Trans-Chalcone (1-3-diphenyl-2-propen-1-one) as a Therapeutic Candidate in Joint Inflammation via Reduction of TNF-α, IL-1ß, IL-6, and IL-17 in Rodents: An In Vivo Study by RT-PCR and ELISA analysis.

Autoimmune disorders include vast and distinct illnesses and are characterized by an immune system-mediated attack on the body's own tissues. Because of their ability to impact any portion of the body, their clinical symptoms are incredibly varied. The variations in symptoms are normally linked with the release and activation of vasoactive, chemotactic substances and cytokines. Cytokines perform a multitude of vital biological tasks, such as immune response control, inflammation, proliferation, and tissue repair. The reversal of inflammatory cytokines and leukocyte infiltration into the inflamed tissue by natural compounds provides an effective remedy for autoimmune diseases. Here, the oral administration of trans-chalcone (TC) for 28 days was tested with gradually increasing doses (30, 60, and 120 mg/kg) in complete Freund's adjuvant (CFA)-provoked joint tissue stiffness in rats. Paw edema, arthritic index, joint stiffness, thermal and flexion pain, C-reactive protein, and rheumatoid factor (RF) levels were determined to check the tested drug effectiveness in a chronic inflammatory model. Molecular docking studies revealed strong binding affinity with inflammatory cytokines and mediators such as TNF-α, IL-17, COX-2, and iNOS; further, they were quantified at the mRNA level by RT-PCR and ELISA analysis. Oral administration of TC significantly ameliorated paw edema, thymus and spleen indices, joint stiffness, thermal and flexion pain, C-reactive protein, RF, mobility, and stance of the treated animals. This therapeutic effectiveness was linked with a reduction in the mRNA expression of proinflammatory cytokines such as IL-1ß, IL-6, and IL-17. The findings of the reported research confirmed the effectiveness of TC in ameliorating joint stiffness and flexion pain by prominently lowering the inflammatory cytokines.

Effect of cevimeline and different concentration of gum arabic on parotid salivary gland function in methotrexate-induced xerostomia: a comparative study.

OBJECTIVE: This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate. METHODS: One hundred twenty-five rats were divided into five equal groups of twenty-five each. The rats in Group I received basic diets, while those in Groups II, III, IV, and V received 20 mg/kg MTX as a single intraperitoneal dose on day one. Group III received 10 mg/kg CVM dissolved in saline orally and daily, and the other two groups received a 10% W/V aqueous suspension of GA. Therefore, Group IV received 2 ml/kg suspension orally and daily, while Group V received 3 ml/kg suspension orally and daily. After 9 days, the parotid glands were dissected carefully and prepared for hematoxylin and eosin (H&E) staining as a routine histological stain and caspase-3 and Ki67 immunohistochemical staining. Quantitative data from α-Caspase-3 staining and Ki67 staining were statistically analysed using one-way ANOVA followed by Tukey's multiple comparisons post hoc test. RESULTS: Regarding caspase-3 and Ki67 immunohistochemical staining, one-way ANOVA revealed a significant difference among the five groups. For Caspase-3, the highest mean value was for group II (54.21 ± 6.90), and the lowest mean value was for group I (15.75 ± 3.67). The other three groups had mean values of 31.09 ± 5.90, 30.76 ± 5.82, and 20.65 ± 3.47 for groups III, IV, and V, respectively. For Ki67, the highest mean value was for group I (61.70 ± 6.58), and the lowest value was for group II (18.14a ± 5.16). The other three groups had mean values of 34.4 ± 9.27, 48.03 ± 8.40, and 50.63 ± 8.27 for groups III, IV, and V, respectively. CONCLUSION: GA, rather than the normally used drug CVM, had a desirable effect on the salivary glands of patients with xerostomia.

From NAFLD to NASH: Understanding the spectrum of non-alcoholic liver diseases and their consequences.

