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OBJECTIVE: Psoriatic disease remains underdiagnosed and undertreated. We developed and validated a suite of novel, sensor-based smartphone assessments (Psorcast app) that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease. METHODS: Participants with psoriasis (PsO) or psoriatic arthritis (PsA) and healthy controls were recruited between June 5, 2019, and November 10, 2021, at 2 academic medical centers. Concordance and accuracy of digital measures and image-based machine learning models were compared to their analogous clinical measures from trained rheumatologists and dermatologists. RESULTS: Of 104 study participants, 51 (49%) were female and 53 (51%) were male, with a mean age of 42.3 years (SD 12.6). Seventy-nine (76%) participants had PsA, 16 (15.4%) had PsO, and 9 (8.7%) were healthy controls. Digital patient assessment of percent body surface area (BSA) affected with PsO demonstrated very strong concordance (Lin concordance correlation coefficient [CCC] 0.94 [95% CI 0.91-0.96]) with physician-assessed BSA. The in-clinic and remote target plaque physician global assessments showed fair-to-moderate concordance (CCCerythema 0.72 [0.59-0.85]; CCCinduration 0.72 [0.62-0.82]; CCCscaling 0.60 [0.48-0.72]). Machine learning models of hand photos taken by patients accurately identified clinically diagnosed nail PsO with an accuracy of 0.76. The Digital Jar Open assessment categorized physician-assessed upper extremity involvement, considering joint tenderness or enthesitis (AUROC 0.68 [0.47-0.85]). CONCLUSION: The Psorcast digital assessments achieved significant clinical validity, although they require further validation in larger cohorts before use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and freely available.
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Artritis Psoriásica , Aprendizaje Automático , Psoriasis , Teléfono Inteligente , Humanos , Artritis Psoriásica/diagnóstico , Femenino , Masculino , Psoriasis/diagnóstico , Adulto , Persona de Mediana Edad , Prueba de Estudio Conceptual , Aplicaciones Móviles , Reproducibilidad de los ResultadosRESUMEN
Introduction Refractive errors (REs) are on the rise among medical students due to the high academic pressure of long hours of reading and their association with close technology. Uncorrected REs cause impaired vision and blindness with considerable morbidity. Documenting the prevalence of REs among medical students helps with early detection and appropriate remedial measures to prevent eye morbidity. Aim The aim of the study was to find the prevalence of REs among medical students at Raichur Institute of Medical Sciences, a medical institution in Raichur City, Karnataka, India. Methodology This hospital-based cross-sectional study was conducted with a total of 425 medical students. An examination of the eye for REs was carried out using a streak retinoscope. The REs were noted in myopia <-0.5 diopters (D), hypermetropia >+0.5 D, and astigmatism >0.5 cylinder D. The data was statistically subjected. Categorical measurements have been presented as frequency (percentage). The chi-square test was applied to the association between the parameters. A p-value less than 0.05 was considered statistically significant. Results Among the 425 observed participants, 160 (37.6%) subjects had REs. Among the REs in the total population, myopia 78 (18.4%) was the most prevalent, followed by hypermetropia and astigmatism, both with 41 (9.6%) and 41 (9.6%) prevalence, respectively. Gender-wise and age-wise, myopia was highly prevalent in both genders and in all age groups except the 20 years age group. Conclusion The prevalence of REs in our study among medical students is a matter of concern, although it is less compared to other previous studies in different geographical areas of India. Regular checkups, early detection, and immediate treatment are very important to prevent further ocular complications.
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Salicylic acid (SA) finds extensive applications in the treatment of rheumatic and skin diseases because of its analgesic, anti-inflammatory and exfoliating properties. As it is lipophilic in nature, there is a need for appropriate delivery systems to harness these properties for different applications. Herein, we examined the suitability of Pluronic P123/F127 micellar systems as delivery media by investigating the structural, flow and antimicrobial properties of P123/F127-SA solutions and hydrogels using DLS, SANS, rheological and zone inhibition measurement techniques. SA modulates the aggregation characteristics of these surfactant systems and brings about spherical-to-worm-like micelle-to-vesicular structural transitions in the hydrophobic Pluronic P123 system, a spherical-to-worm-like micellar transition in the mixed P123/F127 system and an onset of inter-micellar attraction in the hydrophilic Pluronic F127 system. SA-solubilized systems of both hydrophobic and hydrophilic Pluronics inhibit the growth of Gram-positive and Gram-negative bacteria with comparable MIC values. This suggests that the interaction of SA molecules with the bacterial cell membrane remains unobstructed upon encapsulation in Pluronic micelles. F127 hydrogel-based SA formulations with rheological properties suitable for topical applications and up to 15% SA loading were prepared. These will be useful SA ointments as F127 is an FDA-approved excipient for topical drug delivery applications. The results indicate that Pluronics remain effective as delivery agents for SA and exhibit interesting structural polymorphism upon its solubilization.
