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1.
Bioinform Biol Insights ; 18: 11779322241280580, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39372506

RESUMO

Providencia rettgeri has increasingly been responsible for several infections, including urinary tract, post-burn wounds, neonatal sepsis, and others. The emergence of drug-resistant isolates of P rettgeri, accompanied by intrinsic and acquired antibiotic resistance, has exacerbated the challenge of treating such infections, necessitating the development of novel therapeutics. Hypothetical proteins (HPs) form a major portion of cellular proteins and can be targeted by these novel therapeutics. In this study, 410 HPs from a pan-drug-resistant (PDR) P rettgeri strain (MRSN845308) were functionally annotated and characterized by physicochemical properties, localization, virulence, essentiality, druggability, and functionality. Among 410 HPs, the VirulentPred 2.0 tool and VICMpred combinedly predicted 33 HPs as virulent, whereas 48 HPs were highly interacting proteins based on the STRING v12 database. BlastKOALA and eggNOG-mapper v2.1.12 predicted 13 HPs involved in several metabolic pathways like Riboflavin metabolism and Lipopolysaccharide biosynthesis. Overall, 83 HPs were selected as primary drug targets; however, only 80 remained after nonhomology searching and essentiality analysis. In addition, all were detected as novel drug targets according to DrugBank 5.1.12. Considering the potential of membrane and extracellular proteins, 29 HPs (extracellular, outer, and inner membrane) were selected based on the combined prediction from PSORTb v3.0.3, CELLO v.2.5, BUSCA, SOSUIGramN, and PSLpred. According to the prevalence of those HPs in different strains of P rettgeri sequences in National Center for Biotechnology Information Identical Protein Groups (NCBI-IPG), 5 HPs were selected as final drug targets. In addition, 5 other HPs annotated as transporter proteins were also added to the list. As no crystal structures of our targets are present, 3-dimensional structures of selected HPs were predicted by the AlphaFold Server powered by AlphaFold 3. Our findings might facilitate a better understanding of the mechanism of virulence and pathogenesis, and up-to-date annotations can make uncharacterized HPs easy to identify as targets for novel therapeutics.

2.
BMC Med Educ ; 24(1): 1106, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39375750

RESUMO

BACKGROUND: Despite an empathic doctor patient relationship being of utmost importance to improve health care outcomes, this aspect is scarcely explored in dental students of Pakistan. This primary objective of the present study was to assess the reliability and validity of the Jefferson Scale of Empathy- Health Professions Student (JSE- HPS) version in a sample of Pakistani dental students. The study also compared the differences in empathy levels of dental students studying in different academic years. METHODS: This comparative cross-sectional study was conducted on a sample of 304 students from first to final year from selected 02 private and 02 public dental colleges of Karachi, Pakistan from December 2021- January 2022. The self-administered Jefferson Scale of Empathy- Health Professions Student (JSE-HPS) version was used for data collection. This questionnaire includes 20 items that can be answered on a 7-point Likert scale. After attendance sheets were obtained, random student names were marked, and questionnaire distributed by hand to these students. All forms were collected right after to maximize response rate. RESULTS: A total of 304 forms with complete data were returned, a response rate of 86.9%. Females (97.79 ± 15 94) were more empathetic than males (94.16 ± 12.13) (p = 0.001). Students of third-year were the most empathetic (p = 0.000). Internal consistency of questionnaire was acceptable (Cronbach's α- 0.77). Factor analysis revealed factor related to belief that patient's perspectives improve health outcome had 14 items with factor coefficient > 0.4 contributing to largest proportion of variance (23.15%). CONCLUSIONS: Our study shows JSE- HPS to have acceptable internal consistency. Structural validity of the scale evaluated by confirmatory factor analysis reported results that were in concordance to those suggested by developers of this scale. In our study population, like other studies, females were more empathic than males. Third-year dental students were more empathetic than students of other undergraduate years.


