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1.
Food Chem ; 463(Pt 4): 141460, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39357309

RESUMO

This review focuses on trace element speciation in edible mushrooms, providing information on analytical methods, available literature data, and health risk assessment. All steps of analytical procedures were presented, including extraction, separation and quantification. It compiles fragmented literature data on trace element speciation, focusing on arsenic, chromium, selenium, mercury, and antimony. Key findings include non-bioaccumulative chromium, the prevalence of Sb(V), mercury accumulation in contaminated sites, diverse arsenic and selenium speciation. Safe intake limits by agencies like USEPA indicate low risk for Cr(VI) and Sb but significant hazards from mercury and methylmercury, especially in contaminated areas: about 10 % of samples exceed safe limits for inorganic arsenic, and selenium enrichment often surpasses safety thresholds. The review underscores the need for standardized methods, speciation analyses of all toxicologically relevant species, and research on cooking impacts to improve health risk evaluations: establishing safe conditions for mushroom consumption remains a far-fetched goal.

2.
Materials (Basel) ; 17(19)2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39410388

RESUMO

This study aims to compare the cyclic fatigue resistance of nickel-titanium (NiTi) endodontic instruments, focusing on the impact of various alloy treatments and manufacturing processes across different generations of these instruments; Twenty instrumentation systems from different generations, comprising both continuous and reciprocating motion designs, were tested. Four hundred instruments underwent cyclic fatigue testing using an INSTRON machine, with the time and number of cycles to fracture (NCF) recorded for each instrument. Statistical analyses were performed to compare the fatigue resistance between systems, generations, and motion types; Instruments treated with advanced thermal processing, such as Excalibur, Reciproc Blue, and TruNatomy, demonstrated superior resistance to fracture, whereas systems like Protaper Universal, K3XF, and 2Shape showed the lowest resistance. Reciprocating instruments generally exhibited higher cyclic fatigue resistance than continuously rotating instruments; Technological advancements in NiTi instrument design, especially the implementation of heat-treated alloys, have improved cyclic fatigue resistance, enhancing the safety and efficiency of endodontic treatments. Reciprocating systems, in particular, exhibit superior fracture resistance, suggesting their greater utility in challenging clinical conditions.

3.
Sci Rep ; 14(1): 22071, 2024 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333147

RESUMO

The Silurian-Devonian transition played a crucial role in the development of early terrestrial ecosystems due to the rapid diversification of early vascular plants. However, records of Pridolian plants in western Gondwana are scarce, limited to outcrops located in southern Bolivia. In this contribution, an association of fossil plants housed in the Rinconada Formation is presented. This association corresponds to primitive fossil flora with reproductive structures and sterile axes linked to basal tracheophytes. The fossil assemblage is composed of Aberlemnia caledonica, Caia langii Cooksonia cf. cambrensis, C. paranensis, C. cf. pertoni, Hostinella sp, Cf. Isidrophyton sp, Salopella marcensis, Steganoteca striata, two morphotypes of doubtful taxonomy, and graptolites colonies. The association between flora remains and graptolites, represents a parautochthonous assemblage in an inner marine platform, dominated by gravity flows. This record has paleophytogeographic importance indicating the extension of the northwest Gondwana-southern Laurusia unit to more southern areas of Gondwana. This expansion would have been favored by the post-glacial climatic improvement of the Late Silurian, together with a great radiation capacity and environmental flexibility of the flora. Furthermore, the biochron is extended of three taxa (A. caledonica, C. paranensis and Cf. Isidrophyton sp) first known from the Lochkovian, to the Pridoli.