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Hidrogeles , Poloxaleno , Poloxámero , Polietilenos , Polipropilenos , Poloxámero/química , Ácido Salicílico/farmacología , Antibacterianos , Bacterias Gramnegativas , Bacterias Grampositivas , MicelasRESUMEN
OBJECTIVE: Individuals of racially and ethnically diverse backgrounds are underrepresented in psoriatic arthritis (PsA) research/clinical trials, despite evidence that their disease presentation, severity and course may be distinct. Here we aim to describe how race, ethnicity and other socioeconomic factors inform disease characteristics in PsA. METHODS: 817 consecutive patients with PsA from a large, diverse metropolitan area, were enrolled in an observational, longitudinal registry. Demographics, medical history, medication use, and psoriatic disease phenotype and activity were all recorded and analyzed. RESULTS: The population was 77.4% non-Hispanic White, 2.2% Black, 7.1% Asian, and 9.9% identified as other races or multiracial, and 11.8% identified as Hispanic. Hispanic and non-White individuals had higher tender joint counts (p= 0.033) with similar swollen joint counts (p= 0.308) and medication use (p= 0.171). They also had high rates of radiographic axial disease. Hispanic individuals were significantly more likely to have higher tender joint counts (p= 0.029), higher RAPID3 scores (p= 0.004), and moderate-severe psoriasis (p= 0.010) compared with non-Hispanic White individuals. CONCLUSION: In this diverse cohort, 22.6% of patients identified as underrepresented racial and/or ethnic groups, mostly Asian or Hispanic. Despite similar swollen joint counts and medication use, non-white individuals have higher tender joint counts compared with white individuals. Phenotypically, they also were more likely to have radiographic axial involvement. These findings may reflect differences in PsA presentation, experience and outcomes in individuals of various racial and ethnic groups, which need to be taken into consideration in clinical care and research design.
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BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.
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Artritis Psoriásica , Productos Biológicos , Consenso , Técnica Delphi , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Artritis Psoriásica/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Productos Biológicos/administración & dosificación , Administración Oral , Vacunación/normas , Adulto , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2 , Metotrexato/uso terapéutico , Metotrexato/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/uso terapéuticoRESUMEN
A novel and distinct mutant with a phenotype, aeroplane wing (ae) is reported for the first time in the urban malaria vector Anopheles stephensi. The main aim of this study was to establish the mode of inheritance of the ae gene performing genetic crossings between the mutants and wild types. These mutants show extended open wings that are visible to naked eyes in both the sexes. Mutants were first noticed in a nutritionally stressed isofemale colony. Strategic genetic crosses revealed that the ae gene is a recessive, autosomal, and monogenic trait having full penetrance with uniform expression in its adult stage. Egg morphometric analysis confirmed that these mutants were intermediate variant. No significant differences were observed in the wing venation and size of ae mutants compared to their control parental lines. Further cytogenetic analysis on the ovarian polytene chromosome of ae mutant showed an inversion (3Li) on the 3L arm like its parental line. This ae mutant would be a prominent marker and could be useful to study the functions of related specific genes within its genome.
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OBJECTIVE: To evaluate whether the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a responsive instrument in psoriatic arthritis (PsA) and whether it differentiates between axial and peripheral disease activity in PsA. METHODS: Individuals with PsA initiating therapy in a longitudinal cohort study based in the United States were included. Axial PsA (axPsA), most often also associated with peripheral disease, was defined as fulfillment of the Assessment of Spondyloarthritis international Society axial spondyloarthritis classification criteria or presence of axial disease imaging features. Baseline BASDAI, individual BASDAI items, patient global assessment, patient pain, and Routine Assessment of Patient Index Data 3, and score changes following therapy initiation were descriptively reported. Standardized response means (SRMs) were calculated as the mean change divided by the SD of the change. RESULTS: The mean (SD) baseline BASDAI score at the time of therapy initiation was 5.0 (2.2) among those with axPsA (n = 40) and 4.8 (2.0) among those with peripheral-only disease (n = 79). There was no significant difference in patient-reported outcome scores between the groups. The mean change for BASDAI was similar among axial vs peripheral disease (-0.75 vs -0.83). SRMs were similar across axial vs peripheral disease for BASDAI (-0.37 vs -0.44) and the individual BASDAI items. CONCLUSION: BASDAI has reasonable responsiveness in PsA but does not differentiate between axPsA and peripheral PsA. (ClinicalTrials.gov: NCT03378336).
