. The purpose of this study was to compare epidural anaesthesia combined with caudal anaesthesia, spinal anaesthesia and single-space epidural anaesthesia for caesarean section with respect to postoperative comfort and intraoperative anaesthesia quality.MethodsIn this clinical trial, 150 patients undergoing elective caesarean section were recruited and randomized into three groups according to a ratio of 1:1:1to receive epidural anaesthesia only, spinal anaesthesia only or epidural anaesthesia combined with caudal anaesthesia. The primary outcome was postoperative comfort in the three groups. Secondary outcomes included intraoperative anaesthesia quality and the incidences of nausea, vomiting, postdural puncture headache, maternal bradycardia, or hypotension.ResultsMore patients were satisfied with the intraoperative anaesthesia quality in the EAC group than in the EA group (P = 0.001). The obstetrician was more significantly satisfied with the intraoperative anaesthesia quality in the SA and EAC groups than in the EA group (P = 0.004 and 0.020, respectively). The parturients felt more comfortable after surgery in the EA and EAC groups (P = 0.007). The incidence of maternal hypotension during caesarean section was higher in the SA group than in the EA and EAC groups (P = 0.001 and 0.019, respectively).ConclusionsEpidural anaesthesia combined with caudal anaesthesia may be a better choice for elective caesarean section. Compared with epidural anaesthesia and spinal anaesthesia, it has a higher quality of postoperative comfort and intraoperative anaesthesia.

Economic Assessment of Specialized Ingredient-treated Feed for Crossbred Dairy Cattle in Subtropical Climates

This experiment aimed to reduce the cost of feeding dairy cattle that were crossbred using a total of twenty-four crossbred animals. Four groups of six animals each were randomly selected from among the animals. Group 2 (76% treated feed), Group 3 (49% treated feed), Group 4 (100% treated green fodder), and Group 4 (Control) made up Group 1 (Gr-1). The remaining feed A-1, A-2, A-3, A-4, A-5, and A-6 received 1.5% urea+5% molasses+0.5% salt, 1.5% urea+5% molasses+1.5% salt, 1.5% urea+10% molasses+1.5% salt, 5% molasses+0.5% salt, and 10% molasses+0.5% salt were applied, respectively. Each animal at the farm cost 81Rs to feed on average. By contrast, under typical conditions, the feeding expenses for the first group in the A1, A2, A3, A4, A5, and A6 groups were 35, 35, 67, 71, 36, and 70 rupees, respectively. There was a decrease of 43, 42, 11, 11, 44, and 10 rupees as a result. In the second group, the reduction for the A1, A2, A3, A4, A5, and A6 treatment groups was 30Rs, 29Rs, 10Rs, 9Rs, 30Rs, and 10Rs, respectively. In the third group, the reduction was 19Rs, 18Rs, 5Rs, 4Rs, 21Rs, and 7Rs, respectively.

Volumetric analysis after caries excavation with caries detecting dyes and chemomechanical caries removal agents using 3D scanner-a randomised clinical trial