Assuntos
Fósseis , Fósseis/anatomia & histologia , Embriófitas/classificação , Embriófitas/anatomia & histologia , Ecossistema , Bolívia , Evolução Biológica , Paleontologia
4.
Mol Biol Evol ; 41(10)2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39241178

RESUMO

It has been proposed that the phenotypic differences in cognitive abilities between humans and our closest living relatives, chimpanzees, are largely due to changes in the regulation of neurodevelopmental genes. We have previously found that the neurodevelopmental transcription factor gene NPAS3 accumulates the largest number of human accelerated regions (HARs), suggesting it may play some role in the phenotypic evolution of the human nervous system. In this work, we performed a comparative functional analysis of NPAS3-HAR202 using enhancer reporter assays in transgenic zebrafish and mice. We found that the Homo sapiens HAR202 ortholog failed to drive reporter expression to the zebrafish nervous system, in high contrast to the strong expression displayed by the rest of the vertebrate ortholog sequences tested. Remarkably, the HAR202 ortholog from archaic humans (Neanderthals/Denisovans) also displayed a pan-vertebrate expression pattern, despite the fact that archaic and modern humans have only one nucleotide substitution. Moreover, similar results were found when comparing enhancer activity in transgenic mice, where we observed a loss of activity of the modern human version in the mouse developing brain. To investigate the functional importance of HAR202, we generated mice lacking HAR202 and found a remarkable decrease of Npas3 expression in the forebrain during development. Our results place HAR202 as one of the very few examples of a neurodevelopmental transcriptional enhancer displaying functional evolution in the brain as a result of a fast molecular evolutionary process that specifically occurred in the human lineage.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Elementos Facilitadores Genéticos , Proteínas do Tecido Nervoso , Prosencéfalo , Peixe-Zebra , Animais , Humanos , Prosencéfalo/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Camundongos , Peixe-Zebra/genética , Evolução Molecular , Camundongos Transgênicos , Regulação da Expressão Gênica no Desenvolvimento
5.
Eur Phys J E Soft Matter ; 47(9): 61, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39343851

RESUMO

The molecular nature of the phases that conform the two-liquid scenario is elucidated in this work in the light of a molecular principle governing water structuring, which unveils the relevance of the contraction and reorientation of the second molecular shell to allow for the existence of coordination defects in water's hydrogen bond network. In turn, such principle is shown to also determine the behavior of hydration and nanoconfined water while enabling to define conditions for wettability (quantifying hydrophobicity and predicting drying transitions), thus opening the possibility to unravel the active role of water in central fields of research.

7.
Surg Oncol Clin N Am ; 33(4): 669-681, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39244286

RESUMO

This article examines disparities in head and neck cancer across the cancer care continuum. It provides a public health lens to understand multilevel determinants of health behavior and the importance of social determinants of health. This article reviews the evidence base showing profound differences in incidence, treatment, and survival for patients with head and neck cancer by race, ethnicity, socioeconomic status, and geography. Continued research is needed to understand and address disparities for patients with head and neck cancer.


Assuntos
Neoplasias de Cabeça e Pescoço , Disparidades em Assistência à Saúde , Humanos , Neoplasias de Cabeça e Pescoço/terapia , Fatores Socioeconômicos , Acessibilidade aos Serviços de Saúde
10.
J Bacteriol ; 206(9): e0022724, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39171915

