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1.
Clin Nutr ESPEN ; 57: 764-769, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37739735

RESUMO

INTRODUCTION: Hyperuricemia (HU) is a health risk that may go undiagnosed and is on the rise in both developed and developing countries. Gout, the most common inflammatory arthritis characterized by painful, disabling acute attack, is widely known to be caused by hyperuricemia. Its prevalence ranges from 2.6% to 36% in different populations. The commonly used drugs for alleviating uric acid and gout have obvious side effects, so herbal therapeutic drugs are in high demand. The aim of the present study was to evaluate the efficacy and safety of Aristolochia rotunda Linn in Hyperuricemia. METHODS: Present study was designed as a single-blind randomized standard controlled trial with 20 patients in each group. Participants in the test group were administered A. rotunda Linn 4 gms in two divided doses in capsule form and the control group was given Febuxostat 40 mg once daily after meals for 28 days. Participants were asked to follow up weekly for the assessment of subjective parameters. The objective parameter was assessed pre- and post-trial. The results were analysed statistically. RESULTS: After the intervention, the test and control groups showed a statistically significant reduction in serum uric acid p = 0.021 and p < 0.01 respectively, while the reduction in the control group was found to be more statistically significant than the test group (p = 0.009). Subjective parameters also showed statistical significance at the end of the trial. CONCLUSION: This study shows that the A. rotunda Linn in a dose of 4 gm for 28 days effectively lowers serum uric acid. The trial was registered in the clinical trial registry of India under CTRI No. CTRI//2020/02/031587.


Assuntos
Aristolochia , Gota , Hiperuricemia , Humanos , Hiperuricemia/tratamento farmacológico , Ácido Úrico , Método Simples-Cego , Gota/complicações , Gota/tratamento farmacológico
2.
Phys Chem Chem Phys ; 25(25): 16991-17000, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37335558

RESUMO

Magnetic conversion can be accomplished in a variety of ways, as organic molecules with switchable magnetic characteristics offer numerous technological applications. It is crucial to find magnetism-switchable systems because, in the field of organic magnetic materials, the redox-induced magnetic reversal is very simple to achieve and shows significant applications. Herein, we computationally design isoalloxazine-based diradicals through oxidizing N10 and adding a nitroxide to C8 as the spin source (i.e. 8-nitroxide-isoalloxazine 10-oxide, an m-phenylene-like nitroxide diradical expanded with a redox unit as a side-modulator) and its N1/N5-hydrogenated/protonated diradical derivatives and introducing substituents (-OH, -NH2, and -NO2) to C6. We demonstrate that the basically modified structure exhibits ferromagnetic (FM) characteristics with a magnetic coupling constant (J) of 561.3 cm-1 calculated at the B3LYP/6-311+G(d,p) level, obeying the meta-phenylene-mediated diradical character, and dihydrogenation can lead to an AFM diradical with considerably large J (-976.1 cm-1). Surprisingly, protonation at N1 or N5 can lead to distinctly different magnetic variations (561.3 → -1602.9 cm-1 at N1 versus 561.3 → 379.1 cm-1 at N5). Analyses indicate that small singlet-triplet energy gaps and small energy gaps between the highest occupied and lowest unoccupied molecular orbitals (HOMO, LUMO) of the closed shell singlet state are the key features of these isoalloxazine diradicals, and aromaticity variations, significant spin delocalization from the π-conjugated structure and spin polarization from the non-Kekule structure induced by modification are responsible for the magnetic conversion. Furthermore, the spin alternation rule, the singly occupied molecular orbital (SOMO) effect, and the SOMO-SOMO energy splitting of the triplet state are used to analyze these distinct variations. This work provides a novel understanding of the structures and characteristics of modified isoalloxazine diradicals, as well as essential details for the intricate design and characterization of new isoalloxazine-based potential organic magnetic switches.

