Metagenomic perspectives on antibiotic resistance genes in tap water: The environmental characteristic, potential mobility and health threat.

As an emerging environmental contaminant, antibiotic resistance genes (ARGs) in tap water have attracted great attention. Although studies have provided ARG profiles in tap water, research on their abundance levels, composition characteristics, and potential threat is still insufficient. Here, 9 household tap water samples were collected from the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) in China. Additionally, 75 sets of environmental sample data (9 types) were downloaded from the public database. Metagenomics was then performed to explore the differences in the abundance and composition of ARGs. 221 ARG subtypes consisting of 17 types were detected in tap water. Although the ARG abundance in tap water was not significantly different from that found in drinking water plants and reservoirs, their composition varied. In tap water samples, the three most abundant classes of resistance genes were multidrug, fosfomycin and MLS (macrolide-lincosamide-streptogramin) ARGs, and their corresponding subtypes ompR, fosX and macB were also the most abundant ARG subtypes. Regarding the potential mobility, vanS had the highest abundance on plasmids and viruses, but the absence of key genes rendered resistance to vancomycin ineffective. Generally, the majority of ARGs present in tap water were those that have not been assessed and are currently not listed as high-threat level ARG families based on the World Health Organization Guideline. Although the current potential threat to human health posed by ARGs in tap water is limited, with persistent transfer and accumulation, especially in pathogens, the potential danger to human health posed by ARGs should not be ignored.

The effect of different types of water sources on dental unit waterline contamination: A systematic review and meta analysis.

To systematically review the effect of different types of water sources on dental unit waterline (DUWL) contamination. 5 databases were searched from their inception to December 23, 2023. Two reviewers independently extracted the data and assessed the quality of the literature. The risk ratio (RR) was used as measure of effect size in meta-analysis. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for evaluating quality of the evidence. Meta-analysis was completed by RevMan 5.4.5 studies involving 561 water samples were quantified for meta-analysis. The results indicated that no significant differences were found in view of contamination rate (RR = 1.01; 95 % CI, 0.72-1.41; P = 0.96, I 2  = 62 %; GRADE low)and detection rate of Pseudomonas aeruginosa (RR = 0.78; 95 % CI, 0.15-4.13; P = 0.77; I 2  = 83 %; GRADE very low) between using purified water and tap water as water sources of DUWL. The available evidence suggests that there is no significant difference between purified water and tap water in controlling DUWL contamination. However, the conclusions need to be further validated through more randomized controlled trials with robust design and a large sample size.

Estimating the risk of gastrointestinal illness associated with drinking tap water in Norway: a prospective cohort study.

BACKGROUND: The delivery of safe drinking water has high public health relevance, as reflected in the Sustainable Development Goals (SDG6). Several precautionary actions have reduced the burden associated with infectious diseases in high-income countries; however, pollution in source waters, inadequate disinfection, and premise plumbing, along with an increased awareness that intrusion in the drinking water distribution system, represents risk factors for gastrointestinal illness linked to consume of drinking water. Sporadic cases of waterborne infections are expected to be underreported since a sick person is less likely to seek healthcare for a self-limiting gastrointestinal infection. Hence, knowledge on the true burden of waterborne diseases is scarce. The primary aim with the present study was to estimate the risk of gastrointestinal illness associated with drinking tap water in Norway. METHODS: We conducted a 12-month prospective cohort study where participants were recruited by telephone interview after invitation based on randomised selection. A start up e-survey were followed by 12 monthly SMS questionnaires to gather information on participants characteristics and drinking tap water (number of 0.2L glasses per day), incidence, duration and symptoms associated with gastrointestinal illness. Associations between the exposure of drinking tap water and the outcome of risk of acute gastrointestinal illness (AGI) were analysed with linear mixed effects models. Age, sex, education level and size of the drinking water supply were identified as potential confounders and included in the adjusted model. RESULTS: In total, 9,946 persons participated in this cohort study, accounting for 11.5% of all invited participants. According to the data per person and month (99,446 monthly submissions), AGI was reported for 5,508 person-months (5.5 per 100 person-months). Severe AGI was reported in 819 person-months (0.8 per 100 person-months). Our study estimates that 2-4% of AGI in Norway is attributable to drinking tap water. CONCLUSIONS: This is the largest cohort study in Norway estimating the burden of self-reported gastrointestinal infections linked to the amount of tap water drunk in Norway. The data indicate that waterborne AGI is not currently a burden in Norway, but the findings need to be used with caution. The importance of continued efforts and investments in the maintenance of drinking water supplies in Norway to address the low burden of sporadic waterborne cases and to prevent future outbreaks needs to be emphasised.