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Artritis Psoriásica , Espondiloartritis , Espondilitis Anquilosante , Humanos , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/complicaciones , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/tratamiento farmacológico , Estudios Longitudinales , Índice de Severidad de la Enfermedad , Espondiloartritis/complicacionesRESUMEN
Ewing sarcoma (EWS) is an aggressive pediatric malignancy of the bone and soft tissues in need of novel therapeutic options. To identify potential therapeutic targets, we focused on essential biological pathways that are upregulated by EWS-FLI1, the primary oncogenic driver of EWS, including mitotic proteins such as Aurora kinase A (AURKA) and kinesin family member 15 (KIF15) and its binding partner, targeting protein for Xklp2 (TPX2). KIF15/TPX2 cooperates with KIF11, a key mitotic kinesin essential for mitotic spindle orientation. Given the lack of clinical-grade KIF15/TPX2 inhibitors, we chose to target KIF11 (using SB-743921) in combination with AURKA (using VIC-1911) given that phosphorylation of KIF15S1169 by Aurora A is required for its targeting to the spindle. In vitro, the drug combination demonstrated strong synergy (Bliss score ≥ 10) at nanomolar doses. Colony formation assay revealed significant reduction in plating efficiency (1-3%) and increased percentage accumulation of cells in the G2/M phase with the combination treatment (45-52%) upon cell cycle analysis, indicating mitotic arrest. In vivo studies in EWS xenograft mouse models showed significant tumor reduction and overall effectiveness: drug combination vs. vehicle control (p ≤ 0.01), SB-743921 (p ≤ 0.01) and VIC-1911 (p ≤ 0.05). Kaplan-Meier curves demonstrated superior overall survival with the combination compared to vehicle or monotherapy arms (p ≤ 0.0001).
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This work engrosses the production and further chemical modifications of EPS produced by Lactobacillus plantarum BR2 and subsequent evaluation of their biological properties showed greater antioxidant properties for the derivatives compared to its native unmodified form. Of the three derivatives, acetylated EPS (a-EPS), carboxymethylated EPS (Cm-EPS), and sulphated EPS (s-EPS), a-EPS exhibited the highest DPPH radical scavenging and total antioxidant activity in a dose-dependent manner. At all tested concentrations, a-EPS showed higher scavenging activity, and a maximum activity of 73.81% at 2 mg/mL. Meanwhile, s-EPS showed the highest reducing power potential and hydroxyl radical scavenging activities. At 2 mg/mL concentration, the order of reducing power was observed to be s-EPS (41.39%) > a-EPS (37.43%) > Cm-EPS (24.02) > BR2 control EPS (16%) and the hydroxyl radical scavenging activity for the s-EPS was 54.43%. The highest reducing power activity exhibited by s-EPS is 2.6-fold higher and a 1.5-fold increase in the scavenging activity of native BR2 EPS after the sulphonyl group addition was observed. The increase in these activities is due to the addition of various functional groups that contributes largely to the scavenging abilities of different free radicals. The s-EPS and Cm-EPS derivatives also exhibited increased cholesterol-lowering activity of 40 and 34.5%, respectively, than the native EPS. Interestingly, there were hardly any inhibitions on cell growth and viability of normal L929 fibroblast cell lines upon treatment with these EPSes. The improved antioxidant properties resulting from chemical modification opened better avenues for EPS application in the food and pharma sectors. Thus, the potentiality of chemically modified EPS may be explored further in the development of functional foods. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03718-5.
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BACKGROUND: Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized. OBJECTIVE: To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic. METHODS: This prospective cohort analysis evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients. RESULTS: One thousand thirty-nine patients were analyzed (490 GR [47.2%], 65 MBF [6.3%]). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter 2 variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was Tumor necrosis factor-α inhibitor to IL-17 inhibitor use. LIMITATIONS: Biologic adherence between visits was not evaluated. CONCLUSION: Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up.