AimThis research aimed to use an extra-oral 3D scanner for conducting volumetric analysis after caries excavation using caries-detecting dyes and chemomechanical caries removal agents in individuals with occlusal and proximal carious lesions.MethodsPatients with occlusal (A1, A2, A3) and proximal carious lesions (B1, B2, B3) were treated with the conventional rotary technique, caries detecting dyes (CDD) and chemomechanical caries removal (CMCR) method on 90 teeth (n = 45 for each). Group A1, B1: Excavation was performed using diamond points. Group A2, B2: CDD (Sable Seek™ caries indicator, Ultradent) was applied and left for 10 s, and then the cavity was rinsed and dried. For caries removal, diamond points or excavators were used. Group A3 and B3: BRIX3000 papain gel was applied with a micro-brush for 20 s and was activated for 2 min, and then the carious tissue was removed with a sharp spoon excavator. Post-excavation cavity volume analysis was performed using a 3D scanner. The time required and the verbal pain score (VPS) for pain were scored during excavation. Post-restoration evaluation was performed at 1, 3, and 6 months FDI (Federation Dentaire Internationale) criteria.ResultsComparison of age, time and volume with study groups were made using Independent Sample’ t’ test and one-way analysis of variance (ANOVA) for two and more than two groups, respectively. Using Cohen’s Kappa Statistics, evaluators 1 and 2 agreed on caries removal status aesthetic, functional and biological properties at different follow-ups. The chi-square test revealed that the rotary groups [A1(2.5 ± 0.4 min) B1(4.0 ± 0.4 min)] had significantly less (p = 0.000) mean procedural time than CDD [A2(4.5 ± 0.4 min) B2(5.7 ± 0.4 min)] and CMCR [A3(5.4 ± 0.7 min) B3(6.2 ± 0.6 min)] groups. The CMCR group showed better patient acceptance and less pain during caries excavation than the rotary and CDD groups. CMCR group showed significantly less mean caries excavated volume(p = 0.000). Evaluation of restoration after 1-, 3-, and 6-month intervals was acceptable for all the groups.ConclusionBrix3000 helps effectively remove denatured teeth with less pain or sensitivity. The time required for caries removal was lowest in the rotary method and highest in the brix3000 group, while the volume of caries removed was the lowest for brix3000 and highest for the rotary group.

Comparative Evaluation of the Push-Out Bond Strength of Glass Ionomer Cement, Mineral Trioxide Aggregate, Biodentine, and Endosequence Root Repair Material in Repair of Furcation Perforations: An In Vitro Study

ABSTRACT Introduction: An in vitro comparative analysis was performed to calculate the push-out bond strength of commercially existing root repairing cements like glass ionomer cement (GIC), biodentine, mineral trioxide aggregate (MTA), and endosequence root repair material (RRM) employed in furcation perforation, with or without blood contamination present. Materials and Methods: Eighty molars were selected and subjected to furcal perforations. They were categorized based on the cement used for repair (GIC, MTA, biodentine, and endosequence RRM); furthermore, they were sub-divided into two sub-groups, that is, blood contaminated and non-contaminated. For 24 hours, all the samples were kept in an incubator till the materials were fully set. Then these samples were examined for push-out bond strength measurement. Results: The 24-hour push-out bond strength of was the highest in biodentine and the lowest in glass ionomer cement. The push-out bond strength of endosequence RRM, MTA, and GIC was influenced by blood contamination. Conclusion: The push-out bond strength of biodentine was the highest as compared to endosequence RRM, MTA angelus, and GIC. The push-out bond strength of endosequence RRM and MTA angelus after 24 hours with or without blood contamination showed insignificant differences. Group 1A (GIC contaminated with blood) displayed the least push-out bond strength among other groups.

Antibacterial effect of red laser-activated silver nanoparticles synthesized with grape seed extract against Staphylococcus aureus and Escherichia coli.