Assuntos
Empatia , Estudantes de Odontologia , Humanos , Estudantes de Odontologia/psicologia , Feminino , Estudos Transversais , Masculino , Paquistão , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem , Adulto
3.
mBio ; : e0160024, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258903

RESUMO

Hantaviruses are rodent-borne viruses that cause severe disease in infected humans. In the New World, major hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV) causing hantavirus pulmonary syndrome. In the Old World, major hantaviruses include Hantaan virus (HTNV) and Puumala virus (PUUV) causing hemorrhagic fever with renal syndrome. Here, we produced a pan-hantavirus therapeutic (SAB-163) comprised of fully human immunoglobulin purified from the plasma of transchromosomic bovines (TcB) vaccinated with hantavirus DNA plasmids coding for the major glycoproteins of ANDV, SNV, HTNV, and PUUV. SAB-163 has potent neutralizing antibodies (PRNT50 > 200,000) against the four targeted hantavirus and cross-neutralization against several other heterotypic hantaviruses. At a dosage of 10 mg/kg, SAB-163 is bioavailable in Syrian hamsters out to 70 days post-treatment with a half-life of 10-15 days. At this same dosage, SAB-163 administered 1 day before, or 5 days after exposure, protected all hamsters from lethal disease caused by ANDV. At a higher dose, partial but significant protection was achieved as late as day 6. SAB-163 also protected hamsters in the HTNV, PUUV, and SNV infection models when administered 1 day before or up to 3 days after challenge. This pan-hantavirus therapeutic is attractive because it is fully human, multi-targeted, safe, stable at 4°C, and effective in animal models. SAB-163 was evaluated for safety in GLP human tissue binding studies and a GLP rabbit toxicity study at 365 and 730 mg/kg and is investigational new drug enabled for phase 1 clinical trial(s). IMPORTANCE: This candidate polyclonal human IgG product was produced using synthetic gene-based vaccines and transgenic cows. Having now gone through cGMP production, GLP safety testing, and efficacy testing in animals, SAB-163 is the world's most advanced anti-hantavirus antibody-based medical countermeasure, aside from convalescent human plasma. Importantly, SAB-163 targets the most prevalent hantaviruses on four continents.

4.
Lancet Reg Health Am ; 37: 100836, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39100240

RESUMO

Background: In the United States (U.S.), hantavirus pulmonary syndrome (HPS) and non-HPS hantavirus infection are nationally notifiable diseases. Criteria for identifying human cases are based on clinical symptoms (HPS or non-HPS) and acute diagnostic results (IgM+, rising IgG+ titers, RT-PCR+, or immunohistochemistry (IHC)+). Here we provide an overview of diagnostic testing and summarize human Hantavirus disease occurrence and genotype distribution in the U.S. from 2008 to 2020. Methods: Epidemiological data from the national hantavirus registry was merged with laboratory diagnostic testing results performed at the CDC. Residual hantavirus-positive specimens were sequenced, and the available epidemiological and genetic data sets were linked to conduct a genomic epidemiological study of hantavirus disease in the U.S. Findings: From 1993 to 2020, 833 human hantavirus cases have been identified, and from 2008 to 2020, 335 human cases have occurred. Among New World (NW) hantavirus cases detected at the CDC diagnostic laboratory (representing 29.2% of total cases), most (85.0%) were detected during acute disease, however, some convalescent cases were detected in states not traditionally associated with hantavirus infections (Connecticut, Missouri, New Jersey, Pennsylvania, Tennessee, and Vermont). From 1993 to 2020, 94.9% (745/785) of U.S. hantaviruses cases were detected west of the Mississippi with 45.7% (359/785) in the Four Corners region of the U.S. From 2008 to 2020, 67.7% of NW hantavirus cases were detected between the months of March and August. Sequencing of RT-PCR-positive cases demonstrates a geographic separation of Orthohantavirus sinnombreense species [Sin Nombre virus (SNV), New York virus, and Monongahela virus]; however, there is a large gap in viral sequence data from the Northwestern and Central U.S. Finally, these data indicate that commercial IgM assays are not concordant with CDC-developed assays, and that "concordant positive" (i.e., commercial IgM+ and CDC IgM+ results) specimens exhibit clinical characteristics of hantavirus disease. Interpretation: Hantaviral disease is broadly distributed in the contiguous U.S, viral variants are localised to specific geographic regions, and hantaviral disease infrequently detected in most Southeastern states. Discordant results between two diagnostic detection methods highlight the need for an improved standardised testing plan in the U.S. Hantavirus surveillance and detection will continue to improve with clearly defined, systematic reporting methods, as well as explicit guidelines for clinical characterization and diagnostic criteria. Funding: This work was funded by core funds provided to the Viral Special Pathogens Branch at CDC.

