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1.
JAMA Surg ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38865138
2.
Clin Transl Sci ; 17(6): e13853, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38847347

ABSTRACT

The evidence of rivaroxaban's pharmacokinetics in obese compared with non-obese populations remains inconclusive. We aimed to compare the pharmacokinetic profile of rivaroxaban between obese and non-obese populations under fed state. Participants who met the study's eligibility criteria were assigned into one of two groups: obese (body mass index ≥35 kg/m2) or non-obese (body mass index 18.5-24.9 kg/m2). A single dose of rivaroxaban 20 mg was orally administered to each participant. Nine blood samples over 48 h, and multiple urine samples over 18 h were collected and analyzed for rivaroxaban concentration using ultra-performance liquid chromatography coupled with tandem mass detector. Pharmacokinetic parameters were determined using WinNonlin software. Thirty-six participants were recruited into the study. No significant changes were observed between obese and non-obese participants in peak plasma concentration, time to reach peak plasma concentration, area under the plasma concentration-time curve over 48 h or to infinity, elimination rate constant, half-life, apparent volume of distribution, apparent clearance, and fraction of drug excreted unchanged in urine over 18 h. Rivaroxaban's exposure was similar between the obese and non-obese subjects, and there were no significant differences in other pharmacokinetic parameters between the two groups. These results suggest that dose adjustment for rivaroxaban is probably unwarranted in the obese population.


Subject(s)
Factor Xa Inhibitors , Obesity , Rivaroxaban , Humans , Rivaroxaban/pharmacokinetics , Rivaroxaban/administration & dosage , Rivaroxaban/blood , Male , Female , Adult , Factor Xa Inhibitors/pharmacokinetics , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/blood , Middle Aged , Administration, Oral , Body Mass Index , Area Under Curve , Half-Life , Young Adult
3.
Arch Pharm (Weinheim) ; : e2400225, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822393

ABSTRACT

The current review outlines all possible recent synthetic platforms to quinoxaline derivatives and the potent stimulated apoptosis mechanisms targeted by anticancer therapies. The currently reported results disclosed that quinoxaline derivatives had promising anticancer potencies against a wide array of cancer cell lines, better than the reference drugs, through target inhibition. This review summarizes some potent quinoxaline derivatives with their synthesis strategies and their potential activities against various molecular targets. Quinoxalines can be considered an important scaffold for apoptosis inducers in cancer cells through inhibiting some molecular targets, so they can be further developed as target-oriented chemotherapeutics.

4.
RSC Adv ; 14(28): 19752-19779, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38899036

ABSTRACT

Due to the importance of the fluorinated heterocycles as main components of marketed drugs where 20% of the anticancer and antibiotic drugs contain fluorine atoms, this review describes the reported five-membered heterocycles and their benzo-fused systems having directly connected fluorine atom(s). The in vivo and in vitro anticancer and antimicrobial activities of these fluorinated heterocycles are well reported. Some fluorinated heterocycles were found to be lead structures for drug design developments where their activities were almost equal to or exceeded the potency of the reference drugs. In most cases, the fluorine-containing heterocycles showed promising safety index via their reduced cytotoxicity in non-cancerous cell lines. SAR study assigned that fluorinated heterocycles having various electron-donating or electron-withdrawing substituents significantly affected the anticancer and antimicrobial activities.

