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1.
Neuropsychopharmacology ; 49(7): 1193-1201, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38615126

RESUMEN

Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)-a mitochondrial protein-in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using [11C]PBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two [11C]PBR28 PET-MRI scans. Females with ASD exhibited elevated [11C]PBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower [11C]PBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable [11C]PBR28 SUVR across time in both groups. Elevated regional [11C]PBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional [11C]PBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD.


Asunto(s)
Trastorno del Espectro Autista , Encéfalo , Tomografía de Emisión de Positrones , Receptores de GABA , Humanos , Femenino , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/diagnóstico por imagen , Proyectos Piloto , Receptores de GABA/metabolismo , Tomografía de Emisión de Positrones/métodos , Adulto , Adulto Joven , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Caracteres Sexuales , Adolescente , Masculino
2.
Mol Pharm ; 21(3): 1402-1413, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38331430

RESUMEN

Despite decades of work, small-cell lung cancer (SCLC) remains a frustratingly recalcitrant disease. Both diagnosis and treatment are challenges: low-dose computed tomography (the approved method used for lung cancer screening) is unable to reliably detect early SCLC, and the malignancy's 5 year survival rate stands at a paltry 7%. Clearly, the development of novel diagnostic and therapeutic tools for SCLC is an urgent, unmet need. CD133 is a transmembrane protein that is expressed at low levels in normal tissue but is overexpressed by a variety of tumors, including SCLC. We previously explored CD133 as a biomarker for a novel autoantibody-to-immunopositron emission tomography (PET) strategy for the diagnosis of SCLC, work that first suggested the promise of the antigen as a radiotheranostic target in the disease. Herein, we report the in vivo validation of a pair of CD133-targeted radioimmunoconjugates for the PET imaging and radioimmunotherapy of SCLC. To this end, [89Zr]Zr-DFO-αCD133 was first interrogated in a trio of advanced murine models of SCLC─i.e., orthotopic, metastatic, and patient-derived xenografts─with the PET probe consistently producing high activity concentrations (>%ID/g) in tumor lesions combined with low uptake in healthy tissues. Subsequently, a variant of αCD133 labeled with the ß-emitting radiometal 177Lu─[177Lu]Lu-DTPA-A″-CHX-αCD133─was synthesized and evaluated in a longitudinal therapy study in a subcutaneous xenograft model of SCLC, ultimately revealing that treatment with a dose of 9.6 MBq of the radioimmunoconjugate produced a significant increase in median survival compared to a control cohort. Taken together, these data establish CD133 as a viable target for the nuclear imaging and radiopharmaceutical therapy of SCLC.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Animales , Ratones , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Detección Precoz del Cáncer , Línea Celular Tumoral , Carcinoma Pulmonar de Células Pequeñas/diagnóstico por imagen , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Tomografía de Emisión de Positrones/métodos
4.
Brain ; 147(7): 2566-2578, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38289855

RESUMEN

Compartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. PET targeting the 18 kDa mitochondrial translocator protein (TSPO) is a molecular-specific approach to quantifying immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. This study aimed to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple sclerosis cases using in vivo simultaneous MR-PET with 11C-PBR28, a second-generation TSPO radioligand, and ex vivo immunohistochemistry. Forty-nine multiple sclerosis patients (21 with secondary progressive and 28 with relapsing-remitting multiple sclerosis) with mixed or high affinity binding for 11C-PBR28 underwent 90-min 11C-PBR28 simultaneous MR-PET. Tracer binding was measured using 60-90 min normalized standardized uptake value ratios sampled at mid-cortical depth and ∼3 mm above the pial surface. Data in multiple sclerosis patients were compared to 21 age-matched healthy controls. To characterize the nature of 11C-PBR28 PET uptake, the meningeal and cortical lesion cellular expression of TSPO was further described in post-mortem brain tissue from 20 cases with secondary progressive multiple sclerosis and five age-matched healthy donors. Relative to healthy controls, patients with multiple sclerosis exhibited abnormally increased TSPO signal in the cortex and meningeal tissue, diffusively in progressive disease and more localized in relapsing-remitting multiple sclerosis. In multiple sclerosis, increased meningeal TSPO levels were associated with increased Expanded Disability Status Scale scores (P = 0.007, by linear regression). Immunohistochemistry, validated using in situ sequencing analysis, revealed increased TSPO expression in the meninges and adjacent subpial cortical lesions of post-mortem secondary progressive multiple sclerosis cases relative to control tissue. In these cases, increased TSPO expression was related to meningeal inflammation. Translocator protein immunostaining was detected on meningeal MHC-class II+ macrophages and cortical-activated MHC-class II+ TMEM119+ microglia. In vivo arterial blood data and neuropathology showed that endothelial binding did not significantly account for increased TSPO cortico-meningeal expression in multiple sclerosis. Our findings support the use of TSPO-PET in multiple sclerosis for imaging in vivo inflammation in the cortico-meningeal brain tissue compartment and provide in vivo evidence implicating meningeal inflammation in the pathogenesis of the disease.


