The Influence of Lactobacillus spp. Secondary Metabolites Isolated from Immature Egyptian Honey on Human Pathogens, Transcription of Virulence Genes and Lung Cancer.

This work aimed to isolate, and identify Lactic Acid Bacteria LAB from Egyptian immature citrus honey, and characterize their secondary metabolites, as well as determine the antibacterial activities and transcription of virulence genes (stx1, stx2, and eae) influenced by these bacterial secondary metabolites. From twenty hives, twenty immature citrus bee honey samples were taken. Traditional cultural and biochemical testing were used, followed by molecular confirmation. Further, LAB isolates' antibacterial and cytotoxic properties were investigated. 16S rRNA gene sequencing were assessed and, two lactic acid bacterial isolates were identified as Lactobacillus acidophilus Ch2 and Levilactobacillus brevis Ch1. Both isolates have good antagonistic action against clinical pathogens, with Levilactobacillus brevis Ch1 exhibiting the best antibacterial activity against all indicator pathogens examined. When compared to untreated cancer cells, the isolates demonstrated significant cytotoxic activity. Ch1 and Ch2 cell viability percentages were 39.5% and 18.76%, respectively. Furthermore, when exposed to Levilactobacillus brevis Ch1 metabolites, Shiga-producing Escherichia coli (STEC) virulence gene expression was suppressed. To identify bacterial secondary metabolites, a high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF) approach was developed. Twenty-seven metabolites from diverse chemical classes were discovered in the crude extracts with antibacterial and anticancer characteristics. This is the first thorough investigation on the metabolic profile of LAB isolated from immature Egyptian honey and the findings suggested that isolates or their secondary metabolites could be used in the food sector as medicinal alternatives or as a biocontrol agent.

The impact of anxiety and depression on lumbar spine surgical outcomes: a Michigan Spine Surgery Improvement Collaborative study.

OBJECTIVE: The presence of depression and anxiety has been associated with negative outcomes in spine surgery patients. While it seems evident that a history of depression or anxiety can negatively influence outcome, the exact additive effect of both has not been extensively studied in a multicenter trial. The purpose of this study was to investigate the relationship between a patient's history of anxiety and depression and their patient-reported outcomes (PROs) after lumbar surgery. METHODS: Patients in the Michigan Spine Surgery Improvement Collaborative registry undergoing lumbar spine surgery between July 2016 and December 2021 were grouped into four cohorts: those with a history of anxiety only, those with a history of depression only, those with both, and those with neither. Primary outcomes were achieving the minimal clinically important difference (MCID) for the Patient-Reported Outcomes Measurement Information System Physical Function 4-item Short Form (PROMIS PF), EQ-5D, and numeric rating scale (NRS) back pain and leg pain, and North American Spine Society patient satisfaction. Secondary outcomes included surgical site infection, hospital readmission, and return to the operating room. Multivariate Poisson generalized estimating equation models were used to report incidence rate ratios (IRRs) from patient baseline variables. RESULTS: Of the 45,565 patients identified, 3941 reported a history of anxiety, 5017 reported a history of depression, 9570 reported both, and 27,037 reported neither. Compared with those who reported having neither, patients with both anxiety and depression had lower patient satisfaction at 90 days (p = 0.002) and 1 year (p = 0.021); PROMIS PF MCID at 90 days (p < 0.001), 1 year (p < 0.001), and 2 years (p = 0.006); EQ-5D MCID at 90 days (p < 0.001), 1 year (p < 0.001), and 2 years (p < 0.001); NRS back pain MCID at 90 days (p < 0.001) and 1 year (p < 0.001); and NRS leg pain MCID at 90 days (p < 0.001), 1 year (p = 0.024), and 2 years (p = 0.027). Patients with anxiety only (p < 0.001), depression only (p < 0.001), or both (p < 0.001) were more likely to be readmitted within 90 days. Additionally, patients with anxiety only (p = 0.015) and both anxiety and depression (p = 0.015) had higher rates of surgical site infection. Patients with anxiety only (p = 0.006) and depression only (p = 0.021) also had higher rates of return to the operating room. CONCLUSIONS: The authors observed an association between a history of anxiety and depression and negative outcome after lumbar spine surgery. In addition, they found an additive effect of a history of both anxiety and depression with an increased risk of negative outcome when compared with either anxiety or depression alone.

Does Tighter Glycemic Control Beyond Hemoglobin A1c of 8% Improve Outcome for Lumbar Spine Surgery? A MSSIC Study.