5.
Animals (Basel) ; 14(10)2024 May 16.
Article in English | MEDLINE | ID: mdl-38791702

ABSTRACT

Heat stress is one of the stressors that negatively affect broiler chickens, leading to a reduction in production efficiency and profitability. This reduction affects the economy in general, especially in hot and semi-hot countries. Therefore, improving heat tolerance of broiler chicks is a key to sustained peak performance, especially under adverse environmental heat stress conditions. The present study investigated three early feed withdrawal regimes (FWD) as a potential mitigation for thermal stress exposure. A total of 240 unsexed one-day-old Cobb-500 chicks were randomly recruited to one of four experimental groups using a completely randomized design (10 birds × 6 replicates). The experimental groups included the control group with no feed withdrawal (control), while the other three groups were subjected to early feed withdrawal for either 24 h on the 5th day of age (FWD-24), 12 h on the 3rd and 5th day of age (FWD-12), or 8 h on the 3rd, 4th, and 5th day of age (FWD-8), respectively. Production performance was monitored throughout the experiment. Meanwhile, blood and liver samples were taken at the end of the experimental period to evaluate major physiological dynamic changes. Our findings demonstrated that under chronic heat stress conditions, FWD treatments significantly improved broilers' production performance and enhanced several physiological parameters compared with the control. Serum levels of thyroid hormones were elevated, whereas leptin hormone was decreased in FWD groups compared with the control. Moreover, serum total protein, globulin, and hemoglobin levels were higher, while total cholesterol and uric acid were lower in the FWD groups. Furthermore, FWD groups showed significantly higher antioxidant marker activity with a significantly lower lipid peroxidation level. Immunoglobulin levels, lysozyme, complement factor C3, and liver heat shock protein 70 (HSP70) concentration were also elevated in FWD compared with the control. Also, serum interleukin-1ß (IL-1ß) and interferon-gamma (IFN-γ) significantly increased with FWD. Based on our findings, early feed withdrawal can be applied as a promising non-invasive nutritional strategy for broilers reared under chronic heat stress conditions. Such a strategy promotes the alleviation of the deleterious effects of heat stress on broiler performance, immunity, and redox status, owing to the onset of physiological adaptation and the development of thermotolerance ability.

6.
J Alzheimers Dis ; 99(3): 1047-1064, 2024.
Article in English | MEDLINE | ID: mdl-38758999

ABSTRACT

Background: Higher allostatic load (AL), a multi-system measure of physiological dysregulation considered a proxy for chronic stress exposure, is associated with poorer global cognition (GC) in older non-Hispanic white adults. However, evidence of these associations in middle-aged and older US-based Hispanic/Latino adults is limited. Objective: To examine associations of AL with level of cognition, performance in cognition 7 years later, and change in cognition over 7 years among middle-aged and older US-based Hispanic/Latino adults. Methods: We used data (n = 5,799, 45-74 years at baseline) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation of Neurocognitive Aging (SOL-INCA). The AL score comprised 16 biomarkers representing cardiometabolic, glucose, cardiopulmonary, parasympathetic, and inflammatory systems (higher scores = greater dysregulation). Cognitive outcomes included GC and individual tests of verbal learning and memory, world fluency (WF), Digit Symbol Substitution (DSS), and Trail Making (Parts A & B). Survey-linear regressions assessed associations of AL with performance in cognition at baseline, 7 years later, and via 7-year cognitive change scores adjusting for sociodemographic characteristics, lifestyle factors, and depressive symptoms. Results: Higher AL was associated with lower baseline performance in GC and WF; and lower 7-year follow-up performance in these same measures plus DSS and Trail Making Parts A & B. Higher AL was associated with more pronounced 7-year change (reduction) in GC and on WF and DSS tests. Conclusions: Findings extend previous evidence in predominantly older non-Hispanic white cohorts to show that AL is related to level of and change in GC (as well as WF and DSS) among middle-aged and older US-based Hispanic/Latino adults.


Subject(s)
Allostasis , Cognition , Hispanic or Latino , Neuropsychological Tests , Humans , Male , Allostasis/physiology , Female , Middle Aged , Hispanic or Latino/psychology , Aged , Cognition/physiology , Neuropsychological Tests/statistics & numerical data , Aging/physiology , Aging/psychology , Cognitive Dysfunction , United States/epidemiology , Biomarkers/blood , Cognitive Aging/physiology
7.
JAMA Netw Open ; 7(3): e240900, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38436958