Living organisms, particularly humans, frequently encounter microorganisms such as bacteria, fungi, and viruses in their surroundings. Silver nanoparticles are widely used in biomedical devices because of their antibacterial and antiviral properties. The study evaluates the efficacy of red laser and silver nanoparticles from grape seed extract (AgNPs-GSE) in reducing Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria, which cause infections. The sample comprised three groups: a control group without laser irradiation (T0), Escherichia coli samples (A1 and A2) irradiated with a 405-nm diode laser at different times and concentrations of silver nanoparticles, and Staphylococcus aureus samples (A3 and A4) illuminated with a 405-nm diode laser at different times and concentrations. Bacteria in groups A2 and A4 were treated with a photosensitizer (PS) made from grape seed extracts, incubated for 10min, and then irradiated for 90, 120, 150, and 180s. The samples were cultured on TSA media, set at 37°C, counted using a Quebec colony counter, and analyzed using ANOVA and Tukey tests with a significance level of p < 0.05. The study illustrated that the combination of 10µl of AgNPs-GSE, exposure to a red laser at 405nm, and an energy density of 3.44J/cm2 effectively photoinactivated both Escherichia coli and Staphylococcus aureus bacteria. For Escherichia coli bacteria irradiated for 180s with concentrations of 1mM, 1.5mM, and 2mM AgNPs-GSE, bacterial viability decreased by 64.50%, 70.74%, and 79.53%, respectively. Similarly, Staphylococcus aureus bacteria, subjected to irradiation for 180s with concentrations of 1mM, 1.5mM, and 2mM AgNPs-GSE, demonstrated reductions in bacterial viability by 70.23%, 73.47%, and 85.04%, respectively. The findings from the present study indicate that at an energy density of 3.44J/cm2, it was possible to inactivate Escherichia coli by 79.53% and Staphylococcus aureus by 85.04%.

Characterization of immune responses and immunopathology in turkeys experimentally infected with clostridial dermatitis-producing strains of Clostridium septicum

Clostridium septicum is one of the major causative agents of clostridial dermatitis (CD), an emerging disease of turkeys, characterized by sudden deaths and necrotic dermatitis. Despite its economic burden on the poultry industry, the immunopathological changes and pathogen-specific immune responses are poorly characterized. Here, we used three strains of C. septicum, namely Str. A1, Str. B1 and Str. C1, isolated from CD field outbreaks, to experimentally infect turkeys to evaluate local (skin and muscle) and systemic (spleen) pathological and immunological responses. Results showed that while all three strains produced an acute disease, Str. A1 and B1 caused significantly higher mortality when compared to Str. C1. Gross and histopathology evaluation showed that birds infected with Str. A1 and B1 had severe inflammatory, edematous, granulomatous and necrotic lesions in the skin, muscle and spleen, while these lesions produced by Str. C1 were relatively less severe and mostly confined to skin and/or muscle. Immune gene expression in these tissues showed that Str. B1-infected birds had significantly higher expression of interleukin (IL)−1β, IL-6 and interferon (IFN)γ genes compared to uninfected control, suggesting a robust inflammatory response both locally as well as systemically. The transcription of IL-1β and IFNγ in the muscle or spleen of Str. A1-infected birds and IL-1β in the skin of Str. C1-infected group was also significantly higher than control. Additionally, Str. A1 or B1-infected groups also had significantly higher IL-4 transcription in these tissues, while birds infected with all three strains developed C. septicum-specific serum antibodies. Furthermore, splenic cellular immunophenotyping in the infected turkeys showed a marked reduction in CD4+ cells. Collectively, it can be inferred that host responses against C. septicum involve an acute inflammatory response along with antibody production and that the disease severity seem to depend on the strain of C. septicum involved in CD in turkeys.

Tactics of combined/complex treatment of breast cancer patients with isolated metastatic lesion of supraclavicular or parasternal lymph nodes

The article presents data on 134 breast cancer patients who were diagnosed with lesions of the parasternal, supraclavicular, subclavian and axillary lymph nodes. The effectiveness of surgical or radiation exposure to the supraclavicular/parasternal lymph nodes in their metastatic lesion was analyzed. The survival assessment showed that after 1 year of follow-up, the values of the indicator were almost the same, amounting to 96.3 and 96.4 %, respectively, in groups 1A (surgical treatment) and 1B (radiation therapy). After 3 years, the indicator value was slightly higher in subgroup 1B – 80.4 %, while in group 1A it was 77.8 %, 5-year survival in group 1A was at the level of 33.3 %, in group 1B the indicator value was higher and amounted to 44.6 %, in group 2–78.4 %. At the same time, there were no statistically significant differences in all the terms of the study. We believe that the results of our study are fully consistent with the current trend in the treatment of breast cancer, which can be defined by the phrase ‘the less surgery, the better’. According to our data, surgical removal of metastatically altered supraclavicular and parasternal lymph nodes is inferior to radiation therapy when comparing 5-year overall survival.