5.
BMC Ophthalmol ; 24(1): 345, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143519

RESUMO

BACKGROUND: Oculocutaneous albinism (OCA) is a genetically heterogeneous condition that is associated with reduced or absent melanin pigment in the skin, hair, and eyes, resulting in reduced vision, high sensitivity to light, and rapid and uncontrolled eye movements. To date, seventeen genes have been associated with OCA including syndromic and non-syndromic forms of the condition. METHODS: Whole exome sequencing (WES) was performed to identify pathogenic variants in nine Pakistani families with OCA, with validation and segregation of candidate variants performed using Sanger sequencing. Furthermore, the pathogenicity of the identified variants was assessed using various in-silico tools and 3D protein structural analysis software. RESULTS: WES identified biallelic variants in three genes explaining the OCA in these families, including four variants in TYR, three in OCA2, and two in HPS1, including two novel variants c.667C > T: p.(Gln223*) in TYR, and c.2009 T > C: p.(Leu670Pro) in HPS1. CONCLUSIONS: Overall, this study adds further knowledge of the genetic basis of OCA in Pakistani communities and facilitates improved management and counselling services for families suffering from severe genetic diseases in Pakistan.


Assuntos
Albinismo Oculocutâneo , Sequenciamento do Exoma , Síndrome de Hermanski-Pudlak , Mutação , Linhagem , Humanos , Albinismo Oculocutâneo/genética , Paquistão , Feminino , Masculino , Síndrome de Hermanski-Pudlak/genética , Criança , Adulto , Adolescente , Análise Mutacional de DNA , Monofenol Mono-Oxigenase/genética , Pré-Escolar , Proteínas de Membrana Transportadoras/genética , Adulto Jovem , Proteínas de Membrana
6.
Anim Genet ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956930

RESUMO

To date, only 10 of the more than 30 fur colours that had been observed in American mink (Neogale vison) have been linked to specific genes. The Royal pastel fur colour is part of a large family of brownish colours that are quite similar to one another, making breeding and selecting processes more difficult. Here we carried out whole-genome sequencing of five American minks with Royal pastel (b/b) phenotypes originating from two distinct mink populations. We identified an insertion of endogenous retroviral element type 1 (ERV1) into the first intron of the gene encoding the HPS3 protein, which regulates the trafficking of tyrosinase-containing vesicles to maturing melanosomes. With Cas9-targeted nanopore sequencing, we reconstructed the full-length sequence of the 11.7 Kb ERV1 insertion and observed hypermethylation that spread to the HPS3 gene promoter region. These findings highlight the role of HPS3 in the formation of melanosomes and melanin, as well as the genetic process regulating the intensity and spectrum of hair colour. Moreover, in mink breeding projects, these data are also useful for tracking economically important fur qualities.

7.
Am J Respir Cell Mol Biol ; 71(4): 442-452, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38864759

RESUMO

Lamellar bodies (LBs) are tissue-specific lysosome-related organelles in type II alveolar cells that are the main site for the synthesis, storage, and secretion of pulmonary surfactants. Defects in pulmonary surfactants lead to a variety of respiratory and immune-related disorders. LB biogenesis is closely related to their function, but the underlying regulatory mechanism is largely unclear. Here, we found that deficiency of HPS6, a subunit of BLOC-2 (biogenesis of lysosome-related organelles complex-2), led to a reduction of the steady-state concentration of vacuolar-type H+-ATPase and an increase in the luminal pH of LBs. Furthermore, we observed increased LB size, accumulated surfactant proteins, and altered lipid profiling of lung tissue and BAL fluid due to HPS6 deficiency. These findings suggest that HPS6 regulates the distribution of vacuolar-type H+-ATPase on LBs to maintain its luminal acidity and LB homeostasis. This may provide new insights into the LB pathology.