BACKGROUND AND OBJECTIVES: Diabetes mellitus is associated with increased risk of postoperative adverse outcomes. Previous studies have emphasized the role of glycemic control in postoperative complications. This study aims to ascertain whether controlling hemoglobin A1c (HbA1c) lower than 8% preoperatively results in meaningful risk reduction or improved outcomes. METHODS: We used patient-level data from the Michigan Spine Surgery Improvement Collaborative registry, focusing on patients who underwent elective lumbar spine surgery between 2018 and 2021. The primary outcomes were length of stay and the occurrence of postoperative adverse events. Secondary outcomes included patient satisfaction, achievement of a minimum clinically important difference (MCID) of Patient-Reported Outcomes Measurement Information System-Physical Function, the EuroQol-5D and NRS of leg and back pain, and return to work. RESULTS: A total of 11 348 patients were included in this analysis. Patients with HbA1c above the thresholds before surgery had significantly higher risks of urinary retention for all 3 possible threshold values (incidence rate ratio [IRR] = 1.30, P = .015; IRR = 1.35, P = .001; IRR = 1.25, P = .011 for the HbA1c cutoffs of 8%, 7.5%, and 7%, respectively). They also had longer hospital stay (IRR = 1.04, P = .002; IRR = 1.03, P = .001; IRR = 1.03, P < .001 for the HbA1c cutoffs of 8%, 7.5%, and 7%, respectively) and had higher risks of developing any complication with HbA1c cutoff of 7.5% (IRR = 1.09, P = .010) and 7% (IRR = 1.12, P = .001). Diabetics with preoperative HbA1c above all 3 thresholds were less likely to achieve Patient-Reported Outcomes Measurement Information System MCID at the 90-day follow-up (IRR = .81, P < .001; IRR = .86, P < .001; IRR = .90, P = .007 for the HbA1c cutoffs of 8%, 7.5%, and 7%, respectively) and less likely to achieve EuroQol-5D MCID at the 2-year follow-up (IRR = .87, P = .027; IRR = .84, P = .005 for the HbA1c cutoffs of 7.5% and 7%, respectively). CONCLUSION: Our study suggests that reducing HbA1c below 8% may have diminishing returns regarding reducing complications after spine surgery.

A nationwide analysis of the outcomes in hospitalized patients with atrial fibrillation and temperature-related illnesses.

OBJECTIVES: The authors evaluated mortality and indices of cost of care among inpatients with Atrial Fibrillation (AF) and a diagnosis of a Temperature-Related Illness (TRI). The authors also assessed trends in the prevalence of TRIs among AF hospitalizations. METHODS: In this cross-sectional study, the authors used discharge data from the Nationwide Inpatient Sample (NIS) collected between January 2005 and September 2015 to identify patients with a diagnosis of AF and TRI. Outcomes of interest included in-hospital mortality, invasive mechanical ventilation, hospital length of stay, and cost of hospitalization. RESULTS: A total of 37,933 encounters were included. The median age was 79 years. Males were slightly overrepresented relative to females (54.2% vs. 45.8%, respectively). Although Blacks were only 6.6% of the cohort, they represented 12.2% of the TRI cases. Compared to non-TRI-related hospitalizations, a diagnosis of a TRI was associated with an increased likelihood of invasive mechanical ventilation (16.5% vs. 4.1%, p < 0.001), longer length-of-stay (5 vs. 4 days, p < 0.001), higher cost of care (10,082 vs. 8,607, in US dollars p < 0.001), and increased mortality (18.6% vs. 5.1%, p < 0.001). Compared to non-TRI, cold-related illness portends higher odds of mortality 4.68, 95% Confidence Interval (4.35-5.04), p < 0.001, and heat-related illness was associated with less odds of mortality, but this was not statistically significant 0.77 (0.57-1.03), p = 0.88. CONCLUSION: The occurrence of TRI among hospitalized AF patients is small but there is an increasing trend in the prevalence, which more than doubled over the decade in this study. Individuals with AF who are admitted with a TRI face significantly poorer outcomes than those admitted without a TRI including higher mortality. Cold-related illness is associated with higher odds of mortality. Further research is required to elucidate the pathogenic mechanisms underlying these findings and identify strategies to prevent TRIs in AF patients.

Association between histamine 2 receptor antagonists and sepsis outcomes in ICU patients: a retrospective analysis using the MIMI-IV database.