Characterization of Chemoresistance in Pancreatic Cancer: A Look at MDR-1 Polymorphisms and Expression in Cancer Cells and Patients.

Pancreatic malignancy is the fourth cause of cancer-related death in Western countries and is predicted to become the second leading cause of cancer-related mortality by 2030. The standard therapies (FOLFIRINOX and gemcitabine with nab-paclitaxel) are not resolutive because this type of cancer is also characterized by a high chemoresistance, due in part to the activity of the ATP Binding Cassette (ABC) pumps accounting for the reduction in the intracellular concentration of the drugs. In this work, we analyze the occurrence of single-nucleotide polymorphisms (SNPs) in the MDR-1 gene, in different pancreatic cancer cell lines, and in tissues from pancreatic cancer patients by DNA sequencing, as well as the expression levels of MDR-1 mRNA and protein, by qRT-PCR and Western Blot analysis. We found that gemcitabine-resistant cells, in conjunction with homozygosis of analyzed SNPs, showed high MDR-1 basal levels with further increases after gemcitabine treatment. Nevertheless, we did not observe in the human PDAC samples a correlation between the level of MDR-1 mRNA and protein expression and SNPs. Preliminary, we conclude that in our small cohort, these SNPs cannot be used as molecular markers for predicting the levels of MDR-1 mRNA/protein levels and drug responses in patients with PDAC.

A novel TAp73-inhibitory compound counteracts stemness features of glioblastoma stem cells.

Glioblastoma (GB) is the most common and fatal type of primary malignant brain tumor for which effective therapeutics are still lacking. GB stem cells, with tumor-initiating and self-renewal capacity, are mostly responsible for GB malignancy, representing a crucial target for therapies. The TP73 gene, which is highly expressed in GB, gives rise to the TAp73 isoform, a pleiotropic protein that regulates neural stem cell biology; however, its role in cancer has been highly controversial. We inactivated TP73 in human GB stem cells and revealed that TAp73 is required for their stemness potential, acting as a regulator of the transcriptional stemness signatures, highlighting TAp73 as a possible therapeutic target. As proof of concept, we identified a novel natural compound with TAp73-inhibitory capacity, which was highly effective against GB stem cells. The treatment reduced GB stem cell-invasion capacity and stem features, at least in part by TAp73 repression. Our data are consistent with a novel paradigm in which hijacking of p73-regulated neurodevelopmental programs, including neural stemness, might sustain tumor progression, pointing out TAp73 as a therapeutic strategy for GB.

Multi-omics analysis of overexpressed tumor-associated proteins: gene expression, immunopeptide presentation, and antibody response in oropharyngeal squamous cell carcinoma, with a focus on cancer-testis antigens.

