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1.
Diagnostics (Basel) ; 14(16)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39202254

RESUMEN

BACKGROUND: Multidrug-resistant HIV strains challenge treatment efficacy and increase mortality rates. Next-generation sequencing (NGS) technology swiftly detects variants, facilitating personalized antiretroviral therapy. AIM: This study aimed to validate the Vela Diagnostics NGS platform for HIV drug resistance mutation analysis, rigorously assessed with clinical samples and CAP proficiency testing controls previously analyzed by Sanger sequencing. METHOD: The experimental approach involved the following: RNA extraction from clinical specimens, reverse transcription polymerase chain reaction (RT-PCR) utilizing the Sentosa SX 101 platform, library preparation with the Sentosa SQ HIV Genotyping Assay, template preparation, sequencing using the Sentosa SQ301 instrument, and subsequent data analysis employing the Sentosa SQ Suite and SQ Reporter software. Drug resistance profiles were interpreted using the Stanford HIV Drug Resistance Database (HIVdb) with the HXB2 reference sequence. RESULTS: The Vela NGS system successfully identified a comprehensive array of drug resistance mutations across the tested samples: 28 nucleoside reverse transcriptase inhibitors (NRTI), 25 non-nucleoside reverse transcriptase inhibitors (NNRTI), 25 protease inhibitors (PI), and 10 integrase gene-specific variants. Dilution experiments further validated the system's sensitivity, detecting drug resistance mutations even at viral loads lower than the recommended threshold (1000 copies/mL) set by Vela Diagnostics. SCOPE: This study underscores the validation and clinical applicability of the Vela NGS system, and its implementation may offer clinicians enhanced precision in therapeutic decision-making for individuals living with HIV.

2.
Acad Emerg Med ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054590

RESUMEN

BACKGROUND: Disparities in health outcomes, including increased chronic disease prevalence and decreased life expectancy for Indigenous people, have been shown across settings affected by white settler colonialism including Canada, the United States, Australia, and New Zealand. Emergency departments (EDs) represent a unique setting in which urgent patient need and provider strain interact to amplify inequities within society. The aim of this scoping review was to map the ED-based interventions aimed at improving equity in care for Indigenous patients in EDs. METHODS: This scoping review was conducted using the procedures outlined by Arksey and O'Malley and guidance on conducting scoping reviews from the Joanna Briggs Institute. A systematic search of MEDLINE, CINAHL, SCOPUS, and EMBASE was conducted. RESULTS: A total of 3636 articles were screened by title and abstract, of which 32 were screened in full-text review and nine articles describing seven interventions were included in this review. Three intervention approaches were identified: the introduction of novel clinical roles, implementation of chronic disease screening programs in EDs, and systems/organizational-level interventions. CONCLUSIONS: Relatively few interventions for improving equity in care were identified. We found that a minority of interventions are aimed at creating organizational-level change and suggest that future interventions could benefit from targeting system-level changes as opposed to or in addition to incorporating new roles in EDs.

3.
Psychol Assess ; 36(8): 505-511, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39073383

RESUMEN

This study aimed to investigate the relationship between age and base rates of failure (BRFail) on various performance validity tests (PVTs) administered in medical-legal settings. Archival data were analyzed from 3,297 adults (Mage = 42.3 years; Meducation = 11.2) referred for psychological or neuropsychological assessments in a medical-legal or forensic civil disability context who passed the Word Memory Test. BRFail on 10 PVTs (three freestanding and seven embedded) were reported at multiple cutoffs across five age groups ranging from 16 years to 69 years. BRFail increased with age on most embedded PVTs, with a couple of notable exceptions. Reliable Digit Span was unrelated to age at ≤6 but produced elevated BRFail among older examinees at ≤7. Within freestanding PVTs, a positive relationship emerged between age and BRFail on most instruments/cutoffs. Older age is associated with an increased risk of false positive errors on many embedded PVTs that rely on raw scores. Although freestanding PVTs tend to be more resistant to the effects of age, several commonly used cutoffs may still produce increased false positive rates in older examinees. Taken together, results suggest that PVT scores should be interpreted in the context of patient characteristics, in an evidence-based manner, rather than by rigidly applying omnibus cutoffs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Pruebas Neuropsicológicas , Humanos , Adulto , Pruebas Neuropsicológicas/estadística & datos numéricos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto Joven , Adolescente , Factores de Edad , Reproducibilidad de los Resultados , Psicometría , Simulación de Enfermedad/diagnóstico , Simulación de Enfermedad/psicología
4.
Artículo en Inglés | MEDLINE | ID: mdl-38994609

