Comparison of Effectiveness and Safety of Oxycodone Hydrochloride and Fentanyl for Post-operative Pain Following Total Hip Arthroplasty: A Randomized Triple-Blind Trial.

Background: Total hip replacement (THR) is frequently associated with intense post-surgical pain. Effective pain management is of crucial importance to improving patient's condition and increasing his/her satisfaction in the post-operative time. Objectives: This study aimed to compare the analgesic effect and safety of oxycodone and fentanyl after THR. Methods: Seventy-two cases scheduled for elective THR were included in this randomized, triple-blind trial. The patients were equally randomized into 2 groups: Fentanyl group (50 ug of fentanyl) and oxycodone group (oxycodone 4 mg). Drugs were received 20 min prior to the end of the operation. Results: Post-operative visual analog scale (VAS) measurements at rest and movement at the post-anesthesia care unit (PACU) and in the ward, 2 h, 4 h, and 8 h post-operatively exhibited a significantly reduced value in the oxycodone group compared to the fentanyl group (P-value < 0.05). Time to first rescue for analgesia was delayed significantly in the oxycodone compared to the fentanyl group (P-value < 0.001). Fentanyl consumption (ug) in the 1st post-operative 12 h, 24 h, and 48 h decreased significantly in the oxycodone group compared to the fentanyl group (P-value < 0.001). Post-operative nausea, vomiting, headache, and pruritus were matched between the 2 groups (P > 0.05). Conclusions: A bolus dose of 4 mg of oxycodone provided superior analgesic efficacy than 50 ug fentanyl as evidenced by significantly lower pain score, delayed onset to first request for analgesia, and the smaller amount of fentanyl consumption at 12, 24, and 48 h post-total hip arthroplasty compared to fentanyl. The incidence of adverse events was comparable between the 2 groups.

Nurses' knowledge and protective health behaviors about prevention of COVID-19 pandemic complications at Baghdad Teaching Hospitals.

BACKGROUND: Coronavirus disease (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus, SARS-CoV-2. Infection with SARS-CoV-2 primarily occurs through binding to angiotensin-converting enzyme-2 (ACE2), which is abundantly expressed in various anatomical sites, including the nasopharynx, lungs, cardiovascular system, and gastrointestinal and genitourinary tracts. This study aimed to nurses' knowledge and protective health behaviors about prevention of covid-19 pandemic complications. MATERIALS AND METHODS: A descriptive design study was conducted from October 1, 2022, to March 15, 2023. A non-probability purposive sample of 50 nurses from different educational levels, genders, and departments at Baghdad teaching hospitals was selected. Data collected were analyzed using SPSS version 25.0. RESULTS: The study comprised an equal distribution of male and female participants, with the majority (44%) aged between 22 and 30 years. A significant proportion (52%) of nurses held institute degrees. Forty-six percent were single, and the majority (74%) had 1-5 years of experience. The mean scores were 0.70 for nurses' knowledge and 3.22 for nurses' protective health behaviors. CONCLUSIONS: The findings indicate that nurses possess satisfactory knowledge and exhibit high levels of protective health behaviors regarding complications associated with the COVID-19 pandemic. It is recommended to conduct future research focusing on nurses' knowledge and practices related to patient care in the context of a pandemic.

Effects of antisperm antibodies post vasectomy reversal on pregnancy rates.

OBJECTIVE: To investigate the correlation between antisperm antibodies (ASAs), pregnancy rates, and the method of conception following vasectomy reversal. This is particularly relevant as patients undergoing vasectomy reversal often express concerns about the potential inhibitory effects of ASAs on achieving pregnancy. Additionally, the American Urological Association guidelines for vasectomy emphasize the need for further research to address this question. PATIENT AND METHODS: We conducted a retrospective analysis involving chart reviews and phone interviews with individuals who underwent vasectomy reversal at our institution between May 2015 and April 2023. Patients who underwent vasectomy reversal for reasons other than fertility, as well as those lacking postoperative semen analysis with ASA data, were excluded. We classified patients based on low (below 50%) or high (50% or above) ASA levels determined by their initial postoperative semen analysis. The primary outcome measured was the pregnancy rate, including details on the method of conception. RESULTS: A total of 145 patients were subjected to chart review. The median age at the time of surgery was 43 years, with a median obstruction interval of 7.7 years. The median age of their partners was 29 years. The majority (80%) of patients underwent bilateral vasovasostomy. Among them, 60 patients (41.4%) exhibited low (< 50%) ASA levels, while 85 (58.6%) had high (≥ 50%) ASA levels. Follow-up phone interviews were completed by 48 patients. Among them, the 19 men with low ASA levels, 13 (68.4%) achieved pregnancy, with 6 (31.6%) experiencing spontaneous conception. For the 29 men with high ASA levels, 21 (72.4%) achieved pregnancy, including 11 (38%) through spontaneous conception. The p-value from Fisher's exact test was 0.2. CONCLUSIONS: Our findings suggest that ASA levels do not show a significant association with either the pregnancy rate or the method of conception following vasectomy reversal.

