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1.
Phys Rev Lett ; 132(22): 225001, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38877942

ABSTRACT

We report on an experimental observation of the streaking of betatron x rays in a curved laser wakefield accelerator. The streaking of the betatron x rays was realized by launching a laser pulse into a plasma with a transverse density gradient. By controlling the plasma density and the density gradient, we realized the steering of the laser driver, electron beam, and betatron x rays simultaneously. Moreover, we observed an energy-angle correlation of the streaked betatron x rays and utilized it in diagnosing the electron acceleration process in a single-shot mode. Our work could also find applications in advanced control of laser beam and particle propagation. More importantly, the angular streaked betatron x ray has an intrinsic spatiotemporal correlation, which makes it a promising tool for single-shot pump-probe applications.

2.
J Proteome Res ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829961

ABSTRACT

Asparaginase-based therapy is a cornerstone in acute lymphoblastic leukemia (ALL) treatment, capitalizing on the methylation status of the asparagine synthetase (ASNS) gene, which renders ALL cells reliant on extracellular asparagine. Contrastingly, ASNS expression in acute myeloid leukemia (AML) has not been thoroughly investigated, despite studies suggesting that AML with chromosome 7/7q deletions might have reduced ASNS levels. Here, we leverage reverse phase protein arrays to measure ASNS expression in 810 AML patients and assess its impact on outcomes. We find that AML with inv(16) has the lowest overall ASNS expression. While AML with deletion 7/7q had ASNS levels slightly lower than those of AML without deletion 7/7q, this observation was not significant. Low ASNS expression correlated with improved overall survival (46 versus 54 weeks, respectively, p = 0.011), whereas higher ASNS levels were associated with better response to venetoclax-based therapy. Protein correlation analysis demonstrated association between ASNS and proteins involved in methylation and DNA repair. In conclusion, while ASNS expression was not lower in patients with deletion 7/7q as initially predicted, ASNS levels were highly variable across AML patients. Further studies are needed to assess whether patients with low ASNS expression are susceptible to asparaginase-based therapy due to their inability to augment compensatory ASNS expression upon asparagine depletion.

3.
Cureus ; 16(5): e59710, 2024 May.
Article in English | MEDLINE | ID: mdl-38841008

ABSTRACT

INTRODUCTION: Preoperative anxiety can negatively impact patient outcomes by influencing the intraoperative requirements for anesthetics and analgesics, increasing postoperative pain intensity, and augmenting the need for analgesia. Moreover, it may contribute to higher rates of postoperative morbidity and mortality following certain types of surgery. This study investigates the anxiolytic and sedative properties of sublingual melatonin as a premedication agent in young females undergoing cesarean section under spinal anesthesia. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in Nasiriyah, Iraq. Eighty females were included, 40 in each group, based on specific inclusion and exclusion criteria. Premedication was administered in the morning, 60 minutes before the procedure. In the melatonin group (M), patients received 10 mg of sublingual melatonin, while the placebo group (P) received placebo premedication. Anxiety and sedation levels were evaluated three times: before taking premedication, five minutes before the insertion of the spinal needle, and one hour postoperatively, using the visual analog scale and Richmond Sedation Scale. RESULTS: The results show a highly significant P-value regarding anxiety levels between the M Group and P Group (p-value < 0.001). There was a significant difference in the median sedation scores between the studied groups at pre-spinal insertion and postoperatively (p-value < 0.001). The mean heart rate in the M Group was significantly lower than in the P Group (p-value = 0.0019). Significant differences were noted in systolic and diastolic blood pressures between the two groups, measured five minutes before and after spinal needle insertion (p-value < 0.001). CONCLUSION: These findings contribute to understanding the impact of sublingual melatonin as an anxiolytic and sedative premedication agent on patients undergoing elective cesarean sections under spinal anesthesia. Further research is warranted to fully elucidate the benefits and implications of melatonin administration in such procedures.