RESUMEN

Obesity is now recognised as an emerging public health problem across the globe. Its incidence has been growing in the last two decades. Furthermore, as per the obesity treatment guidelines, a comprehensive approach that incorporates behavioural treatment, medications, lifestyle modifications, and/or bariatric surgery is the best way to manage weight. A novel dual agonist of Glucose-dependent insulinotropic peptide (GIP) and Glucagon-like peptide -1 (GLP- 1) receptors, Tirzepatide, was recently approved for the management of obesity. Tirzepatide manages blood sugar levels and enhances weight loss more than GLP-1 receptor agonists.

5.
PLoS One ; 19(4): e0296518, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38635744

RESUMEN

INTRODUCTION: Pain affects all children, and in hospitals across North America, this pain is often undertreated. Children who visit the emergency department (ED) experience similar undertreatment, and they will often experience a painful procedure as part of their diagnostic journey. Further, children and their caregivers who experience social injustices through marginalization are more likely to experience healthcare disparities in their pain management. Still, most of our knowledge about children's pain management comes from research focused on well-educated, white children and caregivers from a middle- or upper-class background. The aim of this scoping review is to identify, map, and describe existing research on (a) how aspects of marginalization are documented in randomized controlled trials related to children's pain and (b) to understand the pain treatment and experiences of marginalized children and their caregivers in the ED setting. METHODS AND ANALYSIS: The review will follow Joanna Briggs Institute methodology for scoping reviews using the Participant, Concept, Context (PCC) framework and key terms related to children, youth, pain, ED, and aspects of marginalization. We will search Medline, Embase, PsychInfo, CINAHL, Web of Science, Cochrane Library Trials, iPortal, and Native Health Database for articles published in the last 10 years to identify records that meet our inclusion criteria. We will screen articles in a two-step process using two reviewers during the abstract and full-text screening stages. Data will be extracted using Covidence for data management and we will use a narrative approach to synthesize the data. ETHICS AND DISSEMINATION: Ethical approval is not required for this review. Findings will be disseminated in academic manuscripts, at academic conferences, and with partners and knowledge users including funders of pain research and healthcare professionals. Results of this scoping review will inform subsequent quantitative and qualitative studies regarding pain experiences and treatment of marginalized children in the ED.


Asunto(s)
Disparidades en Atención de Salud , Manejo del Dolor , Adolescente , Niño , Humanos , Servicio de Urgencia en Hospital , Dolor , Manejo del Dolor/métodos , Investigación Cualitativa , Proyectos de Investigación , Literatura de Revisión como Asunto , Marginación Social
6.
Biol Reprod ; 111(2): 483-495, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38625059

RESUMEN

Both obesity and exposure to environmental genotoxicants, such as 7,12-dimethylbenz[a]anthracene, negatively impair female reproductive health. Hyperphagic lean KK.Cg-a/a (n = 8) and obese KK.Cg-Ay/J (n = 10) mice were exposed to corn oil as vehicle control (CT) or 7,12-dimethylbenz[a]anthracene (1 mg/kg/day) for 7d intraperitoneally, followed by a recovery period. Obesity increased liver and spleen weight (P < 0.05), and 7,12-dimethylbenz[a]anthracene exposure decreased uterine weight (P < 0.05) in obese mice. Primordial follicle loss (P < 0.05) caused by 7,12-dimethylbenz[a]anthracene exposure was observed in obese mice only. Primary (lean P < 0.1; obese P < 0.05) and secondary (lean P < 0.05, obese P < 0.1) follicle loss initiated by 7,12-dimethylbenz[a]anthracene exposure continued across recovery. Reduced pre-antral follicle number in lean mice (P < 0.05), regardless of 7,12-dimethylbenz[a]anthracene exposure, was evident with no effect on antral follicles or corpora lutea number. Immunofluorescence staining of DNA damage marker, γH2AX, did not indicate ongoing DNA damage but TRP53 abundance was decreased in follicles (P < 0.05) of 7,12-dimethylbenz[a]anthracene-exposed obese mice. In contrast, increased (P < 0.05) superoxide dismutase was observed in the corpora lutea of 7,12-dimethylbenz[a]anthracene-exposed obese mice and reduced (P < 0.05) TRP53 abundance was noted in preantral and antral follicles of 7,12-dimethylbenz[a]anthracene-exposed obese mice. This study indicates that obesity influences ovotoxicity caused by a genotoxicant, potentially involving accelerated primordial follicle activation and hampering normal follicular dynamics.