RESUMO

As a biological byproduct from both humans and microbes, glycerol's contribution to microbial homeostasis in the oral cavity remains understudied. In this study, we examined glycerol metabolism by Streptococcus sanguinis, a commensal associated with oral health. Genetic mutants of glucose-PTS enzyme II (manL), glycerol metabolism (glp and dha pathways), and transcriptional regulators were characterized with regard to glycerol catabolism, growth, production of hydrogen peroxide (H2O2), transcription, and competition with Streptococcus mutans. Biochemical assays identified the glp pathway as a novel source for H2O2 production by S. sanguinis that is independent of pyruvate oxidase (SpxB). Genetic analysis indicated that the glp pathway requires glycerol and a transcriptional regulator, GlpR, for expression and is negatively regulated by PTS, but not the catabolite control protein, CcpA. Conversely, deletion of either manL or ccpA increased the expression of spxB and a second, H2O2-non-producing glycerol metabolic pathway (dha), indicative of a mode of regulation consistent with conventional carbon catabolite repression (CCR). In a plate-based antagonism assay and competition assays performed with planktonic and biofilm-grown cells, glycerol greatly benefited the competitive fitness of S. sanguinis against S. mutans. The glp pathway appears to be conserved in several commensal streptococci and actively expressed in caries-free plaque samples. Our study suggests that glycerol metabolism plays a more significant role in the ecology of the oral cavity than previously understood. Commensal streptococci, though not able to use glycerol as a sole carbohydrate source for growth, benefit from the catabolism of glycerol through production of both ATP and H2O2. IMPORTANCE: Glycerol is an abundant carbohydrate in the oral cavity. However, little is understood regarding the metabolism of glycerol by commensal streptococci, some of the most abundant oral bacteria. This was in part because most streptococci cannot grow on glycerol as the sole carbon source. In this study, we show that Streptococcus sanguinis, a commensal associated with dental health, can degrade glycerol for persistence and competition through two pathways, one of which generates hydrogen peroxide at levels capable of inhibiting Streptococcus mutans. Preliminary studies suggest that several additional commensal streptococci are also able to catabolize glycerol, and glycerol-related genes are actively expressed in human dental plaque samples. Our findings reveal the potential of glycerol to significantly impact microbial homeostasis, which warrants further exploration.


Assuntos
Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Glicerol , Peróxido de Hidrogênio , Boca , Streptococcus mutans , Glicerol/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Streptococcus mutans/genética , Streptococcus mutans/metabolismo , Streptococcus mutans/crescimento & desenvolvimento , Boca/microbiologia , Streptococcus sanguis/metabolismo , Streptococcus sanguis/genética , Humanos , Biofilmes/crescimento & desenvolvimento
11.
Laryngoscope ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39119758

RESUMO

OBJECTIVES: To compare the efficacy of the 445-nm blue laser to the 585-nm pulsed dye laser (PDL) and 532-nm potassium-titanyl-phosphate (KTP) laser in the treatment of benign laryngeal lesions. DATA SOURCES: Cochrane Library, PubMed, Scopus, and CINAHL. REVIEW METHODS: Following PRISMA guidelines, databases were searched from inception through January 29, 2024, for studies reporting the use of photoangiolytic lasers for treatment of benign laryngeal lesions, including the 585-nm PDL, 532-nm KTP laser, and 445-nm blue laser. Outcome measures included lesion resolution (%), mean differences (Δ) in Voice Handicap Index (VHI-10), and summed dysphonia grade, roughness, and breathiness (GRB) scale. RESULTS: A total of 45 studies were included for meta-analysis, consisting of 348 patients treated with PDL, 550 patients with KTP laser, and 338 patients with blue laser. Treatment with blue laser resulted in the greatest lesion resolution (94.0%; 95% confidence interval [CI]: 90.2%-96.7%), followed by KTP laser (90.4%; 95% CI: 84.1%-95.2%), and PDL (86.9%; 95% CI: 62.9%-99.2%). VHI-10 improved significantly in patients following treatment with blue laser (Δ13.3; 95% CI: 10.7-16.0; p < 0.0001), KTP laser (Δ10.3; 95% CI: 7.4-13.3; p < 0.0001), and PDL (Δ7.4; 95% CI: 4.8-10.1; p < 0.0001). GRB improved significantly in patients following treatment with blue laser (Δ4.1; 95% CI: 2.9-5.2; p < 0.0001), KTP laser (Δ3.0; 95% CI: 2.0-4.0; p < 0.0001), and PDL (Δ2.5; 95% CI: 0.8-4.2; p = 0.005). CONCLUSIONS: Photoangiolytic lasers are effective in treating benign laryngeal lesions. Blue lasers are promising for laryngeal laser surgery. Laryngoscope, 2024.