Asunto(s)
Meninges , Esclerosis Múltiple , Tomografía de Emisión de Positrones , Receptores de GABA , Humanos , Receptores de GABA/metabolismo , Receptores de GABA/genética , Femenino , Masculino , Persona de Mediana Edad , Adulto , Tomografía de Emisión de Positrones/métodos , Meninges/metabolismo , Meninges/diagnóstico por imagen , Meninges/patología , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Anciano , Corteza Cerebral/metabolismo , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patología , Imagen por Resonancia Magnética , Esclerosis Múltiple Crónica Progresiva/metabolismo , Esclerosis Múltiple Crónica Progresiva/diagnóstico por imagen , Esclerosis Múltiple Crónica Progresiva/patología , Acetamidas , Piridinas
5.
Chemosphere ; 349: 140971, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38122942

RESUMEN

The manufacturing sector is paying close attention to plastic matrix composites (PMCs) reinforced with natural fibres for improving their products. Due to the fact that PMC reinforced with naturally occurring fibres is more affordable and has superior mechanical qualities. Based on the application material requirements, An important step in the production of PMC is choosing the right natural fibres for reinforcing and determining how much of each. This investigation aimed that Artificial Intelligence (AI) or soft computing based approaches are used to determine the right amount of natural fibres in PMCs to make the manufacturing process simpler. However, techniques in the literature are not concentrated on finding suitable material. Hence in this investigation, a local search with support vector machine (LS-SVM) optimization technique is proposed for the optimal selection of appropriate proportions of suitable fibres. Modelling of the Proposed LS-SVM Optimization was demonstrated. In this proposed technique around four kinds of polymers/plastics and 14 natural fibres are considered, which are optimized in various proportions. The optimization performance is evaluated based on the tensile strength, flexural yield strength and flexural yield modulus. The proposed LS-SVM Optimization was evacuated by developing solutions for medical applications (Case 1), Transportation applications (Case 2) and other notable applications (Case 3) in terms of tensile and flexural properties of the material. The maximum flexure stress in case 1, case 2, and case 3 is observed as 53 MPa, 45 MPa and 26 MPa respectively. Similarly, the maximum flexure stress in case 1, case 2, and case 3 is observed as 53 MPa, 45 MPa and 26 MPa respectively. Hence the proposed method recommended for choosing optimal decision on the choice of fiber and their quantity in the composite matrix.


Asunto(s)
Polímeros , Máquina de Vectores de Soporte , Inteligencia Artificial , Ensayo de Materiales , Resistencia a la Tracción
6.
J Microbiol Biol Educ ; 24(3)2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38108004

RESUMEN

Logistical challenges in large enrollment classes are often mentioned as obstacles to active learning. Writing is an integral part of being a scientist and is often one of the first tools considered by STEM instructors to increase student engagement, but iterative writing assignments in large classes require creativity on the part of the instructor. We found an association between writing-to-learn assignments designed to be consistent with inclusive learning pedagogies and student performance measures in a large enrollment undergraduate biology course. They provide ample opportunity for deliberate practice and inclusive engagement, components of the "heads and hearts" hypothesis posed to explain the variation in active learning impacts on the performance of minoritized students.