Asunto(s)
9,10-Dimetil-1,2-benzantraceno , Obesidad , Folículo Ovárico , Animales , Femenino , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/metabolismo , Ratones , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Obesidad/inducido químicamente , Obesidad/metabolismo , Ratones Obesos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética
7.
Emerg Med J ; 41(4): 210-217, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38365437

RESUMEN

OBJECTIVE: Unplanned return emergency department (ED) visits can reflect clinical deterioration or unmet need from the original visit. We determined the characteristics and outcomes of patients with COVID-19 who return to the ED for COVID-19-related revisits. METHODS: This retrospective observational study used data for all adult patients visiting 47 Canadian EDs with COVID-19 between 1 March 2020 and 31 March 2022. Multivariable logistic regression assessed the characteristics associated with having a no return visit (SV=single visit group) versus at least one return visit (MV=return visit group) after being discharged alive at the first ED visit. RESULTS: 39 809 patients with COVID-19 had 44 862 COVID-19-related ED visits: 35 468 patients (89%) had one visit (SV group) and 4341 (11%) returned to the ED (MV group) within 30 days (mean 2.2, SD=0.5 ED visit). 40% of SV patients and 16% of MV patients were admitted at their first visit, and 41% of MV patients not admitted at their first ED visit were admitted on their second visit. In the MV group, the median time to return was 4 days, 49% returned within 72 hours. In multivariable modelling, a repeat visit was associated with a variety of factors including older age (OR=1.25 per 10 years, 95% CI (1.22 to 1.28)), pregnancy (1.86 (1.46 to 2.36)) and presence of comorbidities (eg, 1.72 (1.40 to 2.10) for cancer, 2.01 (1.52 to 2.66) for obesity, 2.18 (1.42 to 3.36) for organ transplant), current/prior substance use, higher temperature or WHO severe disease (1.41 (1.29 to 1.54)). Return was less likely for females (0.82 (0.77 to 0.88)) and those boosted or fully vaccinated (0.48 (0.34 to 0.70)). CONCLUSIONS: Return ED visits by patients with COVID-19 within 30 days were common during the first two pandemic years and were associated with multiple factors, many of which reflect known risk for worse outcomes. Future studies should assess reasons for revisit and opportunities to improve ED care and reduce resource use. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04702945.


Asunto(s)
COVID-19 , Readmisión del Paciente , Adulto , Femenino , Humanos , COVID-19/epidemiología , COVID-19/terapia , Canadá/epidemiología , Estudios Retrospectivos , Servicio de Urgencia en Hospital , Organización Mundial de la Salud
8.
Biol Reprod ; 110(2): 419-429, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-37856498

RESUMEN

Histones are slowly evolving chromatin components and chromatin remodeling can incorporate histone variants differing from canonical histones as an epigenetic modification. Several identified histone variants are involved with the environmental stress-induced DNA damage response (DDR). Mechanisms of DDR in transcriptionally inactive, prophase-arrested oocytes and epigenetic regulation are under-explored in ovarian toxicology. The study objective was to identify ovarian proteomic and histone modifications induced by DMBA exposure and an influence of obesity. Post-pubertal wildtype (KK.Cg-a/a; lean) and agouti (KK.Cg-Ay/J; obese) female mice, were exposed to either corn oil (control; CT) or DMBA (1 mg/kg) for 7d via intraperitoneal injection (n = 10/treatment). Ovarian proteome analysis (LC-MS/MS) determined that obesity altered 225 proteins (P < 0.05) with histone 3 being the second least abundant (FC = -5.98, P < 0.05). Histone 4 decreased by 3.33-fold, histone variant H3.3 decreased by 3.05-fold, and H1.2, H1.4 and H1.1(alpha) variants increased by 1.59, 1.90 and 2.01-fold, respectively (P < 0.05). DMBA exposure altered 48 proteins in lean mice with no observed alterations in histones or histone variants. In obese mice, DMBA exposure altered 120 proteins and histone 2B abundance increased by 0.30-fold (P < 0.05). In DMBA-exposed mice, obesity altered the abundance of 634 proteins. Histones 4, 3 and 2A type 1-F decreased by 4.03, 3.71, 0.43-fold, respectively, whereas histone variant H1.2 and linker histone, H15 increased by 2.72- and 3.07-fold, respectively (P < 0.05). Thus, DMBA exposure alters histones and histone variants, and responsivity is more pronounced during obesity, potentially altering ovarian transcriptional regulation.


