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1.
Artigo em Inglês | MEDLINE | ID: mdl-38856935

RESUMO

Identifying body fluids can be a critical clue that aids in reconstructing the crime scene. Semen and vaginal fluid identification is crucial, especially in cases of sexual assault. The majority of forensic studies focused on identifying normal body fluids and neglected the expression variation of semen in pathology. To differentiate between vaginal fluids, fertile and infertile semen samples (oligospermia and azoospermia) using miR 20b and miR197. A total of 48 body fluid samples, divided as 16 vaginal fluids, 16 fertile semen, and 16 infertile semen samples (8 with oligospermia and 8 with azoospermia), were collected, and the expression levels of miR-20b and miR-197 were detected by the SYBR Green real-time quantitative PCR technique. Our results showed significant different expression of these miRNAs in normal semen compared to vaginal and infertile semen. Moreover, we designed a model based on Fisher's discriminant function to forecast the group affiliations of unidentified samples. With three novel equations, we were able to accurately distinguish between semen and vaginal fluid, fertile and infertile semen, and oligospermia and azoospermia semen samples with validation accuracy of 81.3%, 100%, and 100%, respectively. MiR-20b and miR-197 expression levels are efficient and appropriate markers to distinguish semen from vaginal fluid and to differentiate between fertile and infertile semen samples. However, the present study is a preliminary study based on clinical samples, and the potential role of these markers in differentiating real crime scene samples is still unknown, so we recommend further research to investigate these markers expression while using forensic samples.

2.
Macromol Rapid Commun ; : e2400263, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878267

RESUMO

The rapid expansion of modern industry underscores the urgent need to address heavy metal pollution, which is a threat to human health and the environment. Efforts are underway to develop precise and cost-effective technologies for detecting heavy metal ions (M+-ion). One promising approach involves the use of conjugated microporous polymers (CMPs) modified with triphenylamine (TPA) and perylene (Peryl), known as TPA-Peryl-CMP, which emits strong red fluorescence. Various analytical techniques, such as BET analysis, Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and thermogravimetric analysis (TGA), were utilized to characterize the synthesized TPA-Peryl-CMP and understand its functional properties. In addition to its remarkable fluorescence behavior, TPA-Peryl-CMP shows promise as a sensor for Fe3+ ions using a turn-off strategy. Due to its exceptional stability and robust π-electron system, this platform demonstrates remarkable sensitivity and selectivity, significantly improving detection capabilities for specific analytes. Detailed procedures related to the mechanism for detecting Fe3+ ions were outlined for sensing Fe3+ ions, revealing a notably strong linear correlation within the concentration range of 0 to 3 µM, with a correlation coefficient of 0.9936 and an LOD of 20 nM. It is anticipated that the development of such a kind of TPA-Peryl-CMP will observe broader applications in the detection of various analytes related to environmental and biological systems, either directly or through further modifications. This article is protected by copyright. All rights reserved.