4.
Poult Sci ; 103(8): 103732, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38925079

ABSTRACT

The incidence of chronic respiratory disease (CRD) due to Mycoplasma gallisepticum (MG) contamination in hatching eggs poses a serious threat to poultry health and hatchability. Implementing effective sanitization methods while safeguarding the hatching potential of embryos is crucial. This study aimed to explore novel techniques for sanitizing hatching-fertile eggs to prevent and manage MG-associated CRD. The primary objective was to assess the efficacy of acidic electrochemically stimulated water (ECS), focusing on MG disinfection. Additionally, the study investigated 2 application methods, 1) electrostatic disinfection (ED) and 2) cold fog (CF) disinfection, to evaluate their bactericidal effects against MG-contaminated eggs. Deliberately infected MG strains were used for the experimental design, which compared the disinfection efficacy of ECS with its acidic properties. The comparison involved ED, which applies an electrostatic charge to water particles, and CF disinfection, a cold mist technique. Both methods aimed to target MG without compromising egg-hatching potential. The results indicated a significant (p < 0.05) reduction in colony-forming units per milliliter (CFU/mL). However, both application methods demonstrated distinct bactericidal effects. Eggs treated with electrostatic disinfection showed a significant (p < 0.001) reduction in embryonic mortality during incubation (10%) compared to control untreated eggs (18%). Similarly, the CF method exhibited a significant (p < 0.001) decrease in embryonic mortality (13%). The ECS potential in reducing embryonic mortality within the pH range of 2.5 to 6.5 was noted. Both the ED and CF methods show promise for preventing MG-induced hatchery infection while maintaining egg-hatching potential. This study presents innovative techniques to control MG in hatching eggs, contributing to improved poultry health and reduced CRD incidence.

5.
Heliyon ; 10(9): e30267, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38711666

ABSTRACT

Wastewater-based epidemiology (WBE) has been proven effective for the monitoring of infectious disease outbreaks during mass gathering events and for timely public health interventions. As part of Qatar's efforts to monitor and combat the spread of infectious diseases during the FIFA World Cup Qatar 2022™ (FWC'22), wastewater surveillance was used to monitor the spread of SARS-CoV-2, human enterovirus, and poliovirus. The screening covered five major wastewater treatment plants servicing the event locations between October 2022 and January 2023. Viruses were concentrated from the wastewater samples by PEG precipitation, followed by qRT-PCR to measure the viral load in the wastewater. As expected, SARS-CoV-2 and enterovirus RNA were detected in all samples, while poliovirus was not detected. The concentration of SARS-CoV-2 was correlated with population density, such as areas surrounding the World Cup venues, and with the number of reported clinical cases. Additionally, we observed temporal fluctuations in viral RNA concentrations, with peak levels coinciding with the group stage matches of the FWC'22. This study has been useful in providing public health authorities with an efficient and cost-effective surveillance system for potential infectious disease outbreaks during mega-events.

6.
Haematologica ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695144

ABSTRACT

Patients with relapsed acute myeloid leukemia (rAML) experience dismal outcomes. We performed a comprehensive analysis of patients with rAML to determine the genetic dynamics and survival predictive factors. We analyzed 875 patients with newly diagnosed AML who received intensive treatment (IT) or low-intensity treatment (LIT). Of these patients, 197 experienced subsequent rAML. Data was available for 164 patients, with a median time from CR/CRi to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation (alloSCT). At relapse mutations in genes involved in pathway signaling tended to disappear, whereas clonal hematopoiesis-related mutations or TP53 tended to persist. Patients with normal karyotypes tended to acquire cytogenetic abnormalities at relapse. Patients treated with IT had a higher emergence rate of TP53 mutations (16%), compared to patients treated with LIT (1%, P = 0.009). The overall response rates were 38% and 35% for patients treated with salvage IT or LIT, respectively. Seventeen patients (10%) underwent alloSCT after salvage therapy. The median overall survival (OS) duration after relapse was 5.3 months, with a 1-year OS rate of 17.6%. Complex karyotype (hazard ratio [HR] = 2.14, P < 0.001), a KMT2A rearrangement (HR = 3.52, P = 0.011), time in remission < 12 months (HR = 1.71, P = 0.011), and an elevated white blood cell count at relapse (HR = 2.38, P = 0.005) were independent risk factors for OS duration. More effective frontline and maintenance therapies are warranted to prevent rAML.