Assuntos
Células Epiteliais Alveolares , ATPases Vacuolares Próton-Translocadoras , ATPases Vacuolares Próton-Translocadoras/metabolismo , ATPases Vacuolares Próton-Translocadoras/genética , Animais , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Camundongos , Concentração de Íons de Hidrogênio , Lisossomos/metabolismo , Camundongos Endogâmicos C57BL , Organelas/metabolismo , Camundongos Knockout
8.
Intern Med ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38719600

RESUMO

Herein, we report a case of Hermansky-Pudlak syndrome (HPS) in which respiratory symptoms improved with pirfenidone treatment. A 43-year-old Japanese woman with oculocutaneous albinism presented with a cough and dyspnea. High-resolution computed tomography revealed areas of reticular and frosted lung opacities. The diagnosis of HPS was confirmed by a prolonged bleeding time and HPS1 gene mutation. Generally, there is no effective treatment for interstitial pneumonia associated with HPS except for lung transplantation. In the present case, the cough and dyspnea improved with pirfenidone administration. Therefore, clinicians should administer pirfenidone in challenging transplantation cases and during the waiting period for transplantation.

9.
ChemMedChem ; 19(15): e202400195, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687188

RESUMO

A series of N-glycosyl- 6BrCaQ conjugates was synthesized through a Pd-catalyzed cross-coupling reaction between brominated N-glycosyl quinolin-2-one derivatives and various nitrogen nucleophiles. Antiproliferative assays revealed that this new series of analogues represents a promising class of antitumor compounds as illustrated by the high biological activity observed for several derivatives towards different cancer cell lines compared to the non-glycosylated congeners.


Assuntos
Amidas , Antineoplásicos , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Paládio , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Catálise , Paládio/química , Amidas/química , Amidas/farmacologia , Amidas/síntese química , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Estrutura Molecular , Quinolonas/química , Quinolonas/farmacologia , Quinolonas/síntese química , Relação Dose-Resposta a Droga , Quinolinas/química , Quinolinas/farmacologia , Quinolinas/síntese química
10.
Antioxidants (Basel) ; 13(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38539828

RESUMO

Scientific evidence attests that the epidermis receives excessive ultraviolet B (UVB) radiation, triggering the generation of substantial quantities of reactive oxygen species (ROS), which disrupted the delicate equilibrium of oxidation-reduction, leading to oxidative stress and inflammation. The historical use of honeysuckle polyphenols (HPs) has garnered our attention due to their efficacy in inhibiting oxidative damage. In this study, HPs were prepared from honeysuckle flowers employing an ultrasonic-assisted extraction method and quantitatively analyzed by a LC-MS/MS, and the mechanisms underlying HPs' antioxidative and anti-inflammatory effects on a UVB-irradiated HaCaT cell model were systematically investigated. The results showed that HPs had a significant cellular repair effect on UVB-irradiated HaCaT cells (p < 0.001). The mechanism of action indicated that HPs could allow Nrf2 to enter the nucleus by regulating the dissociation of Nrf2 from Keap1, which further increases the activity of downstream proteases (SOD and CAT), increases ROS scavenging, and reduces the intracellular malondialdehyde (MDA) level. In addition, HPs could down-regulate Toll-like receptor 4 (TLR4) and inhibit NF-κB (P65) dissociating from IκBα, resulting in a decrease in NF-κB (P65) entry into the nucleus and a decrease in inflammatory factors (TNF-α, IL-6, and IL-1ß). In addition, four key compounds in HPs, including chlorogenic acid, quercetin, isorhamnetin, and luteolin, were selected to verify the mechanism of HPs repairing UVB damage using molecular docking techniques. The experiment suggested that four key active compounds could effectively occupy the Kelch homologue (Kelch) structural domain of Keap1, competitively bind with Nrf2, and facilitate the promotion of Nrf2 binding, ultimately enhancing the translocation of Nrf2 into the nucleus. In addition, four key active compounds could effectively interact with NF-κB (P65) through hydrogen bonding, van der Waals forces, and electrostatic forces to inhibit its entry into the nucleus. In summary, HPs can effectively repair the damage of HaCaT cells by UVB radiation and can be used to develop health and cosmetic products for the treatment of UV radiation-induced diseases.