Asunto(s)
Epigénesis Genética , Histonas , Ratones , Femenino , Animales , Histonas/metabolismo , Cromatografía Liquida , Proteómica , Espectrometría de Masas en Tándem , Cromatina , Obesidad/inducido químicamente , Obesidad/genética
9.
Biochem Genet ; 62(1): 413-435, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37358673

RESUMEN

The phenylalanine ammonia lyase (PAL) catalyses the first step of phenylpropanoid metabolic pathway which leads to the biosynthesis of a diverse group of secondary metabolites. Orchids serve as a rich source of metabolites and the availability of genome or transcriptome for selected orchid species provides an opportunity to analyse the PAL genes in orchids. In the present study, 21 PAL genes were characterized using bioinformatics tools in nine orchid species (Apostasia shenzhenica, Cypripedium formosanum, Dendrobium catenatum, Phalaenopsis aphrodite, Phalaenopsis bellina, Phalaenopsis equestris, Phalaenopsis lueddemanniana, Phalaenopsis modesta and Phalaenopsis schilleriana). Multiple sequence alignment confirmed the presence of PAL-specific conserved domains (N-terminal, MIO, core, shielding and C-terminal domain). All these proteins were predicted to be hydrophobic in nature and to have cytoplasmic localisation. Structural modelling depicted the presence of alpha helices, extended strands, beta turns and random coils in their structure. Ala-Ser-Gly triad known for substrate binding and catalysis of MIO-domain was found to be completely conserved in all the proteins. Phylogenetic study showed that the PALs of pteridophytes, gymnosperms and angiosperms clustered together in separate clades. Expression profiling showed tissue-specific expression for all the 21 PAL genes in the various reproductive and vegetative tissues which suggested their diverse role in growth and development. This study provides insights to the molecular characterization of PAL genes which may help in developing biotechnological strategies to enhance the synthesis of phenylpropanoids in orchids and other heterologous systems for pharmaceutical applications.


Asunto(s)
Fenilanina Amoníaco-Liasa , Transcriptoma , Fenilanina Amoníaco-Liasa/genética , Fenilanina Amoníaco-Liasa/química , Fenilanina Amoníaco-Liasa/metabolismo , Metabolismo Secundario , Filogenia , Alineación de Secuencia
10.
Cureus ; 15(11): e48417, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38074052

RESUMEN

Every person expresses their blissful moments through a smile. The elegance of the smile depends majorly on the colour of the gingiva. One of the factors that determines the colour of the gingiva is the amount of melanin pigment in the gingival epithelium. The intensity of melanin pigmentation differs from one person to another, and it is prevalent among all ethnicities. Most people are aesthetically concerned and widely prefer pink gingiva, leading to a demand for gingival depigmentation. There are various suggested treatment modalities for gingival depigmentation, like scalpel, electrosurgery, LASER, cryosurgery, etc. However, the recurrence of pigmentation is common in the depigmentation procedure. The current study attempts to determine the post-operative healing of gingival tissues following split-thickness epithelial excision with and without topical application of Vitamin C (ascorbic acid).

11.
Elife ; 122023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37772793

RESUMEN

The pre-Bötzinger complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetized and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviors. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviors have been associated with the development and progression of diseases.