BACKGROUND: Sepsis is marked by elevated histamine, which is a vasodilator that increases vascular permeability. Although human studies are lacking, murine models of sepsis have indicated potential protective effects of histamine 2 receptor antagonist administration (H2RAs). OBJECTIVE: To assess any association between H2RA use in sepsis-3 patients admitted to the ICU and mortality, mechanical ventilation, length of stay, and markers of renal, liver, and lung dysfunction. DESIGN: Retrospective cohort study. SETTING: Intensive care units of the Beth Israel Deaconess Medical Center (BIDMC) accessed via the MIMIC-IV database spanning an 11-year period from 2008 to 2019. PATIENTS (OR PARTICIPANTS): A total of 30,591 patients met the inclusion criteria for sepsis-3 on admission (mean age 66.49, standard deviation 15.92). MAIN MEASURES: We collected patient age, gender, ethnicity, comorbidities (contained within the Charlson comorbidity index), SOFA score, OASIS score, APS III score, SAPS II score, H2RA use, creatinine, BUN, ALT, AST, and P/F ratios. Primary outcomes were mortality, mechanical ventilation, and ICU length of stay. KEY RESULTS: A total of 30,591 patients met inclusion criteria over the 11-year sample period. The 28-day in hospital mortality rate was significantly lower among patients who received an H2RA (12.6% vs 15.1%, p < 0.001) as compared to those who did not receive an H2RA. Patients receiving an H2RA had significantly lower adjusted odds of mortality (0.802, 95% CI 0.741-0.869, p < 0.001), but significantly higher adjusted odds of invasive mechanical ventilation (4.426, 95% CI 4.132-4.741, p < 0.001) and significantly higher ICU LOS (3.2 days vs. 2.4 days, p < 0.001) as compared to the non-H2RA group. H2RA use was also associated with decreased severity of acute respiratory distress syndrome (ARDS) and lower serum creatinine. CONCLUSION: Among patients hospitalized in the ICU for sepsis, the use of an H2RA was associated with significantly lower odds of mortality, decreased severity of ARDS, and a lower incidence of renal insufficiency.

Association of prolonged symptom duration with poor outcomes in lumbar spine surgery: a Michigan Spine Surgery Improvement Collaborative study.

OBJECTIVE: There is a scarcity of large multicenter data on how preoperative lumbar symptom duration relates to postoperative patient-reported outcomes (PROs). The objective of this study was to determine the effect of preoperative and baseline symptom duration on PROs at 90 days, 1 year, and 2 years after lumbar spine surgery. METHODS: The Michigan Spine Surgery Improvement Collaborative registry was queried for all lumbar spine operations between January 1, 2017, to December 31, 2021, with a follow-up of 2 years. Patients were stratified into three subgroups based on symptom duration: < 3 months, 3 months to < 1 year, and ≥ 1 year. The primary outcomes were reaching the minimal clinically important difference (MCID) for the PROs (i.e., leg pain, Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS PF), EQ-5D, North American Spine Society satisfaction, and return to work). The EQ-5D score was also analyzed as a continuous variable to calculate quality-adjusted life years. Multivariable Poisson generalized estimating equation models were used to report adjusted risk ratios, with the < 3-month cohort used as the reference. RESULTS: There were 37,223 patients (4670 with < 3-month duration, 9356 with 3-month to < 1-year duration, and 23,197 with ≥ 1-year duration) available for analysis. Compared with patients with a symptom duration of < 1 year, patients with a symptom duration of ≥ 1 year were significantly less likely to achieve an MCID in PROMIS PF, EQ-5D, back pain relief, and leg pain relief at 90 days, 1 year, and 2 years postoperatively. Similar trends were observed for patient satisfaction and return to work. With the EQ-5D score as a continuous variable, a symptom duration of ≥ 1 year was associated with 0.04, 0.05, and 0.03 (p < 0.001) decreases in EQ-5D score at 90 days, 1 year, and 2 years after surgery, respectively. CONCLUSIONS: A symptom duration of ≥ 1 year was associated with poorer outcomes on several outcome metrics. This suggests that timely referral and surgery for degenerative lumbar pathology may optimize patient outcome.

Identification of Antimicrobial Metabolites from the Egyptian Soil-Derived Amycolatopsis keratiniphila Revealed by Untargeted Metabolomics and Molecular Docking.