Introduction: The human leukocyte antigen complex (HLA) is essential for inducing specific immune responses to cancer by presenting tumor-associated peptides (TAP) to T cells. Overexpressed tumor associated antigens, mainly cancer-testis antigens (CTA), are outlined as essential targets for immunotherapy in oropharyngeal squamous cell carcinoma (OPSCC). This study assessed the degree to which presentation, gene expression, and antibody response (AR) of TAP, mainly CTA, are correlated in OPSCC patients to evaluate their potential as immunotherapy targets. Materials and methods: Snap-frozen tumor (NLigand/RNA=40), healthy mucosa (NRNA=6), and healthy tonsils (NLigand=5) samples were obtained. RNA-Seq was performed using Illumina HiSeq 2500/NovaSeq 6000 and whole exome sequencing (WES) utilizing NextSeq500. HLA ligands were isolated from tumor tissue using immunoaffinity purification, UHPLC, and analyzed by tandem MS. Antibodies were measured in serum (NAb=27) utilizing the KREX™ CT262 protein array. Data analysis focused on 312 proteins (KREX™ CT262 panel + overexpressed self-proteins). Results: 183 and 94 of HLA class I and II TAP were identified by comparative profiling with healthy tonsils. Genes from 26 TAP were overexpressed in tumors compared to healthy mucosa (LFC>1; FDR<0.05). Low concordance (r=0.25; p<0.0001) was found between upregulated mRNA and class I TAP. The specific mode of correlation of TAP was found to be dependent on clinical parameters. A lack of correlation was observed both between mRNA and class II TAP, as well as between class II tumor-unique TAP (TAP-U) presentation and antibody response (AR) levels. Discussion: This study demonstrates that focusing exclusively on gene transcript levels fails to capture the full extent of TAP presentation in OPSCC. Furthermore, our findings reveal that although CTA are presented at relatively low levels, a few CTA TAP-U show potential as targets for immunotherapy.

Long-term association between water intake and kidney function in a population at high cardiovascular risk.

OBJECTIVES: The evidence on water intake in the prevention of kidney function decline is scarce at population level in well-being individuals at high cardiovascular risk. Therefore, we aimed to longitudinally evaluate the associations between total water intake and subtypes and kidney function, through estimated-Glomerular Filtration Rate (eGFR). METHODS: Three-year prospective analysis conducted in 1986 older adults (aged 55-75 year) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus study. Water intake was assessed using validated beverage and food frequency questionnaires. Serum creatinine-based eGFR (SCr-based eGFR; ml/min/1.73 m2) was estimated using the CKD-EPI equation at baseline, one-year and 3-years of follow-up. Mixed-effects linear regression models were fitted to evaluate the associations between baseline total water intake and subtypes, and SCr-based eGFR over 3-years of follow-up. RESULTS: Participants in the highest baseline tertile of total water intake, plain water and water from all fluids showed a lower decrease in SCr-based eGFR after 3-years of follow-up, compared to those in the lowest tertile. Participants with the highest tap water consumption showed a lower SCr-based eGFR decline after 1-year and 3-years of follow-up, in comparerd to participants in the lowest intake category (T3 vs. T1: ß: 1.4 ml/min/1.73 m2; 95%CI: 0.5-2.3, ß: 1.0; 95%CI: 0.1-2.0, respectively). CONCLUSIONS: Plain water rather than other water sources, and especially tap water, was associated with lower kidney function decline assessed through eGFR over 3-years of follow-up, in older individuals at high cardiovascular risk. TRIAL REGISTRATION: ISRCTN89898870. Retrospectively registered on 24 July 2014.

Presence of N, N'-Substituted p-Phenylenediamine Quinones in Tap Water: Implication for Human Exposure.