Abstract C042: Discovery of a core inflammatory gene network associated with poor prognosis and characterized immune infiltration pattern in pancreatic ductal adenocarcinoma

Abstract Introduction: Inflammation has a significant impact on the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) and is closely associated with disease prognosis. However, the inflammation features and immune infiltration profiles vary greatly among patients. It is still unclear how inflammation is associated with PDAC prognosis, and contradictory findings have been reported frequently. Therefore, it is essential to explore the core inflammatory genes and the related immune infiltration pattern in PDAC. Method: We analyzed bulk RNA sequencing data of 183 PDAC patients from the Cancer Genome Altas by combining 104 inflammatory gene sets (IGSs, 3427 genes in total) from the Molecular Signatures Database. Firstly, we calculated the inflammatory gene expression matrix using the gene set variation analysis (GSVA). Secondly, consensus clustering was executed to evaluate the stability of clustering for the above matrix. Furthermore, the overall survival (OS) and differential expression analyses were used to screen for core inflammatory genes. Finally, immune infiltration pattern among groups were profiled with CIBERSORT. Results: The 183 PDAC patients were initially clustered into two distinct groups according to the consensus clustering of our formed GSVA inflammatory gene expression matrix. Group 1 (94 patients) exhibited evident inflammation features, while Group 2 (89 patients) displayed limited inflammation features. However, no significant difference in OS was observed (p=0.33). We hypothesized that there might be a core inflammatory gene network (CIGN) which is potently related to poor prognosis in PDAC, rather than the overall inflammation features reflected by the collection of all IGSs. Therefore, Group 1 was further clustered into two subgroups: Group 1A (61 patients, high inflammation features) and Group 1B (33 patients, medium). Interestingly, a strong association with poor prognosis was found for Group 1B (medium) (p=0.045), while patients from Group 1A (high) and Group 2 (limited) presented no significant difference in OS (p=0.98). Finally, we discovered a CIGN consisting of two inflammatory genes, PLAU and DCBLD2, which were upregulated in Group 1B and positively correlated with poor prognosis. This association was also validated with two other PDAC datasets. The built CIGN defined groups showed the greatest association with poor prognosis (p=0.0045). As for the immune infiltration pattern, CIGN group showed a higher accumulation of M0 macrophages and neutrophils compared to non-CIGN group, while CD8+ T cells infiltration in CIGN group was much lowerer, implying a more immune suppressive TME in CIGN patients. Conclusion: Despite the lack of association between overall inflammation features and prognosis in PDAC, a CIGN associated with poor prognosis was discovered in this work with a characterized immune infiltration pattern. The CIGN may serve as diagnosis markers and potential therapeutic targets for PDAC toward precision medicine. Fundings: Hong Kong Theme-based Scheme (T12-201/20-R) Citation Format: Liu Yang, Zheng Chen, Yalan Sheng, Debajyoti Chowdhury, Hiu Fung Yip, Shuangying Qiao, Meiheng Sun, Aiping Lu, Fangfei Li. Discovery of a core inflammatory gene network associated with poor prognosis and characterized immune infiltration pattern in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C042.

Effectiveness of preoperative ultrasonography in predicting metachronous contralateral inguinal hernia in children: a single-arm prospective study using a historical control for comparison.