The influence of oral antioxidants on men with infertility: a systemic review.

OBJECTIVE: This study aims to investigate the current evidence regarding the impact of oral antioxidant supplementation on semen parameters of infertile men. MATERIALS AND METHODS: We conducted a systematic search of PubMed, and Cochrane electronic databases, adhering to modified Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The focus was on studies exploring the effects of antioxidant therapy on infertile men, with an examination of antioxidants in terms of types, doses, rationale for use, and their impact on semen parameters measures. RESULTS: A total of 18 studies that met the inclusion criteria were included in this study. Out of these, 14 studies reported a significantly positive influence of antioxidant therapy on basic semen parameters and advanced sperm function. These comprised 11 randomized clinical trials and 7 prospective studies. Commonly utilized antioxidants included Vitamin E, Vitamin C, carnitines, co-enzyme Q10, N-acetyl cysteine, zinc, selenium, folic acid, and lycopene. CONCLUSIONS: Overall, antioxidants generally demonstrate a favorable effect on semen parameters of infertile men. However, further research is necessary to pinpoint the optimal antioxidant regimen that can be applied safely and effectively in clinical practice.

Saudi expert consensus on acquired hemophilia A diagnosis and management.

Objectives: Acquired hemophilia affects approximately one in 1 million people. Timely diagnosis is key to appropriate disease management and the prevention of life-threatening complications. Patients with this condition may initially be seen by inexperienced physicians and remain underdiagnosed for several years. This consensus statement is aimed at providing guidelines for all practitioners in the Kingdom of Saudi Arabia (KSA) to diagnose and manage acquired hemophilia A. Methods: This consensus statement reflects the opinions drafted by a group of hematology specialists, who used an explicit systematic process to identify areas of agreement and disagreement. Results: This consensus statement provides a guide for all practitioners in the KSA regarding the diagnosis of clinical presentation, relevance, characteristics of bleeding symptoms, and case management; it additionally provides guidance for non-specialists. All management aspects, including diagnosis and treatment modalities, are discussed. Conclusions: Patients with acquired hemophilia may initially be seen by physicians who lack appropriate expertise in diagnosing and managing this condition. This consensus statement from the premier experts on the disease in the KSA provides details for diagnosing and managing acquired hemophilia.

Hippocampus, amygdala, and insula activation in response to romantic relationship dissolution stimuli: A case-case-control fMRI study on emerging adult students.

BACKGROUND: Romantic relationship dissolutions (RRDs) are associated with posttraumatic stress symptoms (PTSS). Functional magnetic resonance imaging in RRD studies indicate overlapping neural activation similar to posttraumatic stress disorder. These studies combine real and hypothetical rejection, and lack contextual information and control and/or comparison groups exposed to non-RRD or DSM-5 defined traumatic events. AIM: We investigated blood oxygen level dependent (BOLD) activation in the hippocampus, amygdala, and insula of participants with RRDs compared with other traumatic or non-trauma stressors. METHODS: Emerging adults (mean age = 21.54 years; female = 74.7 %) who experienced an RRD (n = 36), DSM-5 defined trauma (physical and/or sexual assault: n = 15), or a non-RRD or DSM-5 stressor (n = 28) completed PTSS, depression, childhood trauma, lifetime trauma exposure, and attachment measures. We used a general and customised version of the International Affective Picture System to investigate responses to index-trauma-related stimuli. We used mixed linear models to assess between-group differences, and ANOVAs and Spearman's correlations to analyse factors associated with BOLD activation. RESULTS: BOLD activity increased between index-trauma stimuli as compared to neutral stimuli in the hippocampus and amygdala, with no significant difference between the DSM-5 Trauma and RRD groups. Childhood adversity, sexual orientation, and attachment style were associated with BOLD activation changes. Breakup characteristics (e.g., initiator status) were associated with increased BOLD activation in the hippocampus and amygdala, in the RRD group. CONCLUSION: RRDs should be considered as potentially traumatic events. Breakup characteristics are risk factors for experiencing RRDs as traumatic. LIMITATION: Future studies should consider more diverse representation across sex, ethnicity, and sexual orientation.