ABSTRACT

Importance: Although recent guidelines recommend against performance of preoperative urine culture before nongenitourinary surgery, many clinicians still order preoperative urine cultures and prescribe antibiotics for treatment of asymptomatic bacteriuria in an effort to reduce infection risk. Objective: To assess the association between preoperative urine culture testing and postoperative urinary tract infection (UTI) or surgical site infection (SSI), independent of baseline patient characteristics or type of surgery. Design, Setting, and Participants: This cohort study analyzed surgical procedures performed from January 1, 2017, to December 31, 2019, at any of 112 US Department of Veterans Affairs (VA) medical centers. The cohort comprised VA enrollees who underwent major elective noncardiac, nonurological operations. Machine learning and inverse probability of treatment weighting (IPTW) were used to balance the characteristics between those who did and did not undergo a urine culture. Data analyses were performed between January 2023 and January 2024. Exposures: Performance of urine culture within 30 days prior to surgery. Main Outcomes and Measures: The 2 main outcomes were UTI and SSI occurring within 30 days after surgery. Weighted logistic regression was used to estimate odds ratios (ORs) for postoperative infection based on treatment status. Results: A total of 250 389 VA enrollees who underwent 288 858 surgical procedures were included, with 88.9% (256 753) of surgical procedures received by males and 48.9% (141 340) received by patients 65 years or older. Baseline characteristics were well balanced among treatment groups after applying IPTW weights. Preoperative urine culture was performed for 10.5% of surgical procedures (30 384 of 288 858). The IPTW analysis found that preoperative urine culture was not associated with SSI (adjusted OR [AOR], 0.99; 95% CI, 0.90-1.10) or postoperative UTI (AOR, 1.18; 95% CI, 0.98-1.40). In analyses limited to orthopedic surgery and neurosurgery as a proxy for prosthetic implants, the adjusted risks for UTI and SSI were also not associated with preoperative urine culture performance. Conclusions and Relevance: This cohort study found no association between performance of a preoperative urine culture and lower risk of postoperative UTI or SSI. The results support the deimplementation of urine cultures and associated antibiotic treatment prior to surgery, even when using prosthetic implants.


Subject(s)
Orthopedic Procedures , Surgical Wound Infection , United States/epidemiology , Male , Humans , Propensity Score , Cohort Studies , Surgical Wound Infection/diagnosis , Surgical Wound Infection/epidemiology , Urinalysis , Anti-Bacterial Agents/therapeutic use
8.
J Contemp Dent Pract ; 25(2): 180-185, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38514417

ABSTRACT

AIM: To evaluate the intensity of postendodontic pain (PEP) using final irrigation with side-vented needle (SV), EndoActivator (EA), and Ultra X (UX) in single-visit endodontics (SVE) with F-One rotary files. MATERIALS AND METHODS: A total 150 patients indicated for endodontic treatment were selected. Single-visit endodontics treatment was performed under local anesthesia. For the final irrigation protocol, they were divided into three groups: group I (SV), group II (EA), and group III (UX). The severity of PEP was assessed using visual analogue scale (VAS) score after 6, 12, 24, and 48 hours. Analgesics taken by patients, for pain, were also recorded. Finally, the data were tabulated and statistically analyzed using SPSS 20.0 software at a level of significance being 0.05. RESULTS: Postendodontic pain was less in group III (UX) and group II (EA) compared with group I (SV) at 6 and 12 hours, which is statistically significant (p < 0.05). There was no statistically significant difference found after 24 hours and 48 hours. CONCLUSION: The intensity of PEP was minimum in patients treated with EndoActivator and ultrasonic along with single rotary file systems. The incidence of analgesic intake was similar in all three groups. How to cite this article: Kathiria NV, Attur K, Bagda KM, et al. Postendodontic Pain Using Single File System with Different Irrigation Protocols in Single-visit Root Canal Treatment: A Randomized Control Trial. J Contemp Dent Pract 2024;25(2):180-185.