To analyze the value of ultrasonography in predicting metachronous contralateral inguinal hernia (MCIH) and diagnosing contralateral persistent processus vaginalis (CPPV) in children with unilateral inguinal hernia, a prospective study was conducted. All participants underwent a preoperative ultrasound on the contralateral groin. Patients in group A1 received operating procedure according to ultrasound results (patients with negative contralateral US results received hernia repair on the affected side), and patients in group A2 received operation according to laparoscopic results (patients received hernia repair and CPPV ligation). All patients were followed up 2years and compared to a historical control (group B) who underwent open hernia repair only on the affected side regardless of contralateral US results. In groups A1 and A2, laparoscopic exploration revealed the presence of a CPPV in 490 cases. Ultrasound was found to be accurate in 104 out of the 490 cases with four false-positive and 386 false-negative results. This yielded an accuracy of 59.3%, a sensitivity of 21.2%, and a specificity of 99.2%. 10 patients in group A1, and 74 patients in group B developed MCIH. The accuracy, sensitivity, and specificity of the value of ultrasonography in predicting MCIH were 89.3%, 52.4%, and 92.5%, respectively. Preoperative ultrasonography of the contralateral groin is currently unable to accurately detect CPPV, but it appears to be a promising method in predicting MCIH by using rigorous diagnosing criteria.

Effect of up-regulation of micro-ribonucleic acid-22 and NLRP3 inhibition on viability of malignant melanoma cells

Purpose: To determine the effect of up-regulation of micro-ribonucleic acid-22 (miR-22) targeting nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) on the proliferation and invasiveness of malignant melanoma cells, as well as the underlying mechanisms.&#x0D; Methods: Mouse-derived melanoma B16 cells were subjected to thawing, sub-culture and transfection. The cells were assigned to groups (A1 - A5) in line with different transfections viz: A1 (miR-22 mimic overexpression-transfected), A2 (miR-22 inhibitor-transfected), A3 (miR-22 mimic+siNLRP3-transfected), A4 (miR-22 mimic NC sequence-transfected), and A5 (un-transfected).&#x0D; Results: The miR-22 expression was significantly up-regulated in A1, relative to A2, A3, A4, and A5 groups, but significantly lower, relative to A3, A4, and A5. The NLRP3 mRNA and protein levels were significantly lower in A1 than in other groups, but significantly up-regulated in A2, relative to A3, A4, and A5 (p &lt; 0.05). Cell proliferation rate and colony formation rate were significantly lower in A1 group but were significantly up-regulated in A2, relative to A3, A4, and A5.&#x0D; Conclusion: Targeting NLRP3 inhibition by up-regulating miR-22 expression level significantly reduces the proliferation, invasiveness, and matrix metalloproteinase levels of melanoma B16 cells, thereby reducing the occurrence and development of malignant melanoma. The results provide some useful reference data for the treatment of malignant melanoma at the gene level.

High diversity, abundance, and expression of hydrogenases in groundwater.

Hydrogen may be the most important electron donor available in the subsurface. Here we analyse the diversity, abundance and expression of hydrogenases in 5 proteomes, 25 metagenomes, and 265 amplicon datasets of groundwaters with diverse geochemistry. A total of 1545 new [NiFe]-hydrogenase gene sequences were recovered, which considerably increased the number of sequences (1999) in a widely used database. [NiFe]-hydrogenases were highly abundant, as abundant as the DNA-directed RNA polymerase. The abundance of hydrogenase genes increased with depth from 0 to 129m. Hydrogenases were present in 481 out of 1245 metagenome-assembled genomes. The relative abundance of microbes with hydrogenases accounted for ~50% of the entire community. Hydrogenases were actively expressed, making up as much as 5.9% of methanogen proteomes. Most of the newly discovered diversity of hydrogenases was in "Group 3b", which has been associated with sulfur metabolism. "Group 3d", facilitating the interconversion of electrons between hydrogen and NAD, was the most abundant and mainly observed in methanotrophs and chemoautotrophs. "Group 3a", associated with methanogenesis, was the most abundant in proteomes. Two newly discovered groups of [NiFe]-hydrogenases, observed in Methanobacteriaceae and Anaerolineaceae, further expanded diversity. Our results highlight the vast diversity, abundance and expression of hydrogenases in groundwaters, suggesting a high potential for hydrogen oxidation in subsurface habitats.