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A newly isolated culture is identified as Streptococcus lutetiensis with significant starch saccharifying activity. Along with considerable amylolytic property (â¼ 2.71 U/mL), the culture exhibited significant production of exopolysaccharide (EPS) in starch medium. Interestingly, the glycosyl transferase activity which is essential in the biosynthesis of polysaccharide is also detected in the culture and after screening and process optimization, a maximum EPS titre of 19.92 ± 0.5 g/L was obtained from cassava starch. The crude EPS, after purification and characterization (monosaccharide analysis, FT-IR, TGA, GPC NMR, and SEM) was found to be of dextran nature with a Mw of 1275.36 kDa. Dextran type exopolysaccharide are synthesized by dextransucrase enzyme by the transfer of glucosyl residues from sucrose to dextran polymer. Interestingly, the glycosyl transferase enzyme activity which is essential in the biosynthesis of EPS is also detected in the culture. The particle size (447.8 dnm) and the zeta potential (-33.4) analysis of the purified EPS showed that the EPS produced is a stable molecule and has a random coil confirmation when exposed to alkaline condition with shear thinning property. One step conversion of sustainable low-cost starchy raw materials without adding external enzymes for hydrolysis, improved the economic viability of EPS production.
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Dextranos , Almidón , Espectroscopía Infrarroja por Transformada de Fourier , Streptococcus , Transferasas , Polisacáridos BacterianosRESUMEN
Glycosyltransferases synthesize a variety of exopolysaccharides (EPS) with different properties by altering the type of glycosidic linkage, degree of branching, length, mass, and conformation of the polymers. The genome analysis of an EPS-producing, Lactobacillus plantarum BR2 (Accession No: MN176402) showed twelve glycosyltransferase genes, and the gene BR2gtf (1116 bp), annotated as an EPS biosynthetic glycosyltransferase was cloned into the pNZ8148 vector. The recombinant pNZ8148 vector along with pNZ9530, a regulatory plasmid, were electroporated to L. plantarum BR2 for the over-expression of gtf gene under a nisin-controlled expression system and the glycosyltransferase activity of the recombinant and the wild-type strains were analysed. The recombinant strain showed 54.4% increase in EPS production with the maximum EPS production of 23.2 ± 0.5 g/L in a 5 L bioreactor study after 72 h of fermentation. This study shows an effective molecular strategy possibly to be adopted in lactic acid bacteria to enhance exopolysaccharide production.
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Lactobacillales , Lactobacillus plantarum , Nisina , Lactobacillus plantarum/genética , Lactobacillus plantarum/metabolismo , Nisina/genética , Nisina/metabolismo , Lactobacillales/metabolismo , Plásmidos , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Polisacáridos Bacterianos/metabolismoRESUMEN
Ewing Sarcoma (EWS) is the second most common osseous malignancy in children and young adults after osteosarcoma, while it is the fifth common osseous malignancy within adult age population. The clinical presentation of EWS is quite often non-specific, with the most common symptoms at presentation consisting of pain, swelling or general discomfort. The dearth of clinically relevant diagnostic or predictive biomarkers continues to remain a pressing clinical challenge. Identification of tumor specific biomarkers can lend towards an early diagnosis, expedited initiation of therapy, monitoring of therapeutic response, and early detection of recurrence of disease. We carried-out a complex analysis of cell lines and cell line derived small extracellular vesicles (sEVs) using label-free-based Quantitative Proteomic Profiling with an intent to determine shared and distinct features of these tumor cells and their respective sEVs. We analyzed EWS cells with different EWS-ETS fusions (EWS-FLI1 type I, II, and III and EWS-ERG) and their corresponding sEVs. Non-EWS controls included osteosarcoma, rhabdomyosarcoma, and benign cells, i.e., osteoid osteoma and mesenchymal stem cells. Proteomic profiling identified new shared markers between cells and their corresponding cell-derived sEVs and markers which were exclusively enriched in EWS-derived sEVs. These exo-biomarkers identified were validated by in silico approaches of publicly available protein databases and by capillary electrophoresis based western analysis (Wes). Here, we identified a protein biomarker named UGT3A2 and found its expression highly specific to EWS cells and their sEVs compared to control samples. Clinical validation of UGT3A2 expression in patient tumor tissues and plasma derived sEV samples demonstrated its specificity to EWS, indicating its potential as a EWS biomarker.