Non-alcoholic fatty liver disease (NAFLD) has become one of the most frequent chronic liver diseases worldwide in recent decades. Metabolic diseases like excessive blood glucose, central obesity, dyslipidemia, hypertension, and liver function abnormalities cause NAFLD. NAFLD significantly increases the likelihood of liver cancer, heart disease, and mortality, making it a leading cause of liver transplants. Non-alcoholic steatohepatitis (NASH) is a more advanced form of the disease that causes scarring and inflammation of the liver over time and can ultimately result in cirrhosis and hepatocellular carcinoma. In this review, we briefly discuss NAFLD's pathogenic mechanisms, their progression into NASH and afterward to NASH-related cirrhosis. It also covers disease epidemiology, metabolic mechanisms, glucose and lipid metabolism in the liver, macrophage dysfunction, bile acid toxicity, and liver stellate cell stimulation. Additionally, we consider the contribution of intestinal microbiota, genetics, epigenetics, and ecological factors to fibrosis progression and hepatocellular carcinoma risk in NAFLD and NASH patients.

GOAT rs10096097 and CREB1 rs6740584 single nucleotide polymorphisms are associated with type 2 diabetes mellitus in Egyptians.

Diabetes mellitus (DM) is a chronic disorder that affects nearly half a billion people around the world and causes millions of deaths annually. Treatment of diabetes or related complications represents an economic burden not only for developing countries but also for the developed ones. Hence, new efficient therapeutic and preventive strategies and screening tools are necessary. The current work aimed to assess the potential association of single nucleotide polymorphisms (SNPs) in ghrelin O-acyltransferase (GOAT) rs10096097, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) rs6740584, and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) rs62521874 genes with type 2 DM susceptibility in Egyptians. A total of 96 patients with type 2 DM along with 72 healthy individuals participated in this study. Genotyping was executed via real-time polymerase chain reaction (PCR), and the serum protein levels of GOAT, CREB, and MafA were measured by enzyme-linked immunosorbent assay (ELISA). Genotyping revealed a significant association of GOAT rs10096097 and CREB1 rs6740584 SNPs with type 2 diabetes risk, with significantly higher GOAT rs10096097 G allele and CREB1 rs6740584 T allele frequencies in diabetic patients than in controls. However, insignificant association was identified between the MafA rs62521874 SNP and diabetes in the examined sample of the Egyptian residents. Serum GOAT, CREB1, and MafA protein levels did not vary significantly between diabetic and control individuals. Yet, significant variation in serum GOAT and CREB1 levels was detected between CREB1 rs6740584 genotypes within the diabetic group, with CT and TT genotype carriers showing higher levels than AA genotype patients. GOAT rs10096097 and CREB1 rs6740584, but not MafA rs62521874, SNPs are associated with type 2 diabetes risk in the studied Egyptians.

Dietary chamomile flowers extract improved performance and mitigated aflatoxin B1 toxicity in rabbits.

Aflatoxin B1 (AFB1) is among the poisonous mycotoxins that contaminate food and feed. Limited studies are available on the efficacy of chamomile (Cha) against oxidative stress, liver damage and pro-inflammatory response induced by AFB1. The present study aims to evaluate the effects of Cha on the performance and protective effects against AFB1 in growing rabbits. The experimental rabbits were divided into four different groups, including Cha (70 mg kg day-1), AFB1 (AF; 30 µg kg day-1), AFB1+Cha (AFLCha) and control (CON). The results indicated that the AFB1 treatment had lower values of performance, and carcass parameters compared to the Cha and AFLCha treatments. Furthermore, the Cha and AFLCha groups had lower values of liver and kidney function activities compared to the AFB1 treatment. The higher values of antioxidant enzymes were observed in Cha and AFLCha treatments than in the AFB1 treatment. AFB1 treatments had higher levels of malondialdehyde and liver functions with lower levels of antioxidant enzymes (glutathione and superoxide dismutase) compared to Cha and CON groups. In conclusion, dietary Cha could mitigate the oxidative stress of AFB1-induced liver deterioration.