3.
Int. j. morphol ; 41(2): 383-388, abr. 2023. ilus
Artigo em Inglês | LILACS | ID: biblio-1440338

RESUMO

SUMMARY: In elasmobranch fishes, variations in gross structural organization of cerebellum has been extensively explored. The basic histological features of cerebellum although conserved in the group but the comparative account on subtle cellular variations is largely underestimated. The present study aims to explore the histological and cellular variations in different layers of cerebellar cortex of the representative elasmobranchs' species belonging to different habitat. Our findings showed that the histological architecture of cerebellar granular layer between the examined species varies noticeably. By and large increase cellular density were observed in all the layers of cerebellum in the representative species of shark compared to ray. The findings were then compared and discussed with reference to their habitat and behavior.


En los peces elasmobranquios, las variaciones en la organización estructural general del cerebelo se han explorado ampliamente. Las características histológicas básicas del cerebelo, aunque se conservan en el grupo, pero la descripción comparativa de las variaciones celulares sutiles es limitada. El presente estudio tiene como objetivo explorar las variaciones histológicas y celulares en diferentes capas de la corteza cerebelosa de las especies representativas de elasmobranquios pertenecientes a diferentes hábitats. Nuestros hallazgos mostraron que la arquitectura histológica de la capa granular del cerebelo entre las especies examinadas varía notablemente. Se observó un gran aumento de la densidad celular en todas las capas del cerebelo en las especies representativas de tiburón en comparación con la raya. Luego, los hallazgos se compararon y discutieron con referencia a su hábitat y comportamiento.


Assuntos
Animais , Cerebelo/anatomia & histologia , Elasmobrânquios/anatomia & histologia , Evolução Biológica
4.
J Phys Chem A ; 126(49): 9165-9177, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36456531

RESUMO

Proton transfer modulation in an organic diradical is apparently the most conspicuously attractive phenomenon. In this work, we have computationally designed the trans and cis forms of photochromic azobenzene- (AB-) bridged diradicals by considering AB as coupler and two nitroxide (NO) as spin sources and a -OH attaching at the ortho site as modulator. Our object is that through intramolecular proton transfer to protonate the azo-unit (-N═N-) the magnetic coupling characteristics of the designed diradicals can be modulated in their photocontrolled trans and cis forms. The calculated results indicate that PT can significantly regulate the magnetic spin coupling constants, J = -701.3 cm-1 ↔ -286.2 cm-1 for the trans form and -544.1 cm-1 ↔ -328.1 cm-1 for the cis form. In particular, we discover that these designed magnetic molecules can undergo magnetic conversion between antiferromagnetic and ferromagnetic coupling through PT, besides there is considerable increase in the magnitude of their magnetic coupling constants J, (e.g., -59.97 to 172.4 cm-1) for the trans-mode at the m/m linking site. Moreover, we discover that the nitroxide radicals at different linking positions have a significant impact and remarkably alter the magnetic spin coupling characteristics of AB-based diradicals. Besides, various radical groups are used as spin sources which corroborated our assumptions and tended to the same conclusion. This work offers a novel understanding of the spin interaction mechanism and a viable approach for the rational design of new AB-based magnets which are beneficial for further applications in the future.

5.
Med Teach ; : 1-7, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36272400

RESUMO

INTRODUCTION: Role modelling is considered an essential component of teaching in various educational settings and impact students' professional development. Most studies found in the literature have explored the influence of positive role models and limited data is available about the negative role modelling. This study explores the effects of negative role modelling of teachers on the professional development of future doctors. METHODS: A qualitative exploratory study was done in three medical colleges of Lahore, Pakistan. Fifteen, telephonic, semi-structured interviews were done with fifth-year MBBS students. A thematic analysis was done through manual coding of transcribed interviews. RESULTS: A total of 374 codes were generated in the first cycle of coding, that was merged to 42 in the second cycle. These codes led to 4 subthemes that finally emerged as two themes. The first theme was "Students & patients: In the same boat" highlighting the damaging effects of negative role modelling. The second theme was "Taking the bad with the good" focusing on the ambivalent response of students towards the unprofessional behaviours of their role models. CONCLUSION: Negative role modelling exponentially affects the attitude and behaviour of medical students especially in informal settings and have detrimental effects on patient care. Students lose some degree of humanism while unconsciously observing the unethical behaviours, to become a part of hospital culture whereas some students show determination to channelize their resentment to reforms.