Synthesis, structural, molecular docking, and in vitro biological activities of Cu-doped ZnO nanomaterials.

Copper-doped ZnO nanoparticles with the formula Zn1-x(Cu)O, where x = 0.0, 0.03, 0.05, and 0.07 were produced using the co-precipitation process. Physical, chemical, and structural properties were properly examined. Powdered X-ray diffraction (P-XRD) patterns revealed the formation of hexagonal wurtzite crystal structure in all samples, through atomic substitutional incorporation in the Cu-doped ZnO lattice. The presence of Cu ions and their dissolution in the host ZnO crystal structure was supported by FT-IR spectra. HR-TEM images were used to assess the average size, morphology, and shape regularity of the synthesized samples. The form and homogeneity of the ZnO changed when Cu ions were substituted, as evidenced by FE-SEM/EDX analysis. The presence of copper signals in the Cu-doped samples indicates that the doping was successful. The decrease in zeta potential with an increased copper doping percentage designates that the nanoparticles (NPs) are more stable, which could be attributed to an increase in the ionic strength of the aqueous solution. The synthesized NPs were evaluated for their substantial in vitro antioxidant properties. In addition, the antimicrobial efficacy of the materials was tested against pathogenic microorganisms. Regarding the anti-diabetic activity, the 7Cu ZnO sample showed the highest inhibitory effect on the α-amylase enzyme. No variations were observed in the activities of the acetylcholinesterase enzyme (AChE) and proteinase enzymes with ZnO and samples doped with different concentrations of Cu. Therefore, further studies are recommended to reveal the in-vitro anti-diabetic activity of the studied doped samples. Finally, molecular docking provided valuable insights into the potential binding interactions of Cu-doped ZnO with α-amylase, FabH of E. coli, and Penicillin-binding proteins of S. aureus. These outcomes suggest that the prepared materials may have an inhibitory effect on enzymes and hold promise in the battle against microbial infections and diabetes.

Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidation.

4-Acetylpyridine 1 and malononitrile 2 were allowed to react in a 3MCRs with dimedone 3a or cyclohexa-1,3-dione 3b under reflux to afford 4-methyl-4-(pyridin-4-yl)-5,6,7,8-tetrahydro-4H-chromene derivatives 4a,b respectively. The mechanism of the reaction has been studied and the structures elucidated by analytical, spectral as well as X-ray crystallographic data. Heterocyclic compounds find widespread application in pharmaceutical and agrochemical products. Docking analyses were performed on the synthesized compounds to assess their binding modes with various amino acids of the target protein tubulin (PDB Code - 1SA0). The results indicated promising binding scores for compounds 4a and 4b, suggesting a strong affinity for the tubulin binding site. Finally, ADMET for the synthesized compounds 4a, 4b, 5, 8a and 8b were carried out. The drug likeness and pharmacokinetic properties of the prepared compounds were also evaluated. Notably, all of the novel compounds adhered to Lipinski's rule (Ro5) without any violations.

Exploring the Enigmatic Link: Unraveling the Relationship Between Obesity and Cigarette Smoking Among Diverse College Students at Imam Mohammed Ibn Saud Islamic University in Riyadh, Saudi Arabia.

BACKGROUND: Obesity is defined as an excess of body fat. This medical condition frequently results in a high BMI and an increased risk of a variety of health problems, including diabetes, cardiovascular disease, and certain types of cancer. Cigarette smoking includes inhaling smoke created by the combustion of tobacco. It is linked to a variety of health issues, including lung cancer, heart disease, and respiratory ailments, and is a primary cause of preventable disease and premature death worldwide. The association between obesity and cigarette smoking is complex and incompletely understood. This study aims to investigate the intriguing association between obesity and cigarette smoking among diverse college students at Imam Mohammed Ibn Saud Islamic University in Riyadh, Saudi Arabia. METHODOLOGY: The study was conducted as an observational study, specifically an analytical cross-sectional study, to measure the prevalence of cigarette smoking and obesity and their association. This type of study is chosen because of its advantages including targeting a large sample in a short time and inexpensive way, with no loss to follow-up, unlike some other study designs. RESULTS: In this study, we were able to collect data from 603 participants, of which 57.4% were male and 67.8% of them aged between 20 and 24 years old. Moreover, we found that 39.6% had normal weight; however, the prevalence of obesity, overweight, and underweight were 24%, 28.1%, and 8.3%, respectively. Considering the prevalence of smoking, we found that 22.6% of the participants reported being current smokers, while 5.3% were former smokers. There is a significant difference between participants with different BMIs (P=0.001). The prevalence of smoking was significantly higher in obese and overweighted participants (35.1% and 31.3%, respectively) compared with 28.4% in normal-weighted participants. CONCLUSION: The prevalence of smoking and obesity in this study was significantly higher than reported in different studies. Moreover, we found a significant relationship between smoking and obesity; however, further investigation should be conducted to determine the cause of this relationship.