Monitoring studies have demonstrated the wide presence of N, N'-substituted p-phenylenediamine-derived quinones (PPDQs) in environmental matrices. The general population may be potentially exposed to PPDQs through the consumption of tap water. While, the existence of PPDQs in tap water has not been well examined. To fill this gap, in this study we collected tap water samples from Hangzhou, China, and examined seven homologues of PPDQs in collected samples. All target PPDQs were identified in the collected tap water samples, with distinct detection frequencies (38-89%). PPDQs detected in tap water was dominated by N-(1, 3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPDQ; mean 0.56 ng/L, < LOD-4.0 ng/L). The profiles of PPDQs concentrations in tap water from the four districts of Hangzhou city were slightly different. The daily intake (DI) was found highest for 6PPDQ (mean 14-22 pg/kg bw/day, median 10-15 pg/kg bw/day) through tap water intake. The relatively higher DIs of various PPDQs were displayed for infants (mean 10-22 pg/kg bw/day, median 6.5-15 pg/kg bw/day), relative to the children (8.0-18 pg/kg bw/day, 5.4-12 pg/kg bw/day) and adults (6.7-14 pg/kg bw/day, 4.5-10 pg/kg bw/day). These data are crucial for assessing the overall human exposure to PPDQs. This study first, to our knowledge, reveals the concentrations and profiles of PPDQs in tap water.

Comparative Study of Ropivacaine and Ropivacaine With Dexmedetomidine in Transversus Abdominis Plane (TAP) Block for Post-operative Analgesia in Patients Undergoing Cesarean Sections.

Background Adequate post-operative analgesia in the obstetric patient is necessary to facilitate breastfeeding and the care of the newborn. Considering the limitations of intravenous analgesic options such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, other alternatives have been tried for offering better analgesia with fewer potential side effects. Transversus abdominis plane (TAP) block is one such option that has been tried with various local anesthetic drugs, either alone or in combination with other adjuvants. The addition of dexmedetomidine to bupivacaine in TAP block has been shown to prolong the duration of post-operative analgesia when compared to local anesthetic alone. This study was conducted to determine the efficacy of dexmedetomidine, as an adjuvant to ropivacaine, when administered in TAP block in patients undergoing cesarean section. Methodology The study was a prospective, randomized, parallel assignment, triple-blinded controlled trial. Hundred patients posted for elective lower segment cesarean section, fulfilling the inclusion criteria, were randomly divided into two equal groups, group R and group RD, comprising 50 patients each. Patients in group R were administered bilateral TAP block by landmark technique using ropivacaine alone, whereas patients in group RD were administered TAP block with dexmedetomidine 1 micrograms/kg, in addition to a similar dose of ropivacaine. Mean arterial pressure (MAP), heart rate (HR), visual analog scale (VAS)-R (pain score on VAS scale at rest), VAS-C (pain score on VAS scale on coughing), nausea and vomiting, and Ramsay sedation score were recorded on admission to post-operative care unit (PACU), and at first, fourth, eighth, 12th, 18th, and 24th hours post-operatively. Rescue analgesia was provided with intravenous morphine. Short Assessment of Patient Satisfaction Score (SAPS) was noted on a five-point scale after 24 hours based on patient satisfaction regarding the quality of post-operative analgesia. Results While there was no significant difference between groups R and RD with respect to VAS-C and VAS-R immediately after shifting and at the first, fourth, and eighth hours, a significant difference was observed at the 12th and 18th hours post-operatively. After 24 hours, no significant difference was observed between groups R and RD with respect to VAS-C and VAS-R. While 50% of patients needed rescue analgesia in group R, only 28% of patients needed rescue analgesia in group RD. There was significantly better patient satisfaction measured by the Short Assessment of Patient Satisfaction Score (SAPS) with respect to the quality of analgesia in patients in group RD as compared to those in group R. Conclusions The addition of dexmedetomidine to ropivacaine increased the duration of post-operative analgesia up to 18 hours post-operatively in cases of elective lower segment cesarean section. Also, the quality of post-operative analgesia is better in such patients, as shown by a significant difference in patient satisfaction scores between the two groups.

Comparison of four concentration methods of adenovirus, norovirus and rotavirus in tap water.