3.
Lancet Infect Dis ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38880111

RESUMO

BACKGROUND: A blood-stage Plasmodium falciparum malaria vaccine would provide a second line of defence to complement partially effective or waning immunity conferred by the approved pre-erythrocytic vaccines. RH5.1 is a soluble protein vaccine candidate for blood-stage P falciparum, formulated with Matrix-M adjuvant to assess safety and immunogenicity in a malaria-endemic adult and paediatric population for the first time. METHODS: We did a non-randomised, phase 1b, single-centre, dose-escalation, age de-escalation, first-in-human trial of RH5.1/Matrix-M in Bagamoyo, Tanzania. We recruited healthy adults (aged 18-45 years) and children (aged 5-17 months) to receive the RH5.1/Matrix-M vaccine candidate in the following three-dose regimens: 10 µg RH5.1 at 0, 1, and 2 months (Adults 10M), and the higher dose of 50 µg RH5.1 at 0 and 1 month and 10 µg RH5.1 at 6 months (delayed-fractional third dose regimen; Adults DFx). Children received either 10 µg RH5.1 at 0, 1, and 2 months (Children 10M) or 10 µg RH5.1 at 0, 1, and 6 months (delayed third dose regimen; Children 10D), and were recruited in parallel, followed by children who received the dose-escalation regimen (Children DFx) and children with higher malaria pre-exposure who also received the dose-escalation regimen (High Children DFx). All RH5.1 doses were formulated with 50 µg Matrix-M adjuvant. Primary outcomes for vaccine safety were solicited and unsolicited adverse events after each vaccination, along with any serious adverse events during the study period. The secondary outcome measures for immunogenicity were the concentration and avidity of anti-RH5.1 serum IgG antibodies and their percentage growth inhibition activity (GIA) in vitro, as well as cellular immunogenicity to RH5.1. All participants receiving at least one dose of vaccine were included in the primary analyses. This trial is registered at ClinicalTrials.gov, NCT04318002, and is now complete. FINDINGS: Between Jan 25, 2021, and April 15, 2021, we recruited 12 adults (six [50%] in the Adults 10M group and six [50%] in the Adults DFx group) and 48 children (12 each in the Children 10M, Children 10D, Children DFx, and High Children DFx groups). 57 (95%) of 60 participants completed the vaccination series and 55 (92%) completed 22 months of follow-up following the third vaccination. Vaccinations were well-tolerated across both age groups. There were five serious adverse events involving four child participants during the trial, none of which were deemed related to vaccination. RH5-specific T cell and serum IgG antibody responses were induced by vaccination and purified total IgG showed in vitro GIA against P falciparum. We found similar functional quality (ie, GIA per µg RH5-specific IgG) across all age groups and dosing regimens at 14 days after the final vaccination; the concentration of RH5.1-specific polyclonal IgG required to give 50% GIA was 14·3 µg/mL (95% CI 13·4-15·2). 11 children were vaccinated with the delayed third dose regimen and showed the highest median anti-RH5 serum IgG concentration 14 days following the third vaccination (723 µg/mL [IQR 511-1000]), resulting in all 11 who received the full series showing greater than 60% GIA following dilution of total IgG to 2·5 mg/mL (median 88% [IQR 81-94]). INTERPRETATION: The RH5.1/Matrix-M vaccine candidate shows an acceptable safety and reactogenicity profile in both adults and 5-17-month-old children residing in a malaria-endemic area, with all children in the delayed third dose regimen reaching a level of GIA previously associated with protective outcome against blood-stage P falciparum challenge in non-human primates. These data support onward efficacy assessment of this vaccine candidate against clinical malaria in young African children. FUNDING: The European and Developing Countries Clinical Trials Partnership; the UK Medical Research Council; the UK Department for International Development; the National Institute for Health and Care Research Oxford Biomedical Research Centre; the Division of Intramural Research, National Institute of Allergy and Infectious Diseases; the US Agency for International Development; and the Wellcome Trust.

4.
Future Sci OA ; 10(1): FSO956, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827803

RESUMO

Aim: This systematic review aims to consolidate findings from current clinical trials that compare the effectiveness of insulin infusion at 0.05 IU/kg/h versus 0.1 IU/kg/h in managing pediatric diabetic ketoacidosis. Methods: We searched several databases, including PubMed, Embase, Scopus, Cochrane Central and Web of Science. Our primary outcomes were time to reach blood glucose ≤250 mg/dl and time to resolution of acidosis. Secondary outcomes included rate of blood glucose decrease per hour, incidence of hypoglycemia, hypokalemia, treatment failure, and cerebral edema. Results & conclusion: The present study establishes that a low insulin dose exhibits comparable efficacy to the standard dosage for managing pediatric patients suffering from diabetic ketoacidosis, with a lower incidence of complications.


When kids with type 1 Diabetes (T1DM) face a serious complication called Diabetic Ketoacidosis (DKA), it becomes a life-threatening situation. This condition, responsible for significant mortality, involves high blood sugar, ketone buildup and acidity. Our study delves into a critical aspect of DKA treatment-finding the right insulin dose. By pooling the studies on this point, we discovered that using a lower insulin dose is just as effective as the standard dose in managing DKA in children, with fewer complications. This insight is crucial for improving the care and outcomes for young patients dealing with this challenging condition.