Subject(s)
Dental Pulp Cavity , Root Canal Preparation , Humans , Pain, Postoperative , Randomized Controlled Trials as Topic , Root Canal Preparation/methods , Root Canal Therapy/methods , Ultrasonics , Double-Blind Method
9.
Sci Adv ; 10(13): eadm9859, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38536921

ABSTRACT

Loss-of-function mutations in KEAP1 frequently occur in lung cancer and are associated with poor prognosis and resistance to standard of care treatment, highlighting the need for the development of targeted therapies. We previously showed that KEAP1 mutant tumors consume glutamine to support the metabolic rewiring associated with NRF2-dependent antioxidant production. Here, using preclinical patient-derived xenograft models and antigenic orthotopic lung cancer models, we show that the glutamine antagonist prodrug DRP-104 impairs the growth of KEAP1 mutant tumors. We find that DRP-104 suppresses KEAP1 mutant tumors by inhibiting glutamine-dependent nucleotide synthesis and promoting antitumor T cell responses. Using multimodal single-cell sequencing and ex vivo functional assays, we demonstrate that DRP-104 reverses T cell exhaustion, decreases Tregs, and enhances the function of CD4 and CD8 T cells, culminating in an improved response to anti-PD1 therapy. Our preclinical findings provide compelling evidence that DRP-104, currently in clinical trials, offers a promising therapeutic approach for treating patients with KEAP1 mutant lung cancer.


Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Glutamine/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Enzyme Inhibitors/therapeutic use , Mutation
11.
Braz J Biol ; 83: e276530, 2024.
Article in English | MEDLINE | ID: mdl-38422267

ABSTRACT

A significant public health issue worldwide is metabolic syndrome, a cluster of metabolic illnesses that comprises insulin resistance, obesity, dyslipidemia, hyperglycemia, and hypertension. The creation of natural treatments and preventions for metabolic syndrome is crucial. Chitosan, along with its nanoformulations, is an oligomer of chitin, the second-most prevalent polymer in nature, which is created via deacetylation. Due to its plentiful biological actions in recent years, chitosan and its nanoformulations have drawn much interest. Recently, the chitosan nanoparticle-based delivery of CRISPR-Cas9 has been applied in treating metabolic syndromes. The benefits of chitosan and its nanoformulations on insulin resistance, obesity, diabetes mellitus, dyslipidemia, hyperglycemia, and hypertension will be outlined in the present review, highlighting potential mechanisms for the avoidance and medication of the metabolic syndromes by chitosan and its nanoformulations.


Subject(s)
Chitosan , Dyslipidemias , Hyperglycemia , Hypertension , Insulin Resistance , Metabolic Syndrome , Humans , Metabolic Syndrome/drug therapy , Chitosan/therapeutic use , Obesity
12.
JAMA Surg ; 159(6): 706-707, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38170498

ABSTRACT

This Guide to Statistics and Methods describes common methods for building evidence of validity for a program within health professional education and provides a framework for program evaluation.


Subject(s)
Program Evaluation , Humans
13.
J Immunol ; 212(4): 632-644, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38180236

ABSTRACT

Distinct subsets of T lymphocytes express CX3CR1 under inflammatory conditions, but little is known about CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections. In this study, we used a fate-mapping mouse model to characterize CX3CR1+CD4+ T cells during both acute Nippostrongylus brasiliensis and chronic Schistosoma mansoni murine models of helminth infections, revealing CX3CR1+CD4+ T cells to be an activated tissue-homing subset with varying capacity for cytokine production. Tracking these cells over time revealed that maintenance of CX3CR1 itself along with a TH2 phenotype conferred a survival advantage in the inflamed tissue. Single-cell RNA sequencing analysis of fate-mapped CX3CR1+CD4+ T cells from both the peripheral tissue and the spleen revealed a considerable level of diversity and identified a distinct population of BCL6+TCF-1+PD1+CD4+ T cells in the spleen during helminth infections. Conditional deletion of BCL6 in CX3CR1+ cells resulted in fewer CX3CR1+CD4+ T cells during infection, indicating a role in sustaining CD4+ T cell responses to helminth infections. Overall, our studies revealed the behavior and heterogeneity of CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections and identified BCL6 to be important in their maintenance.


Subject(s)
CD4-Positive T-Lymphocytes , Helminthiasis , Schistosoma mansoni , Animals , Mice , CD4-Positive T-Lymphocytes/metabolism , Helminthiasis/immunology , Inflammation/metabolism , Schistosoma mansoni/physiology
14.
J Neuromuscul Dis ; 11(2): 425-442, 2024.
Article in English | MEDLINE | ID: mdl-38250783

ABSTRACT

Background: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials. Objective: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting. Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources. Results: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0-6) month and at onasemnogene abeparvovec infusion was 3 (1-10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n = 81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related. Conclusion: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec.