Human enteric viruses, as adenovirus (HAdV), norovirus (HuNoV) and rotavirus (RVA) are significant causes of gastroenteritis associated with consumption of contaminated water worldwide. Various methods have been described for their detection and monitoring in water. The aim of this study was to compare the performance of four conditions for concentrating HAdV, HuNoV and RVA from water matrices, in order to develop a single protocol that could simultaneously concentrate all target viruses from tap water. The tested conditions were based on the adsorption-elution using electronegative filters, in which we evaluated cation-coated filtration by MgCl2 with or without acid rinse by H2SO4 and two elution buffers, namely NaOH and tris-glycine-beef extract. Genomic material was extracted and amplified by real-time PCR and real-time RT-PCR using commercial kits. Based on the statistical analysis of amplification results (cycles of quantification), the condition involving cation-coated filtration by MgCl2 using electronegative filters with acid rinse by H2SO4 combined with NaOH elution allowed efficient recovery of both HAdV, HuNoV and RVA from tap water compared to the other conditions. These findings confirm the effectiveness of the approach used to monitor three major enteric viruses in tap water.

Aurivillius-Type SrBi4Ti4O15/PGA Composite Film-Based Flexible Triboelectric Nanogenerators for Energy Harvesting/Storage and Multipurpose Tap-Indication Transducer Applications.

Recent advancements in flexible triboelectric nanogenerators (TENGs) have widely focused on converting mechanical energy into electrical energy to power small wearable electronic gadgets and sensors. To effectively achieve this, an efficient energy-converted power management circuit is required. Herein, we report on Aurivillius-type strontium bismuth titanate (SrBi4Ti4O15) nanoparticles (SBT NPs)-loaded polyglucosamine (PGA) composite film-based flexible TENG to be used for energy harvesting/storage and biomechanical applications. Initially, SBT NPs were synthesized and then, different weight concentrations were loaded into PGA. The TENG devices were fabricated using different wt % composite films (SBT/PGA) and polydimethylsiloxane as positive and negative triboelectric layers, respectively, and aluminum was used as a conductive electrode attached to two tribo films. To evaluate the electrical output from the device, contact-separation operation mode was used. An optimized TENG consisting of 2 wt % SBT/PGA composite film produced the maximum electrical output voltage and current of approximately ∼239 V and ∼7.5 µA, respectively. Efficient TENG energy harvesting and storage circuits have been proposed for storing charges in capacitors and for operating electronic gadgets. The optimized TENG was employed to generate electrical energy from various biomechanical movements. Thereafter, the biodegradability of the composite film was also tested. The fabricated films were completely biodegraded within a few hours. Furthermore, the TENG was utilized as a tap-indication transducer for multipurpose switching applications.

Effects of ShotBlocker® and the Helfer skin tap technique on pain and fear experienced during intramuscular injection among children aged 6-12 years in pediatric emergency units: A randomized controlled trial.

BACKGROUND: In pediatric emergency units, intramuscular injection is one of the most common procedures that cause pain and fear in children. Reducing pain and fear is important for patient comfort. OBJECTIVE: This randomized controlled experimental study aimed to determine the effects of ShotBlocker® and the Helfer skin tap technique on the pain and fear experienced by children aged 6-12 years during intramuscular injection in pediatric emergency units. METHODS: This study was conducted from April 2022 to October 2023 among 177 children aged 6-12 years. ShotBlocker and the Helfer skin tap technique were applied during intramuscular injection among children in the intervention groups (ShotBlocker group: n = 59, Helfer skin tap technique group: n = 59), while children in the control group received routine injections. (n = 59). The levels of pain and fear were measured. RESULTS: In the analysis of the age distribution of the children, the average age of the Helfer skin tap technique group was found to be 8.54 ± 2.00 years; ShotBlocker group, 8.46 ± 1.99 years; and control group, 9.19 ± 2.01 years. There was a significant difference in the post-intervention Wong-Baker Pain Scale and Child Fear Scale scores based on the evaluation of the children, parents, and observer nurses between the groups (p < 0.05). The pain and fear scores of the ShotBlocker group were lower than those of the control group (p < 0.05). CONCLUSIONS: ShotBlocker is more effective in reducing pain than the Helfer skin tap technique among children receiving intramuscular injection. These cheap and easy-to-use methods are recommended for use in emergency units.