6.
J Am Heart Assoc ; 13(9): e034414, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38700032

RESUMO

BACKGROUND: Over the past decade, major society guidelines have recommended the use of newer P2Y12 inhibitors over clopidogrel for those undergoing percutaneous coronary intervention for acute coronary syndrome. It is unclear what impact these recommendations had on clinical practice. METHODS AND RESULTS: All percutaneous coronary intervention procedures (n=534 210) for acute coronary syndrome in England and Wales (April 1, 2010, to March 31, 2022) were retrospectively analyzed, stratified by choice of preprocedural P2Y12 inhibitor (clopidogrel, ticagrelor, and prasugrel). Multivariable logistic regression models were used to examine odds ratios of receipt of ticagrelor and prasugrel (versus clopidogrel) over time, and predictors of their receipt. Overall, there was a significant increase in receipt of newer P2Y12 inhibitors from 2010 to 2020 (2022 versus 2010: ticagrelor odds ratio, 8.12 [95% CI, 7.67-8.60]; prasugrel odds ratio, 6.14 [95% CI, 5.53-6.81]), more so in ST-segment-elevation myocardial infarction than non-ST-segment-elevation acute coronary syndrome indication. The most significant increase in odds of receipt of prasugrel was observed between 2020 and 2022 (P<0.001), following a decline/plateau in its use in earlier years (2011-2019). In contrast, the odds of receipt of ticagrelor significantly increased in earlier years (2012-2017, Ptrend<0.001), after which the trend was stable (Ptrend=0.093). CONCLUSIONS: Over a 13-year-period, there has been a significant increase in use of newer P2Y12 inhibitors, although uptake of prasugrel use remained significantly lower than ticagrelor. Earlier society guidelines (pre-2017) were associated with the highest rates of ticagrelor use for non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction cases while the ISAR-REACT 5 (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome) trial and later society guidelines were associated with higher prasugrel use, mainly for ST-segment-elevation myocardial infarction indication.


Assuntos
Síndrome Coronariana Aguda , Clopidogrel , Intervenção Coronária Percutânea , Guias de Prática Clínica como Assunto , Cloridrato de Prasugrel , Antagonistas do Receptor Purinérgico P2Y , Ticagrelor , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Síndrome Coronariana Aguda/terapia , Intervenção Coronária Percutânea/tendências , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Masculino , Feminino , Ticagrelor/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , País de Gales , Clopidogrel/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Padrões de Prática Médica/tendências , Inglaterra , Fidelidade a Diretrizes/tendências , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio sem Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Fatores de Tempo , Resultado do Tratamento
7.
Sci Rep ; 14(1): 11849, 2024 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-38783019