11.
Plants (Basel) ; 13(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38475526

RESUMO

Nanotechnologies can improve plant growth, protect it from pathogens, and enrich it with bioactive and mineral substances. In order to fill the lack of knowledge about the combined environmental effects of lighting and nanoparticles (NPs) on plants, this study is designed to investigate how different HPS and LED lighting combined with CuO and ZnO NPs influence the elemental composition of ice plants (Mesembryanthemum crystallinum L.). Plants were grown in hydroponic systems with LED and HPS lighting at 250 ± 5 µmol m-2 s-1 intensity, sprayed with aqueous suspensions of CuO (40 nm, 30 ppm) and ZnO (35-45 nm, 800 ppm) NPs; their elemental composition was measured using an ICP-OES spectrometer and hazard quotients were calculated. LED lighting combined with the application of ZnO NPs significantly affected Zn accumulation in plant leaves. Cu accumulation was higher when plants were treated with CuO NPs and HPS illumination combined. The calculated hazard quotients showed that the limits are not exceeded when applying our selected concentrations and growth conditions on ice plants. In conclusion, ice plants had a more significant positive effect on the accumulation of macro- and microelements under LED lighting than HPS. NPs had the strongest effect on the increase in their respective microelements.

12.
Pediatr Radiol ; 54(5): 737-742, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38418631

RESUMO

BACKGROUND: Ultrasound is the modality of choice for the diagnosis of hypertrophic pyloric stenosis (HPS). The evolution of high-frequency transducers in ultrasound has led to inconsistent ways of measuring the pylorus. OBJECTIVE: To standardize the measurements and evaluate the appearance of the normal and hypertrophied pylorus with high-frequency transducers. MATERIALS AND METHODS: We retrospectively analyzed abdominal ultrasounds of infants with suspected HPS from January 2019-December 2020. We classified the layers of the pylorus while assessing the stratified appearance. Two pediatric radiologists measured the muscle thickness of the pylorus independently by two methods for interrater agreement. Measurement (a) includes the muscularis propria and muscularis mucosa. Measurement (b) includes only the muscularis propria. We also evaluated the echogenicity of the muscularis propria. The interrater agreement, mean, range of the muscle thickness, and the diagnostic accuracy of the two sets of measurements were calculated. RESULTS: We included 300 infants (114 F:186 M), 59 with HPS and 241 normal cases. There was a strong agreement between the readers assessed in the first 100 cases, and ICC was 0.99 (95% CI, 0.98-0.99). Measurement (a), median thickness is 2.4 mm in normal cases and 4.8 mm in HPS. Measurement (b), median thickness is 1.4 mm in normal cases and 4.0 mm in HPS. Measurement (a) has an accuracy of 89.7% (95% CI, 85.7-92.8%) with 98.3% sensitivity and 87.6% specificity. Measurement (b) has an accuracy of 98.0% (95% CI, 95.7-99.3%) with 89.8% sensitivity and 100.0% specificity. The pylorus stratification is preserved in all normal cases and 31/59 (52.5%) cases of HPS. There was complete/partial loss of stratification in 28/59 (47.5%) cases of HPS. In all HPS cases, the muscularis propria was echogenic. CONCLUSION: Measuring the muscularis propria solely has a better diagnostic accuracy, decreasing the overlap of negative and positive cases. The loss of pyloric wall stratification and echogenic muscularis propria is only seen in HPS.


Assuntos
Estenose Pilórica Hipertrófica , Piloro , Transdutores , Ultrassonografia , Humanos , Estudos Retrospectivos , Masculino , Feminino , Ultrassonografia/métodos , Piloro/diagnóstico por imagem , Lactente , Estenose Pilórica Hipertrófica/diagnóstico por imagem , Recém-Nascido , Sensibilidade e Especificidade
13.
Clin Ophthalmol ; 18: 337-345, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38332902

RESUMO

Purpose: This study was conducted to evaluate and compare the in vitro disinfection efficacies of six commercial lens cleaning and disinfecting products for planned replacement soft contact lenses. Methods: Disinfection efficacies of five multi-purpose solutions (MPSs) and one hydrogen peroxide solution (HPS) as control were evaluated in the presence of organic soil according to the International Organization for Standardization (ISO, Geneva, Switzerland) ISO 14729 stand-alone test protocol. The five specified compendial organisms, three bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens) and two fungi (Candida albicans and Fusarium solani) were incubated with each solution under standard conditions, after which microbes were recovered and quantified. Results: Each of the solutions evaluated met or exceeded the standard's primary criteria (3-log reduction of bacteria and 1-log reduction of fungi) after incubation for the manufacturer-recommended soaking time, except for COMPLETE MPS, which achieved only 0.4 ± 0.1 average log reduction for C. albicans. However, differences in efficacy between the solutions were noted. Average log reduction across all microbes for Biotrue Hydration Plus (4.6 ± 0.1) was comparable to that for CLEAR CARE PLUS HPS (4.3 ± 0.1) and greater than those for OPTI-FREE puremoist (3.6 ± 0.1), OPTI-FREE Replenish (4.0 ± 0.2), ACUVUE RevitaLens (3.9 ± 0.03), and COMPLETE MPS (3.6 ± 0.1). Biotrue Hydration Plus was especially effective at reducing the population of C. albicans (4.2 ± 0.7-log reduction). Conclusion: Products marketed for planned replacement soft CL disinfection generally meet the ISO 14729 standard's primary criteria for reducing populations of compendial organisms, with larger differences between solutions noted with C. albicans.