Ultrasound-Facilitated, Catheter-Directed Thrombolysis for Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (APE) poses a significant risk to patient health, with treatment options varying in efficacy and safety. Ultrasound-facilitated catheter-directed thrombolysis (USCDT) has emerged as a potential alternative to conventional catheter-directed thrombolysis (CDT) for patients with intermediate to high-risk APE. This study aimed to compare the efficacy and safety of USCDT versus conventional CDT in patients with intermediate to high-risk APE. METHODS: This observational retrospective study was conducted at the Armed Forces Hospital, Al-Hada, Taif, the Kingdom of Saudi Arabia (KSA), on 135 patients diagnosed with APE and treated with either USCDT or CDT (58 underwent CDT, while 77 underwent USCDT). The primary efficacy outcome was the change in the right ventricle to the left ventricle (RV/LV) diameter ratio. Secondary outcomes included changes in pulmonary artery systolic pressure and the Miller angiographic obstruction index score. Safety outcomes focused on major bleeding events. RESULTS: Both USCDT and CDT significantly reduced RV/LV diameter ratio (from 1.35 ± 0.14 to 1.05 ± 0.17, P < 0.001) and systolic pulmonary artery pressure (SPAP) (from 55 ± 7 mmHg to 38 ± 7 mmHg, P < 0.001) at 48- and 12-hours post-procedure, respectively, with no significant differences between treatments. However, USCDT was associated with a significantly lower rate of major bleeding events compared to CDT (0% vs. 3.4%, P = 0.008). Multivariate logistic regression analysis revealed that USCDT was associated with a 71.9% risk reduction of bleeding (OR = 0.281, 95% CI = 0.126 - 0.627, P = 0.002). CONCLUSIONS: USCDT is a safe and effective alternative to CDT for the treatment of intermediate to high-risk APE, as it significantly reduces the risk of major bleeding.

Gamma Irradiated Pasteurella multocida Vaccine induces strong humoral immunity and protects rabbits from disease.

Pasteurella multocida is affecting a multitude of animals and severely affects livestock production. Existing vaccines are mostly chemically inactivated and do not lead to wide protection. Irradiated vaccines are enjoying a renaissance and the concept of "replication defficient but metabolically active" vaccines was recently evaluated in several vaccine trials. P. multocida was isolated from the nasal swab, blood, and lung swab samples from infected rabbits. Gamma irradiation of P. multocida for inhibition of replication was evaluated at an optimized irradiation dose of 10 Kgy established. Four groups of rabbits were (mock) vaccinated with a commercial P. multocida vaccine and three irradiated formulations as liquid, lyophilized formulations with added Trehalose and lyophilized-Trehalose with an "activation" culturing the irradiated bacteria for 24 in broth. Evaluation of humoral immune response by ELISA showed that all three irradiated vaccines produced an effective, protective, and continued IgG serum level after vaccination and bacterial challenge. The IFN-γ expression is maintained at a normal level, within each individual group however, the lyophilized trehalose irradiated vaccine showed peak mean of IFN-γ titer at one week after booster dose (day 21) which was statistically significant. Cumulatively, the results of this study show that gamma-irradiated P. multocida vaccines are safe and protect rabbits against disease. Moreover, Rabbits' immunization with the three irradiated formulations avoided adverse side effects as compared to commercial polyvalent vaccine, the body weight gain for the irradiated vaccine groups indicates less stress compared to the commercial polyvalent vaccine.

The efficacy and safety of Zuranolone for treatment of depression: A systematic review and meta-analysis.

RATIONALE: Zuranolone, a newly FDA-approved synthetic neurosteroid, shows promise in treating depression. OBJECTIVES: Our aim is to evaluate Zuranolone's efficacy and safety in treating depression. METHODS: Five databases were searched until September 2023 for relevant randomized clinical trials evaluating the efficacy and safety of zuranolone. The potential risk of bias in the included trials was evaluated by the Cochrane Risk of Bias II guideline Data were extracted and pooled using Review Manager Software (RevMan 5.3). RESULTS: An analysis of eight studies highlights Zuranolone's efficacy in treating depression compared to placebo across most of the outcomes. Notably, the 30mg and 50mg doses demonstrated significant improvements in reducing HAM-D scores by over 50% within a 15-day follow-up (RR) of 1.46 (95% CI [1.27, 1.68], p < 0.0001) and 1.14 (95% CI [1.01, 1.3], p = 0.04). Additionally, the HAM-D ≤ 7% score analysis revealed significant enhancements with the 30mg dose over both 15-day (RR = 1.82, 95% CI [1.44, 2.31], p < 0.0001) and 45-day (RR = 1.43, 95% CI [1.16, 1.77], p = 0.0008) durations. Adverse Events Drug Discontinuation demonstrated no overall significant difference (OR = 1.33, 95% CI: [0.79, 2.23], p = 0.282). Further, specific adverse events, such as headache, showed no significant overall difference between Zuranolone and placebo (OR = 1.11, 95% CI: [0.84, 1.47], p = 0.47), with dose-dependent analysis revealing less headache in the 30 mg group. CONCLUSION: Zuranolone demonstrates favorable tolerability and safety, particularly at 30mg and 50mg doses after 15 days, suggesting its potential and effective treatment for depression.