Subject(s)
Biological Products , Muscular Atrophy, Spinal , Recombinant Fusion Proteins , Spinal Muscular Atrophies of Childhood , Infant , Infant, Newborn , Humans , Spinal Muscular Atrophies of Childhood/drug therapy , Prospective Studies , Genetic Therapy , Muscular Atrophy, Spinal/drug therapy , Registries
15.
Eur Rev Med Pharmacol Sci ; 28(1): 39-48, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38235896

ABSTRACT

OBJECTIVE: The aim of the study was to assess the disinfection efficacy, bond integrity, and nano hardness of caries-affected dentin (CAD) surface bonded to resin cement when disinfected with chlorhexidine (CHX), Methylene blue activated by Photodynamic therapy (MB-PDT), chitosan, silver diamine fluoride (SDF), chitosan activated by PDT, and SDF-diode laser against S. mutans. MATERIALS AND METHODS: A total of 60 human mandibular molars were extracted non-traumatically and gathered using ICDAS criteria. The dentin surface was prepared, leaving CAD to receive a disinfection procedure. After inoculation with S. mutans, the CAD samples were divided into six groups and disinfected with various disinfectants (n = 10) CHX, MB-PDT, chitosan, chitosan-PDT, SDF, and SDF+ diode laser. Survival rates of S. mutans were analyzed following the restoration of samples with resin cement via the etch and rinse method to assess SBS. Also, nano hardness was analyzed. Statistical analysis was performed by using the ANOVA and the Tukey multiple test (p<0.05). The Kruskal-Wallis test was used to evaluate the change in survival rate. RESULTS: Related to the survival rates, the SDF+ diode laser displayed the highest reduction in S. mutans levels and chitosan presented the lowest level of disinfection. The intergroup comparison revealed that CHX and chitosan-PDT displayed comparable outcomes of S. mutans survival rate to that of SDF+ diode laser (p>0.05). Likewise, MB-PDT and SDF displayed a comparable survival rate of S. mutans to Chitosan disinfection (p>0.05). Considering SBS and nano hardness, the highest SBS and NH were exhibited by the SDF+ diode laser, and the lowest SBS and NH values were exhibited by MB-PDT. The intragroup comparison revealed that CAD specimens disinfected with Chitosan-PDT showed comparable SBS and NH values to the SDF+ diode laser (p>0.05). CHX, chitosan, and SDF exhibited bond values and NH comparable to MB-PDT (p<0.05). CONCLUSIONS: Synergistic use of Silver diamine fluoride with diode laser and chitosan activated by PDT can be used as an alternative to CHX for controlling S. mutans growth, promoting enhanced bond efficacy and nano hardness for bonding resin cement to the caries-affected dentin.


Subject(s)
Chitosan , Photochemotherapy , Quaternary Ammonium Compounds , Silver Compounds , Humans , Methylene Blue , Dentin , Disinfection , Adhesives , Resin Cements , Dental Caries Susceptibility , Chlorhexidine/pharmacology , Chlorhexidine/therapeutic use , Materials Testing , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Fluorides, Topical
16.
Heliyon ; 10(1): e23586, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38173479

ABSTRACT

Energy consumption and emissions of a vehicle are highly influenced by road contexts and driving behavior. Especially, driving on horizontal curves often necessitates a driver to brake and accelerate, which causes additional fuel consumption and emissions. This paper proposes a novel optimal ecological (eco) driving scheme (EDS) using nonlinear model predictive control (MPC) considering various road contexts, i.e., curvatures and surface conditions. Firstly, a nonlinear optimization problem is formulated considering a suitable prediction horizon and an objective function based on factors affecting fuel consumption, emissions, and driving safety. Secondly, the EDS dynamically computes the optimal velocity trajectory for the host vehicle considering its dynamics model, the state of the preceding vehicle, and information of road contexts that reduces fuel consumption and carbon emissions. Finally, we analyze the effect of different penetration rates of the EDS on overall traffic performance. The effectiveness of the proposed scheme is demonstrated using microscopic traffic simulations under dense and mixed traffic environment, and it is found that the proposed EDS substantially reduces the fuel consumption and carbon emissions of the host vehicle compared to the traditional (human-based) driving system (TDS), while ensuring driving safety. The proposed scheme can be employed as an advanced driver assistance system (ADAS) for semi-autonomous vehicles.