14.
Elife ; 122024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38180318

RESUMO

The unlimited expansion of human progenitor cells in vitro could unlock many prospects for regenerative medicine. However, it remains an important challenge as it requires the decoupling of the mechanisms supporting progenitor self-renewal and expansion from those mechanisms promoting their differentiation. This study focuses on the expansion of human pluripotent stem (hPS) cell-derived pancreatic progenitors (PP) to advance novel therapies for diabetes. We obtained mechanistic insights into PP expansion requirements and identified conditions for the robust and unlimited expansion of hPS cell-derived PP cells under GMP-compliant conditions through a hypothesis-driven iterative approach. We show that the combined stimulation of specific mitogenic pathways, suppression of retinoic acid signaling, and inhibition of selected branches of the TGFß and Wnt signaling pathways are necessary for the effective decoupling of PP proliferation from differentiation. This enabled the reproducible, 2000-fold, over 10 passages and 40-45 d, expansion of PDX1+/SOX9+/NKX6-1+ PP cells. Transcriptome analyses confirmed the stabilization of PP identity and the effective suppression of differentiation. Using these conditions, PDX1+/SOX9+/NKX6-1+ PP cells, derived from different, both XY and XX, hPS cell lines, were enriched to nearly 90% homogeneity and expanded with very similar kinetics and efficiency. Furthermore, non-expanded and expanded PP cells, from different hPS cell lines, were differentiated in microwells into homogeneous islet-like clusters (SC-islets) with very similar efficiency. These clusters contained abundant ß-cells of comparable functionality as assessed by glucose-stimulated insulin secretion assays. These findings established the signaling requirements to decouple PP proliferation from differentiation and allowed the consistent expansion of hPS cell-derived PP cells. They will enable the establishment of large banks of GMP-produced PP cells derived from diverse hPS cell lines. This approach will streamline SC-islet production for further development of the differentiation process, diabetes research, personalized medicine, and cell therapies.


Assuntos
Diabetes Mellitus , Células-Tronco Pluripotentes , Humanos , Pâncreas , Via de Sinalização Wnt , Bioensaio
15.
Artigo em Inglês | MEDLINE | ID: mdl-38218377

RESUMO

Albinism is a widespread departure from a typical body colouration due to altered melanin production. The Wels catfish (Silurus glanis) is among the largest freshwater fish species in the world, and albino individuals occur both in the wild and in aquaculture. Here, we performed transcriptome-wide analysis of albino and normally pigmented S. glanis using four tissues (skin, dorsal fin, whole eye and liver) to identify genes associated with albinism by exploring patterns of differential expression (DE) and differential alternative splicing (DAS). Multi-tissue analyses revealed a large number of genes in skin (n = 1355) and fin (n = 614) tissue associated with the albino phenotype in S. glanis, while the number of DE genes in eye and liver tissues was lower (n = 188, n = 189, respectively). Several DE genes across multiple tissues were detected as the most promising candidates (e.g., hsp4, hsp90b1, raph1, uqcrfs1, adcy-family and wnt-family) potentially causally linked to the albino phenotype in Wels catfish. Moreover, our findings supported earlier observations of physiological differences between albino and normally pigmented individuals, particularly in energy metabolism and immune response. In contrast, there were only a few pigmentation-related genes observed among DAS genes (4 in skin, 2 in fin), the overlap between DAS and DE genes was low (n = 25) and did not include known pigmentation-related genes. This suggests that DAS and DE in Wels catfish are, to a large extent, independent processes, and the observed alternative splicing cases are probably not causally linked with albinism in S. glanis. This work provides the first transcriptome-wide multi-tissue insights into the albinism of Wels catfish and serves as a valuable resource for further understanding the genetic mechanisms of pigmentation in fish.