Effects of Concomitant Use of N-acetylcysteine and Cyclosporine A on Acetaminophen-induced Acute Kidney Injury in Mice

Background: Acetaminophen (APAP), a commonly used analgesic, causes acute kidney injury (AKI) in overdose although it is rare. Mitochondrial dysfunction plays a major role in the pathophysiology of renal damage, although the exact molecular mechanism is unknown. This study aimed to evaluate the potential therapeutic effect of cyclosporin A (CsA), a mitochondrial membrane permeability transition pore (MPTP) inhibitor, with N-acetylcysteine (NAC) in APAP-induced AKI. Methods: Male BALB/c mice were divided into control, APAP, APAP+NAC, APAP+CsA and APAP+NAC+CsA groups (n=6). A single dose of APAP (400 mg/kg) was administered intraperitoneally. All other treatments (1200 mg/kg NAC, 50 mg/kg CsA) were performed intraperitoneally 3 h after APAP administration. All animals were decapitated and blood samples and kidney tissue samples were collected for evaluation. Serum creatinine (Cr) and blood urea nitrogen (BUN) levels were measured. The kidney tissue 8-hydroxy-deoxyguanosine (8-OHdG), cytochrome c (Cytc) and 3-nitrotyrosine (3-NT) levels and cytochrome c (Cytc) expressions were determined. Result: Increased Cr and BUN levels, histopathological examinations and expressions of 8-OHdG, 3-NT and Cytc were detected in the APAP group. Combined NAC+CsA treatment sufficiently reversed oxidative stress, serum Cr and BUN levels and histopathological alterations induced by APAP. Moreover, cytc levels and renal tubular injury were remarkably reduced by combined drug treatment compared to the APAP+NAC group. These data suggest that the therapeutic effect of combined NAC+CsA treatment in mice with APAP-induced nephrotoxicity can be related to the combination of the antioxidant effect of NAC and the mitochondrial MPTP inhibitor effect of CsA.

Neural responses to decision-making in suicide attempters with youth major depressive disorder

An improved understanding of the factors associated with suicidal attempts in youth suffering from depression is crucial for the identification and prevention of future suicide risk. However, there is limited understanding of how neural activity is modified during the process of decision-making. Our study aimed to investigate the neural responses in suicide attempters with major depressive disorder (MDD) during decision-making. Electroencephalography (EEG) was recorded from 79 individuals aged 16–25 with MDD, including 39 with past suicide attempts (SA group) and 40 without (NSA group), as well as from 40 age- and sex- matched healthy controls (HCs) during the Iowa Gambling Task (IGT). All participants completed diagnostic interviews, self-report questionnaires. Our study examined feedback processing by measuring the feedback-related negativity (FRN), ΔFN (FRN-loss minus FRN-gain), and the P300 as electrophysiological indicators of feedback evaluation. The SA group showed poorest IGT performance. SA group and NSA group, compared with HC group, exhibited specific deficits in decision-making (i.e., exhibited smaller (i.e., blunted) ΔFN). Post hoc analysis found that the SA group was the least sensitive to gains and the most sensitive to losses. In addition, we also found that the larger the value of ΔFN, the better the decision-making ability and the lower the impulsivity. Our study highlights the link between suicide attempts and impaired decision-making in individuals with major depressive disorder. These findings constitute an important step in gaining a better understanding of the specific reward-related abnormalities that could contribute to the young MDD patients with suicide attempts.