7.
NEJM Evid ; 3(6): EVIDoa2300362, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38804782

ABSTRACT

BACKGROUND: An inflammatory bone marrow microenvironment contributes to acquired bone marrow failure syndromes. CK0801, an allogeneic T regulatory (Treg) cell therapy product, can potentially interrupt this continuous loop of inflammation and restore hematopoiesis. METHODS: In this phase 1 dose-escalation study of CK0801 Treg cells, we enrolled patients with bone marrow failure syndromes with suboptimal response to their prior therapy to determine the safety and efficacy of this treatment for bone marrow failure syndromes. RESULTS: We enrolled nine patients with a median age of 57 years (range, 19 to 74) with an underlying diagnosis of aplastic anemia (n=4), myelofibrosis (n=4), or hypoplastic myelodysplasia (n=1). Patients had a median of three prior therapies for a bone marrow failure syndrome. Starting dose levels of CK0801 were 1 × 106 (n=3), 3 × 106 (n=3), and 10 × 106 (n=3) cells per kg of ideal body weight. No lymphodepletion was administered. CK0801 was administered in the outpatient setting with no infusion reactions, no grade 3 or 4 severe adverse reactions, and no dose-limiting toxicity. At 12 months, CK0801 induced objective responses in three of four patients with myelofibrosis (two had symptom response, one had anemia response, and one had stable disease) and three of four patients with aplastic anemia (three had partial response). Three of four transfusion-dependent patients at baseline achieved transfusion independence. Although the duration of observation was limited at 0.9 to 12 months, there were no observed increases in infections, no transformations to leukemia, and no deaths. CONCLUSIONS: In previously treated patients, CK0801 demonstrated no dose-limiting toxicity and showed evidence of efficacy, providing proof of concept for targeting inflammation as a therapy for bone marrow failure. (Funded by Cellenkos Inc.; Clinicaltrials.gov number, NCT03773393.).


Subject(s)
Anemia, Aplastic , Bone Marrow Failure Disorders , Humans , Middle Aged , Aged , Male , Adult , Female , Bone Marrow Failure Disorders/therapy , Anemia, Aplastic/therapy , Bone Marrow Diseases/therapy , Young Adult , Primary Myelofibrosis/therapy , T-Lymphocytes, Regulatory/immunology
8.
Open Vet J ; 14(4): 1029-1042, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38808298

ABSTRACT

Background: Postpartum ovarian dysfunction [ovarian cyst (OC) and persistent follicle (PF)] has been an important issue. Finding effective hormonal treatments to improve reproductive performance in dairy cows has become a necessity. Aim: Improve reproductive performance and ovarian activity in postpartum cows with specific customized treatment for OC and PFs. Methods: The study included 48 cows at 14 days P.P, which received two dosages of 500 µg IM cloprostenol, 14 days apart as presynchronization protocol. Ultrasound ovarian scans 14 days after the last injection for 4 weeks. The cows were divided into three groups according to ovarian status: OC (n = 14), PF (n = 12), and NE (n = 22). In the OC group, received 500 µg IM cloprostenol and 100 µg IM cystoriline, a second dose of cloprostenol 14 days later and a second dose of cystoriline 36 hours later, and AI after 24 hours (GnRH+ PG/PG/GnRH). In the PF group, was fitted with progesterone-releasing intravaginal device (PRID) for 9 days; the same day, they received 100 µg cystoreline then 500 µg cloprostenol 7 days later, after PRID removal AI 56 hours later (PRID + GnRH/PG). In the NE group, artificial insemination was implemented until 28 days depending on estrus detection. Results: The ovarian activity was greatly affected by the customized treatments, leading to enhanced follicular and luteal activity, particularly after the PGF2α injection. The OC and PF groups showed substantial estrus responses of 71.43% and 75.02%, respectively, during AI time. While the NE group had an ovulation rate of 54.5% and a pregnancy rate of 31.8%, the treatment groups showed marked improvements in reproductive performance. The ovulation rates in the OC and PF groups were 71.43% and 75% and the pregnancy rates at the 1st artificial insemination were 64.28% and 66.7%. Conclusion: Improving reproductive performance and minimizing the time to first service are possible advantages of early case-specific treatment for postpartum cows with OC and PFs.