Room-Temperature Synthesis of Covalent Organic Frameworks using Gamma-Irradiation in Open-Air Conditions.

Covalent organic frameworks (COFs), which have layered stacking structures, extended π-conjugation, and periodic frameworks have become a promising class of materials for a wide range of applications. However, their synthetic pathways frequently need high temperatures, enclosed systems under high pressures, an inert atmosphere, and extended reaction time, which restrict their practicality in real-world applications. Herein, the use of gamma irradiation is presented to synthesize highly crystalline COFs at room temperature under an open-air condition within a short time. This is demonstrated that there is no significant difference in crystallinity of COFs by gamma irradiation under air, N2 or Ar atmosphere conditions. Moreover, this approach can successfully fabricate COFs in the vessel with different degrees of transparency or even in a plastic container. Importantly, this strategy is applicable not only to imine linkage of COFs but also effective to the imide linkages of COFs. Most importantly, these COFs demonstrate improved crystallinity, surface area, and thermal stability in comparison to the corresponding materials synthesized via the solvothermal method. Finally, a COF synthesized through gamma irradiation exhibits remarkable photocatalytic activity in promoting the sacrificial hydrogen evolution from water, displaying a more catalytic efficiency compared with that of its solvothermal analogue.

Diagnostic accuracy of ePOS score in predicting DNR labeling after ICU admission: A prospective observational study (ePOS-DNR).

Background: Resuscitation can sometimes be futile and making a do-not-resuscitate (DNR) decision is in the best interest of the patient. The electronic poor outcome screening (ePOS) score was developed to predict 6-month poor outcomes of critically ill patients. We explored the diagnostic accuracy of the ePOS score in predicting DNR decisions in the intensive care unit (ICU). Methods: This study was conducted at the ICU of a tertiary referral hospital in Saudi Arabia between March and May 2023. Prospectively, we calculated ePOS scores for all eligible consecutive admissions after 48 h in the ICU and recorded the DNR orders. The ability of the score to predict DNR was explored using logistic regression. Youden's ideal cut-off value was calculated using the DeLong method, and different diagnostic accuracy measures were generated with corresponding 95 % confidence intervals (CIs). Results: We enrolled 857 patients, 125 received a DNR order and 732 did not. The average ePOS score of DNR and non-DNR patients was 28.2±10.7 and 15.2±9.7, respectively. ePOS score, as a predictor of DNR order, had an area under receiver operator characteristic (AUROC) curve of 81.8 % (95% CI: 79.0 to 84.3, P <0.001). Youden's ideal cut-off value >17 was associated with a sensitivity of 87.2 (95% CI: 80.0 to 92.5, P <0.001), specificity of 63.9 (95% CI: 60.3 to 67.4, P <0.001), positive predictive value of 29.2 (95% CI: 24.6 to 33.8, P <0.001), negative predictive value of 96.7 (95% CI: 95.1 to 98.3, P <0.001), and diagnostic odds ratio 12.1 (95% CI: 7.0 to 20.8, P <0.001). Conclusions: In this study, the ePOS score performed well as a diagnostic test for patients who will be labeled as DNR during their ICU stay. A cut-off score >17 may help guide clinical decisions to withhold or commence resuscitative measures.

Comparison of qPCR and metagenomic sequencing methods for quantifying antibiotic resistance genes in wastewater.