6.
Neurol India ; 70(3): 1176-1179, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35864659

RESUMO

Background: Symptomatic spinal epidural veins (SEV) are a rare cause of neurologic dysfunction. Treatment is centered upon addressing the underlying venous pathology to relieve mechanical compression of the neurologic structures. However, open surgical ligation is often associated with considerable blood loss. Objective: We discuss a unique case of a large symptomatic epidural venous varix and potential treatment strategy. Methods and Materials: A 15-year-old female presented with a 1-year history of left L5 radicular pain and weakness. Lumbar MRI demonstrated a central L5/S1 herniated disc and a large extradural anomalous SEV compressing the exiting left L5 nerve root at the L5/S1 neuroformina. The SEV was treated using a transvenous liquid embolic agent providing symptomatic relief. At 16-months follow-up, she reported recurrent symptoms. She ultimately underwent a left L5/S1 MIS decompression without complication. Conclusion: Transvenous liquid embolization of large symptomatic SEV may provide temporary neurologic relief and decrease morbidity associated with open surgical treatment options.


Assuntos
Embolização Terapêutica , Deslocamento do Disco Intervertebral , Radiculopatia , Varizes , Adolescente , Embolização Terapêutica/efeitos adversos , Espaço Epidural , Feminino , Humanos , Deslocamento do Disco Intervertebral/diagnóstico , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/patologia , Vértebras Lombares/cirurgia , Radiculopatia/diagnóstico , Radiculopatia/etiologia , Radiculopatia/terapia , Varizes/complicações , Varizes/diagnóstico , Varizes/terapia
7.
Pediatr Emerg Care ; 38(8): e1462-e1468, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35904957

RESUMO

OBJECTIVE: The aim of the study was to examine the perception of pediatric emergency medicine (PEM) program directors (PDs), associate PDs (APDs) and first-year fellows regarding the preparedness of new PEM fellows who have graduated from pediatric residency programs. METHODS: Unique surveys were created and electronically distributed to PEM PDs/APDs and first-year PEM fellows. Individual and institutional demographic information was collected. Using a 5-point Likert scale, survey items centered the perceived preparedness of first-year PEM fellows within 5 domains: professionalism, independence/autonomy, psychomotor skills, clinical evaluation and management, and academia/scholarship. RESULTS: Forty percent (48/119) of eligible PDs and APDs and 56% (82/147) of eligible first-year PEM fellows responded. Most PDs/APDs strongly agreed or agreed that incoming fellows perform adequately in areas of professionalism, independence/autonomy, and clinical evaluation and management. The PDs/APDs perceived fellows to be less prepared in the academia/scholarship domain and several psychomotor skills. Most first-year PEM fellows perceived themselves as prepared in areas of professionalism and clinical evaluation and management. Fellows had varied feelings of preparedness in the domains of independence/autonomy, psychomotor skills, and academia/scholarship. Overall, most PDs/APDs (54%) and fellows (84%) feel that pediatric residency training was strong or very strong. CONCLUSIONS: Most respondents in both groups felt that in general, pediatric residency programs adequately train residents for PEM fellowship. Both groups felt that the strengths of general pediatric training were among the domains of professionalism and clinical evaluation and management, whereas psychomotor skills and academia and scholarship were areas of improvement. These findings may be used by general pediatric residency and PEM fellowship programs to guide curriculum development.


Assuntos
Medicina de Emergência , Internato e Residência , Medicina de Emergência Pediátrica , Criança , Currículo , Educação de Pós-Graduação em Medicina , Medicina de Emergência/educação , Bolsas de Estudo , Humanos , Inquéritos e Questionários
8.
Pediatr Emerg Care ; 38(2): e816-e820, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35100781