Modulation of the rat intestinal microbiota in the course of Anisakis pegreffii infection.

Background: Anisakis are globally distributed, marine parasitic nematodes that can cause human health problems, including symptoms such as vomiting, acute diarrhea, and allergic reactions. As parasitic nematodes that primarily affect the patient's digestive tract, intestinal helminths can interact directly with the host microbiota through physical contact, chemicals, or nutrient competition. It is widely accepted that the host microbiota plays a crucial role in the regulation of immunity. Materials and methods: Nematodes collected from the abdominal cavity of marine fish were identified by molecular biology and live worms were artificially infected in rats. Infection was determined by indirect ELISA based on rat serum and worm extraction. Feces were collected for 16S rDNA-based analysis of microbiota diversity. Results: Molecular biology identification based on ITS sequences identified the collected nematodes as A. pegreffii. The success of the artificial infection was determined by indirect ELISA based on serum and worm extraction from artificially infected rats. Microbiota diversity analysis showed that a total of 773 ASVs were generated, and PCoA showed that the infected group was differentiated from the control group. The control group contained five characterized genera (Prevotellaceae NK3B31 group, Turicibacter, Clostridium sensu stricto 1, Candidatus Stoquefichus, Lachnospira) and the infected group contained nine characterized genera (Rodentibacter, Christensenella, Dubosiella, Streptococcus, Anaeroplasma, Lactococcus, Papillibacter, Desulfovibrio, Roseburia). Based on the Wilcoxon test, four processes were found to be significant: bacterial secretion system, bacterial invasion of epithelial cells, bacterial chemotaxis, and ABC transporters. Conclusion: This study is the first to analyze the diversity of the intestinal microbiota of rats infected with A. pegreffii and to determine the damage and regulation of metabolism and immunity caused by the infection in the rat gut. The findings provide a basis for further research on host-helminth-microbe correlationships.

Production of Disinfective Coating Layer to Facial Masks Supplemented with Camellia sinensis Extract.

Although usefulness of masks for protection against respiratory pathogens, accumulation of pathogens on their surface represents a source of infection spread. Here we prepared a plant extract-based disinfecting layer to be used in coating masks thus inhibiting their capacity to transmit airborne pathogens. To reach this, a polypropylene membrane base was coated with a layer of polyvinyledine difluoride polymer containing 500 µg/ml of Camellia sinensis (Black tea) methanolic extract. Direct inhibitory effects of C. sinensis were initially demonstrated against Staphylococcus aureus (respiratory bacteria), influenza A virus (enveloped virus) and adenovirus 1 (non-enveloped virus) which were directly proportional to both extract concentration and incubation time with the pathogen. This was later confirmed by the capacity of the supplemented membrane with the plant extract to block infectivity of the above mentioned pathogens, recorded % inhibition values were 61, 72 and 50 for S. aureus, influenza and adenovirus, respectively. In addition to the disinfecting capacity of the membrane its hydrophobic nature and pore size (154 nm) prevented penetration of dust particles or water droplets carrying respiratory pathogens. In summary, introducing this layer could protect users from infection and decrease infection risk upon handling contaminated masks surfaces.

Polyurethane reinforced with micro/nano waste slag as a shielding panel for photons (experimental and theoretical study).