RESUMO

The resistance to antibiotics in Gram-negative bacilli causing sepsis is a warning sign of failure of therapy. Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) represent major Gram-negative bacilli associated with sepsis. Quinolone resistance is an emerging resistance among E. coli and K. pneumoniae. Therefore, the present study aimed to study the presence of plasmid-mediated quinolone resistance (PMQR) genes qnrA, qnrB, and qnrS by polymerase chain reaction (PCR) in E. coli and K. pneumoniae isolated from pediatric patients with sepsis. This was a retrospective cross-sectional study that included pediatric patients with healthcare-associated sepsis. The E. coli and K. pneumoniae isolates were identified by microbiological methods. PMQR genes namely qnrA, qnrB, and qnrS were detected in E. coli and K. pneumoniae isolates by PCR. The results were analyzed by SPPS24, and the qualitative data was analyzed as numbers and percentages and comparison was performed by Chi-square test, P was significant if < 0.05. The most prevalent gene detected by PCR was qnrA (75%), followed by qnrB (28.1%), and qnrS (25%). The most frequently detected qnr gene in E coli and K. pneumoniae was qnrA (28.8%, and 16.3% respectively). The present study highlights the high prevalence of ciprofloxacin resistance among E. coli and K. pneumoniae isolated from pediatric patients with healthcare-associated sepsis. There was a high frequency of PMQR genes in E. coli and K. pneumoniae isolated from pediatric patients. Therefore, it is important to monitor the spread of PMQR genes in clinical isolates to ensure efficient antibiotic use in those children. The finding denotes the importance of an antibiotics surveillance program.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Escherichia coli , Klebsiella pneumoniae , Plasmídeos , Quinolonas , Sepse , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Criança , Quinolonas/farmacologia , Plasmídeos/genética , Farmacorresistência Bacteriana/genética , Sepse/microbiologia , Sepse/tratamento farmacológico , Estudos Retrospectivos , Estudos Transversais , Antibacterianos/farmacologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico , Feminino , Masculino , Pré-Escolar , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/tratamento farmacológico , Testes de Sensibilidade Microbiana , Lactente , Proteínas de Bactérias/genética
8.
J Cardiovasc Echogr ; 34(1): 7-13, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818315

RESUMO

Introduction: The Trifecta bioprosthetic valve has been commonly used for surgical aortic valve replacement (SAVR). Multiple studies have been done to define the rate of structural valve degeneration (SVD) and failure (SVF), but the outcomes are still debatable. Therefore, we aim to conduct this single-center study to estimate the rate and predictors of SVD/SVF. Methodology: This retrospective observational cohort single-center study was conducted between 2014 and 2019 among Trifecta SAVR patients. Data were patient's characteristics collected from electronic medical records at baseline and follow-up (3-5 years). Statistical analysis was performed with a significance level of P ≤ 0.05. Results: A total of 271 eligible patients were identified. Most of our sample were males (57.9%), with a mean age of 71.1 ± 10.6 years. The mean baseline preoperative ejection fraction (EF) was 53.0%, with no change (P = 0.88) in the immediate postoperative EF (53.6%). A most recent follow-up EF revealed a significant increase of EF (55.2%), P = 0.01. Furthermore, there was a significant increase from peak velocity to PVMRE (mean difference [MD] ± standard error of mean (SEM) [0.15 ± 0.04], P < 0.01), an increase in pressure gradient (PGIPE) to PGMRE (MD ± SEM [1.70 ± 0.49], P < 0.01), and a decrease in Doppler velocity index (DVIIPE) to DVIMRE (MD ± SEM [-0.037 ± 0.01], P = 0.01). Regarding the SVF rate, 13 (4.8%) patients had failed valves requiring replacement throughout the study period. Conclusions: Over a 5-year follow-up period, 4.8% had SVF with an SVD of 23.2%, with the majority of SVD not being clinically significant except in six patients. These results corroborate with a previously published study suggesting a bad clinical outcome of Trifecta valve placement.

9.
J Viral Hepat ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771311

RESUMO

Patients living with HIV infection (PLWH) are at risk of acquiring HBV and HDV. The present study aimed to determine the prevalence and characteristics of HIV-HDV-HBV tri-infection in comparison with HIV-HBV coinfection and to estimate severities and outcomes of associated liver diseases in Mauritanian PLWH. Two-hundred-ninety-two consecutive HBsAg-positive PLWH were included (mean age: 37 years). Clinical data were recorded. Anti-HDV antibodies, HBV and HDV viral loads (VLs) and genotype were determined. APRI, FIB-4 and FibroScan were performed to evaluate the severity of liver disease. The anti-HDV antibodies prevalence was 37% and HDV RNA was positive in 40.7% of patients. Genetic diversities were found with HDV genotype 1 (93%) and HBV genotypes D (42.5%) and E (38%). The HBV VL was detectable in 108 patients at inclusion, and mutations associated with HBV resistance were found in 20. For almost all variables studied, including FIB-4 and APRI scores, no significant differences were found between anti-HDV-Ab positive or negative patients. FibroScan examination, which was performed in 110 patients at end-of-follow-up showed higher, but NS values, in HDV positive patients. After a mean follow-up of 24.55 ± 8.01 months (n = 217 patients), a highly significant worsening of APRI and FIB-4 scores was found. Moreover, patients with HDV showed more severe liver disease progression despite an efficient therapy. In a substantial Mauritanian cohort of relatively young PLWH, we found high HDV prevalence and worsening liver disease. In high-risk countries, screening for HDV and providing appropriate follow-up and treatments are warranted in PLWH.