A Study to Assess the Efficacy of Ultrasound-guided Bilateral Erector Spinae Plane Block for Total Abdominal Hysterectomy under Spinal Anesthesia: A Prospective Randomized Control Study

Abstract Background: Postoperative discomfort after a total abdominal hysterectomy (TAH) is severe. The Erector spinae plane block (ESPB) is the latest addition to the multimodal pain management regimen, providing both visceral and somatic analgesia. Aim: The aim of this study was assessed the postoperative analgesic efficacy of ultrasound-guided bilateral ESPB for TAH. Materials and Methods: 70 female patients aged 40 to 60 years, American society of anaesthesiology (ASA) physical status class I and II posted for TAH were enrolled. Group ESPB+SA(n=35) received bilateral ESPB using 0.25% ropivacaine hydrochloride 15ml with 0.5µ/kg dexmedetomidine on each side before spinal anaesthesia, while group SA (n=35) received only spinal anaesthesia. Postoperative follow-up for 24 hours.Statistical analysis used: Independent-samples student t-test. Results: The total dose of tramadol injection consumed in the first 24 hours postoperatively in group ESPB+SA was significantly low (110.34mg) as compared to group SA (334.29mg) (P &lt; 0.001). Time for first rescue analgesia was prolonged significantly in group ESPB+SA while it was very short in Group SA(P &lt; 0.001). Postoperatively the mean modified defense and veterans pain rating scale (DVPRS) for pain was lower in group ESPB+SA than in group SA, and the difference was statistically significant (P &lt; 0.001). Similarly, scores for other modified DVPRS components, such as sleep, activity, mood and stress were lower in the ESPB+SA group. Conclusions: Bilateral ultrasound-guided ESPB prior to spinal anaesthesia offers effective and prolonged postoperative analgesia, with significantly lower postoperative tramadol use and a higher satisfaction score in patients undergoing TAH under spinal anaesthesia.

Comparison of Urinary Biomarkers in Diagnosis of Ureteropelvic Junction Obstruction and Differentiation from Nonobstructive Dilatation.

Differentiation of nonobstructive dilatation (NOD) from ureteropelvic junction obstruction (UPJO) is a challenge in children with antenatally detected hydronephrosis. The aim of this study is to compare the utility of urinary biomarkers: carbohydrate antigen (CA 19-9), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM) in diagnosing UPJO. A prospective study was conducted after obtaining ethical clearance between 2021 and 2022. Group 1 - control group (n = 30): children with normal antenatal ultrasound with no urinary symptoms. Group 2 - study group (n = 48): children with unilateral hydronephrosis: Group 2a - NOD (n = 24): children stable on ultrasound and diuretic renogram and Group 2b - UPJO (n = 24): children who worsened to Grade 4 hydronephrosis on ultrasound/worsening of differential renal function (10% drop) on renogram who underwent pyeloplasty. Urinary biomarkers NGAL, KIM-1, and CA 19-9 were measured using the enzyme-linked immune absorbent assay method. The urine CA 19-9 level was 128.05 ± 4.08 U/mL in the UPJO group, and this was significantly higher (P = 0.001) than NOD, 70.29 ± 4.41, and controls, 1.91 ± 1.57. The urine NGAL level was 21.41 ± 4.44 pg/mL in UPJO, and this was significantly higher than controls, 2.669 ± 0.513, but not NOD, 24.55 ± 2.67. The urine KIM level was 817 ± 15.84 pg/mL in the UPJO group, and this was significantly higher than controls, 285 ± 8.10, but not NOD, 768.23 ± 15.12. Receiver operating characteristic analysis of CA 19-9 revealed a urine biomarker cutoff of 95 U/mL for diagnosing UPJO (sensitivity 95%; specificity 96%; and area under the curve 0.99). CA 19-9 is a superior marker compared to NGAL and KIM in differentiating UPJO from NOD. Further studies with larger numbers are warranted.

Comparative assessment of nanosized intracanal medicaments on penetration and fracture resistance of root dentin - An in vitro study.