Subject(s)
Cattle Diseases , Cloprostenol , Insemination, Artificial , Ovarian Cysts , Postpartum Period , Animals , Female , Cattle , Ovarian Cysts/veterinary , Cloprostenol/administration & dosage , Cloprostenol/pharmacology , Cattle Diseases/therapy , Cattle Diseases/drug therapy , Insemination, Artificial/veterinary , Pregnancy , Ovarian Follicle/drug effects , Ovarian Follicle/physiology , Progesterone/administration & dosage , Estrus Synchronization
9.
Biology (Basel) ; 13(5)2024 May 08.
Article in English | MEDLINE | ID: mdl-38785810

ABSTRACT

The rising demand for safe plant compounds and herbal products that contribute positively to human health is in line with current market trends. Plants belonging to the Satureja genus, particularly the aromatic medicinal S. montana L. from the Lamiaceae family, are well suited to these trends as they serve as pharmaceutical raw materials. This research aimed to assess the influence of sowing date and fertilization doses, as well as their interaction, on the fresh weight, essential oil content, and composition of S. montana. Experimental cultivation involved varying nitrogen and phosphorus levels. The second cut had the highest fresh weight and oil production compared to the first cut. The highest total plant biomass was achieved with autumn sowing and fertilization at 55 kg N/ha and 37 kg P/ha, whereas Spring sowing exhibited higher essential oil production, with the maximum oil % with 74 kg P/ha and oil yield after applying 55 kg N/ha and 74 kg P/ha. The GC-MS analysis revealed that carvacrol was the predominant compound, with it being recommended to grow S. montana in Spring at doses of 55 kg N/ha and 74 kg P/ha for the superior oil yield. Additionally, S. montana essential oil demonstrated notable biological and antimicrobial activity, positioning it as a potential alternative to chemical food preservatives.

10.
Foods ; 13(10)2024 May 13.
Article in English | MEDLINE | ID: mdl-38790803

ABSTRACT

Illicium verum, commonly known as star anise, represents one of the notable botanical species and is recognized for its rich reservoir of diverse bioactive compounds. Beyond its culinary application as a spice, this plant has been extensively utilized in traditional medicine. Given the contemporary emphasis on incorporating natural resources into food production, particularly essential oils, to enhance sensory attributes and extend shelf life, our study seeks to elucidate the chemical composition and evaluate the antibacterial (in vitro, in situ) and insecticidal properties of Illicium verum essential oil (IVEO). Also, microbiological analyses of pumpkin sous vide treated with IVEO after inoculation of Salmonella enterica were evaluated after 1 and 7 days of study. GC/MS analysis revealed a significantly high amount of (E)-anethole (88.4%) in the investigated EO. The disc diffusion method shows that the antibacterial activity of the IVEO ranged from 5.33 (Streptococcus constellatus) to 10.33 mm (Citrobacter freundii). The lowest minimal inhibition concentration was found against E. coli and the minimum biofilm inhibition concertation was found against S. enterica. In the vapor phase, the best antimicrobial activity was found against E. coli in the pears model and against S. sonei in the beetroot model. The application of the sous vide method in combination with IVEO application decreased the number of microbial counts and eliminated the growth of S. enterica. The most isolated microbiota identified from the sous vide pumpkin were Bacillus amyloliquefaciens, B. cereus, B. licheniformis, and Ralstonia picketii. Modifications to the protein composition of biofilm-forming bacteria S. enterica were suggested by the MALDI TOF MS instigations. The IVEO showed insecticidal potential against Harmonia axyridis. Thanks to the properties of IVEO, our results suggest it can be used in the food industry as a natural supplement to extend the shelf life of foods and as a natural insecticide.