Actinomycetes are prolific producers of bioactive secondary metabolites. The prevalence of multidrug-resistant (MDR) pathogens has prompted us to search for potential natural antimicrobial agents. Herein, we report the isolation of rare actinobacteria from Egyptian soil. The strain was identified as Amycolatopsis keratiniphila DPA04 using 16S rRNA gene sequencing. Cultivation profiling, followed by chemical and antimicrobial evaluation of crude extracts, revealed the activity of DPA04 ISP-2 and M1 culture extracts against Gram-positive bacteria. Minimum inhibitory concentrations (MIC) values ranged from 19.5 to 39 µg/mL. Chemical analysis of the crude extracts using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) led to the identification of 45 metabolites of different chemical classes. In addition, ECO-0501 was identified in the cultures with significant antimicrobial activity. Multidrug resistance in Staphylococcus aureus is reported to be related to the multidrug efflux pump (MATE). ECO-0501 and its related metabolites were subjected to molecular docking studies against the MATE receptor as a proposed mechanism of action. ECO-0501 and its derivatives (AK_1 and N-demethyl ECO-0501) had better binding scores (-12.93, -12.24, and -11.92 kcal/mol) than the co-crystallized 4HY inhibitor (-8.99 kcal/mol) making them promising candidates as MATE inhibitors. Finally, our work established that natural products from this strain could be useful therapeutic tools for controlling infectious diseases.

Influence of time from admission to norepinephrine administration and volume of fluids received on outcomes of patients meeting sepsis-3 criteria: a retrospective study using the MIMIC-IV database.

Objectives: Vasopressors are a cornerstone in the management of sepsis, marked by distributive shock often unresponsive to fluid resuscitation. Prior research and clinician surveys have suggested that earlier usage of vasopressors corresponds to improved outcomes. Methods: A retrospective cohort was constructed using patient data contained within the Medical Information Mart for Intensive Care-IV database. Analytic cohort included a total of 2079 patients meeting sepsis-3 criteria with a ≥2-point rise in Sequential Organ Failure Assessment score and administered norepinephrine (NE) as first-line vasopressor within 24 hours of admission to the intensive care unit (ICU). Patients receiving other vasopressors or missing documented fluid resuscitation information were excluded. Primary end points included mortality, use of invasive mechanical ventilation and length of stay which were analyzed in a multivariate logistic regression model for the primary effect of time from ICU admission to NE administration using covariates. Results: Time to NE use was defined as either early, using <6 hours from time of ICU admission or late using >6 hours to ≤24 hours. Patients who received early NE had significantly lower adjusted odds of mortality (0.75, 95% CI 0.57 to 0.97, p=0.026), higher adjusted odds of invasive mechanical ventilation (1.48, 95% CI 1.01 to 2.16, p=0.045), no significant difference in hospital length of stay (difference in days 0.6 (95% CI -3.24 to 2.04)) and lower ICU length of stay (difference in days -0.9 (95% CI -1.74 to -0.01)), as compared with the late NE group. Conclusion: Among patients admitted to the ICU for sepsis, early use of NE was associated with significantly lower odds of mortality but higher odds of mechanical ventilation, and no significant difference in length of hospital stay but less time in the ICU. Furthermore, the volume of fluids received prior to NE use may have a significant impact on optimal NE timing. Level of evidence: Level IV-therapeutic care/management.

Cholinesterase Inhibitors from an Endophytic Fungus Aspergillus niveus Fv-er401: Metabolomics, Isolation and Molecular Docking.

Alzheimer's disease poses a global health concern with unmet demand requiring creative approaches to discover new medications. In this study, we investigated the chemical composition and the anticholinesterase activity of Aspergillus niveus Fv-er401 isolated from Foeniculum vulgare (Apiaceae) roots. Fifty-eight metabolites were identified using UHPLC-MS/MS analysis of the crude extract. The fungal extract showed acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory effects with IC50 53.44 ± 1.57 and 48.46 ± 0.41 µg/mL, respectively. Two known metabolites were isolated, terrequinone A and citrinin, showing moderate AChE and BuChE inhibitory activity using the Ellman's method (IC50 = 11.10 ± 0.38 µg/mL and 5.06 ± 0.15 µg/mL, respectively for AChE, and IC50 15.63 ± 1.27 µg/mL and 8.02 ± 0.08 µg/mL, respectively for BuChE). As evidenced by molecular docking, the isolated compounds and other structurally related metabolites identified by molecular networking had the required structural features for AChE and BuChE inhibition. Where varioxiranol G (-9.76 and -10.36 kcal/mol), penicitrinol B (-9.50 and -8.02 kcal/mol), dicitrinol A (-8.53 and -7.98 kcal/mol) and asterriquinone CT5 (-8.02 and -8.25 kcal/mol) showed better binding scores as AChE and BuChE inhibitors than the co-crystallized inhibitor (between -7.89 and 7.82 kcal/mol) making them promising candidates for the development of new drugs to treat Alzheimer's.