12.
Am J Otolaryngol ; 45(6): 104464, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39106680

RESUMO

INTRODUCTION: While the presence of human papillomavirus (HPV) is known to affect the outcomes of oropharyngeal squamous cell carcinoma (OPSCC), there is a significant gap in research regarding the potential sex-based differences. This systematic review-metanalysis (SR-MA) aims to evaluate if sex is a prognostic factor in HPV-associated OPSCC. METHODS: A systematic review and meta-analysis was performed. COCHRANE Library, CINAHL, PubMed, and Scopus were searched for English-language articles from 1966 to October 2023. Studies with multivariable analysis of overall survival (OS) based on sex were included. Adjusted hazard ratios (aHRs) with a 95 % confidence interval (CI) were presented for the reported outcome. A meta-analysis of single means, proportions, and aHRs with a 95 % CI was conducted. RESULTS: This SR-MA included 24 studies (n = 101,574). The proportion of female patients was 16.6 % [15.4 %-17.8 %]. A meta-analysis of all included studies with OS showed no significant difference in survival between male and female patients. In US-based studies, no significant difference in OS is observed between male and female patients. International studies reported a better OS for female patients (aHR = 0.68, 95 % CI, 0.48-0.95). CONCLUSION: This meta-analysis suggests that sex does not represent a significant prognostic factor for patients affected by HPV associated OPSCC. When stratified by geographic location, findings suggests that female patients from the US with HPV OPSCC have similar OS than male patients but in international studies it suggests male patients have worse OS.

13.
Alzheimers Dement ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090679

RESUMO

INTRODUCTION: Triggering receptor expressed on myeloid cells 2 (TREM2) agonists are being clinically evaluated as disease-modifying therapeutics for Alzheimer's disease. Clinically translatable pharmacodynamic (PD) biomarkers are needed to confirm drug activity and select the appropriate therapeutic dose in clinical trials. METHODS: We conducted multi-omic analyses on paired non-human primate brain and cerebrospinal fluid (CSF), and stimulation of human induced pluripotent stem cell-derived microglia cultures after TREM2 agonist treatment, followed by validation of candidate fluid PD biomarkers using immunoassays. We immunostained microglia to characterize proliferation and clustering. RESULTS: We report CSF soluble TREM2 (sTREM2) and CSF chitinase-3-like protein 1 (CHI3L1/YKL-40) as PD biomarkers for the TREM2 agonist hPara.09. The respective reduction of sTREM2 and elevation of CHI3L1 in brain and CSF after TREM2 agonist treatment correlated with transient microglia proliferation and clustering. DISCUSSION: CSF CHI3L1 and sTREM2 reflect microglial TREM2 agonism and can be used as clinical PD biomarkers to monitor TREM2 activity in the brain. HIGHLIGHTS: CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2) reflects brain target engagement for a novel TREM2 agonist, hPara.09. CSF chitinase-3-like protein 1 reflects microglial TREM2 agonism. Both can be used as clinical fluid biomarkers to monitor TREM2 activity in brain.

14.
Artigo em Inglês | MEDLINE | ID: mdl-39110231

RESUMO

PURPOSE: To determine factors associated with steroid responsiveness and efficacy of biologic disease-modifying anti-rheumatic (DMARD) use in patients with Cogan Syndrome (CS). METHODS: A systematic search of Cochrane Library, PubMed, CINAHL, and Scopus was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Any study describing audiometric or vestibular data and pharmacologic treatment in patients with CS was included. Due to limited literature, only case reports/case series were included. RESULTS: Seventy case reports or case series studies comprising 79 individual cases of CS were included. A difference in vestibular symptoms with a higher prevalence in the steroid-resistant group than the steroid-responsive group was found (79.5% vs 57.9%, p = 0.04). Eighteen (60.0%) patients treated only with oral steroids had no audiological improvement, while twelve (n = 12; 85.7%) patients treated with biologic DMARD showed audiological improvement. The steroid-responsive group had an overall better response to DMARDs than the steroid-resistant group (62.1% vs 45.0%; 100.0% vs 77.8%). CONCLUSIONS: Our study synthesized the available literature to better characterize steroid resistance in patients with Cogan syndrome and treatment outcomes. Vestibular symptoms were noted to be more prevalent in patients who were eventually labeled as steroid resistant. There were higher rates of audiological improvement in patients given biologic DMARDs rather than conventional DMARDs or steroids only. Further studies are needed to characterize each individual vestibular symptom and investigate the utility and timing of biologic DMARDs in managing patients with Cogan syndrome.