10.
Foodborne Pathog Dis ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804146

RESUMO

Plasmid-mediated colistin resistance is an emerging One Health challenge at the human-food-environment interface. In this study, 12 colistin-resistant Escherichia coli carrying mcr-1.1 gene were characterized using whole-genome sequencing. This is the first report from locally produced chicken meat in the United Arab Emirates. The characterized isolates harbored virulence-associated factors ranging from 4 to 17 genes per isolate. The multilocus sequence type 1011 was identified in 5 (41.6%) isolates. Six (50.0%) of the isolates harbored blaCTX-M-55. All of the E. coli isolates contained Incl2 plasmids. This study highlights for the first time chicken meat as a potential reservoir of mcr-1.1 carrying E. coli in the UAE. This study has implications for food safety and underscores the need for comprehensive surveillance strategies to monitor the spread of colistin resistance. Results presented in this short communication address knowledge gaps on the epidemiology of plasmid-mediated colistin resistance in the Middle East food production chain.

11.
Toxicol Res (Camb) ; 13(3): tfae071, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38720817

RESUMO

Astaxanthin (ASX), a red pigment belonging to carotenoids, has antioxidant activity and anti-oxidative stress effect. Atrazine (ATZ), a frequently used herbicide, whose degradation products are the cause for nephrosis and other oxidative stress associated diseases. This study was aimed to reveal the potential protective mechanism of astaxanthin against atrazine-induced nephrosis. Atrazine was orally given (250 mg/kg bw) to the mice along with astaxanthin (100 mg/kg bw) for 28 days. Serum biochemical indicators, oxidative stress biomarkers, ATPase activities, ion concentration, histomorphology, and various renal genes expression linked with apoptosis, Nrf2 signaling pathway, and aquaporins (AQPs) were assessed. It was found that serum creatinine (SCr), blood urea nitrogen (BUN), and MDA levels were significantly increased after the treatment of atrazine, whereas serum renal oxidative stress indicators like CAT, GSH, T-AOC, SOD decreased. Renal histopathology showed that atrazine significantly damaged renal tissues. The activities of Ca 2+-Mg 2+-ATPase were increased whereas Na +-K +-ATPase decreased significantly (P < 0.05). Moreover, results confirmed that the expression of AQPs, Nrf2, and apoptosis genes were also altered after atrazine administration. Interestingly, astaxanthin supplementation significantly (P < 0.05) improved atrazine-induced nephrotoxicity via decreasing SCr, BUN, oxidative stress, ionic homeostasis and reversing the changes in AQPs, Nrf2, and apoptosis gene expression. These findings collectively suggested that astaxanthin has strong potential ameliorative impact against atrazine induced nephrotoxicity.

12.
Am J Perinatol ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744322

RESUMO

OBJECTIVES: Our objective was to investigate the prevalence of small intestinal atresia and Hirschsprung's disease (HD) in infants with Down syndrome (DS) and its impact on outcomes. STUDY DESIGN: We analyzed the National Inpatient Sample dataset. We included infants with DS, small intestinal atresia, HD, and the concomitant occurrence of both conditions. Regression analysis was used to control clinical and demographic variables. RESULTS: A total of 66,213,034 infants were included, of whom, 99,861 (0.15%) had DS. The concomitant occurrence of small intestinal atresia and HD was more frequent in infants with DS compared with the general population, adjusted odds ratio (aOR): 122, 95% confidence interval (CI): 96-154, (p < 0.001). Infants with DS and concomitant small intestinal atresia and HD had higher mortality compared with those without these conditions, aOR: 8.59, 95% CI: 1.95-37.8. CONCLUSION: Infants with DS are at increased risk of concomitant small intestinal atresia and HD, and this condition is associated with increased mortality. KEY POINTS: · Infants with Down syndrome are at increased risk of congenital GI anomalies.. · Infants with Down syndrome are at increased risk of necrotizing enterocolitis.. · Increased mortality in Down syndrome infants with concomitant small intestinal atresia and Hirschsprung's disease..