7.
Indian J Med Res ; 158(4): 351-362, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37988028

RESUMEN

BACKGROUND OBJECTIVES: In view of anecdotal reports of sudden unexplained deaths in India's apparently healthy young adults, linking to coronavirus disease 2019 (COVID-19) infection or vaccination, we determined the factors associated with such deaths in individuals aged 18-45 years through a multicentric matched case-control study. METHODS: This study was conducted through participation of 47 tertiary care hospitals across India. Cases were apparently healthy individuals aged 18-45 years without any known co-morbidity, who suddenly (<24 h of hospitalization or seen apparently healthy 24 h before death) died of unexplained causes during 1 st October 2021-31 st March 2023. Four controls were included per case matched for age, gender and neighborhood. We interviewed/perused records to collect data on COVID-19 vaccination/infection and post-COVID-19 conditions, family history of sudden death, smoking, recreational drug use, alcohol frequency and binge drinking and vigorous-intensity physical activity two days before death/interviews. We developed regression models considering COVID-19 vaccination ≤42 days before outcome, any vaccine received anytime and vaccine doses to compute an adjusted matched odds ratio (aOR) with 95 per cent confidence interval (CI). RESULTS: Seven hundred twenty nine cases and 2916 controls were included in the analysis. Receipt of at least one dose of COVID-19 vaccine lowered the odds [aOR (95% CI)] for unexplained sudden death [0.58 (0.37, 0.92)], whereas past COVID-19 hospitalization [3.8 (1.36, 10.61)], family history of sudden death [2.53 (1.52, 4.21)], binge drinking 48 h before death/interview [5.29 (2.57, 10.89)], use of recreational drug/substance [2.92 (1.1, 7.71)] and performing vigorous-intensity physical activity 48 h before death/interview [3.7 (1.36, 10.05)] were positively associated. Two doses lowered the odds of unexplained sudden death [0.51 (0.28, 0.91)], whereas single dose did not. INTERPRETATION CONCLUSIONS: COVID-19 vaccination did not increase the risk of unexplained sudden death among young adults in India. Past COVID-19 hospitalization, family history of sudden death and certain lifestyle behaviors increased the likelihood of unexplained sudden death.


Asunto(s)
Consumo Excesivo de Bebidas Alcohólicas , COVID-19 , Adulto Joven , Humanos , Estudios de Casos y Controles , Vacunas contra la COVID-19 , Consumo Excesivo de Bebidas Alcohólicas/complicaciones , Muerte Súbita/etiología , COVID-19/epidemiología , COVID-19/complicaciones
8.
PLoS One ; 18(10): e0292955, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37851600

RESUMEN

Coriander, fenugreek, nigella etc. are collectively known as seed spices. They are "High value and low volume crops" and considered cash crops for the growers of arid and semi-arid regions of India. Coriander, fenugreek and nigella are grown during the rabi season and take hardly 130-140 days to attain full maturity. In this context, farmers are not able to develop income from available arable land round the year, even though they have sufficient resources as well as manpower. Therefore, coriander, fenugreek and nigella-based cropping systems, four of each (total 12) were evaluated during 3 consecutive years (2019-20 to 2021-22) for their productivity, resource-use efficiency, economics and soil fertility. The results showed that among the seed spices-based cropping systems, maximum system productivity (5193 kg ha-1), production efficiency (18.81 kg ha-1 day-1), water-use efficiency (2.31 kg ha-1 mm-1), economic efficiency (11.85 US $ ha-1 day-1), net return (3270 US $ ha-1), benefit:cost ratio (3.27) and available N (165.6 kg ha-1) were observed under nigella-green coriander-mungbean cropping system. Hence, seed spices growers are recommended to adopt nigella-green coriander-mungbean cropping system in order to realize better productivity, resource-use efficiency, soil fertility and profitability.