11.
Am Soc Clin Oncol Educ Book ; 44(3): e433694, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38781565

ABSTRACT

The management of brain metastases, a potentially devastating complication of advanced cancers, has become increasingly complex with advancements in local and systemic therapies. Improved outcomes and extended survival for patients with metastatic solid tumors have led to a surge in the prevalence and possibly incidence of brain metastases, affecting up to 40% of individuals with solid tumors. Enhanced imaging technologies contribute to more accurate and early detection, shaping the understanding of the intricate landscape of this condition. Traditionally, surgery and radiation stood as the mainstays of treatment because of the limited efficacy of systemic therapies within the brain. However, emerging clinical data, particularly in melanoma, lung, and breast cancers, reveal promising results with novel systemic treatments such as immunotherapy and targeted therapies. Despite the historical exclusion of patients with active brain metastases from clinical trials, a shift is occurring toward a more inclusive approach. This chapter delves into the multifaceted challenges associated with managing brain metastases, with a focus on the evolving landscape of systemic approaches as well as the intricacies of shared decision making, providing a comprehensive overview of the current state and future directions in navigating the complexities of brain metastases management.


Subject(s)
Brain Neoplasms , Disease Management , Humans , Brain Neoplasms/secondary , Brain Neoplasms/therapy , Combined Modality Therapy
13.
Open Vet J ; 14(3): 822-829, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38682144

ABSTRACT

Background: Reproductive efficiency affects dairy cow profitability. Ovarian function in postpartum (P.P.) has been better understood using ultrasound and hormonal assays. Optimizing ovulation synchronization and carefully timing artificial insemination (TAI) can greatly enhance reproductive rates in dairy cows. Aim: This experiment was designed to investigate the reproductive performance and ovarian activity in early postpartum lactating dairy cows using the Presynch-PGF2α, Ovsynch protocol, and TAI. Methods: Randomly the cows were assigned to a control group and a treatment group, based on the chronological order of their calving date. On day 14 P.P., both groups received two cloprostenol treatments, 14 days apart. Ultrasonographic inspections were conducted on day 14 to check ovarian activity and uterine contents. On day 11, after presynchronization, cows in the treatment group were given 100 µg IM. of cystorelin, followed by a luteolytic dose of 500 µg IM., cloprostenol on day 7, and a second dose of cystorelin on day 8 (36 hours later). After the second cystorelin injection by 16-20 hours, cows were inseminated, while the control group had all cows displaying spontaneous estrus between day 0 and day 28 were artificially inseminated. Results: Ovarian activity began to improve at 82.61% on day 19 P.P., with complete recovery between days 24 and 27 P.P. The second cloprostenol injection approached, causing follicular size to reach 8.41 ± 1.04 mm. After the second injection, ovarian activity switched from follicular to luteal, with corpus luteum rates of 23.91% and 26.1%. The presynchronized PGF2α regimen significantly enhanced ovarian activity from days 19-35 P.P. Ovulation and pregnancy rates in the Ovsynch group were 54.2% and 41.7% at the first timed artificial insemination (TAI), compared to 54.5% and 31.8% in the control group. There was no significant impact between them; it was just high in the presynchronized Ovsynch group. However, the P.P. period was minimized to 47-49 days till the first AI reached a 41.7% pregnancy rate and 20.8% at the second AI, for an overall 62.5%. Conclusion: The current study concludes that presynchronization during preservice in clinically normal P.P. dairy cows reduces P.P. duration, increases ovarian activity performance, and reduces ovarian dysfunctions from day 19 to day 35 P.P., as well as improves the pregnancy rate.