RESUMO

OBJECTIVE: Our primary aim was to describe pediatric residents' use of a workplace procedural training cart. An exploratory aim was to examine if the cart associated with increased resident procedural experiences with real patients. METHODS: Guided by the procedural training construct of "Learn, See, Practice, Prove, Do, Maintain," we created a novel workplace procedural training cart with videos (learn and see) and simulation equipment (practice and prove). An electronic logbook recorded resident use data, and a brief survey solicited residents' perceptions of the cart's educational impact. We queried our electronic medical record to compare the proportion of real procedures completed by residents before and after the intervention. RESULTS: From August 1 to December 31, 2019, 24 pediatric residents (10 interns and 14 seniors) rotated in the pediatric emergency department. Twenty-one cart encounters were logged, mostly by interns (67% [14/21]). The 21 cart encounters yielded 32 learning activities (8 videos watched and 24 procedures practiced), reflecting the residents' interest in laceration repair (50% [4/8], 54% [13/24]) and lumbar puncture (38% [3/8], 33% [8/24]). All users agreed (29% [6/21]) or strongly agreed (71% [15/21]) the cart encouraged practice and improved confidence in independently performing procedures. No changes were observed in the proportion of actual procedures completed by residents. CONCLUSIONS: A workplace procedural training cart was used mostly by pediatric interns. The cart cultivated residents' perceived confidence in real procedures but was not used by all residents or influenced residents' procedural behaviors in the pediatric emergency department.


Assuntos
Internato e Residência , Local de Trabalho , Criança , Competência Clínica , Humanos , Punção Espinal , Inquéritos e Questionários
9.
Pediatr Emerg Care ; 38(2): e1022-e1024, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34116554

RESUMO

ABSTRACT: We report the case of a 3-year-old boy who presented to the pediatric emergency department in undifferentiated shock with an acute abdomen. Point-of-care ultrasound revealed viscous perforation with a large amount of free fluid. Intraoperatively, a single magnet was discovered as the likely cause of bowel perforation and the resulting state of shock.


Assuntos
Abdome Agudo , Corpos Estranhos , Perfuração Intestinal , Abdome Agudo/diagnóstico por imagem , Abdome Agudo/etiologia , Criança , Pré-Escolar , Ingestão de Alimentos , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Humanos , Perfuração Intestinal/diagnóstico por imagem , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Imãs/efeitos adversos , Masculino , Sistemas Automatizados de Assistência Junto ao Leito
10.
Pediatr Emerg Care ; 38(2): e746-e751, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34542989

RESUMO

BACKGROUND: The ease of instruction for point-of-care ultrasound (POCUS) to detect suprapatellar bursa (SPB) effusions in pediatric patients is unknown. Considering in person limitations because of the coronavirus pandemic, strategies for POCUS education by remote learning are necessary. METHODS: We crafted a 90-minute didactic training that was presented via a remote learning format. The main outcome of interest was the interobserver reliability of SPB effusion assessment by novice sonologists compared with POCUS faculty. Novice sonologists were pediatric emergency medicine (PEM) fellows. Pediatric emergency medicine fellows interpreted longitudinal SPB examinations obtained in our pediatric emergency department from July 2013 to June 2020. Assessments were performed 2 months after the remote training. Pediatric emergency medicine fellows had a limited experience performing these musculoskeletal scans and were blinded to POCUS faculty and each other's assessments. Interobserver reliability was assessed with Cohen κ coefficient. Second, we calculated test characteristics of knee radiography compared with PEM POCUS faculty determination of SPB effusion by ultrasound. We further explored how effusion size measured by POCUS impacted the diagnosis by knee radiography. A receiver operator characteristic curve of knee radiography diagnosis of SPB effusion was created using the maximal height of SPB effusion by POCUS as the predictor variable. RESULTS: A total of 116 SPB scans in 71 patients were assessed. From this group, 70 scans were of affected knees and 46 scans were of contralateral, asymptomatic knees. The mean age of patients was 10 years and 46% were girl. The prevalence of SPB effusions was 42%. The κ coefficients between the 3 novice sonologists and POCUS faculty were 0.75 (0.62-0.87), 0.77 (0.65-0.89), and 0.83 (0.72-0.93) with 88%, 89%, and 91% agreement. Knee radiography exhibited an overall sensitivity of 65% (95% confidence interval [CI], 46-79%), specificity of 84% (95% CI, 60-97%), negative predictive value of 55% (95% CI, 43-66%), and positive predictive value of 88% (95% CI, 73-96%) to diagnose SPB effusions. The area under the receiver operator characteristic curve was 0.850. With an SPB height cutoff of 4 mm as true positives, radiography had a sensitivity of 81% and a specificity of 83%. CONCLUSIONS: After a remote teleconference didactic session, PEM fellows were able to successfully diagnose SPB effusions using a longitudinal view with substantial interobserver reliability. Knee radiography exhibited limited sensitivity to rule out SPB effusions.