15.
Int. braz. j. urol ; 50(4): 398-414, July-Aug. 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1569218

RESUMO

ABSTRACT Background and Objective Salvage robot assisted radical prostatectomy (sRARP) is performed for patients with biochemical or biopsy proven, localized prostate cancer recurrences after radiation or ablative therapies. Traditionally, sRARP has been avoided by lower volume surgeons due to technical demand and high complication rates. Post-radiation sRARP outcomes studies exist but remain few in number. With increasing use of whole gland and focal ablative therapies, updates on sRARP in this setting are needed. The aim of this narrative review is to provide an overview of recently reviewed studies on the oncologic outcomes, functional outcomes, and complications after post-radiation and post-ablative sRARP. Tips and tricks are provided to guide surgeons who may perform sRARP. Materials and Methods We performed a non-systematic literature search of PubMed and MEDLINE for the most relevant articles pertaining to the outlined topics from 2010-2022 without limitation on study design. Only case reports, editorial comments, letters, and manuscripts in non-English languages were excluded. Key Content and Findings Salvage robotic radical prostatectomy is performed in cases of biochemical recurrence after radiation or ablative therapies. Oncologic outcomes after sRARP are worse compared to primary surgery (pRARP) though improvements have been made with the robotic approach when compared to open salvage prostatectomy. Higher pre-sRARP PSA levels and more advanced pathologic stage portend worse oncologic outcomes. Patients meeting low-risk, EAU-biochemical recurrence criteria have improved oncologic outcomes compared to those with high-risk BCR. While complication rates in sRARP are higher compared to pRARP, Retzius sparing approaches may reduce complication rates, particularly rectal injuries. In comparison to the traditional open approach, sRARP is associated with a lower rate of bladder neck contracture. In terms of functional outcomes, potency rates after sRARP are poor and continence rates are low, though Retzius sparing approaches demonstrate acceptable recovery of urinary continence by 1 year, post-operatively. Conclusions Advances in the robotic platform and improvement in robotic experience have resulted in acceptable complication rates after sRARP. However, oncologic and functional outcomes after sRARP in both the post-radiation and post-ablation settings are worse compared to pRARP. Thus, when engaging in shared decision making with patients regarding the initial management of localized prostate cancer, patients should be educated regarding oncologic and functional outcomes and complications in the case of biochemically recurrent prostate cancer that may require sRARP.

16.
bioRxiv ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38979179

RESUMO

As a biological byproduct from both humans and microbes, glycerol's contribution to microbial homeostasis in the oral cavity remains understudied. Here we examined glycerol metabolism by Streptococcus sanguinis, a commensal associated with oral health. Genetic mutants of glucose-PTS enzyme II ( manL ), glycerol metabolism ( glp and dha pathways), and transcriptional regulators were characterized with regard to glycerol catabolism, growth, production of hydrogen peroxide (H 2 O 2 ), transcription, and competition with Streptococcus mutans . Biochemical assays identified the glp pathway as a novel source of H 2 O 2 production by S. sanguinis that is independent of pyruvate oxidase (SpxB). Genetic analysis indicated that the glp pathway requires glycerol and a transcriptional regulator, GlpR, for expression and is negatively regulated by PTS, but not the catabolite control protein, CcpA. Conversely, deletion of either manL or ccpA increased expression of spxB and a second, H 2 O 2 -non-producing glycerol metabolic pathway ( dha ), indicative of a mode of regulation consistent with conventional carbon catabolite repression (CCR). In a plate-based antagonism assay and competition assays performed with planktonic and biofilm-grown cells, glycerol greatly benefited the competitive fitness of S. sanguinis against S. mutans. The glp pathway appears to be conserved in several commensal streptococci and actively expressed in caries-free plaque samples. Our study suggests that glycerol metabolism plays a more significant role in the ecology of the oral cavity than previously understood. Commensal streptococci, though not able to use glycerol as a sole carbohydrate for growth, benefit from catabolism of glycerol through production of both ATP and H 2 O 2 . Importance: Glycerol is an abundant carbohydrate found in oral cavity, both due to biological activities of humans and microbes, and as a common ingredient of foods and health care products. However, very little is understood regarding the metabolism of glycerol by some of the most abundant oral bacteria, commensal streptococci. This was in part because most streptococci cannot grow on glycerol as the sole carbon source. Here we show that Streptococcus sanguinis , an oral commensal associated with dental health, can degrade glycerol for persistence and competition through two independent pathways, one of which generates hydrogen peroxide at levels capable of inhibiting a dental pathobiont, Streptococcus mutans . Preliminary studies suggest that several other commensal streptococci are also able to catabolize glycerol, and glycerol-related genes are being actively expressed in human dental plaque samples. Our findings reveal the potential of glycerol to significantly impact microbial homeostasis which warrants further exploration.