Subject(s)
Cattle , Estrus Synchronization , Fertility , Ovulation , Libya , Female , Animals , Postpartum Period , Estrus Synchronization/methods , Ovary/diagnostic imaging , Ovary/drug effects , Fertility/drug effects , Fertility/physiology , Progesterone/metabolism , Ovulation/drug effects , Ultrasonography/veterinary , Dinoprost/pharmacology , Gonadotropin-Releasing Hormone/pharmacology , Cloprostenol/pharmacology , Insemination, Artificial/veterinary
14.
Cureus ; 16(3): e56543, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38646369

ABSTRACT

BACKGROUND: Preoperative anxiety in children has been linked to various postoperative consequences, such as postoperative regressive behavioral issues, extended distress during the recovery period, eating disorders, and bedwetting. The current study aimed to investigate the efficacy of low-dose oral melatonin in alleviating preoperative anxiety among children in the Iraqi population. STUDY DESIGN: A randomized, double-blinded comparative study was undertaken, involving children aged four to 14 years scheduled for elective cardiac catheterization under general anesthesia. The study comprised a total of 80 children. The involved individuals were randomly assigned to two groups, each with 40 subjects. Group A received 0.5 mg/kg melatonin as premedication, while Group B received a placebo. RESULTS: The two groups demonstrated similarity in mean age, weight, cardiac disease, and gender distribution. Statistically significant reductions in anxiety scores were observed in the melatonin group compared to the placebo group. Particularly, children administered 0.5 mg/kg melatonin exhibited the most substantial anxiolysis and venipuncture compliance (P < 0.05). Additionally, children who were premedicated with melatonin experienced decreased cognition, maximum sedation, successful parental separation, and psychomotor impairment (P < 0.05). CONCLUSIONS: Melatonin demonstrated an effective sedation level without significant side effects, making it a preferred choice due to its efficacy, safety, current availability, and cost-effectiveness compared to other anesthetic agents used in premedication procedures.

15.
Environ Monit Assess ; 196(5): 428, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38573523

ABSTRACT

Carbonaceous materials produced from agricultural waste (palm kernel shell) by pyrolysis can be a proper type of low-cost adsorbent for wide uses in radioactive effluent treatment. In this context, the as-produced bio-char (labeled as PBC) and its sub-driven sulfuric acid and zinc oxide activated carbons (labeled as PBC-SA, and PBC-Zn respectively) were employed as adsorbents for uranium sorption from aqueous solution. Various analytical techniques, including SEM (Scanning Electron Microscopy), EXD (X-ray Diffraction), BET (Brunauer-Emmett-Teller), FTIR (Fourier Transform Infrared Spectroscopy), and Zeta potential, provide insights into the material characteristics. Kinetic and isotherm investigations illuminated that the sorption process using the three sorbents is nicely fitted with Pseudo-second-order-kinetic and Langmuir isotherm models. The picked data display that the equilibrium time was 60 min, and the maximum sorption capacity was 9.89, 16.8, and 21.9 mg/g for PBC, PBC-SA, and PBC-Zn respectively, which reflects the highest affinity for zinc oxide, activated bio-char, among the three adsorbents, for uranium taking out from radioactive wastewater. Sorption thermodynamics declare that the sorption of U(VI) is an exothermic, spontaneous, and feasible process. About 92% of the uranium-loaded PBC-Zn sorbent was eluted using 1.0 M CH3COONa sodium ethanoate solution, and the sorbent demonstrated proper stability for 5 consecutive sorption/desorption cycles.