Individual and environmental correlates of tap water consumption among adolescents in Canada.

The study objective was to identify correlates of tap water consumption among adolescents. French-speaking adolescents from the province of Québec (Canada) were recruited in person and online from March to July 2023 using diverse recruitment strategies. Water consumption was measured using the validated French version of a questionnaire specifically designed to measure adolescents' beverage intake. Participants answered an online survey on their attitude towards tap and bottled water which also measured individual and environmental factors that can influence tap water consumption. A total of 218 adolescents (14-17 years; 55.5% female) completed the survey. On average, 79.2% of adolescents' water intake came from tap and 33.5% of them consumed exclusively tap water. Thinking that bottled water is more convenient than tap water was a significant correlate of adolescents' tap water consumption (OR = 0.70; 95% CI: 0.51, 0.95; p = 0.0219). Adolescents who believed that bottled water is more convenient than tap water were less likely to consume exclusively tap water. Public health interventions aimed at promoting adolescents' tap water should strive to make tap water intake be perceived as convenient as bottled water, such as encouraging teenagers to always carry along a reusable water bottle, installing drinking fountains in popular public areas, and increasing the visibility of such fountains.

How does the citizens' choice of water use actions based on their empirical knowledge affect the water quality in a rural community of the Philippines?

This research assessed water quality, based on the purpose of water consumption, in households in the municipality of Barbaza, the Province of Antique, Philippines, according to the national water quality guidelines. The effects of the empirical/traditional water use actions taken by local people on the quality of the water they use were investigated through a descriptive study using water quality measurements. Most of the drinking water in the community did not meet the required standards of pH, total dissolved solids (TDS), or coliform. Tap water and well water samples generally met the pH and TDS standards. However, Escherichia coli (E. coli) and coliform were detected, and nitrogen pollution in well water was also confirmed. Local practices, such as using old clothes as filters for well pumps, increased the coliform concentration from 0-10 CFU/mL to too numerous to count (TNTC) levels of more than 100 CFU/mL. Storing well water in a bucket also affected both E. coli and coliform concentrations. Such empirical/traditional water use actions create a high risk of exposing local people to harmful microorganisms. This research integrated citizen science into the methodology for local water management, which could assist governors, practitioners, and citizens, particularly in Southeast Asia, where strong community relationships exist.

Total Correction for Tetralogy of Fallot in Patients Weighing Over 10 kg: Experiences and Follow-Up Outcomes.

Background Although the recommended time for total correction of tetralogy of Fallot (TOF) is during infancy, sometimes TOF cases present to healthcare setups after pre-school age, with some cases presenting even beyond adolescence in developing countries. The objective of this study was to assess patients with TOF weighing 10 kg and above who underwent definitive corrective surgical techniques such as transannular patch (TAP), valve-sparing right ventricular outflow tract (RVOT) pericardial patch augmentation, non-ventriculotomy infundibular resection for postoperative complications, hospital stay, and right ventricular (RV) dysfunction in the immediate postoperative period and subsequent outpatient department follow-ups. Methodology This comprehensive, retrospective cohort study included single-center data collected between January 16, 2018, and January 15, 2024. The study included 63 patients diagnosed with TOF weighing 10 kg and above, ensuring a robust and representative sample. Results Of the 119 patients who underwent total correction for TOF, 63 met the study's inclusion criteria of TOF weighing above 10 kg. Of the 63 patients, 55.6% were males, and 44.4% were females. The mean weight of the study participants was 33.4 kg. The mean age was 15.9 years. Of the 63 patients, 39 underwent TAP surgery, 18 underwent RVOT patch augmentation, and six underwent total correction by non-ventriculotomy infundibular resection. There was a significant difference between the type of surgery groups and RV dysfunction, with the TAP group showing a higher incidence of RV dysfunction, indicating a potential risk factor associated with this technique. Conclusions Although TAP has significant immediate postoperative complications compared to other techniques, its long-term follow-up suggests that long-term survival and quality of life, as measured by major adverse cardiac events such as heart failure, arrhythmias, and reoperation rates, are commensurable in adulthood. This indicates that despite the initial challenges, TAP can provide satisfactory outcomes in the long run.