Assuntos
Albinismo , Peixes-Gato , Animais , Processamento Alternativo , Peixes-Gato/genética , Peixes-Gato/metabolismo , Albinismo/genética , Transcriptoma , Perfilação da Expressão Gênica
16.
Int J Lab Hematol ; 46(2): 250-258, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37904344

RESUMO

INTRODUCTION: Sepsis, a syndrome of organ dysfunction caused by an unregulated host response to infection. This study aimed to develop a novel sepsis diagnostic model of hematological parameters and evaluate its effectiveness in the early identification and prognosis of sepsis in emergency departments. METHODS: A retrospective study was conducted in Emergency Department. Cell population data parameters related to monocytes and neutrophils were obtained using the Mindary BC-6800 plus hematology analyzer. Receiver operating characteristic (ROC) curve analysis, logistic regression analysis was performed to assess the performance of the parameters and establish a diagnostic and prognostic model of sepsis, which was then verified with a validation cohort. RESULTS: Mon_XW exhibited the best diagnostic performance (area under the ROC curve [AUC] = 0.848, 95% confidence interval [CI]: 0.810-0.885, p < 0.001), followed by Neu_Y and Neu_YW (AUC = 0.777 95% CI: 0.730-0.824, p < 0.001). Logistic regression analysis identified Mon_XW and Neu_Y as independent predictors, which were used to establish a diagnostic model named hematological parameter for sepsis (HPS). HPS demonstrated the best diagnostic performance with an AUC of 0.862 (95% CI: 0.826-0.898, p < 0.001), sensitivity of 70.0%, and specificity of 87.1%, compared to C-reactive protein (CRP) and procalcitonin (PCT). The validation cohort also found that the positive predictive value of HPS was 70.4% and the negative predictive value was 92.2%. CONCLUSION: The developed HPS model showed promising diagnostic efficacy for sepsis in the emergency department, which outperformed CRP and PCT in terms of sensitivity and specificity. By enabling early identification and prognosis of sepsis, that contributes to reducing sepsis-related mortality.


Assuntos
Sepse , Humanos , Estudos Retrospectivos , Sepse/diagnóstico , Prognóstico , Pró-Calcitonina , Proteína C-Reativa/análise , Curva ROC , Serviço Hospitalar de Emergência
17.
J Eval Clin Pract ; 30(2): 153-161, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37641432

RESUMO

AIM: Empathic behaviour has a direct link to the positive clinical outcomes. Health professionals, which include dietitians, are increasingly expected to demonstrate the impact of their care on patient outcomes. To date, there is limited research exploring the empathic behaviour of dietetics students. METHODS: This cross-sectional study evaluated the psychometric properties of Jefferson Scale of Empathy-Healthcare Provider Student (JSE-HPS) and empathic behaviour of dietetics students. RESULTS: Undergraduate dietetics students from one private and two public universities in Malaysia participated (n = 455). Item and scale psychometric properties were examined using principal component analysis and differences in mean empathy scores for students were assessed across years of study and types of universities. A 3-factor solution emerged in the results, accounting for 26.76%, 10.75% and 6.3% of the variance. The JSE-HPS demonstrated good internal consistency (α = 0.83). Despite students enroled at public universities scoring higher mean empathy scores than students enroled at the private university, the difference was not significant. The only significant difference was between the empathy level of first and third year students (p = 0.033). CONCLUSION: As empathy underpins patient-centred management in the nutrition care process, it should be well integrated into curriculum delivery so that appropriate levels of empathy can be developed to prepare work-ready healthcare professionals.