Surveillance methods of circulating antibiotic resistance genes (ARGs) are of utmost importance in order to tackle what has been described as one of the greatest threats to humanity in the 21st century. In order to be effective, these methods have to be accurate, quickly deployable, and scalable. In this study, we compare metagenomic shotgun sequencing (TruSeq DNA sequencing) of wastewater samples with a state-of-the-art PCR-based method (Resistomap HT-qPCR) on four wastewater samples that were taken from hospital, industrial, urban and rural areas. ARGs that confer resistance to 11 antibiotic classes have been identified in these wastewater samples using both methods, with the most abundant observed classes of ARGs conferring resistance to aminoglycoside, multidrug-resistance (MDR), macrolide-lincosamide-streptogramin B (MLSB), tetracycline and beta-lactams. In comparing the methods, we observed a strong correlation of relative abundance of ARGs obtained by the two tested methods for the majority of antibiotic classes. Finally, we investigated the source of discrepancies in the results obtained by the two methods. This analysis revealed that false negatives were more likely to occur in qPCR due to mutated primer target sites, whereas ARGs with incomplete or low coverage were not detected by the sequencing method due to the parameters set in the bioinformatics pipeline. Indeed, despite the good correlation between the methods, each has its advantages and disadvantages which are also discussed here. By using both methods together, a more robust ARG surveillance program can be established. Overall, the work described here can aid wastewater treatment plants that plan on implementing an ARG surveillance program.

Infection Prevention and Control: Baseline Knowledge and Practices of TBAs in Rural Kano, Northwestern Nigeria.

BACKGROUND: Maternal infections remain a significant contributor to maternal mortality worldwide. Majority of births in northern Nigeria occur at home and are attended by Traditional Birth Attendants (TBAs). Little has been documented about their knowledge and practice on infection prevention and control practices in Kano, northern Nigeria. OBJECTIVES: This study evaluated the level as well as factors associated with TBAs' infection prevention and control knowledge and practices. METHODS: The study is the baseline phase of a quasi-experimental study, conducted in a rural LGA in Kano State, Nigeria. Using an adapted tool, 163 eligible TBAs were surveyed. Knowledge and practice of IPC were scored, aggregated, and dichotomized into good or poor. Binary logistic regression analysis was used to predict knowledge and practice of IPC. RESULTS: Majority (79.1%) of the TBAs exhibited poor IPC knowledge but many (78.5%) reported good practice. Good knowledge of IPC was predicted by the TBAs' age: a six-fold increased likelihood (AOR=6.25, 95% CI: 1.02- 38.53) and almost five-fold increased likelihood (AOR=4.75, 95% CI: 1.39- 16.24) for those in their second and fourth decades of life. TBAs who reported poor practice of IPC were 83% less likely (AOR=0.17, 95% CI: 0.03- 0.92) to have good knowledge of IPC. TBAs' practice was only linked to previous training (AOR=0.17, 95% CI: 0.04- 0.76). CONCLUSION: TBAs knowledge of IPC was low although reported practice was good. The need for tailored training interventions to enhance knowledge and skills for safe delivery care is paramount to improve maternal and neonatal outcomes.

CONTEXTE: Les infections maternelles restent une contribution significative à la mortalité maternelle dans le monde. La majorité des accouchements dans le nord du Nigeria ont lieu à domicile et sont assistés par des TBA. Peu de choses ont été documentées sur leurs connaissances et leurs pratiques en matière de prévention et de contrôle des infections à Kano, dans le nord du Nigeria. OBJECTIFS: Cette étude a évalué le niveau de connaissances et de pratiques des TBA en matière de prévention et de contrôle des infections, ainsi que les facteurs associés. MÉTHODES: L'étude est la phase de base d'une étude quasiexpérimentale, menée dans une LGA rurale de l'État de Kano, au Nigeria. En utilisant un outil adapté, 163 TBA éligibles ont été interrogés. Les connaissances et les pratiques en matière de PCI ont été évaluées, agrégées et dichotomisées en bonnes ou mauvaises. Une analyse de régression logistique binaire a été utilisée pour prédire les connaissances et les pratiques en matière de PCI. RÉSULTATS: La majorité (79,1 %) des TBA présentaient des connaissances médiocres en PCI, mais beaucoup (78,5 %) ont déclaré avoir de bonnes pratiques. De bonnes connaissances en PCI étaient prédites par l'âge des TBA : une probabilité multipliée par six (AOR=6,25, IC à 95 % : 1,02-38,53) et presque multipliée par cinq (AOR=4,75, IC à 95 % : 1,39-16,24) pour ceux dans leur deuxième et quatrième décennies de vie. Les TBA qui ont déclaré une mauvaise pratique de la PCI étaient 83 % moins susceptibles (AOR=0,17, IC à 95 % : 0,03-0,92) d'avoir de bonnes connaissances en PCI. La pratique des TBA était uniquement liée à une formation antérieure (AOR=0,17, IC à 95 % : 0,04­0,76). CONCLUSION: Les connaissances des TBA en matière de PCI étaient faibles bien que les pratiques déclarées étaient bonnes. La nécessité d'interventions de formation sur mesure pour améliorer les connaissances et les compétences en matière de soins de l'accouchement sécurisés est primordiale pour améliorer les résultats maternels et néonatals. MOTS-CLÉS: Accoucheuses Traditionnelles, Mortalité Maternelle, Infection Maternelle, Nigeria.