13.
Sci Rep ; 14(1): 11147, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750082

RESUMO

Biofloc (BF) stands out as a promising system for sustainable shrimp farming. Optimizing various culture conditions, such as stocking density, carbohydrate source, and feeding management, is crucial for the widespread adoption of the BF system. This study compares the growth performance of white-leg shrimp (Litopenaeus vannamei) in culture ponds at low density (LD) with 50 organisms/m2 and high density (HD) with 200 organisms/m2. Post-larvae of white-leg shrimp were stocked for 16 weeks in both LD and HD groups. The LD group exhibited a superior survival rate, growth rate, and feed consumption compared to the HD group. The BF from the LD system recorded a significantly higher protein content (16.63 ± 0.21%) than the HD group (15.21 ± 0.34%). Heterotrophic bacterial counts in water did not significantly differ with stocking density. However, Vibrio count in water samples was higher in the HD group (3.59 ± 0.35 log CFU/mL) compared to the LD group (2.45 ± 0.43 log CFU/mL). The whole shrimp body analysis revealed significantly higher protein and lipid content in the LD group. In contrast, the total aerobic bacterial count in shrimp from the HD group was high, with the identification of Salmonella enterica ssp. arizonae. Additionally, Vibrio counts in shrimp samples were significantly higher in the HD group (4.63 ± 0.32 log CFU/g) compared to the LD group (3.57 ± 0.22 log CFU/g). The expression levels of immune-associated genes, including prophenoloxidase, transglutaminase, penaiedin 3, superoxide dismutase, lysozyme, serine proteinase, and the growth-related gene ras-related protein (rap-2a), were significantly enhanced in the LD group. Conversely, stress-related gene expression increased significantly in the HD group. Hepatopancreases amylase, lipase, and protease were higher in the LD group, while trypsin activity did not differ significantly. Antioxidant enzyme activity (catalase, glutathione, glutathione peroxidase, and superoxide dismutase) significantly increased in the LD group. The histological structure of hepatopancreas, musculature, and female gonads remained similar in both densities. However, negative effects were observed in the gills' histology of the HD group. These results suggest that increasing stocking density is associated with significantly negative biological, microbial, and physiological effects on white-leg shrimp under the BF system.


Assuntos
Aquicultura , Penaeidae , Animais , Penaeidae/microbiologia , Penaeidae/crescimento & desenvolvimento , Penaeidae/metabolismo , Penaeidae/fisiologia , Penaeidae/imunologia , Aquicultura/métodos , Vibrio , Brancos
14.
PLoS One ; 19(5): e0300645, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753855

RESUMO

For a car that is propelled by an armature-controlled DC motor This study proposes an adjustable linear positioning control. In this paper, to optimize the parameters of the car's position controller the sine cosine optimization algorithm (SCA) is utilized, with support from the Balloon effect (BE), The BE is incorporated to enhance the responsiveness of the traditional sine cosine optimization algorithm when faced with external disturbances and variations in system parameters. In the proposed approach, the determined value of the open loop transfer function of the motor and the updated values of the controller gains serve as the basis for the modified sine cosine algorithm's objective function (OF). Under the influence of changes in motor parameters and step load disturbances, the system using the suggested controller is evaluated. Results from simulations and experiments show that the proposed adaptive controller, which implements the modified sine cosine algorithm, enhances the system's overall performance in the presence of load disturbances and parameter uncertainties.