17.
Sudan j. med. sci ; 19(1): 1-6, 2024. figures, tables
Article in English | AIM (Africa) | ID: biblio-1552433

ABSTRACT

Background: Peripheral neuropathy is a serious complication of diabetes, which has socioeconomic consequences as well as a reduced quality of life. Early neuropathic process recognition and management could alter its course and considerably reduce the associated morbidity and mortality. This study determines the effect of long-term glycemic control on diabetic peripheral neuropathy in people with type 2 diabetes (T2DM). Methods: A hospital-based study was carried out at the National Centre of Neurosciences and Ibrahim Malik Hospital in Khartoum. All individuals who were older than 18 years and have had T2DM for less than 10 years were recruited. Using accepted techniques, the BMI, HbA1c level, and nerve conduction studies (NCS) were measured. Data were analyzed using the Statistical Package for Social Sciences (SPSS), version 25.0 software. P-value ≤ 0.05 was considered significant. Results: Of the 95 patients with T2DM, 52 were male patients. Our findings showed that as the duration of diabetes increased, the sensory velocity reduced from 64.07 ± 3.22 to 54.00 ± 5.34 and the motor nerve from 63.39 ± 2.38 to 53.87 ± 2.08 (P = 0.05, P = 0.003, respectively). Additionally, with increased duration of diabetes, a significant decrease was seen in both motor nerve amplitude from 8.79 ± 3.11 to 6.94 ± 1.84 (P = 0.05) and sensory nerve amplitude from 25.71 ± 5.70 to 19.51 ± 6.51 (P = 0.003). Also, all parameters of NCS (velocity and amplitude) decreased when Hb A1c was >6 ­ sensory velocity from 63.96 ± 2.36 to 55.49 ± 2.43 (P = 0.03) and motor velocity from 63.00 ± 2.59 to 51.44 ± 1.66 (P = 0.02). And sensory amplitude decreased from 26.91 ± 1.26 to 20.85 ± 2.1 (P = 0.05), while motor amplitude decreased from 6.88 ± 3.55 to 6.61 ± 3.29 (P = 0.05). Additionally, there is a substantial (P = 0.05) correlation between sensory and motor amplitudes and the BMI. Conclusion: High BMI and poorly controlled (high HbA1c) long-term diabetes had a negative impact on all nerve conduction study parameters


Subject(s)
Humans , Male , Female
18.
J Genet Eng Biotechnol ; 21(1): 169, 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-38108957

ABSTRACT

BACKGROUND: Lactobacillus delbrueckii was one of the most common milk lactic acid bacterial strains (LAB) which characterized as probiotic with many health influencing properties. RESULTS: Among seven isolates, KH1 isolate was the best producer of folic acid with 100 µg/ml after 48 h of incubation; FolE gene expression after 24 h of incubation was in the highest value in case of KH1 with three folds. Lactose was the best carbon source for this KH1, besides the best next isolates KH80 and KH98. The selected three LAB isolates were identified through 16S rDNA as Lactobacillus delbrueckii. These three isolates have high tolerance against acidic pH 2-3; they give 45, 10, and 22 CFUs at pH 3, besides 9, 6, and 4 CFUs at pH2, respectively. They also have resistance against elevated bile salt range 0.1-0.4%. KH1 recorded 99% scavenging against 97.3% 1000 µg/ml ascorbic acid. Docking study exhibits the binding mode of folic acid which exhibited an energy binding of - 8.65 kcal/mol against DHFR. Folic acid formed four Pi-alkyl, Pi-Pi, and Pi-sigma interactions with Ala9, Ile7, Phe34, and Ile60. Additionally, folic acid interacted with Glu30 and Asn64 by three hydrogen bonds with 1.77, 1.76, and 1.96 Å. CONCLUSION: LAB isolates have probiotic properties, antioxidant activity, and desired organic natural source for folic acid supplementation that improve hemoglobin that indicated by docking study interaction.