Genome-Based Analysis of the Potential Bioactivity of the Terrestrial Streptomyces vinaceusdrappus Strain AC-40.

Streptomyces are factories of antimicrobial secondary metabolites. We isolated a Streptomyces species associated with the Pelargonium graveolens rhizosphere. Its total metabolic extract exhibited potent antibacterial and antifungal properties against all the tested pathogenic microbes. Whole genome sequencing and genome analyses were performed to take a look at its main characteristics and to reconstruct the metabolic pathways that can be associated with biotechnologically useful traits. AntiSMASH was used to identify the secondary metabolite gene clusters. In addition, we searched for known genes associated with plant growth-promoting characteristics. Finally, a comparative and pan-genome analysis with three closely related genomes was conducted. It was identified as Streptomyces vinaceusdrappus strain AC-40. Genome mining indicated the presence of several secondary metabolite gene clusters. Some of them are identical or homologs to gene clusters of known metabolites with antimicrobial, antioxidant, and other bioactivities. It also showed the presence of several genes related to plant growth promotion traits. The comparative genome analysis indicated that at least five of these gene clusters are highly conserved through rochei group genomes. The genotypic and phenotypic characteristics of S. vinaceusdrappus strain AC-40 indicate that it is a promising source of beneficial secondary metabolites with pharmaceutical and biotechnological applications.

Postoperative opioid prescription and patient-reported outcomes after elective spine surgery: a Michigan Spine Surgery Improvement Collaborative study.

OBJECTIVE: This study was designed to assess how postoperative opioid prescription dosage could affect patient-reported outcomes after elective spine surgery. METHODS: Patients enrolled in the Michigan Spine Surgery Improvement Collaborative (MSSIC) from January 2020 to September 2021 were included in this study. Opioid prescriptions at discharge were converted to total morphine milligram equivalents (MME). A reference value of 225 MME per week was used as a cutoff. Patients were divided into two cohorts based on prescribed total MME: ≤ 225 MME and > 225 MME. Primary outcomes included patient satisfaction, return to work status after surgery, and whether improvement of the minimal clinically important difference (MCID) of the Patient-Reported Outcomes Measurement Information System 4-question short form for physical function (PROMIS PF) and EQ-5D was met. Generalized estimated equations were used for multivariate analysis. RESULTS: Regression analysis revealed that patients who had postoperative opioids prescribed with > 225 MME were less likely to be satisfied with surgery (adjusted OR [aOR] 0.81) and achieve PROMIS PF MCID (aOR 0.88). They were also more likely to be opioid dependent at 90 days after elective spine surgery (aOR 1.56). CONCLUSIONS: The opioid epidemic is a serious threat to national public health, and spine surgeons must practice conscientious postoperative opioid prescribing to achieve adequate pain control. The authors' analysis illustrates that a postoperative opioid prescription of 225 MME or less is associated with improved patient satisfaction, greater improvement in physical function, and decreased opioid dependence compared with those who had > 225 MME prescribed.

A nationwide analysis of the outcomes in hospitalized patients with atrial fibrillation and temperature-related illnesses

Abstract Objectives The authors evaluated mortality and indices of cost of care among inpatients with Atrial Fibrillation (AF) and a diagnosis of a Temperature-Related Illness (TRI). The authors also assessed trends in the prevalence of TRIs among AF hospitalizations. Methods In this cross-sectional study, the authors used discharge data from the Nationwide Inpatient Sample (NIS) collected between January 2005 and September 2015 to identify patients with a diagnosis of AF and TRI. Outcomes of interest included in-hospital mortality, invasive mechanical ventilation, hospital length of stay, and cost of hospitalization. Results A total of 37,933 encounters were included. The median age was 79 years. Males were slightly overrepresented relative to females (54.2% vs. 45.8%, respectively). Although Blacks were only 6.6% of the cohort, they represented 12.2% of the TRI cases. Compared to non-TRI-related hospitalizations, a diagnosis of a TRI was associated with an increased likelihood of invasive mechanical ventilation (16.5% vs. 4.1%, p< 0.001), longer length-of-stay (5 vs. 4 days, p <0.001), higher cost of care (10,082 vs. 8,607, in US dollars p <0.001), and increased mortality (18.6% vs. 5.1%, p <0.001). Compared to non-TRI, cold-related illness portends higher odds of mortality 4.68, 95% Confidence Interval (4.35-5.04), p <0.001, and heat-related illness was associated with less odds of mortality, but this was not statistically significant 0.77 (0.57-1.03), p= 0.88. Conclusion The occurrence of TRI among hospitalized AF patients is small but there is an increasing trend in the prevalence, which more than doubled over the decade in this study. Individuals with AF who are admitted with a TRI face significantly poorer outcomes than those admitted without a TRI including higher mortality. Cold-related illness is associated with higher odds of mortality. Further research is required to elucidate the pathogenic mechanisms underlying these findings and identify strategies to prevent TRIs in AF patients.