Asunto(s)
Fabaceae , Suelo , Agricultura/métodos , Clima Desértico , India
9.
J Microbiol Biol Educ ; 24(2)2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37614887

RESUMEN

Education about scientific publishing and manuscript peer review is not universally provided in undergraduate science courses. Since peer review is integral to the scientific process and central to the identity of a scientist, we envision a paradigm shift where teaching peer review becomes integral to undergraduate science education. We hypothesize that teaching undergraduates how to peer review scientific manuscripts may facilitate their development of scientific literacy and identity formation. To this end, we developed a constructivist, service-learning curriculum for biology undergraduates to learn about the mechanisms of peer review using preprints and then to write and publish their own peer reviews of preprints as a way to authentically join the scientific community of practice. The curriculum was implemented as a semester-long intervention in one class and, in another class, as an embedded module intervention. Students' scientific literacy and peer review ability were assessed using quantitative methods. Student's perceptions of their scientific literacy and identity were assessed using thematic analysis of students' reflective writing. Here, we present data on the improvement in the peer review ability of undergraduates in both classes and data on the curriculum's interrelated impact on students' development of scientific literacy, identity, and belonging in peer and professional discourse spaces. These data suggest that undergraduates can and should be trained in peer review to foster the interrelated development of their scientific literacy, scientific identity, and sense of belonging in science.

10.
PLoS One ; 18(8): e0288784, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37556422

RESUMEN

An incubation experiment was conducted to monitor the effect of different organic matter inputs with the graded application of gypsum at different time intervals on soil pH, sodium (Na) content and available plant nutrients like nitrogen (N) and sulphur (S) in alkaline soil. The experiment was formulated with nine treatments, i.e. control (T1), recommended dose of fertilizer (RDF) (T2), RDF+Gyp1 (T3), RDF+FYM5+Gyp2 (T4), RDF+FYM10+Gyp1 (T5), RDF+PM5+Gyp2 (T6), RDF+PM10+Gyp1 (T7), RDF+FYM2.5+PM2.5+Gyp2 (T8), RDF+FYM5+PM5+Gyp1 (T9) with three replications. Periodical soil samples were taken at six and twelve months intervals. Results showed that the addition of organic matter reduced the pH and Na content in the soil. More reduction was observed at one year period as compared to six months. The addition of farmyard manure (FYM) and pressmud (PM) at 10 t/ha with gypsum (1 t/ha) improved available N and available S content as compared to organic inputs (5 t/ha) with gypsum (2 t/ha) in soil. Pressmud application with FYM showed better availability of plant nutrients and a reduction of soil pH (8.39 to 7.79) and Na content from 626 to 391 mEq/L in the soil during the incubation period. During the study, the application of treatment T9 (FYM and PM in equal ratio with 1 t/ha gypsum) showed a better availability of available N (175 to 235 kg/ha) and S (15.44 to 23.24 kg/ha) and reduced the active ion concentration of Na. This study is very useful for the management of sodium toxicity, improving soil health and the mineralization rate of organic matter through the application of organic inputs for sustainable crop production.


Asunto(s)
Sulfato de Calcio , Suelo , Suelo/química , Nutrientes , Producción de Cultivos , Productos Agrícolas , Fertilizantes/análisis
11.
RSC Adv ; 13(26): 17705-17709, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37313000

RESUMEN

We report the in vitro characterization and in vivo evaluation of a novel 89Zr-labeled radioimmunoconjugate synthesized using a site-selective bioconjugation strategy based on the oxidation of tyrosinase residues exposed by the deglycosylation of the IgG and the subsequent strain-promoted oxidation-controlled 1,2-quinone cycloaddition between these amino acids and trans-cyclooctene-bearing cargoes. More specifically, we site-selectively modified a variant of the A33 antigen-targeting antibody huA33 with the chelator desferrioxamine (DFO), thereby producing an immunoconjugate (DFO-SPOCQhuA33) with equivalent antigen binding affinity to its parent immunoglobulin but attenuated affinity for the FcγRI receptor. This construct was subsequently radiolabeled with [89Zr]Zr4+ to create a radioimmunoconjugate - [89Zr]Zr-DFO-SPOCQhuA33 - in high yield and specific activity that exhibited excellent in vivo behavior in two murine models of human colorectal carcinoma.