Assuntos
Dietética , Estudantes de Medicina , Estudantes de Enfermagem , Humanos , Empatia , Estudos Transversais , Pessoal de Saúde
18.
Plants (Basel) ; 12(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38068676

RESUMO

Early detection of pathogenic fungi in controlled environment areas can prevent major food production losses. Grey mould caused by Botrytis cinerea is often detected as an infection on lettuce. This paper explores the use of vegetation indices for early detection and monitoring of grey mould on lettuce under different lighting conditions in controlled environment chambers. The aim was focused on the potential of using vegetation indices for the early detection of grey mould and on evaluating their changes during disease development in lettuce grown under different lighting conditions. The experiment took place in controlled environment chambers, where day/night temperatures were 21 ± 2/17 ± 2 °C, a 16 h photoperiod was established, and relative humidity was 70 ± 10% under different lighting conditions: high-pressure sodium (HPS) and light-emitting diode (LED) lamps. Lettuces were inoculated by 7-day-old fungus Botrytis cinerea isolate at the BBCH 21. As a control, non-inoculated lettuces were grown under HPS and LEDs (non-inoculated). Then, the following were evaluated: Anthocyanin Reflectance Index 2 (ARI2); Carotenoid Reflectance Index 2 (CRI2); Structure Intensive Pigment Index (SIPI); Flavanol Reflectance Index (FRI); Greenness (G); Greenness 2 (G2); Redness (R); Blue (B); Blue Green Index 2 (BGI2); Browning Index 2 (BRI2); Lichtenthaler Index 1 (LIC1); Pigment Specific Simple Ratio (PSSRa and PSSRb); Gitelson and Merzlyak (GM1 and GM2); Zarco Tejada-Miller Index (ZMI); Normalized Difference Vegetation Index (NDVI); Simple Ratio (SR); Red-Eye Vegetation Stress Index (RVSI); Photochemical Reflectance Index (PRI); Photochemical Reflectance Index 515 (PRI515); Water Band Index (WBI); specific disease index for individual study (fD); Healthy Index (HI); Plant Senescence Reflectance (PSRI); Vogelmann Red Edge Index (VREI1); Red Edge Normalized Difference Vegetation Index (RENDVI); and Modified Red Edge Simple Ratio (MRESRI). Our results showed that the PSRI and fD vegetation indices significantly detected grey mould on lettuce grown under both lighting systems (HPS and LEDs) the day after inoculation. The results conclusively affirmed that NDVI, PSRI, HI, fD, WBI, RVSI, PRI, PRI515, CRI2, SIPI, chlorophyll index PSSRb, and coloration index B were identified as the best indicators for Botrytis cinerea infection on green-leaf lettuce (Lactuca sativa L. cv Little Gem) at the early stage of inoculated lettuce's antioxidative response against grey mould with a significant increase in chlorophyll indices.

19.
Ecohealth ; 20(4): 402-415, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38091181

RESUMO

Previous research conducted in central-east region of Argentina recorded potential orthohantavirus host rodents in diverse environments, but no research has focused particularly on islands, the environments that present the greatest risk to humans. For this reason, the aims of this research were to determine the orthohantavirus host in the rodent community focused on islands of Paraná River Delta, central-east region of Argentina, to identify temporal and spatial factors associated with orthohantavirus prevalence variations, to compare the functional traits of seropositive and seronegative rodents, and to explore the association between orthohantavirus prevalence and rodent community characteristics between August 2014 and May 2018. With a trapping effort of 14,600 trap-nights, a total of 348 sigmodontine rodent specimens belonging to seven species were captured 361 times. The overall antibody prevalence was 4.9%. Particularly, 14.9% of Oligoryzomys flavescens and 1.5% of Oxymycterus rufus, mainly reproductively active adult males, had antibodies against orthohantavirus. Even though O. flavescens inhabit all islands, our results suggest spatial heterogeneity in the viral distribution, with two months after periods of low temperature presenting increases in seroprevalence. This could be a response to the increased proportion of adults present in the rodent population. In addition, an association was found between the high seroprevalence and the diversity of the rodent assemblage. We also found 1.5% of O. rufus exposed to orthohantavirus, which shows us that further investigation of the ecology of the virus is needed to answer whether this species act as a spillover or a new competent host.


Assuntos
Infecções por Hantavirus , Síndrome Pulmonar por Hantavirus , Orthohantavírus , Doenças dos Roedores , Humanos , Masculino , Animais , Roedores , Áreas Alagadas , Argentina/epidemiologia , Estudos Soroepidemiológicos , Doenças dos Roedores/epidemiologia , Reservatórios de Doenças , Infecções por Hantavirus/epidemiologia , Sigmodontinae
20.
Front Microbiol ; 14: 1343080, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149269

RESUMO

[This corrects the article DOI: 10.3389/fmicb.2023.1233433.].

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