Small Incision Upper Blepharoplasty in the Treatment of Upper Eyelid Solitary Nasal Pad Fat Protrusion.

Purpose: The aim of this article is to investigate the efficacy of small incision blepharoplasty in the treatment of upper eyelid single nasal pad fat bulge. Materials and Methods: This is a prospective study of 43 eyes of 24 patients who underwent small incision upper blepharoplasty for the treatment of solitary nasal pad fat bulge. All patients underwent a comprehensive ophthalmic examination, periorbital evaluation, and patient satisfaction evaluation using Global Aesthetic Improvement Scale (GAIS) and Blepharoplasty Outcomes Evaluation (BOE) at baseline, 1 week, 3 months, and 6 months after the surgery. All patients underwent small incision upper eyelid blepharoplasty for excision of nasal fat pad bulge. Results: Baseline nasal fat bulge was graded into grades 1, 2, and 3 in 4 (9.3%), 12 (27.9%), and 27 (62.8%) eyes, respectively. While at 6-month follow-up, grade 0 was recorded in 38 (88.4%) eyes, and grade 1 was recorded in 5 (11.6%) eyes. The mean operative time was 11.7 ± 1.9 min. GAIS showed degrees 1, 2, and 3 in 2 (8.3%), 19 (79.2%), and 3 (12.5%) patients at 6-month follow-up, respectively. Twenty-two patients (91.7%) reported a BOE scale of more than 95%, whereas two patients (8.3%) reported a scale of 80-90% at 6-month follow-up. Conclusion: Our cohort highlights the beneficial effects of small incision upper blepharoplasty in the treatment of upper eyelid solitary or lone nasal pad fat bulge, providing a safe, short-timing, and effective option.

Hepatoprotective and renoprotective effects of silymarin against salinomycin-induced toxicity in adult rabbits.

Background and Aim: Salinomycin sodium, a licensed coccidiostat in rabbits, is used for fattening at a dose of 20-25 mg/kg. Salinomycin toxicity may arise from many risk factors (e.g., overdosage or use in non-target animal species). Silymarin extracted from milk thistle has antioxidant, anti-inflammatory, and antiviral properties. This study aimed to investigate the adverse impacts of oral administration of salinomycin for 28 consecutive days and how to reduce its risks and side effects by administering silymarin. Materials and Methods: Eighty-four male New Zealand White bucks (1.750-2.000 kg) were randomly divided into seven groups (12 each). Group one was the control. Groups two and three were administered salinomycin orally (doses of 20 and 40 mg/kg ration). Group four was administered salinomycin (20 mg/kg ration) and silymarin (6.5 mg/kg body weight [BW]). Group five received salinomycin (40 mg/kg ration) and silymarin (13 mg/kg BW). Groups six and seven were administered silymarin at doses of 6.5 and 13 mg/kg BW. Rabbits were euthanized and slaughtered on day 29 using the Halal method. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, urea, total proteins, albumin, total cholesterol, and high- and low-density lipoprotein (HDL and LDL) were analyzed in serum. Glutathione (GSH), superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) were estimated in the liver. A histopathological investigation was performed on the liver and kidney. Results: The MDA activity, AST, ALT, total protein, albumin, total cholesterol, triglyceride, LDL, urea, and creatinine values were significantly elevated in groups two and three. The GSH, catalase, SOD, and HDL were significantly lower in these groups than in the control group. There were moderate pathologic changes in the liver and kidney of the third group. However, the results of the fourth and fifth groups improved more than those of the second and third groups. The results of the sixth and seventh groups were nearly the same as those of the control group. Conclusion: Salinomycin toxicity was caused by oxidative damage because of reactive oxygen species formation. Silymarin (6.5 or 13 mg/kg BW) tends to prevent and treat accidental toxicity. However, the high dose of silymarin (13 mg/kg BW) had more renal and hepatoprotective capacities.

An Adaptive and Spectrally Efficient Multi-Channel Medium Access Control Protocol for Dynamic Ad Hoc Networks.