12.
Conserv Biol ; 37(2): e14023, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36424867

RESUMEN

Scientists in higher education institutions around the globe recognize the importance of engaging with public stakeholders to share their enthusiasm, explain their science, and encourage primary and secondary students to enter the sciences. However, without direct consideration of students' and teachers' perspectives and interests, scientists may design activities around their own goals, limiting the impact on school stakeholders (i.e., students, teachers, paraprofessional staff, students' parents, and other caregivers). We drew from natural and social science research to describe how expanding the conception of place beyond the biophysical can help engage school stakeholders in meaningful ways. We describe the multidimensional PLACE framework that we developed to integrate perspectives, knowledge, and values of all stakeholders in engagement programming. The framework is organized around topics that stakeholders should discuss early on to ensure successful partnerships. We recommend that scientists identify and use pedagogy that is inclusive; language framed around dialogic communication methods; aims and motivations centered on engagement; cultural funds of knowledge of place (i.e., disciplinary, personal, or experiential knowledge); and evaluation of engagement based on meaningful metrics. Two case studies are presented to illustrate how the PLACE framework components, when addressed, can lead to robust, successful partnerships between scientists and schools.


Pedagogía crítica del lugar para mejorar las actividades ecológicas participativas Resumen Alrededor del mundo, los científicos de las instituciones de educación superior reconocen lo importante que es involucrarse con los actores públicos para compartir su entusiasmo, explicar la ciencia que trabajan y alentar a los estudiantes de primaria y secundaria a formar parte de las ciencias. Sin embargo, si los científicos no consideran las perspectivas e intereses de los docentes y estudiantes, pueden terminar diseñando actividades para lograr sus propios objetivos, lo que limita el impacto sobre los actores escolares (estudiantes, docentes, personal para-profesional, familias y otros cuidadores). Partimos de las ciencias naturales y sociales para describir cómo la expansión del concepto de lugar más allá de lo biofísico puede ayudar a que los actores escolares se involucren de maneras significativas. Describimos el marco multidimensional PLACE que desarrollamos para integrar el conocimiento, las perspectivas y los valores de todos los actores dentro de la programación de la participación. El marco está organizado en torno a los temas que los actores deberían discutir al inicio para asegurar colaboraciones exitosas. Recomendamos que los científicos identifiquen y usen una pedogagía inclusiva; lenguaje enmarcado en los métodos de comunicación por diálogo; objetivos y motivaciones centradas en la participación; recursos culturales del conocimiento del lugar (conocimiento disciplinario, personal o por experiencias); y una evaluación de la participación con base en medidas significativas. Presentamos dos estudios de caso para ilustrar cómo, cuando se utilizan, los componentes del marco PLACE pueden resultar en colaboraciones sólidas y exitosas entre los científicos y las escuelas.


Asunto(s)
Conservación de los Recursos Naturales , Estudiantes , Humanos , Instituciones Académicas , Motivación , Ciencias Sociales
14.
Ecol Soc ; 27(2)2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36381294

RESUMEN

How a society relates to nature is shaped by the dominant social paradigm (DSP): a society's collective view on social, economic, political, and environmental issues. The characteristics of the DSP have important consequences for natural systems and their conservation. Based on a synthesis of academic literature, we provide a new gradient of 12 types of human-nature relationships synthesized from scientific literature, and an analysis of where the DSP of industrialized, and more specifically, neoliberal societies fit on that gradient. We aim to answer how the industrialized DSP relates to nature, i.e., what types of human-nature relationships this DSP incorporates, and what the consequences of these relationships are for nature conservation and a sustainable future. The gradient of human-nature relationships is based on three defining characteristics: (1) a nature-culture divide, (2) core values, and (3) being anthropocentric or ecocentric. We argue that the industrialized DSP includes elements of the anthropocentric relationships of mastery, utilization, detachment, and stewardship. It therefore regards nature and culture as separate, is mainly driven by instrumental values, and drives detachment from and commodification of nature. Consequently, most green initiatives and policies driven by an industrialized and neoliberal DSP are based on economic incentives and economic growth, without recognition of the needs and limits of natural systems. This leads to environmental degradation and social inequality, obstructing the path to a truly sustainable society. To reach a more ecocentric DSP, systemic changes, in addition to individual changes, in the political and economic structures of the industrialized DSP are needed, along with a change in values and approach toward nature, long-term sustainability, and conservation.