Subject(s)
Uranium , Zinc Oxide , Charcoal , Environmental Monitoring , Thermodynamics
16.
Ir J Med Sci ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38625658

ABSTRACT

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease that is linked to several motor and nonmotor symptoms, including sleep disturbances. Patient quality of life has been shown to be disproportionally impacted by disease. OBJECTIVES: To investigate sleep quality among individuals with PD, and to assess the severity of sleep disturbances and their impact on daytime activities. SUBJECTS AND METHODS: A case‒control with 44 patients with Parkinson's disease and 80 apparently healthy control participants was recruited from several hospitals and clinics. Each participant provided a thorough medical history and underwent a physical examination, and a questionnaire comprising the standard PSQI was used to assess sleep quality. Independent samples t test and Spearman's correlation analysis were used with a p value equal to or less than 0.05 which was considered significant. RESULTS: The mean global PSQI score was 11.55 ± 4.412 for PD patients and 5.73 ± 3.22 for the control group with significant p value, Sleep latency onset was 75.57 min for PD patients and 22.81 min for the control group with significant p value. There was no significant correlation between age and other sleep-related variables. A total of 86.4% of patients with Parkinson's disease suffered from varying degrees of daytime dysfunction compared to 61.25% of the controls. CONCLUSION: Parkinson's disease patients had poorer sleep quality than the controls. Age and sex were not found to be expected as a factor for sleep quality in patients with Parkinson's disease. Daytime dysfunction rates are high in patients with Parkinson's disease.

17.
Cancer Discov ; : OF1-OF15, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38588588

ABSTRACT

Gut-microbiota modulation shows promise in improving immune-checkpoint blockade (ICB) response; however, precision biomarker-driven, placebo-controlled trials are lacking. We performed a multicenter, randomized placebo-controlled, biomarker-stratified phase I trial in patients with ICB-naïve metastatic melanoma using SER-401, an orally delivered Firmicutes-enriched spore formulation. Fecal microbiota signatures were characterized at baseline; patients were stratified by high versus low Ruminococcaceae abundance prior to randomization to the SER-401 arm (oral vancomycin-preconditioning/SER-401 alone/nivolumab + SER-401), versus the placebo arm [placebo antibiotic/placebo microbiome modulation (PMM)/nivolumab + PMM (NCT03817125)]. Analysis of 14 accrued patients demonstrated that treatment with SER-401 + nivolumab was safe, with an objective response rate of 25% in the SER-401 arm and 67% in the placebo arm (though the study was under-powered related to poor accrual during the COVID-19 pandemic). Translational analyses demonstrated that vancomycin preconditioning was associated with the disruption of the gut microbiota and impaired immunity, with incomplete recovery at ICB administration (particularly in patients with high baseline Ruminococcaceae). These results have important implications for future microbiome modulation trials. SIGNIFICANCE: This first-of-its-kind, placebo-controlled, randomized biomarker-driven microbiome modulation trial demonstrated that vancomycin + SER-401 and anti-PD-1 are safe in melanoma patients. Although limited by poor accrual during the pandemic, important insights were gained via translational analyses, suggesting that antibiotic preconditioning and interventional drug dosing regimens should be carefully considered when designing such trials.

18.
Clin Neurol Neurosurg ; 240: 108252, 2024 05.
Article in English | MEDLINE | ID: mdl-38522223

ABSTRACT

BACKGROUND: Septated chronic subdural hematomas (cSDH) have high rates of recurrence despite surgical evacuation. Middle meningeal artery embolization (MMAE) has emerged as a promising adjuvant for secondary prevention, yet its efficacy remains ill-defined. METHODS: This is a retrospective review of septated cSDH cases treated at our institution. The surgery-only group was derived from cases performed before 2018, and the surgery+MMAE group was derived from cases performed 2018 or later. The primary outcome was reoperation rate. Secondary outcomes were recurrence, change in hematoma thickness, and midline shift. RESULTS: A total of 34 cSDHs in 28 patients (surgery+MMAE) and 95 cSDHs in 83 patients (surgery-only) met the inclusion criteria. No significant difference in baseline characteristics between groups was identified. The reoperation rate was significantly higher in the surgery-only group (n = 16, 16.8%) compared with the surgery+MMAE cohort (n = 0, 0.0%) (p=0.006). A reduced incidence of recurrence (p=0.011) was also seen in the surgery+MMAE group. CONCLUSIONS: MMAE for septated cSDH was found to be highly effective in preventing recurrence and reoperation. MMAE is an adjunct to surgical evacuation may be of particular benefit in this patient cohort.