Medium access control (MAC) protocols in ad hoc networks have evolved from single-channel independent transmission mechanisms to multi-channel concurrent mechanisms to efficiently manage the demands placed on modern networks. The primary aim of this study is to compare the performance of popular multi-channel MAC (MMAC) protocols under saturated network traffic conditions and propose improvements to the protocols under these conditions. A novel, dynamically adaptive MMAC protocol was devised to take advantage of the performance capabilities of the evaluated protocols in changing wireless ad hoc network conditions. A simulation of the familiar MAC protocols was developed based on a validated simulation of the IEEE 802.11 standard. Further, the behaviors and performances of these protocols are compared against the proposed MMAC protocols with a varying number of ad hoc stations and concurrent wireless channels in terms of throughput, Jain's fairness index, and channel access delay. The results show that the proposed MMAC protocol, labeled E-SA-MMAC, outperforms the existing protocols in throughput by up to 11.9% under a constrained number of channels and in channel access delays by up to 18.3%. It can be asserted from these observations that the proposed approach provides performance benefits against its peers under saturated traffic conditions and other factors, such as the number of available wireless channels, and is suitable for dynamic ad hoc network deployments.

Addressing Missing Data in GC × GC Metabolomics: Identifying Missingness Type and Evaluating the Impact of Imputation Methods on Experimental Replication.

Missing data is a significant issue in metabolomics that is often neglected when conducting data preprocessing, particularly when it comes to imputation. This can have serious implications for downstream statistical analyses and lead to misleading or uninterpretable inferences. In this study, we aim to identify the primary types of missingness that affect untargeted metabolomics data and compare strategies for imputation using two real-world comprehensive two-dimensional gas chromatography (GC × GC) data sets. We also present these goals in the context of experimental replication whereby imputation is conducted in a within-replicate-based fashion─the first description and evaluation of this strategy─and introduce an R package MetabImpute to carry out these analyses. Our results conclude that, in these two GC × GC data sets, missingness was most likely of the missing at-random (MAR) and missing not-at-random (MNAR) types as opposed to missing completely at-random (MCAR). Gibbs sampler imputation and Random Forest gave the best results when imputing MAR and MNAR compared against single-value imputation (zero, minimum, mean, median, and half-minimum) and other more sophisticated approaches (Bayesian principal component analysis and quantile regression imputation for left-censored data). When samples are replicated, within-replicate imputation approaches led to an increase in the reproducibility of peak quantification compared to imputation that ignores replication, suggesting that imputing with respect to replication may preserve potentially important features in downstream analyses for biomarker discovery.

Long-term efficacy of dexamethasone intravitreal implant in the treatment of Vogt-Koyanagi-Harada disease relapsing posterior uveitis.

Purpose: To investigate the efficacy and safety of dexamethasone intravitreal implant in the treatment of relapsing posterior uveitis in patients with chronic recurrent Vogt-Koyanagi-Harada (VKH) disease. Methods: This was a prospective study of 29 eyes of 16 patients with posterior uveitis in chronic recurrent VKH disease. All patients received previous systemic steroid and immunosuppressive regimens. All patients underwent a comprehensive ophthalmic examination, including best-corrected visual acuity (BCVA), Indocyanine green angiography (ICGA), fundus fluorescein angiography (FFA), and spectral-domain optical coherence tomography (SD-OCT). All patients underwent intravitreal injection with sustained-release dexamethasone 0.7 mg implant (Ozurdex®). Primary outcome measures included mean change in BCVA and central foveal thickness (CFT) at 24 months of follow-up compared to the baseline. Results: At 24 month of follow-up, the mean BCVA improved from 0.82 ± 0.13 to 0.38 ± 0.06 logMAR (P < 0.0001). The mean CFT reduced from 505 ± 29 to 244 ± 23 um (P < 0.0001). The mean intraocular pressure (IOP) changed from 15.1 ± 2.2 to 16.9 ± 3.1 mmHg with no significant value (P-value = 0.0955). Twenty-one eyes (72.4%) received one injection, whereas eight eyes (27.6%) required two injections. The mean number of injections was 1.2 ± 0.60. The mean follow-up time was 24.75 ± 0.9 months. No serious ocular or systemic adverse events were noted during the follow-up period. Ocular hypertension was recorded in three (10.3%) eyes and controlled by IOP lowering medications. Cataract progression occurred in 11 (37.9%) eyes. Conclusion: Our cohort highlights the beneficial effects of the dexamethasone implant of 0.7 mg in the treatment of VKH disease relapsing posterior uveitis improving visual acuity, reducing macular edema, and minimizing the burden of systemic steroids in this sample study.