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Background: Tumor-associated macrophages (TAM) are the main component of inflammation along with leukocytes, endothelial cells and fibroblasts together form a tumor microenvironment, with immune cells representing its vital component. Many studies suggested that TAMs cumulating in tumors correlate with a poor prognosis. In prostate cancer, TAMs can increase cancer cell invasion by stimulating tumor angiogenesis, degrading the extracellular matrix, and also suppresses the antitumor functions of cytotoxic T cells resulting in poor prognosis. Aims and Objectives: : 1. To determine the expression of M1 (CD68) and M2 (CD163) in prostate carcinoma (Pca). 2. To find the association between M1, M2 macrophage with Gleason's score and stage of Pca. Materials and Methods: : This is a retrospective observational study. All transurethral resection prostatic (TURP) chips positive for Pca and the clinical details were collected. Radiologic findings with respect to stage of disease, size of lesion, were noted. Results: Among the 62 cases studied, majority of the cases were in-between the age of 61-70 years. Highest cases were seen in Gleason's score 8, 9, and 10 (62%), prostatic specific antigen (PSA) levels 20-80 ng/mL (64%), tumor size 3-6 cm (51.6%), T3 stage (40.3%), N1 lymph node stage (70.9%). M1 stage of (31%). CD68 and CD163 expression was analyzed with Gleason's score, TNM stage and PSA levels. CD68 score 3 correlated with low distant and nodal metastasis 6.2% and 6.8%, respectively. CD163 score 3 correlated with high metastasis to lymph nodes and distant metastasis of 86.3% and 25%, respectively. On further analysis, statistically convincing association between the CD163 expression and Gleason's score, PSA levels, nodal and distant metastasis was found. Conclusion: CD68 expression was correlated with good prognosis with less nodal and distant metastasis and Cd163 expression has poor outcome with increased chances of nodal and distant metastasis. Further exploration of TAM mechanisms and immune checkpoints in the prostate tumor microenvironment can furnish new light and motives for the treatment of Pca.
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Carcinoma , Neoplasias de la Próstata , Masculino , Humanos , Persona de Mediana Edad , Anciano , Antígeno Prostático Específico , Macrófagos Asociados a Tumores/patología , Próstata/patología , Células Endoteliales , Neoplasias de la Próstata/patología , Pronóstico , Microambiente TumoralRESUMEN
OBJECTIVE: To determine the responsiveness to therapy and minimum clinically important improvement (MCII) for patient-reported outcome measures in psoriatic arthritis (PsA) and to examine the impact of baseline disease activity on the ability to demonstrate change. METHODS: A longitudinal cohort study was performed within the PsA Research Consortium. Patients completed several patient-reported outcomes, including the Routine Assessment of Patient Index Data, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Psoriatic Arthritis Impact of Disease 12-item (PsAID12) questionnaire, and others. The mean change in the scores between visits and standardized response means (SRMs) were calculated. The MCII was calculated as the mean change in score among patients who reported minimal improvement. SRMs and MCIIs were compared among subgroups with moderate to highly active PsA and those with lower disease activity. RESULTS: Among 171 patients, 266 therapy courses were included. The mean ± SD age was 51 ± 13.8 years, 53% were female, and the mean swollen and tender joint counts were 3 and 6, respectively, at baseline. SRMs and MCII for all measures were small to moderate, although greater among those with higher baseline disease activity. BASDAI had the best SRM overall and for less active PsA, and the clinical Disease Activity of PsA (cDAPSA) and PsAID12 were best for those with higher disease activity. CONCLUSION: SRMs and MCII were relatively small in this real-world population, particularly among those with lower disease activity at baseline. BASDAI, cDAPSA, and PsAID12 had good sensitivity to change, but selection for use in trials should consider the baseline disease activity of patients to be enrolled.
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Artritis Psoriásica , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Artritis Psoriásica/terapia , Artritis Psoriásica/tratamiento farmacológico , Estudios Prospectivos , Estudios Longitudinales , Índice de Severidad de la Enfermedad , Estudios de Cohortes , Medición de Resultados Informados por el PacienteRESUMEN
Despite therapeutic interventions for glioblastoma (GBM), cancer stem cells (CSCs) drive recurrence. The precise mechanisms underlying CSC resistance, namely inhibition of cell death, are unclear. We built on previous observations that the high cell surface expression of junctional adhesion molecule-A drives CSC maintenance and identified downstream signaling networks, including the cysteine protease inhibitor SerpinB3. Using genetic depletion approaches, we found that SerpinB3 is necessary for CSC maintenance, survival, and tumor growth, as well as CSC pathway activation. Knockdown of SerpinB3 also increased apoptosis and susceptibility to radiation therapy. SerpinB3 was essential to buffer cathepsin L-mediated cell death, which was enhanced with radiation. Finally, we found that SerpinB3 knockdown increased the efficacy of radiation in pre-clinical models. Taken together, our findings identify a GBM CSC-specific survival mechanism involving a cysteine protease inhibitor, SerpinB3, and provide a potential target to improve the efficacy of GBM therapies against therapeutically resistant CSCs.