Anesthetic management of a dog undergoing unilateral adrenalectomy for phaeochromocytoma excision using a partial intravenous anesthetic protocol.

Background: The anesthetic management of adrenalectomies for phaeochromocytoma excision, a catecholamine-secreting tumor, is challenging due to the potential for fatal complications following severe hemodynamic variations, including hypertensive crisis following tumor manipulation or sympathetic stimulation, but also severe hypotension and volume depletion post resection. Case Description: An 11 kg, 15-year-old male neutered Jack Russel Terrier, with mitral valve disease stage B2, was referred for adrenalectomy for phaeochromocytoma resection. The patient was administered per os prazosin 0.11 mg/kg twice a day and amlodipine 0.125 mg/kg once a day for preoperative stabilization. On the day of surgery, the dog received maropitant 1 mg/kg intravenously (IV) and was premedicated with 0.2 mg/kg methadone IV. Anesthesia was induced with alfaxalone 1 mg/kg IV and midazolam 0.2 mg/kg IV and maintained with partial intravenous anesthesia using sevoflurane in 70% oxygen and constant rate infusions of dexmedetomidine 0.5 µg/kg/hour and maropitant 100 µg/kg/hour. After induction of anesthesia, the dog was mechanically ventilated, and a transversus abdominal plane block was performed with ropivacaine 0.2%. The dog remained remarkably stable with a single, self-limiting, hypertension episode recorded intraoperatively. Postoperative rescue analgesia consisted of methadone and ketamine. The dog was discharged 48 hours after surgery, but persistent hypertension was reported at suture removal. Conclusion: The use of a low-dose dexmedetomidine CRI, a maropitant CRI, and a transversus abdominal plane block provided stable perioperative hemodynamic conditions for phaeochromocytoma excision in a dog.

Activating transcription factor 3 mediates apoptosis and cell cycle arrest in TP53-mutated anaplastic thyroid cancer cells.

BACKGROUND: It is believed that loss of p53 function plays a crucial role in the progression of well to poorly differentiated thyroid cancers including anaplastic thyroid carcinoma (ATC). Given the poor prognosis of ATC due to its strong therapeutic resistance, there is a need to establish new therapeutic targets to extend the survival of ATC patients. Activating transcription factor 3 (ATF3) can inhibit the oncogenic activity of mutant p53 and, as a result, contribute to tumor suppression in several TP53-mutated cancers. Herein, we demonstrate that the ectopic overexpression of ATF3 leads to the suppression of oncogenic mutant p53 activity in chemo-resistant 8305 C thyroid cancer cells harboring R273C p53 gene mutation. METHODS: The biological behavior of 8305 C cells was assessed pre- and post-transfection with pCMV6-ATF3 plasmid using MTT assay, fluorescent microscopy, cell cycle, and annexin V/PI flow cytometric analysis. The effect of ectopic ATF3 overexpression on the cellular level of p53 was examined by western blotting assay. The mRNA expression levels of TP53, TAp63, ΔNp63, and SHARP1 were evaluated in ectopic ATF3-expressing cells compared to controls. RESULTS: The overexpression of ATF3 in 8305 C thyroid cancer cells significantly decreased cell viability and induced apoptosis and cell cycle arrest in vitro. The immunoblotting of p53 protein revealed that ATF3 overexpression significantly increased the level of mutant p53 in 8305C cells compared to mock-transfected control cells. Additionally, elevated mRNA levels of TAp63 and SHARP1 and a decreased mRNA level of ΔNp63 were observed in PCMV6-AC-ATF3-transfected 8305 C cells with significant differences compared to the mock and untreated cells. CONCLUSION: In light of our findings, it is evident that therapeutic strategies aimed at increasing ATF3 expression or enhancing the interaction between ATF3 and mutant p53 can be a promising approach for the treatment of p53-mutated metastatic thyroid cancer.