While breathing seems to come easy, it is a complex process in which many muscles coordinate to allow air to flow into the lungs. These muscles also control the flow of air we breathe out to allow us to talk, sing, eat, or drink. The brain circuits that control these muscles, can also influence other parts of the brain. The preBötzinger Complex, which is a key region of brainstem circuits that generate and control breathing, contains neurons that also project widely, connecting to other regions of the brain. This helps to modulate the sense of smell, emotional state, heart rate, and even blood pressure. Understanding how the preBötzinger Complex is organized can untangle how breathing can influence these other processes. Melo et al. wanted to learn whether they could manipulate the activity of a subgroup of preBötzinger Complex neurons that project into the facial nucleus ­ a region of the brain that controls the muscles of the face when we breathe ­ without affecting breathing. If this can be done, it might also be possible to affect blood pressure by manipulating selective preBötzinger neurons, and thus the development of hypertension, without having any impact on breathing. To test this hypothesis, Melo et al. used rats in which the activation of preBötzinger Complex neurons that project into the facial nucleus was blocked. This decreased the activity of the muscles around the nose with hardly any effect on breathing. Melo et al. also found that the state of consciousness of the rat (anesthetized or conscious) could affect how preBötzinger Complex neurons control these muscles. Melo et al. also observed that preBötzinger Complex neurons projecting into the facial nucleus had projections into many other regions in the brainstem. This might help to the coordinate respiratory, cardiovascular, orofacial, and potentially other physiological functions. The findings of Melo et al. set a technical foundation for exploring the influence of specific subgroups of preBötzinger Complex neurons on respiratory modulation of other physiological activities, including blood pressure and heart rate and in conditions, such as hypertension and heart failure. More broadly, most brain regions contain complex and heterogeneous groups of neurons and the strategy validated by Melo et. al. could be applied to unravel other brain-function relationships.


Asunto(s)
Núcleo Motor del Nervio Facial , Ratas , Animales , Centro Respiratorio , Respiración , Neuronas Motoras , Tronco Encefálico
12.
Med Sci Educ ; 33(4): 853-859, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37546208

RESUMEN

Background: Various innovative teaching methods have been designed in an attempt to provide millennial students an interactive and stimulating learning environment. A jigsaw method is one such form of cooperative learning that enables students to develop critical-thinking and ability for effective communication and promotes positive student attitudes toward their own learning. The present study was thus undertaken to introduce a jigsaw-based cooperative learning method and to understand the perception of the students and faculty. Methodology: This was a cross-sectional study conducted among second year MBBS students. Students were randomly divided into 10 parent groups, with 10 students each. The topic was divided into 10 subtopics. Each student in the parent group was allotted a sub-topic. The students who were given the same sub-topic assembled to form an expert group. They interacted and discussed the subtopic. Students finally returned to their parent groups for peer teaching and presentation. A validated questionnaire was used to gather students and faculty feedback. Descriptive statistics were used to analyze responses to the Likert scale questions. Qualitative data was analyzed using thematic analysis. Results: The present study included 95 s year MBBS students. Majority (81%) students agreed that this teaching learning method enhanced their communication skills. Seventy-five percent of the students agreed that the activity helped in overcoming shyness and hesitation in the class. Overall the faculty also agreed that the jigsaw method was helpful for the students. Conclusions: Cooperative learning like jigsaw facilitates learning allowing student-student discussion, improving communication and teaching skills.

14.
J Virol ; 97(7): e0039423, 2023 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-37338373

RESUMEN

Respiratory syncytial virus (RSV) infection does not cause severe disease in most of us despite suffering from multiple RSV infections during our lives. However, infants, young children, older adults, and immunocompromised patients are unfortunately vulnerable to RSV-associated severe diseases. A recent study suggested that RSV infection causes cell expansion, resulting in bronchial wall thickening in vitro. Whether the virus-induced changes in the lung airway resemble epithelial-mesenchymal transition (EMT) is still unknown. Here, we report that RSV does not induce EMT in three different in vitro lung models: the epithelial A549 cell line, primary normal human bronchial epithelial cells, and pseudostratified airway epithelium. We found that RSV increases the cell surface area and perimeter in the infected airway epithelium, which is distinct from the effects of a potent EMT inducer, transforming growth factor ß1 (TGF-ß1), driving cell elongation-indicative of cell motility. A genome-wide transcriptome analysis revealed that both RSV and TGF-ß1 have distinct modulation patterns of the transcriptome, which suggests that RSV-induced changes are distinct from EMT. IMPORTANCE We have previously shown that RSV infects ciliated cells on the apical side of the lung airway. RSV-induced cytoskeletal inflammation contributes to an uneven increase in the height of the airway epithelium, resembling noncanonical bronchial wall thickening. RSV infection changes epithelial cell morphology by modulating actin-protein 2/3 complex-driven actin polymerization. Therefore, it is prudent to investigate whether RSV-induced cell morphological changes contribute to EMT. Our data indicate that RSV does not induce EMT in at least three different epithelial in vitro models: an epithelial cell line, primary epithelial cells, and pseudostratified bronchial airway epithelium.


Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Anciano , Niño , Preescolar , Humanos , Lactante , Actinas/metabolismo , Línea Celular , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal , Infecciones por Virus Sincitial Respiratorio/metabolismo , Virus Sincitiales Respiratorios/metabolismo , Factor de Crecimiento Transformador beta1
15.
bioRxiv ; 2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36993657

RESUMEN

Respiratory syncytial virus (RSV) infection does not cause severe disease in most of us despite suffering from multiple RSV infections in our lives. However, infants, young children, older adults, and immunocompromised patients are unfortunately vulnerable to RSV-associated severe diseases. A recent study suggested that RSV infection causes cell expansion, resulting in bronchial wall thickening in vitro. Whether the virus-induced changes in the lung airway resemble epithelial-mesenchymal transition (EMT) is still unknown. Here, we report that RSV does not induce EMT in three different in vitro lung models: the epithelial A549 cell line, primary normal human bronchial epithelial cells, and pseudostratified airway epithelium. We found that RSV increases the cell surface area and perimeter in the infected airway epithelium, which is distinct from the effects of a potent EMT inducer, TGF-ß1-driven cell elongation-indicative of cell motility. A genome-wide transcriptome analysis revealed that both RSV and TGF-ß1 have distinct modulation patterns of the transcriptome, which suggests that RSV-induced changes are distinct from EMT.

16.
Biol Reprod ; 108(4): 694-707, 2023 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-36702632

RESUMEN

Obesity adversely affects reproduction, impairing oocyte quality, fecundity, conception, and implantation. The ovotoxicant, dimethylbenz[a]anthracene, is biotransformed into a genotoxic metabolite to which the ovary responds by activating the ataxia telangiectasia mutated DNA repair pathway. Basal ovarian DNA damage coupled with a blunted response to genotoxicant exposure occurs in obese females, leading to the hypothesis that obesity potentiates ovotoxicity through ineffective DNA damage repair. Female KK.Cg-a/a (lean) and KK.Cg-Ay/J (obese) mice received corn oil or dimethylbenz[a]anthracene (1 mg/kg) at 9 weeks of age for 7 days via intraperitoneal injection (n = 10/treatment). Obesity increased liver weight (P < 0.001) and reduced (P < 0.05) primary, preantral, and corpora lutea number. In lean mice, dimethylbenz[a]anthracene exposure tended (P < 0.1) to increase proestrus duration and reduced (P = 0.07) primordial follicle number. Dimethylbenz[a]anthracene exposure decreased (P < 0.05) uterine weight and increased (P < 0.05) primary follicle number in obese mice. Total ovarian abundance of BRCA1, γH2AX, H3K4me, H4K5ac, H4K12ac, and H4K16ac (P > 0.05) was unchanged by obesity or dimethylbenz[a]anthracene exposure. Immunofluorescence staining demonstrated decreased (P < 0.05) abundance of γH2AX foci in antral follicles of obese mice. In primary follicle oocytes, BRCA1 protein was reduced (P < 0.05) by dimethylbenz[a]anthracene exposure in lean mice. Obesity also decreased (P < 0.05) BRCA1 protein in primary follicle oocytes. These findings support both a follicle stage-specific ovarian response to dimethylbenz[a]anthracene exposure and an impact of obesity on this ovarian response.


Asunto(s)
9,10-Dimetil-1,2-benzantraceno , Proteína BRCA1 , Ratones , Animales , Femenino , Proteína BRCA1/genética , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Ratones Obesos , ARN Mensajero/metabolismo , Reparación del ADN , Obesidad/inducido químicamente , Obesidad/genética , Daño del ADN
17.
J Biomol Struct Dyn ; 41(12): 5486-5498, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35735783