A Case of the Use of Extracorporeal Carbon Dioxide Removal in a Patient With COVID-19 Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a severe complication of coronavirus disease 2019 (COVID-19) infection marked by increased fluid diffusely in alveolar spaces. The management of ARDS can be complicated by mechanical hyperinflation, and thus a mainstay of treatment has included low tidal volume mechanical ventilation. This, however, can lead to ventilation-associated hypercapnia, which may result in respiratory acidosis. COVID-19-associated ARDS (CARDs) has been described in the literature, and guidelines tend to mimic ARDS management. However, the heterogeneous nature of COVID-19 pulmonary disease with respect to dead space, compliance, and shunting could alter guidelines. As low tidal volume remains a cornerstone in CARDS management, hypercapnic acidosis remains a risk. An emerging technology, extracorporeal CO2 removal devices (ECCO2R), has been granted emergency use authorization by the FDA for the management of CARDS. We present a 44-year-old male patient presenting positive for COVID-19. Following admission, the patient's oxygen status continually deteriorated and the patient went into acute respiratory distress, eventually requiring invasive mechanical ventilation. The patient became hypercapnic and acidotic due to low tidal volume ventilation. ECCO2R was used to manage the patient's hypercapnia, resulting in significant amelioration of his partial pressure of carbon dioxide (PCO2) and pH. The patient was eventually transferred to extracorporeal membrane oxygenation (ECMO) certified facility and survived after a prolonged hospital and rehabilitation course. In the management of CARDS patients who require mechanical respiration, there are many unanswered questions as to the appropriate ventilation strategy. Current practice recommends low tidal volume ventilation, carrying, and increased risk of hypercapnic respiratory acidosis as occurred in our patient. We believe that ECCO2R may be an appropriate bridge between low tidal volume ventilation and ECMO to stabilize acid-base disturbances in ventilated patients.

Techniques for management and avoidance of ventriculoatrial shunt disconnection: illustrative cases.

BACKGROUND: Ventriculoatrial (VA) shunt disconnection can result in distal catheter migration into the cardiopulmonary vasculature. There is little guidance in the current literature on how to prevent and manage this uncommon yet potentially serious complication. The authors reviewed the existing literature and described three instances of distal shunt migration VA shunts and offered insight on methods to mitigate such complications. OBSERVATIONS: Eighteen patients were identified with VA shunts. Of these patients, seven were identified as having a connector in the neck, three of which were associated with distal disconnection and migration. In all three cases, the distal catheter was retrieved via an endovascular approach in conjunction with transesophageal echocardiography to assess for retrieval feasibility. LESSONS: The authors recommended the avoidance of a straight connector when performing VA shunt placement. When distal catheter migration occurs, collaboration with interventional cardiology is advisable when possible.

Evaluation of different bacterial honey isolates as probiotics and their efficient roles in cholesterol reduction.

Continue to hypothesize that honey is a storehouse of beneficial bacteria, and the majority of these isolates are levansucrase producers. Accordingly, ten bacterial strains were isolated from different honey sources. Four honey isolates that had the highest levansucrase production and levan yield were identified by the partial sequencing of the 16S rRNA gene as Achromobacter sp. (10A), Bacillus paralicheniformis (2M), Bacillus subtilis (9A), and Bacillus paranthracis (13M). The cytotoxicity of the selected isolates showed negative blood hemolysis. Also, they are sensitive to the tested antibiotics (Amoxicillin + Flucloxacillin, Ampicillin, Gentamicin, Benzathine benzylpenicillin, Epicephin, Vancomycin, Amikacin, and Zinol). The isolates had strong alkaline stability (pHs 9, 11) and were resistant to severe acidic conditions (29-100 percent). The tested isolates recorded complete tolerance to both H2O2 and the bile salt (0.3% Oxgall powder) after 24 h incubation. The cell-free supernatant of the examined strains had antifungal activities against C. Albicans with varying degrees. Also, isolates 2M and 13M showed strong activities against S. aureus. The isolates showed strong adhesion and auto-aggregation capacity. Isolate 10A showed the highest antioxidant activity (91.45%) followed by 2M (47.37%). The isolates recorded different catalase and protease activity. All isolates produced cholesterol oxidase and lipase with different levels. Besides, the four isolates reduced LDL (low-density lipoprotein) to different significant values. The cholesterol-reducing ability varied not only for strains but also for the time of incubation. The previous results recommended these isolates be used safely in solving the LDL problem.