An experimental study on the curing of desert sand using bio-cement.

In order to promote the development and utilization of desert sand, this study is based on researching the most suitable ratio of bio-cement, analyzing the shear strength and permeability of improved desert sand by combining bio-cement and fly ash, and clarifying the applicability of tap water in bio-cement. The relationship between the two and the microstructural properties was investigated using the results of the straight shear test and the permeability test. The results showed that the urease solution prepared with tap water had a more pronounced temperature resistance. The urea concentration and the corresponding pH environment had a direct effect on the urease activity. The calcium carbonate yield was positively correlated with the calcium concentration, and the urea concentration was higher in the ranges of 1.0-1.5 mol/L. As the enzyme-to-gel ratio decreased, the calcium carbonate precipitate produced per unit volume of urease solution gradually converged to a certain value. The shear strength (increased by 37.9%) and permeability (decreased by about 8.9-68.5%) of the modified desert sand peaked with the increase in fly ash content. The microscopic test results indicated that the fly ash could provide nucleation sites for the bio-cement, effectively improving the mechanical properties of the desert sand. The crystal types of calcium carbonate in the modified desert sand were calcite and aragonite, which were the most stable crystal types. This study provides innovative ideas for interdisciplinary research in the fields of bioengineering, ecology and civil engineering.

Experimental study on the mechanical properties of desert sand improved by the combination of additives and bio-cement.

Bio-cement is a green and energy-saving building material that has attracted much attention in the field of ecological environment and geotechnical engineering in recent years. The aim of this study is to investigate the use of bio-cement (enzyme-induced calcium carbonate precipitation-EICP) in combination with admixtures for the improvement of desert sands, which can effectively improve the mechanical properties of desert sands and is particularly suitable for sand-rich countries. In addition, the suitability of tap water in bio-cement was elucidated and the optimum ratio of each influencing factor when tap water is used as a solvent was derived. The results showed that peak values of unconfined compressive strength (maximum increase of about 130 times), shear strength (increase of 27.09%), calcium carbonate precipitation value (increase of about 4.39 times), and permeability (decrease of about 93.72 times) were obtained in the specimens modified by EICP combined with admixture as compared to the specimens modified by EICP only. The incorporation of skimmed milk powder, though significantly increasing the strength, is not conducive to cost control. The microscopic tests show that the incorporation of admixtures can provide nucleation sites for EICP, thus improving the properties of desert sand. This work can provide new research ideas for cross-fertilization between the disciplines of bio-engineering, ecology, and civil engineering.

The Development and Validation of an Objective Assessment Tool for Performing Ultrasound-Guided Transversus Abdominis Plane Blocks.

The transversus abdominis plane (TAP) block is a regional anesthesia technique used as part of a multimodal pain management plan in patients undergoing abdominal surgery. There are numerous approaches and techniques described in the literature, resulting in a lack of consistency in block performance. This potentially reduces efficacy while increasing risk to the patient. Competency assessment tools have been shown to lower patient risk and improve outcomes by improving provider skill. Checklists are used as formative and summative assessment tools throughout healthcare education, however, there is no validated tool for ultrasound-guided TAP blocks. The purpose of this evidence-based project was to develop a checklist using a modified Delphi method. The primary outcome measure was validation of the assessment tool, established by an expert panel consensus and guided by Messick's validity framework. A 43-item checklist was validated by six certified registered nurse anesthesiologists throughout the United States with expertise in regional anesthesia. Three rounds of feedback were required to exceed the threshold of consensus (0.8), establishing a method of evaluation that may allow future research in educational settings through improved skill assessment among providers performing TAP blocks.