17.
bioRxiv ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38979313

RESUMO

Tooth enamel maturation requires the removal of proteins from the mineralizing enamel matrix to allow for crystallite growth until full hardness is reached to meet the mechanical needs of mastication. While this process takes up to several years in humans before the tooth erupts, it is greatly accelerated in in the faster developing pig. As a result, pig teeth erupt with softer, protein-rich enamel that is similar to hypomineralized human enamel but continues to harden quickly after eruption.Proteins, such as albumin, that bind to enamel crystals and prevent crystal growth and enamel hardening have been suggested as cause for hypomineralized human enamel that does not naturally harden after eruption. However, albumin is abundant in pig enamel. It is unclear whether fast posteruptive enamel hardening in pigs occurs despite the high protein content or requires a facilitated protein loss to allow for crystal growth. This study asked how the protein content in porcine enamel changes after eruption in relation to saliva. Based on previous data demonstrating the high albumin content in erupted porcine enamel, we hypothesize that following pre-eruptive maturation, enamel and saliva derived enzymes facilitate protein removal from porcine enamel after eruption. We analyzed enamel and the saliva proteome at three critical timepoints: at the time of tooth eruption, 2 weeks after eruption, and enamel 6 weeks after eruption. We used only fourth deciduous premolars and saliva samples from animals sacrificed at the respective time points to determine the organic content in tooth enamel, saliva, and saliva proteins within enamel. We found a decrease in the number of proteins and their abundancy in enamel with posteruptive time, including a decrease in serum albumin within enamel. The rapid decrease in the first two weeks is in line with previously reported rapid increase in mineral density of porcine enamel after eruption. In addition to the enamel proteases KLK-4 and MMP-20, we identified serine-, cysteine-, aspartic-, and metalloproteases. Some of these were only identified in enamel, while almost half of the enzymes are in common with saliva at all timepoints. Our findings suggest that the fast posteruptive enamel maturation in the porcine model coincides with saliva exchange and influx of saliva enzymes into porous enamel.