This study not only provides an innovative technique for producing rigid polyurethane foam (RPUF) composites, but it also offers a way to reuse metallurgical solid waste. Rigid polyurethane (RPUF) composite samples have been prepared with different proportions of iron slag as additives, with a range of 0-25% mass by weight. The process of grinding iron slag microparticles into iron slag nanoparticles powder was accomplished with the use of a high-energy ball mill. The synthesized samples have been characterized using Fourier Transform Infrared Spectroscopy, and Scanning Electron Microscope. Then, their radiation shielding properties were measured by using A hyper-pure germanium detector using point sources 241Am, 133 BA, 152 EU, 137Cs, and 60Co, with an energy range of 0.059-1.408 MeV. Then using Fluka simulation code to validate the results in the energy range of photon energies of 0.0001-100 MeV. The linear attenuation coefficient, mass attenuation coefficient, mean free path, half-value layer and tenth-value layer, were calculated to determine the radiation shielding characteristics of the composite samples. The calculated values are in good agreement with the calculated values. The results of this study showed that the gamma-ray and neutron attenuation parameters of the studied polyurethane composite samples have improved. Moreover, the effect of iron slag not only increases the gamma-ray attenuation shielding properties but also enhances compressive strength and the thermal stability. Which encourages us to use polyurethane iron-slag composite foam in sandwich panel manufacturing as walls to provide protection from radiation and also heat insulation.

A retrospective study comparing the results of continuous glucose monitoring to self-blood glucose monitoring for pregnant women with type 1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is associated with adverse maternal and fetal outcomes. Continuous glucose monitoring (CGM) during pregnancy is associated with better glycemic control in women with T1DM. However, no clear benefits have been demonstrated in reducing adverse feto-maternal outcomes in pregnant women with T1DM. DESIGN AND METHODS: This is a retrospective, single-center study of pregnant women with T1DM to evaluate the impact of CGM use on glycemic control and feto-maternal outcomes in pregnant women with T1DM. RESULTS: Of 265 women with T1DM, 92 (34.7%) used CGM, and 173 (65.3%) were managed with capillary blood glucose (CBG) monitoring. The mean (SD) age and BMI at the first visit were 29.4 (4.7) years and 27.2 (5.2) kg/m2, respectively. The mean (SD) HbA1c at the first-trimester visit was 63 (1) mmol/mol, and in the last trimester was 51 (1%). There was no difference in the mean changes in HbA1c between the two groups. Women using CGM had lower insulin requirements (1.02 + 0.37 vs. 0.87 + 0.04 units/kg, p = 0.01). The two groups had no significant differences in maternal or fetal outcomes. CONCLUSION: CGM use in pregnant T1DM women is not associated with improved fetomaternal outcomes.

Impact of flattening filter-free beams on remaining volume at risk in lung cancer treatment.

Modern radiotherapy machines offer a new modality, like flattening filter-free beam (FFF), which is used especially in stereotactic body radiation therapy (SBRT) to reduce treatment time. The remaining volume at risk (RVR) is known as undefined normal tissue, and assists in evaluating late effects such as carcinogenesis. This study aimed to compare the effects of flattening and un-flattened beams on RVR in lung cancer treated by conventional doses using volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT). Twenty-three lung cancer patients with a prescribed dose of 60 Gy delivered in 30 fractions were selected retrospectively. Four treatment plans were generated for each case (VMAT FF, VMAT FFF, IMRT FF and IMRT FFF). Mean doses to RVR and volumes that received low doses (V15Gy, V10Gy and V5Gy) were introduced as RVR evaluation parameters. Variance percentage comparison between flattening filter (FF) and FFF for the RVR evaluation parameters gave 2.38, 1.10, 1.80 and 2.22 for VMAT, and 1.73, 1.18, 1.62 and 1.81 for IMRT. In contrast, VMAT and IMRT RVR evaluation parameters resulted in variance percentage differences of 10.29, 5.02, - 8.84 and - 4.82 for FF, and 11.18, 4.96, - 8.59 and - 4.48for FFF. It is concluded that in terms of RVR evaluation parameters, FFF is clinically beneficial compared to FF for RVR, due to the decrease in mean RVR dose and low-dose irradiated RVR volume. Furthermore, VMAT is preferred in the mean RVR dose and V15Gy, while IMRT is better in V10Gy and V5Gy for RVR.