Subject(s)
Embolization, Therapeutic , Hematoma, Subdural, Chronic , Meningeal Arteries , Recurrence , Humans , Hematoma, Subdural, Chronic/surgery , Male , Female , Embolization, Therapeutic/methods , Aged , Meningeal Arteries/surgery , Meningeal Arteries/diagnostic imaging , Retrospective Studies , Middle Aged , Aged, 80 and over , Reoperation/statistics & numerical data , Treatment Outcome , Secondary Prevention , Neurosurgical Procedures/methods
19.
RSC Adv ; 14(11): 7877-7890, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38449824

ABSTRACT

In this study, a theoretical examination is conducted to investigate the biosensing capabilities of different surface plasmon resonance (SPR) based hybrid multilayer structures, which are composed of two-dimensional (2D) materials. The transfer matrix formulation is implemented to calibrate the results of this study. A He-Ne laser of wavelength = 632.8 nm is used to simulate the results. Many permutations and combinations of layers of silver (Ag), aluminum oxynitride (AlON), and 2D materials were utilized to obtain the optimized structure. Ten dielectrics and twelve 2D materials were tested for a highly sensitive multilayer hybrid sensing design, which is composed of the prism (Ohara S-FPL53)/Ag/AlON/WS2/AlON/sensing medium. The optimized biosensing design is capable of sensing and detecting analytes whose refractive variation is limited between 1.33 and 1.34. The maximum sensitivity, which is achieved by using the proposed design is 488.2° per RIU. Additionally, the quality factor, figure of merit, detection limit, and qualification limit values of the optimized design were also calculated to obtain a true picture of the sensing capabilities. The designing approach based on the multilayer hybrid SPR biosensors has the potential to develop various plasmonic biosensors that are related to food, chemical, and biomedical engineering fields.

20.
Georgian Med News ; (346): 52-55, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38501621

ABSTRACT

In the context of diabetes mellitus (DM), anti-glutamic acid decarboxylase (antiGAD) antibodies are associated with a specific form of the disease called type 1 diabetes. The study aims to evaluate the serum cortisol and serotonin levels in patients with type 2 DM disease. A total of 90 Iraqi participants (30 with type 1 diabetes mellitus, 30 with type 2 diabetes mellitus and 30 healthy subjects as a control group) were enrolled in the study. Blood samples were collected, serum separated, and frozen for future analysis. The level of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was measured for each person who participated in this study (whether DM diseases or control individuals) and AntiGAD (anti-glutamic acid decarboxylase). The study examined the descriptive statistics of HOMA-IR and AntiGAD levels in individuals with different types of diabetes. The results showed that individuals with type 1 diabetes mellitus (T1DM) had a significantly lower HOMA-IR compared to the control group, while individuals with type 2 diabetes mellitus (T2DM) had a significantly higher HOMA-IR. The study also found that both T1DM and T2DM groups had significantly elevated levels of AntiGAD compared to the control group. These findings suggest that insulin resistance is reduced in T1DM individuals but increased in T2DM individuals, and the presence of diabetes is associated with increased levels of AntiGAD. In summary, the results of this study demonstrate significant differences in both HOMA-IR and AntiGAD levels between individuals with diabetes (T1DM and T2DM) and the control group. These findings contribute to our understanding of the pathophysiology of diabetes and highlight the importance of these biomarkers in the diagnosis and management of the disease. Further research is needed to explore the underlying mechanisms behind these observations and to determine their clinical implications.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Insulin Resistance , Humans , Diabetes Mellitus, Type 1/complications , Glutamate Decarboxylase , Antibodies , Blood Glucose/analysis , Insulin
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