Profiling Key Aroma Compounds of Senecio glaucus L. and their Antimicrobial and Antioxidant Activities: Multiplex of GC-MS, NMR and In Silico Studies.

The essential oils of Senecio plants have been used to treat a wide range of ailments. The current study aimed to extract the essential oil of Senecio glaucus obtained from Egypt's Nile delta and determine its chemical profile using GC-MS and NMR analysis. Then, the antimicrobial activity of the oil has been investigated against different fungal and bacterial strains. In addition, its activity as radical scavenger has been evaluated using DPPH, ABTS, and metal chelating techniques. The results revealed the identification of 50 compounds representing 98.80 % of the oil total mass. Sesquiterpenes, including dehydrofukinone (27.15 %) and 4,5-di-epi-aristolochene (10.27 %), as well as monoterpenes, including p-cymene (4.77 %), represented the most predominant constituents. The dehydrofukinone has been isolated and structurally confirmed using 1D and 2D NMR techniques. The oil has showed remarkable antifungal activity against Candida glabrata and C. albicans where the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values were 3.13 µg/mL and 1.50 µg/mL and 12.50 µg/mL and 6.30 µg/mL, respectively that could be attributed to the sesquiterpene ketones present in the aerial tissues of the plant. Also, this oil inhibited the growth of the tested bacteria with MIC ranging from 12.50-100.00 µg/mL. In comparison to ascorbic acid and Trolox, the EO had remarkable scavenging activity of DPPH, ABTS and metal chelating with IC50 values of 313.17±13.4, 493.83±20.1, and 409.13±16.7 µg/mL. The docking studies of the identified compounds of the oil to different microbial targets, including Gyrase B and α-sterol demethylase, showed that the phytol possessed the best binding affinities toward the active sites of both enzymes with ΔG=-7.42 and -7.78 kcal/mol, respectively. In addition, the phytol revealed the highest binding affinity to tyrosine kinase Hck with ΔG=-7.44 kcal/mol.

Fully Characterized Effective Bacteriophages Specific against Antibiotic-Resistant Enterococcus faecalis, the Causative Agent of Dental Abscess.

Background and Objectives: Enterococcus faecalis (E. faecalis) is a primary pathogen responsible for dental abscesses, which cause inflammation and pain when trapped between the crown and soft tissues of an erupted tooth. Therefore, this study aims to use specific phages as an alternative method instead of classical treatments based on antibiotics to destroy multidrug-resistant E. faecalis bacteria for treating dental issues. Materials and Methods: In the current study, twenty-five bacterial isolates were obtained from infected dental specimens; only five had the ability to grow on bile esculin agar, and among these five, only two were described to be extensive multidrug-resistant isolates. Results: Two bacterial isolates, Enterococcus faecalis A.R.A.01 [ON797462.1] and Enterococcus faecalis A.R.A.02, were identified biochemically and through 16S rDNA, which were used as hosts for isolating specific phages. Two isolated phages were characterized through TEM imaging, which indicated that E. faecalis_phage-01 had a long and flexible tail, belonging to the family Siphoviridae, while E. faecalis_phage-02 had a contractile tail, belonging to the family Myoviridae. Genetically, two phages were identified through the PCR amplification and sequencing of the RNA ligase of Enterococcus phage vB_EfaS_HEf13, through which our phages shared 97.2% similarity with Enterococcus phage vB-EfaS-HEf13 based on BLAST analysis. Furthermore, through in silico analysis and annotations of the two phages' genomes, it was determined that a total of 69 open reading frames (ORFs) were found to be involved in various functions related to integration excision, replication recombination, repair, stability, and defense. In phage optimization, the two isolated phages exhibited a high specific host range with Enterococcus faecalis among six different bacterial hosts, where E. faecalis_phage-01 had a latent period of 30 min with 115.76 PFU/mL, while E. faecalis_phage-02 had a latent period of 25 min with 80.6 PFU/mL. They were also characterized with stability at wide ranges of pH (4-11) and temperature (10-60 °C), with a low cytotoxic effect on the oral epithelial cell line at different concentrations (1000-31.25 PFU/mL). Conclusions: The findings highlight the promise of phage therapy in dental medicine, offering a novel approach to combating antibiotic resistance and enhancing patient outcomes. Further research and clinical trials will be essential to fully understand the therapeutic potential and safety profile of these bacteriophages in human populations.