RESUMEN

Type III polyketide synthases (PKSs) catalyse the formation of an array of polyketides with diverse structures that play an important role in secondary metabolism in plants. This group of enzymes is encoded by a multigene family, the Type III polyketide synthase (PKS) gene family. Vast reserves of secondary metabolites in orchids make these plants suitable candidates for research in the area. In this study, genome-wide searches lead to the identification of five PeqPKS, eight DcaPKS and six AshPKS genes in Phalaenopsis equestris, Dendrobium catenatum and Apostasia shenzhenica, respectively. All the members showed the presence of two characteristic conserved domains (Chal_sti_synt_N and Chal_sti_synt_C) and were generally localised in the cytoplasm. The phylogenetic analysis led to the classification of these proteins into two groups: CHS (chalcone synthase (CHS) and non-CHS. A single protein in P. equestris and two proteins each in D. catenatum and A. shenzhenica clustered within the CHS clade. The majority of the genes exhibited similar structural patterns with a single intron. Expression profiling revealed the tissue-specific expression of these genes with high expression in reproductive tissues for most genes. A number of stress-responsive cis-regulatory elements were predicted, noteworthy amongst these are, ABRE and CGTCA that are chiefly responsible for responding to abscisic acid and methyl jasmonate, respectively. Our study provides a reference framework for future studies involving functional elucidation of PKS genes and biotechnological production of polyketides.Communicated by Ramaswamy H. Sarma.


Identification of five PeqPKS, eight DcaPKS and six AshPKS genes in Phalaenopsis equestris, Dendrobium catenatum and Apostasia shenzhenica based on genome-wide analysisPresence of characteristic conserved domains (Chal_sti_synt_N, Chal_sti_synt_C) with cytological localisationPhylogenetic clustering into two groups, CHS chalcone synthase (CHS) and non-CHSExpression profiling revealing high expression in reproductive tissuesPrediction of stress-responsive cis-regulatory elements like ABRE and CGTCA.


Asunto(s)
Sintasas Poliquetidas , Policétidos , Sintasas Poliquetidas/genética , Metabolismo Secundario/genética , Filogenia , Plantas/genética , Policétidos/metabolismo
18.
Essays Biochem ; 67(2): 269-282, 2023 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-36503929

RESUMEN

Cyanobacteria, also known as blue-green algae, are ubiquitous organisms on the planet. They contain tremendous protein machineries that are of interest to the biotechnology industry and beyond. Recently, the number of annotated cyanobacterial genomes has expanded, enabling structural studies on known gene-coded proteins to accelerate. This review focuses on the advances in mass spectrometry (MS) that have enabled structural proteomics studies to be performed on the proteins and protein complexes within cyanobacteria. The review also showcases examples whereby MS has revealed critical mechanistic information behind how these remarkable machines within cyanobacteria function.


Asunto(s)
Cianobacterias , Proteómica , Proteómica/métodos , Cianobacterias/metabolismo , Biotecnología/métodos , Proteínas Bacterianas/metabolismo , Espectrometría de Masas/métodos
19.
Cureus ; 15(12): e50747, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38239539

RESUMEN

Splenic abscess is a rare condition that generally results from hematogenous spread and affects individuals with hemoglobinopathies or immunocompromising conditions. Although optimal management has recently been under contention, this condition was traditionally managed with splenectomy. We present a rare case of a 58-year-old male with chronic pancreatitis that developed a splenic abscess via a contiguous spread of a pancreatic pseudocyst. His condition was complicated by septic shock. The splenic abscess was managed with antibiotics, image-guided percutaneous drainage, and notably without surgical intervention.

20.
Adv Nutr ; 13(6): 2098-2114, 2022 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-36084013

RESUMEN

National health and nutrition monitoring is an important federal effort in the United States and Canada, and the basis for many of their nutrition and health policies. Understanding of child exposures through human milk (HM) remains out of reach due to lack of current and representative data on HM's composition and intake volume. This article provides an overview of the current national health and nutrition monitoring activities for HM-fed children, HM composition (HMC) and volume data used for exposure assessment, categories of potential measures in HM, and associated variability factors. In this Perspective, we advocate for a framework for collection and reporting of HMC data for national health and nutrition monitoring and programmatic needs, including a shared vision for a publicly available Human Milk Composition Data Repository (HMCD-R) to include essential metadata associated with HMC. HMCD-R can provide a central, integrated platform for researchers and public health officials for compiling, evaluating, and sharing HMC data. The compiled compositional and metadata in HMCD-R would provide pertinent measures of central tendency and variability and allow use of modeling techniques to approximate compositional profiles for subgroups, providing more accurate exposure assessments for purposes of monitoring and surveillance. HMC and related metadata could facilitate understanding the complexity and variability of HM composition, provide crucial data for assessment of infant and maternal nutritional needs, and inform public health policies, food and nutrition programs, and clinical practice guidelines.


Asunto(s)
Leche Humana , Estado Nutricional , Lactante , Niño , Humanos , Estados Unidos , Canadá
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