19.
Nature ; 623(7986): 423-431, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37914927

ABSTRACT

Genetically engineered mouse models (GEMMs) help us to understand human pathologies and develop new therapies, yet faithfully recapitulating human diseases in mice is challenging. Advances in genomics have highlighted the importance of non-coding regulatory genome sequences, which control spatiotemporal gene expression patterns and splicing in many human diseases1,2. Including regulatory extensive genomic regions, which requires large-scale genome engineering, should enhance the quality of disease modelling. Existing methods set limits on the size and efficiency of DNA delivery, hampering the routine creation of highly informative models that we call genomically rewritten and tailored GEMMs (GREAT-GEMMs). Here we describe 'mammalian switching antibiotic resistance markers progressively for integration' (mSwAP-In), a method for efficient genome rewriting in mouse embryonic stem cells. We demonstrate the use of mSwAP-In for iterative genome rewriting of up to 115 kb of a tailored Trp53 locus, as well as for humanization of mice using 116 kb and 180 kb human ACE2 loci. The ACE2 model recapitulated human ACE2 expression patterns and splicing, and notably, presented milder symptoms when challenged with SARS-CoV-2 compared with the existing K18-hACE2 model, thus representing a more human-like model of infection. Finally, we demonstrated serial genome writing by humanizing mouse Tmprss2 biallelically in the ACE2 GREAT-GEMM, highlighting the versatility of mSwAP-In in genome writing.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Disease Models, Animal , Genetic Engineering , Genome , Tumor Suppressor Protein p53 , Animals , Humans , Mice , Alleles , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/genetics , COVID-19/virology , DNA/genetics , Drug Resistance, Microbial/genetics , Genetic Engineering/methods , Genome/genetics , Mouse Embryonic Stem Cells/metabolism , SARS-CoV-2/metabolism , Serine Endopeptidases/genetics , Tumor Suppressor Protein p53/genetics
20.
Biomimetics (Basel) ; 8(7)2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37999176

ABSTRACT

Recently, the usage of remote sensing (RS) data attained from unmanned aerial vehicles (UAV) or satellite imagery has become increasingly popular for crop classification processes, namely soil classification, crop mapping, or yield prediction. Food crop classification using RS images (RSI) is a significant application of RS technology in agriculture. It involves the use of satellite or aerial imagery to identify and classify different types of food crops grown in a specific area. This information can be valuable for crop monitoring, yield estimation, and land management. Meeting the criteria for analyzing these data requires increasingly sophisticated methods and artificial intelligence (AI) technologies provide the necessary support. Due to the heterogeneity and fragmentation of crop planting, typical classification approaches have a lower classification performance. However, the DL technique can detect and categorize crop types effectively and has a stronger feature extraction capability. In this aspect, this study designed a new remote sensing imagery data analysis using the marine predators algorithm with deep learning for food crop classification (RSMPA-DLFCC) technique. The RSMPA-DLFCC technique mainly investigates the RS data and determines the variety of food crops. In the RSMPA-DLFCC technique, the SimAM-EfficientNet model is utilized for the feature extraction process. The MPA is applied for the optimal hyperparameter selection process in order to optimize the accuracy of SimAM-EfficientNet architecture. MPA, inspired by the foraging behaviors of marine predators, perceptively explores hyperparameter configurations to optimize the hyperparameters, thereby improving the classification accuracy and generalization capabilities. For crop type detection and classification, an extreme learning machine (ELM) model can be used. The simulation analysis of the RSMPA-DLFCC technique is performed on two benchmark datasets. The extensive analysis of the results portrayed the higher performance of the RSMPA-DLFCC approach over existing DL techniques.

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