Assuntos
Algoritmos , Humanos , Simulação por Computador , Desenho de Equipamento
15.
Clin Exp Dermatol ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38699939

RESUMO

BACKGROUND: Dysregulated interleukin (IL)-17/IL-23 signaling contributes to psoriasis pathogenesis. Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt), a key transcription factor responsible for IL-17 synthesis and a regulator of the T helper 17 cell lineage program. OBJECTIVE: To evaluate the efficacy and safety of cedirogant to treat moderate-to-severe psoriasis. METHODS: In this phase 2b, multicenter, double-blind, 16-week study (NCT05044234), adults aged 18-65 years were randomized 1:1:1:1 to once-daily oral cedirogant 75 mg, 150 mg, 375 mg, or placebo. Assessments included ≥50%/75%/90%/100% improvement from baseline in Psoriasis Area and Severity Index (PASI 50/75/90/100), static Physician Global Assessment 0/1, Psoriasis Symptoms Scale 0, and improvements in itch, adverse events (AEs), pharmacokinetics, and IL-17A/F levels. Efficacy results based on observed cases were summarized descriptively. RESULTS: Of 156 enrolled patients, most were male (70.5%); 39 patients were randomized to each treatment. Only 47 patients completed the study; the study was terminated early due to preclinical findings. At week 16, PASI 75 achievement rates (primary endpoint) were 28.6%, 7.7%, and 41.7% in the cedirogant 75 mg, 150 mg, and 375 mg groups, respectively, and 0% in the placebo group. AE rates were similar in the cedirogant 75 mg, 150 mg, and placebo groups and higher in the cedirogant 375-mg group; most AEs were mild or moderate. CONCLUSIONS: Patients with psoriasis who received cedirogant showed PASI improvement and cedirogant was generally well tolerated. Results should be interpreted in the context of early study termination. Cedirogant development has been discontinued.

17.
EMBO J ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806659

RESUMO

Microtubule-based kinesin motor proteins are crucial for intracellular transport, but their hyperactivation can be detrimental for cellular functions. This study investigated the impact of a constitutively active ciliary kinesin mutant, OSM-3CA, on sensory cilia in C. elegans. Surprisingly, we found that OSM-3CA was absent from cilia but underwent disposal through membrane abscission at the tips of aberrant neurites. Neighboring glial cells engulf and eliminate the released OSM-3CA, a process that depends on the engulfment receptor CED-1. Through genetic suppressor screens, we identified intragenic mutations in the OSM-3CA motor domain and mutations inhibiting the ciliary kinase DYF-5, both of which restored normal cilia in OSM-3CA-expressing animals. We showed that conformational changes in OSM-3CA prevent its entry into cilia, and OSM-3CA disposal requires its hyperactivity. Finally, we provide evidence that neurons also dispose of hyperactive kinesin-1 resulting from a clinic variant associated with amyotrophic lateral sclerosis, suggesting a widespread mechanism for regulating hyperactive kinesins.

18.
J Perinatol ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811756

RESUMO

OBJECTIVE: To examine the association of placental abruption with intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants. METHODS: We examined the National Inpatient Sample (NIS) datasets. Preterm infants <1500 g birth weight (BW) were included. The odds ratios (OR) of developing IVH and severe IVH in association with placental abruption were calculated. Adjusted OR (aOR) were calculated using logistic regression models. RESULTS: The study included 113,445 VLBW infants. IVH occurred in 18.7% in the infants who were born to mothers with history of placental abruption versus 14.7% in infants without placental abruption, aOR 1.25 (95%CI: 1.13-1.38), p < 0.001. Severe IVH occurred in 6.4% in infants born to mothers with history of placental abruption versus 4.0% in those without placental abruption, aOR 1.53 (95%CI: 1.30-1.78), p < 0.001. CONCLUSION: Placental abruption is associated with increased prevalence of IVH and severe IVH in VLBW infants.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38689072