Unleashing new MTDL AChE and BuChE inhibitors as potential anti-AD therapeutic agents: In vitro, in vivo and in silico studies.

Alzheimer's disease (AD) is challenging due to its irreversible declining cognitive symptoms and multifactorial nature. This work tackles targeting both acetylcholinesterase (AChE) and BuChE with a multitarget-directed ligand (MTDL) through design, synthesis, and biological and in silico evaluation of a series of twenty eight new 5-substituted-2-anilino-1,3,4-oxadiazole derivatives 4a-g, 5a-g, 9a-g and 13a-g dual inhibitors of the target biomolecules. In vitro cholinesterases inhibition and selectivity assay of the synthesized derivatives showed excellent nanomolar level inhibitory activities. Compound 5a, the most potent inhibitor, elicited IC50s of 46.9 and 3.5 nM against AChE and BuChE, respectively (SI = 0.07), 5 folds better than the known dual inhibitor Rivastagmine. In vivo and ex vivo investigation showed that 5a significantly inhibited MDA levels and increased GSH contents, thus, attenuating the brain tissue oxidative stress. Additionally, 5a significantly decreased AChE and BuChE levels and inhibited self-mediated ß-amyloid aggregation in brains of treated rats. Histopathological and immunohistochemical evaluation demonstrated lessened damage and decreased caspase-3 and VEGF expression levels. In silico prediction of 5a's pharmacokinetics and toxicity profiles reflected promising results. Finally, 5a demonstrated tight binding interactions with the two target biomolecules upon docking along with stable complex formation with its bio-targets throughout the 100 ns MD trajectories.

Intravascular Imaging-Guided Versus Coronary Angiography-Guided Complex PCI: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Trials evaluating the role of intravascular imaging in percutaneous coronary intervention (PCI) for complex coronary artery disease have yielded mixed results. This study aimed to compare the outcomes of intravascular imaging specifically intravascular ultrasound (IVUS) with those from conventional coronary angiography in complex PCI. METHODS: Comprehensive electronic search of MEDLINE, EMBASE, and Cochrane databases was performed until March 2023 for randomized clinical trials (RCTs) comparing intravascular imaging with coronary angiography in patients undergoing complex PCI. Complex PCI was defined per each study, and included PCI for American College of Cardiology/American Heart Association (ACC/AHA) type B2/C lesions, unprotected left main coronary artery disease, or multivessel stenting. The primary study outcome was major adverse clinical events (MACE). RESULTS: The meta-analysis included 10 RCTs with a total of 6615 patients (3576 in the intravascular imaging group and 3039 in the coronary angiography group). The weighted mean-follow up was 28.9 months. Compared with coronary angiography, intravascular imaging reduced MACE (8% vs. 13.3%; relative risk [RR] 0.63; 95% confidence interval [CI] 0.54-0.73), cardiac death (RR 0.47; 95% CI 0.31-0.73), definite/probable stent thrombosis (RR 0.48; 95% CI 0.24-0.97), target vessel revascularization (RR 0.62; 95% CI 0.46-0.83), and target lesion revascularization (RR 0.61; 95% CI 0.47-0.79). There was no difference between both groups in all-cause death (RR 0.79; 95% CI 0.53-1.18) and myocardial infarction (RR 0.80; 95% CI 0.61-1.04). CONCLUSION: In patients undergoing complex PCI, intravascular imaging-specifically IVUS-reduced MACE by decreasing the incidence of cardiac death, stent thrombosis, and target vessel and target lesion revascularization.

Immunological Signatures in Blood and Urine in 80 Individuals Hospitalized during the Initial Phase of COVID-19 Pandemic with Quantified Nicotine Exposure.