15.
Bioconjug Chem ; 33(9): 1750-1760, 2022 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-35946495

RESUMEN

The synthesis of radioimmunoconjugates via the stochastic attachment of bifunctional chelators to lysines can yield heterogeneous products with suboptimal in vitro and in vivo behavior. In response to this, several site-selective approaches to bioconjugation have been developed, yet each has intrinsic drawbacks, such as the need for expensive reagents or the complexity of incorporating unnatural amino acids into IgGs. Herein, we describe the use of a simple and facile approach to lysine-directed site-selective bioconjugation for the generation of radioimmunoconjugates. This strategy relies upon on the selective modification of single lysine residues within each light chain of the monoclonal antibody (mAb) with a branched azide-bearing perfluorophenyl ester (PFP-bisN3) followed by the ligation of dibenzocyclooctyne (DBCO)-bearing payloads to these bioorthogonal handles via the strain-promoted azide-alkyne cycloaddition. This methodology was used to create [89Zr]Zr-SSKDFO-pertuzumab, a radioimmunoconjugate of the HER2-targeting mAb pertuzumab labeled with desferrioxamine (DFO) and the positron-emitting radiometal zirconium-89 (89Zr). [89Zr]Zr-SSKDFO-pertuzumab was compared to a pair of analogous probes: one synthesized via random lysine modification ([89Zr]Zr-DFO-pertuzumab) and another via thiol-maleimide chemistry ([89Zr]Zr-malDFO-pertuzumab). The bioconjugation strategy was assessed using ESI mass spectrometry, SDS-PAGE, and autoradiography. All three immunoconjugates demonstrated comparable binding to HER2 via flow cytometry and surface plasmon resonance (SPR), and 89Zr-labeled variants of each were synthesized in >99% radiochemical yield and molar activities of up to ∼55.5 GBq/µmol (10 mCi/mg). Subsequently, the in vivo behavior of this trio of 89Zr-immunoPET probes was interrogated in athymic nude mice bearing subcutaneous HER2-expressing BT-474 human breast cancer xenografts. [89Zr]Zr-SSKDFO-pertuzumab, [89Zr]Zr-malDFO-pertuzumab, and [89Zr]Zr-DFO-pertuzumab produced positron emission tomography (PET) images with high tumoral uptake and high tumor-to-healthy organ activity concentration ratios. A terminal biodistribution study complemented the PET results, revealing tumoral activity concentrations of 126.9 ± 50.3%ID/g, 86.9 ± 53.2%ID/g, and 92.5 ± 27.2%ID/g at 144 h post-injection for [89Zr]Zr-SSKDFO-pertuzumab, [89Zr]Zr-malDFO-pertuzumab, and [89Zr]Zr-DFO-pertuzumab, respectively. Taken together, the data clearly illustrate that this highly modular and facile approach to site-selective bioconjugation produces radioimmunoconjugates that are better-defined and more homogeneous than stochastically modified constructs and also exhibit excellent in vitro and in vivo performance. Furthermore, we contend that this lysine-directed strategy holds several key advantages over extant approaches to site-selective bioconjugation, especially in the context of production for the clinic.


Asunto(s)
Neoplasias de la Mama , Inmunoconjugados , Alquinos , Animales , Anticuerpos Monoclonales/química , Azidas , Línea Celular Tumoral , Quelantes , Deferoxamina/química , Ésteres , Femenino , Humanos , Inmunoconjugados/química , Lisina , Maleimidas , Ratones , Ratones Desnudos , Tomografía de Emisión de Positrones/métodos , Compuestos de Sulfhidrilo , Distribución Tisular , Circonio/química
16.
PLoS One ; 17(8): e0272552, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35976904

RESUMEN

There is an alarming shortage of qualified STEM teachers in American PK-12 schools. The COVID-19 pandemic may exacerbate this crisis and consequently affect who participates in future STEM innovation. At three points during the pandemic, we surveyed early career teachers who were supported by the National Science Foundation as they began teaching in high-needs school districts. Teachers who felt connected to their professional and academic communities reported intentions to remain in the profession, while those who felt isolated reported intentions of leaving. It is critical for STEM academics to maintain professional relationships with graduates who pursue STEM teaching professions after graduation.