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Glioblastoma , Inhibidores de Cisteína Proteinasa/metabolismo , Inhibidores de Cisteína Proteinasa/uso terapéutico , Glioblastoma/patología , Humanos , Células Madre Neoplásicas/metabolismo , Transducción de SeñalRESUMEN
Anopheles stephensi is the most menacing malaria vector to watch for in newly urbanising parts of the world. Its fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions in the genome of malaria vectors are implicated in adaptation. We report the genome assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome reported here with a L50 of 4, completes the trilogy of high-resolution genomes of strains with respect to a 16.5 Mbp 2Rb genotype in An. stephensi known to be associated with adaptation to environmental heterogeneity. Unlike the reported genomes of two other strains, STE2 (2R+b/2Rb) and UCI (2Rb/2Rb), IndCh is found to be homozygous for the standard form (2R+b/2R+b). Comparative genome analysis revealed base-level details of the breakpoints and allowed extraction of 22,650 segregating SNPs for typing this inversion in populations. Whole genome sequencing of 82 individual mosquitoes from diverse geographical locations reveal that one third of both wild and laboratory populations maintain the heterozygous genotype of 2Rb. The large number of SNPs can be tailored to 1740 exonic SNPs enabling genotyping directly from transcriptome sequencing. The genome trilogy approach accelerated the study of fine structure and typing of an important inversion in An. stephensi, putting the genome resources for this understudied species on par with the extensively studied malaria vector, Anopheles gambiae. We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse geographical locations cluster with IndCh, pointing to significant convergence resulting from travel and commerce between cities, perhaps, contributing to the survival of the fittest strain.
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Anopheles , Malaria , Animales , Anopheles/genética , Inversión Cromosómica , India , Mosquitos Vectores/genética , AguaRESUMEN
INTRODUCTION: Clinical pharmacist can enthusiastically involve in oncology department through utilizing the skills and knowledge to support wide variety of functions in patient care. The impact of pharmaceutical care services in oncology department were analysed through various approaches including the analysis of knowledge level of patients towards the disease and its management through patient counselling, monitoring of performance status, observing of ADR and drug safety. Incidence of cancer was scrutinized during the study.Methodology: A Prospective interventional study was conducted from November 2019 to March 2020 with the support of institutional ethical approval at oncology department of Lourdes hospital, Ernakulam. 133 patients were included with all type of cancer. Data collected through Performa with KAP questionnaire and direct interview was conducted. Statistical significance was evaluated through p value of <0.001 Result: 123 patients were completed both questionnaire. Among this 69.91% were females and most of the patients belonged to 50 - 65yeras age group and carcinoma was frequently reported type. End of the study showed significant change in the knowledge level of patients after interaction with the clinical pharmacist. 26 ADRs were reported including solitary and multiple ADRs. Recommendations associated with drug reconstitution, administration were frequently given to the nurses. Most of the interventions to improve therapeutic outcome of the patients were accepted by the oncologist. CONCLUSION: Clinical pharmacist can actively participate in all aspects of the oncology department in association with physician and other health care providers to improve the therapeutic outcome and quality of life of patients.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias , Servicios Farmacéuticos , Femenino , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Farmacéuticos , Estudios Prospectivos , Calidad de Vida , Centros de Atención TerciariaRESUMEN
There are many reports on exopolysaccharides of lactic acid bacteria (LAB EPS) such as isolation, production and applications. The LAB EPS have been proved to exhibit significantly improved texture and rheological properties in order to prevent syneresis of fermented foods. Furthermore, they are known to have many biological properties such as mouthwatering flavors, antioxidant activity, cholesterol lowering and antimicrobial activities. Considering their GRAS status, LAB EPS need to be explored for better titre and improved biological properties, where strain improvement by genetic engineering has a major role for making tailor-made EPS. The genetic overview of the EPS production by LAB is an auxiliary area of interest as the process and the biosynthetic pathway involves numerous genes and their proteins. Among them Glycosyltransferases (gtfs) are the key enzymes involved in EPS biosynthesis. Current knowledge of gtfs of LAB and its manipulation is limited. The present review spotlights the importance of glycosyltransferases and their specific role on the biosynthesis of LAB EPS and addresses the functionality and applicability of these enzymes and their products. It enfold the available literature including some patents in recent past to underline the fact that glycosyltransferases are un-reluctantly the key proteins involved in the EPS biosynthesis.