This research analyzes immunological response patterns to SARS-CoV-2 infection in blood and urine in individuals with serum cotinine-confirmed exposure to nicotine. Samples of blood and urine were obtained from a total of 80 patients admitted to hospital within 24 h of admission (tadm), 48 h later (t48h), and 7 days later (t7d) if patients remained hospitalized or at discharge. Serum cotinine above 3.75 ng/mL was deemed as biologically significant exposure to nicotine. Viral load was measured with serum SARS-CoV-2 S-spike protein. Titer of IgG, IgA, and IgM against S- and N-protein assessed specific antiviral responses. Cellular destruction was measured by high mobility group box protein-1 (HMGB-1) serum levels and heat shock protein 60 (Hsp-60). Serum interleukin 6 (IL-6), and ferritin gauged non-specific inflammation. The immunological profile was assessed with O-link. Serum titers of IgA were lower at tadm in smokers vs. nonsmokers (p = 0.0397). IgM at t48h was lower in cotinine-positive individuals (p = 0.0188). IgG did not differ between cotinine-positive and negative individuals. HMGB-1 at admission was elevated in cotinine positive individuals. Patients with positive cotinine did not exhibit increased markers of non-specific inflammation and tissue destruction. The blood immunological profile had distinctive differences at admission (MIC A/B↓), 48 h (CCL19↓, MCP-3↓, CD28↑, CD8↓, IFNγ↓, IL-12↓, GZNB↓, MIC A/B↓) or 7 days (CD28↓) in the cotinine-positive group. The urine immunological profile showed a profile with minimal overlap with blood as the following markers being affected at tadm (CCL20↑, CXCL5↑, CD8↑, IL-12↑, MIC A/B↑, GZNH↑, TNFRS14↑), t48h (CCL20↓, TRAIL↓) and t7d (EGF↑, ADA↑) in patients with a cotinine-positive test. Here, we showed a distinctive immunological profile in hospitalized COVID-19 patients with confirmed exposure to nicotine.

Marginal bone loss in ball versus locator attachments in implant-retained overdentures: systematic review and meta-analysis.

OBJECTIVES: This systematic review compares the impact of ball and locator attachments on marginal bone loss in implant-retained overdentures in completely edentulous patients. METHOD AND MATERIALS: Following PRISMA guidelines, health science librarians completed literature searches from inception to March 17, 2023 in seven databases. There were 15,686 items exported to EndNote from Embase.com, CINAHL (EBSCO), Cochrane Library, Ovid MEDLINE-ALL, PubMed, Scopus, and Web of Science. Hand-searching added four more articles. After deduplication, 6756 items were screened for eligibility. Twenty-nine studies were assessed by full text, of which ten studies, involving 424 subjects, were included in the review. Risk of bias assessment was conducted using the Cochrane Risk of Bias tool and the Newcastle Ottawa Scale. A meta-analysis was performed to synthesize and analyze the collective data from the selected studies. RESULTS: The included studies used diverse methodologies, implant systems, and loading protocols. Most studies reported no significant difference in marginal bone loss between ball and locator attachments. The meta-analysis revealed high heterogeneity. CONCLUSION: The results of this systematic review suggest that ball and locator attachments exhibit similar performance in terms of marginal bone loss in implant-retained overdentures. However, the limited number, risk of bias, and heterogeneity of studies highlight the need for standardized research designs and larger sample sizes in future investigations to draw more definitive conclusions.

Near-infrared Absorption and Emission Probes with Optimal Connection Bridges for Live Monitoring of NAD(P)H Dynamics in Living Systems.