18.
J Pharm Biomed Anal ; 249: 116364, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39047461

RESUMO

In preclinical protein therapeutic development studies, the emergence of anti-drug antibodies (ADA) can potentially impact drug pharmacokinetics and safety. While immunogenicity assessment is not mandatory in preclinical studies, banking samples can be valuable for interpreting unexpected pharmacological responses. Immunoassays that use generic reagents across different drug molecules can simplify ADA assessment and expedite sample evaluations. This work showcases the ability of the Gyrolab automated immunoassay platform to detect and quantify both drug-free and drug-bound (total) ADAs to monoclonal antibody (mAb) therapeutics in cynomolgus monkey preclinical studies. Compared to the previously reported total ADA ELISA, the Gyrolab assay exhibited a wider signal dynamic range and increased drug tolerance. Similar sensitivity, dynamic range and cut point factors were observed for four therapeutic mAbs of different isotypes using the Gyrolab assay. Here we present a comparison of ADA assays using bridging ELISA, total ADA ELISA and total ADA Gyrolab formats in a cynomolgus monkey study where the subjects were treated with a single dose of a mAb therapeutic. We demonstrate that the total ADA assays detected host ADA responses at earlier time points compared to the bridging ELISA. The Gyrolab assay has the best correlation between signal-to-noise (S/N) and titer over a wide ADA concentration range, highlighting the utility of Gyrolab in S/N reporting of ADA response to eliminate the need for secondary titer assays. Collectively, our results demonstrate that the generic ADA Gyrolab assay minimizes the necessity for extensive assay development and optimization for therapeutic mAbs, streamlining preclinical immunogenicity assessment to enable interpretation of pharmacological data.


Assuntos
Anticorpos Monoclonais , Avaliação Pré-Clínica de Medicamentos , Ensaio de Imunoadsorção Enzimática , Macaca fascicularis , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacocinética , Ensaio de Imunoadsorção Enzimática/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Imunoensaio/métodos
19.
European J Pediatr Surg Rep ; 12(1): e45-e49, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39015759

RESUMO

Concomitant presentation of jejunal atresia and Hirschsprung's disease is rare and places children at high risk for developing short bowel syndrome and parenteral nutrition dependence, which can affect the feasibility/timing of pull-through. A patient was born with jejunal atresia with a delayed diagnosis of Hirschsprung's disease. After several procedures and bowel resections, the patient was ultimately left with an end jejunostomy and long Hartman's pouch with short bowel syndrome, dependent on parenteral nutrition. The patient initially presented to our institution at age 2 with failure to thrive secondary to an obstructed/dilated jejunostomy and mild enterocolitis of their defunctionalized segment. The patient subsequently underwent completion of subtotal colectomy and revision of jejunostomy utilizing a serial transverse enteroplasty to manage the dilated bowel and gain length. The patient was able to wean off parenteral nutrition and achieve nutritional autonomy by age 5. Following this, the patient was able to undergo an ileoanal pull-through. After the pull-through, the patient was able to pass stool independently and suffered no major complications to date. Serial transverse enteroplasty can be successfully utilized in patients with a history of Hirschsprung's disease and jejunal atresia to achieve nutritional autonomy and ultimately reestablish gastrointestinal continuity with pull-through.

20.
Molecules ; 29(12)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38930935

RESUMO

Antimony (Sb) contamination poses significant environmental and health concerns due to its toxic nature and widespread presence, largely from anthropogenic activities. This study addresses the urgent need for an accurate speciation analysis of Sb, particularly in water sources, emphasizing its migration from polyethylene terephthalate (PET) plastic materials. Current methodologies primarily focus on total Sb content, leaving a critical knowledge gap for its speciation. Here, we present a novel analytical approach utilizing frontal chromatography coupled with inductively coupled plasma mass spectrometry (FC-ICP-MS) for the rapid speciation analysis of Sb(III) and Sb(V) in water. Systematic optimization of the FC-ICP-MS method was achieved through multivariate data analysis, resulting in a remarkably short analysis time of 150 s with a limit of detection below 1 ng kg-1. The optimized method was then applied to characterize PET leaching, revealing a marked effect of the plastic aging and manufacturing process not only on the total amount of Sb released but also on the nature of leached Sb species. This evidence demonstrates the effectiveness of the FC-ICP-MS approach in addressing such an environmental concern, benchmarking a new standard for Sb speciation analysis in consideration of its simplicity, cost effectiveness, greenness, and broad applicability in environmental and health monitoring.


Assuntos
Antimônio , Espectrometria de Massas , Polietilenotereftalatos , Antimônio/análise , Antimônio/química , Polietilenotereftalatos/química , Espectrometria de Massas/métodos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Monitoramento Ambiental/métodos
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