The antimicrobial potential of conventional medicaments is reduced due to their limited permeability. The use of calcium hydroxide (CH) is known to reduce the root strength. Nano intracanal medicaments have the following advantages over conventional such as higher surface area and chemical reactivity, and due to its nanosize, have better penetrability, supporting its possible use as an intracanal medicament. Nano versions of CH, chitosan (CS), CS + CH, curcumin (T), and its conventional forms are used in our study. The aim of this study was to evaluate and compare the depth of penetration of nanosized intracanal medicaments and their effect on fracture resistance of root dentin. Eighty extracted single-rooted teeth were used after decoronation. Canals were enlarged up to size 30 (0.04° taper) using Neoendo instruments (Orikam, India). Teeth were randomly assigned to two broad groups based on the type of intracanal medicament used; Group A: control (conventional) (n = 40) and Group B: nanosized intracanal medicaments (n = 40). Each group was subdivided into four experimental groups (n = 10), Group A1: CH, Group A2: CS, Group A3: curcumin (T), Group A4: CS + CH, Group B1: nano calcium hydroxide (NCH), Group B2: nano CS (NCS), Group B3: nano curcumin (NT), and Group B4: NCS + nano calcium hydroxide (NCS + NCH). All the specimens were stored in a humidor at 37°C for 4 weeks. Out of 10 specimens from each group, five specimens were used for evaluating the depth of penetration using a confocal laser scanning electron microscope, and the remaining five specimens were used for evaluating fracture resistance in a universal testing machine at the end of 4 weeks. Data were analyzed using one-way ANOVA and intergroup comparison using Tukey's post hoc multiple comparison test. The highest fracture resistance was seen with NCS and the maximum depth of penetration with nano calcium hydroxide (NCH). The fracture resistance and depth of penetration at a 4-week interval were higher in nano forms compared to their micro-sized counterparts with all groups. The coronal section presented the highest depth of penetration of intracanal medicaments followed by the middle and least in the apical section of root dentin with all groups.

NEUROTROPIC PROPERTIES OF RETROVIRUSES IN THE CONTEXT OF ANXIETY-DEPRESSIVE AND COGNITIVE DISORDERS IN HIV-POSITIVE PATIENTS

The aim: a comprehensive assessment and comparison of the prevalence of undiagnosed anxiety-depressive and cognitive symptoms in HIV-positive individuals at different stages of the disease who have been undergoing treatment for an extended period. Materials and methods According to the criteria of the scientific project, 71 HIV-positive individuals undergoing outpatient treatment with a compensated condition were involved. To explore dependencies on clinical stages (ClSt) of HIV infection and search for gender differences, the study was divided into 2 stages, respectively. The research included the collection of epidemiological and clinical-anamnestic data, as well as laboratory studies. Clinical-psychopathological and psychometric methods were used. Inclusion criteria for the study were HIV-positive status, receiving ART for more than 6 months, adulthood, and voluntary consent to participate. The obtained information was statistically processed by mathematical methods of statistics, using ANOVA criteria, Student's t-test, etc. Elements of neurocognitive and anxiety-depressive symptomatology were considered, utilizing GAD-7, HADS, and MMSE scales. Results: In patients of different groups in the first stage of the study, a gradually increasing level of anxiety and cognitive impairments was identified, depending on the stage of HIV infection. In the second stage of the study, gender and stage-related differences in anxiety and cognitive disorders were found in patients of all groups. Conclusions. Individuals in the first clinical stage (I ClSt) exhibited the least anxiety-depressive and cognitive disorders, indicating emotional and cognitive stability at this stage of HIV infection. HIV-infected individuals in the second and third clinical stages (II and III ClSt) demonstrated a progressive tendency toward anxious and depressive disorders, indicating a stage-dependent relationship to the progression of the disease. Patients in the fourth clinical stage (IV ClSt) showed the most pronounced anxious, depressive, and cognitive symptoms, which may be associated with the duration of the illness and antiretroviral therapy (ART). Research results in the female group (Group A1) suggest their lower susceptibility to disorders compared to males (Group A2) in the early stages of HIV infection. In the later stages (III-IV), it was found that women had pronounced anxious and depressive disorders (Group B1), while men exhibited signs of cognitive and depressive disorders (Group B2).