Asunto(s)
COVID-19 , Personal Docente , COVID-19/epidemiología , Humanos , Intención , Pandemias , Instituciones Académicas , Estados Unidos
17.
Environ Dev Sustain ; : 1-32, 2022 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-35645606

RESUMEN

The availability of freshwater is limited for agriculture systems across the globe. A fast-growing population demands need to enhance the food grain production from a limited natural resources. Therefore, researchers and policymakers have been emphasized on the production potential of agricultural crops in a sustainable manner. On the challenging side, freshwater bodies are shrinking with the pace of time further limiting crop production. Poor-quality water may be a good alternative for fresh water in water scarce areas. It should not contain toxic pollutants beyond certain critical levels. Unfortunately, such critical limits for different pollutants as well as permissible quality parameters for different wastewater types are lacking or poorly addressed. Marginal quality water and industrial effluent used in crop production should be treated prior to application in crop field. Hence, safe reuse of wastewater for cultivation of food material is necessary to fulfil the demands of growing population across the globe in the changing scenario of climate.

19.
J Family Med Prim Care ; 11(1): 182-189, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35309654

RESUMEN

Introduction: COVID is a new disease; understanding the transmission dynamics and epidemiological characteristics may help in developing the effective control measures. The study is done 1. To determine the various factors influencing the acquisition of COVID-19 infection among high-risk contacts 2. To estimate the secondary attack rate among high-risk contacts 3. To determine the factors in COVID index cases influencing their secondary attack rate. Methodology: Unmatched case control study was conducted from March to August 2020 among 139 COVID index cases in Madurai district from March-May (Reference period) and their 50 COVID positive (cases), 551 COVID negative (controls) high-risk contacts. Case investigation form* and contact tracing Proforma*were used to collect data. Chi-square test and independent sample t test were used to find out the association. Univariate* and Multivariate logistic regression* were used to predict the risk of various factors in acquisition of COVID infection with the help of adjusted and unadjusted odds ratio. P value < 0.05 was considered statistically significant. Results: Male contacts (P = 0.005, OR = 2.520), overcrowding (P = 0.007, OR = 3.810), and duration of exposure to index case (for 4-7 days P = 0.014, OR = 2.902, for >7 days P = 0.001, OR = 6.748 and for > 12 hours/day P = 0.000, OR = 5.543) were significant factors predicted to be associated with acquisition of COVID infection among high-risk contacts. Reproductive number (R0)* estimated was 1.3. Secondary attack rate (SAR)* estimated among high-risk contacts was 8.32%. Index cases whose outcome was death (P = 0.026); symptomatic index cases (P = 0.000), cases with fever (P = 0.001); sorethroat (P = 0.019); breathlessness (P = 0.010); cough (P = 0.006) and running nose (P = 0.002) had significantly higher mean SAR than their counterparts. Conclusion: Contacts with above said risk factors who were found to be more prone to infection could be given special focus to prevent the transmission in them.

20.
Brain Behav Immun ; 102: 89-97, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35181440

RESUMEN

While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other "sickness behavior"-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus. We compared fifty-seven 'Pre-Pandemic' and fifteen 'Pandemic' datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies. We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomics and serum testing to uncover links between pandemic-related stressors and neuroinflammation. Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects. The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus and precuneus (physical fatigue), compared to those reporting little/no symptoms. Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions. This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings.


Asunto(s)
COVID-19 , Pandemias , Biomarcadores/metabolismo , Encéfalo/metabolismo , Control de Enfermedades Transmisibles , Humanos , Enfermedades Neuroinflamatorias , Receptores de GABA/metabolismo , SARS-CoV-2
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