Characterizing the impact of thermoregulation in patients after cardiac arrest: a retrospective cohort study.

PURPOSE: Core body temperature has been extensively investigated as a thereuptic target in care after cardiac arrest. Nevertheless, the integrity of thermoregulation in patients after cardiac arrest has not been well studied. We sought to evaluate whether low spontaneous body temperature after cardiac arrest is associated with increased death and a worse neurologic outcome, and whether patients with low spontaneous body temperature exhibit features suggestive of impaired thermoregulation. METHODS: We conducted a single-centre retrospective cohort study. We included all adult patients who underwent temperature control with hypothermia after cardiac arrest between 1 January 2014 and 30 June 2020. The primary exposure was low spontaneous core body temperature (< 35 °C) at initiation of hypothermia therapy. The primary outcome was in-hospital death and the secondary outcome was poor neurologic outcomes at discharge. RESULTS: Five hundred and ninety-seven adult patients, comprising both in- and out-of-hospital cardiac arrests, were included. Patients with low spontaneous body temperature also had slightly lower average temperature, and more frequent transient but controlled breakthrough fever episodes in the first 24 hr. In the multivariable logistic regression analysis, low spontaneous body temperature was associated with higher odds of in-hospital death (odds ratio, 2.9; 95% confidence interval, 1.9 to 4.2; P < 0.001). CONCLUSION: In this single-centre retrospective cohort study, low spontaneous core body temperature was associated with poor outcomes in patients after cardiac arrest. Patients with low spontaneous body temperature also exhibited features suggestive of impaired thermoregulation. Further research is needed to determine whether body temperature upon presentation reflects the robustness of the patient's underlying physiology and severity of brain insult after a cardiac arrest.

RéSUMé: OBJECTIF: La température corporelle centrale a fait l'objet d'études approfondies en tant que cible thérapeutique dans les soins après un arrêt cardiaque. Néanmoins, l'intégrité de la thermorégulation après un arrêt cardiaque n'a pas été bien étudiée. Nous avons cherché à évaluer si une température corporelle spontanément basse après un arrêt cardiaque était associée à une augmentation de la mortalité et à une issue neurologique plus grave, et si les individus ayant une température corporelle spontanément basse présentaient des caractéristiques suggérant une altération de la thermorégulation. MéTHODE: Nous avons mené une étude de cohorte rétrospective monocentrique. Nous avons inclus tou·tes les patient·es adultes ayant bénéficié d'un contrôle de température lors d'une hypothermie après un arrêt cardiaque entre le 1er janvier 2014 et le 30 juin 2020. L'exposition principale était une température corporelle centrale spontanément basse (< 35 °C) au début du traitement de l'hypothermie. Le critère d'évaluation principal était le décès à l'hôpital, et le critère d'évaluation secondaire était de mauvaises issues neurologiques à la sortie de l'hôpital. RéSULTATS: Cinq cent quatre-vingt-dix-sept patient·es adultes, ayant subi des arrêts cardiaques à l'hôpital ou hors de l'hôpital, ont été inclus·es. Les patient·es ayant une température corporelle spontanément basse avaient également une température moyenne légèrement plus basse et des épisodes de fièvre paroxystique transitoires mais contrôlés plus fréquents au cours des premières 24 heures. Dans l'analyse de régression logistique multivariée, une température corporelle spontanément basse était associée à une probabilité plus élevée de décès à l'hôpital (rapport de cotes, 2,9; intervalle de confiance à 95 %, 1,9 à 4,2; P < 0,001). CONCLUSION: Dans cette étude de cohorte rétrospective monocentrique, une température corporelle centrale spontanément basse a été associée à de mauvais devenirs après un arrêt cardiaque. Les patient·es présentant une température corporelle spontanément basse présentaient également des caractéristiques suggérant une altération de la thermorégulation. D'autres recherches sont nécessaires pour déterminer si la température corporelle lors de la présentation reflète la robustesse de la physiologie sous-jacente des patient·es et la gravité de la lésion cérébrale après un arrêt cardiaque.

Single-nucleus RNA velocity reveals critical synaptic and cell-cycle dysregulations in neuropathologically confirmed Alzheimer's disease.