Two NAD(P)H-biosensing probes consisting of 1,3,3-trimethyl-3H-indolium and 3-quinolinium acceptors, linked by thiophene, A, and 3,4-ethylenedioxythiophene, B, bridges are detailed. We synthesized probes C and D, replacing the thiophene connection in probe A with phenyl and 2,1,3-benzothiadiazole units, respectively. Probe E was prepared by substituting probe A's 3-quinolinium unit with a 1-methylquinoxalin-1-ium unit. Solutions are non-fluorescent but in the presence of NADH, exhibit near-infrared fluorescence at 742.1 nm and 727.2 nm for probes A and B, respectively, and generate absorbance signals at 690.6 nm and 685.9 nm. In contrast, probes C and D displayed pronounced interference from NADH fluorescence at 450 nm, whereas probe E exhibited minimal fluorescence alterations in response to NAD(P)H. Pre-treatment of A549 cells with glucose in the presence of probe A led to a significant increase in fluorescence intensity. Additionally, subjecting probe A to lactate and pyruvate molecules resulted in opposite changes in NAD(P)H levels, with lactate causing a substantial increase in fluorescence intensity, conversely, pyruvate resulted in a sharp decrease. Treatment of A549 cells with varying concentrations of the drugs cisplatin, gemcitabine, and camptothecin (5, 10, and 20 µM) led to a concentration-dependent increase in intracellular fluorescence intensity, signifying a rise in NAD(P)H levels. Finally, fruit fly larvae were treated with different concentrations of NADH and cisplatin illustrating applicability to live organisms. The results demonstrated a direct correlation between fluorescence intensity and the concentration of NADH and cisplatin, respectively, further confirming the efficacy of probe A in sensing changes in NAD(P)H levels within a whole organism.

Exosomal miR-122, miR-128, miR-200, miR-298, and miR-342 as novel diagnostic biomarkers in NAFL/NASH: Impact of LPS/TLR-4/FoxO3 pathway.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disorder affecting a quarter of the global residents. Progression of NAFL into nonalcoholic steatohepatitis (NASH) may cause cirrhosis, liver cancer, and failure. Gut microbiota imbalance causes microbial components translocation into the circulation, triggering liver inflammation and NASH-related fibrosis. MicroRNAs (miRNAs) regulate gene expression via repressing target genes. Exosomal miRNAs are diagnostic and prognostic biomarkers for NAFL and NASH liver damage. Our work investigated the role of the gut microbiota in NAFLD pathogenesis via the lipopolysaccharide/toll-like receptor 4/Forkhead box protein O3 (LPS/TLR-4/FoxO3) pathway and certain miRNAs as noninvasive biomarkers for NAFL or its development to NASH. miRNA expression levels were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 50 NAFL patients, 50 NASH patients, and 50 normal controls. Plasma LPS, TLR-4, adiponectin, peroxisome proliferator-activated receptor γ (PPAR-γ), and FoxO3 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). In NAFL and NASH patients, miR-122, miR-128, FoxO3, TLR-4, LPS, and PPAR-γ were upregulated while miR-200, miR-298, miR-342, and adiponectin were downregulated compared with the normal control. The examined miRNAs might distinguish NAFL and NASH patients from the normal control using receiver operating characteristic analysis. Our study is the first to examine these miRNAs in NAFLD. Our findings imply that these are potentially promising biomarkers for noninvasive early NAFL diagnosis and NASH progression. Understanding the LPS/TLR-4/FoxO3 pathway involvement in NAFL/NASH pathogenesis may aid disease management.

Trends in Point of Care Ultrasound Familiarity Among Undergraduate Medical Clerkship Educators.

OBJECTIVES: Despite growing use of point of care ultrasound (POCUS), there remains a paucity of data about familiarity with POCUS among educators who dictate curricular content in undergraduate medical education. This paper aims to longitudinally characterize the level of comfort and frequency of POCUS use among faculty involved in undergraduate clerkship education. METHODS: A web-based cross-sectional survey assessing comfort, frequency of use, and awareness of indications for POCUS among faculty involved in Internal Medicine, Family Medicine, and Surgery undergraduate clerkship education in a single urban academic medical center in 2016 and again in 2022. RESULTS: A total of 45 responses from 2016 and 30 responses from 2022 are included. The percentage of faculty "not comfortable" with performing POCUS decreased from 78% to 46%, although the overall change in comfort was not statistically significant. Comfort interpreting POCUS images, frequency of POCUS use, and familiarity with the clinical applications of POCUS all improved. Faculty identified multiple barriers to more frequent POCUS use. CONCLUSIONS: Over a six-year period at one urban, academic medical center, comfort with POCUS and frequency of use have increased slightly but remain low among core faculty responsible for clerkship education. There are still large gaps in knowledge and very few faculty regularly use POCUS, which can be attributed to multiple different barriers.