RESUMO

Tilmicosin (TIL) is a semisynthetic macrolide antibiotic with a broad spectrum of activity derived from tylosin. TIL is effective in the treatment of bovine and ovine respiratory diseases caused by different microbes. In parallel, Rhodiola rosea (RHO) is a popular herbal remedy because of its anti-inflammatory and antioxidant qualities. The experiment lasted for 12 days. Depending on the experimental group, the animals received either distilled water or RHO root extract dissolved in distilled water for 12 days through a stomach tube, and the single subcutaneous injection on day 6 of the experiment of either 500 µL of 0.9% NaCl or TIL dissolved in 500 µL 0.9% NaCl. Samples and blood were collected for serum analysis, gene expression, and immunohistochemistry screening at liver and kidney levels. TIL injection increased serum levels of hepatic and renal markers (ALP, ALT, AST, TC, TG, creatinine, and urea) with decreased total proteins. In parallel, TIL induced hepatic and renal oxidative stress as there was an increase in malondialdehyde levels, with a decrease in catalase and reduced glutathione activities. Of interest, pre-administration of RHO inhibited TIL-induced increase in hepato-renal markers, decreased oxidative stress, and increased liver and kidney antioxidant activities. Quantitative RT-PCR showed that TIL increased the liver's HSP70 (heat shock protein), NFkB, and TNF-α mRNA expression. Moreover, TIL upregulated the expression of desmin, nestin, and vimentin expression in the kidney. The upregulated genes were decreased significantly in the protective group that received RHO. Serum inflammatory cytokines and genes of inflammatory markers were affected in liver tissues (HSP70, NFkB, and TNF-α) and kidney tissues (desmin, nestin, and vimentin)-TIL-induced hepatic vacuolation and congestion together with glomerular atrophy. The immunoreactivity of PCNA and HMGB1 was examined immunohistochemically. At cellular levels, PCNA was decreased while HMGB1 immunoreactivity was increased in TIL-injected rats, which was improved by pre-administration of RHO. RHO administration protected the altered changes in liver and renal histology. Current findings support the possible use of RHO to shield the liver and kidney from the negative effects of tilmicosin.

20.
J Biol Eng ; 18(1): 26, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589951

RESUMO

BACKGROUND: The Environmental Protection Agency has listed eggshell waste as the 15th most significant food industry pollution hazard. Using eggshell waste as a renewable energy source has been a hot topic recently. Therefore, finding a sustainable solution for the recycling and valorization of eggshell waste by investigating its potential to produce acid phosphatase (ACP) and organic acids by the newly-discovered B. sonorensis was the target of the current investigation. RESULTS: Drawing on both molecular and morphological characterizations, the most potent ACP-producing B. sonorensis strain ACP2, was identified as a local bacterial strain obtained from the effluent of the paper and pulp industries. The use of consecutive statistical experimental approaches of Plackett-Burman Design (PBD) and Orthogonal Central Composite Design (OCCD), followed by pH-uncontrolled cultivation conditions in a 7 L bench-top bioreactor, revealed an innovative medium formulation that substantially improved ACP production, reaching 216 U L-1 with an ACP yield coefficient Yp/x of 18.2 and a specific growth rate (µ) of 0.1 h-1. The metals Ag+, Sn+, and Cr+ were the most efficiently released from eggshells during the solubilization process by B. sonorensis. The uncontrolled pH culture condition is the most suitable and favoured setting for improving ACP and organic acids production. Quantitative and qualitative analyses of the produced organic acids were carried out using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Lactic acid, citric acid, and hydroxybenzoic acid isomer were the most common organic acids produced throughout the cultivation process. The findings of TGA, DSC, SEM, EDS, FTIR, and XRD analysis emphasize the significant influence of organic acids and ACP activity on the solubilization of eggshell particles. CONCLUSIONS: This study emphasized robust microbial engineering approaches for the large-scale production of a newly discovered acid phosphatase, accompanied by organic acids production from B. sonorensis. The biovalorization of the eggshell waste and the production of cost-effective ACP and organic acids were integrated into the current study, and this was done through the implementation of a unique and innovative medium formulation design for eggshell waste management, as well as scaling up ACP production on a bench-top scale.

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