Typical differential single-nucleus gene expression (snRNA-seq) analyses in Alzheimer's disease (AD) provide fixed snapshots of cellular alterations, making the accurate detection of temporal cell changes challenging. To characterize the dynamic cellular and transcriptomic differences in AD neuropathology, we apply the novel concept of RNA velocity to the study of single-nucleus RNA from the cortex of 60 subjects with varied levels of AD pathology. RNA velocity captures the rate of change of gene expression by comparing intronic and exonic sequence counts. We performed differential analyses to find the significant genes driving both cell type-specific RNA velocity and expression differences in AD, extensively compared these two transcriptomic metrics, and clarified their associations with multiple neuropathologic traits. The results were cross-validated in an independent dataset. Comparison of AD pathology-associated RNA velocity with parallel gene expression differences reveals sets of genes and molecular pathways that underlie the dynamic and static regimes of cell type-specific dysregulations underlying the disease. Differential RNA velocity and its linked progressive neuropathology point to significant dysregulations in synaptic organization and cell development across cell types. Notably, most of the genes underlying this synaptic dysregulation showed increased RNA velocity in AD subjects compared to controls. Accelerated cell changes were also observed in the AD subjects, suggesting that the precocious depletion of precursor cell pools might be associated with neurodegeneration. Overall, this study uncovers active molecular drivers of the spatiotemporal alterations in AD and offers novel insights towards gene- and cell-centric therapeutic strategies accounting for dynamic cell perturbations and synaptic disruptions.

Induction of breast cancer cell apoptosis by novel thiouracil-fused heterocyclic compounds through boosting of Bax/Bcl-2 ratio and DFT study.

Breast cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel pyrido[2,3-d]pyrimidine derivatives 3,4,(6a-c),(8a,b),9-20 were synthesized and characterized using a variety of spectrum analyses. The geometric and thermal parameters of the novel thiouracil derivatives 3,4,6a,(8a,b),11,12,17,18, 19 were measured using density functional theory (DFT) via DFT/B3LYP/6-31 + G(d,p) basis set. All synthesized compounds were evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) method using MCF-7 and MDA-MB-231 breast cancerous cells, compound 17 had the maximum anticancer activity against both breast cancerous cells, recording the lowest half-maximal inhibitory concentration (IC50) values (56.712 µg/mL for MCF-7 cells and 48.743 µg/mL for MDA-MB-231 cells). The results were confirmed in terms of the intrinsic mechanism of apoptosis, where compound 17 had the highest percentage in the case of both cancer cells and recorded Bax (Bcl-2 associated X)/Bcl-2 (B-cell lymphoma 2) ratio 17.5 and 96.667 for MCF-7 and MDA-MB-231 cells, while compound 19 came after 17 in the ability for induction of apoptosis, where the Bax/Bcl-2 ratio was 15.789 and 44.273 for both cancerous cells, respectively. Also, compound 11 recorded a high Bax/Bcl-2 ratio for both cells. The safety of the synthesized compounds was applied on normal WI-38 cells, showing minimum cytotoxic effect with undetectable IC50. Compounds 17, 11, and 19 recorded a significant increase of p53 upregulated modulator of apoptosis (PUMA) expression levels in the cancerous cells. The DFT method was also used to establish a connection between the experimentally determined values of the present investigated compounds and their predicted quantum chemical parameters. It was concluded that Compounds 17, 11, and 19 had anti-breast cancer potential through the induction of apoptotic Bax/Bcl-2 and PUMA expression levels.

Stabilization of the cubic, fast-ion conducting phase of Li7La3Sn2O12 garnet by gallium doping.

All-solid-state batteries present promising high-energy-density alternatives to conventional Li-ion chemistries, and Li-stuffed garnets based on Li7La3Zr2O12 (LLZO) remain a forerunner for candidate solid-electrolytes. One route to access fast-ion conduction in LLZO phases is to stabilize the cubic LLZO phase by doping on the Li sites with aliovalent ions such as Al3+ or Ga3+. Despite prior attempts, the stabilization of the cubic phase of isostructural Li7La3Sn2O12 (LLSO) by doping on the Li sites has up to now not been realised. Here, we report a novel cubic fast-ion conducting Li7La3Sn2O12-type phase stabilized by doping Ga3+ in place of Li. 0.3 mole of gallium per formula unit of LLSO were needed to fully stabilize the cubic garnet, allowing structural and electrochemical characterizations of the new material. A modified sol-gel synthesis approach is introduced in this study to realise Ga-doping in LLSO, which offers a viable route to preparing new Sn-based candidate solid-electrolytes for all-solid-state battery applications.