Assuntos
Medicina de Emergência Pediátrica , Sistemas Automatizados de Assistência Junto ao Leito , Criança , Serviço Hospitalar de Emergência , Feminino , Humanos , Testes Imediatos , Reprodutibilidade dos Testes , Ultrassonografia
11.
Pediatrics ; 148(3)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34433688

RESUMO

OBJECTIVES: Pediatric emergencies can occur in pediatric primary care offices. However, few studies have measured emergency preparedness, or the processes of emergency care, provided in the pediatric office setting. In this study, we aimed to measure emergency preparedness and care in a national cohort of pediatric offices. METHODS: This was a multicenter study conducted over 15 months. Emergency preparedness scores were calculated as a percentage adherence to 2 checklists on the basis of the American Academy of Pediatrics guidelines (essential equipment and supplies and policies and protocols checklists). To measure the quality of emergency care, we recruited office teams for simulation sessions consisting of 2 patients: a child with respiratory distress and a child with a seizure. An unweighted percentage of adherence to checklists for each case was calculated. RESULTS: Forty-eight teams from 42 offices across 9 states participated. The mean emergency preparedness score was 74.7% (SD: 12.9). The mean essential equipment and supplies subscore was 82.2% (SD: 15.1), and the mean policies and protocols subscore was 57.1% (SD: 25.6). Multivariable analyses revealed that independent practices and smaller total staff size were associated with lower preparedness. The median asthma case performance score was 63.6% (interquartile range: 43.2-81.2), whereas the median seizure case score was 69.2% (interquartile range: 46.2-80.8). Offices that had a standardized process of contacting emergency medical services (EMS) had a higher rate of activating EMS during the simulations. CONCLUSIONS: Pediatric office preparedness remains suboptimal in a multicenter cohort, especially in smaller, independent practices. Academic and community partnerships using simulation can help address gaps and implement important processes like contacting EMS.


Assuntos
Competência Clínica , Emergências , Fidelidade a Diretrizes , Visita a Consultório Médico , Atenção Primária à Saúde , Qualidade da Assistência à Saúde/normas , Lista de Checagem , Humanos , Pediatria , Guias de Prática Clínica como Assunto , Estados Unidos
12.
Pediatr Emerg Care ; 37(1): 34-38, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33394943

RESUMO

ABSTRACT: The cause of acute onset hip pain in children can be difficult to determine. Once trauma is excluded, the workup revolves around determining whether there is a hip effusion and eliminating orthopedic emergencies. Point-of-care-ultrasound can be used as an adjunct in the workup. In this article, we review (1) differential diagnosis of hip pain, with a focus on toxic synovitis; (2) the evaluation of a hip for the presence of effusion, including the point-of-care ultrasound technique; and (3) the management of toxic synovitis.


Assuntos
Artralgia/diagnóstico , Articulação do Quadril/diagnóstico por imagem , Sinovite/diagnóstico , Ultrassonografia/métodos , Dor Aguda/diagnóstico , Dor Aguda/terapia , Anti-Inflamatórios/uso terapêutico , Artralgia/terapia , Artrite Infecciosa/diagnóstico , Criança , Diagnóstico Diferencial , Quadril/diagnóstico por imagem , Articulação do Quadril/patologia , Humanos , Exame Físico/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Sinovite/terapia
13.
Pediatr Emerg Care ; 37(3): 172-174, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32541404

RESUMO

ABSTRACT: We report a case of a 16-year-old adolescent girl who presented to the pediatric emergency department for worsening abdominal pain and vomiting and had significant weight loss over the previous 4 months. Point-of-care ultrasound was used to assess for signs of superior mesenteric artery syndrome.


Assuntos
Síndrome da Artéria Mesentérica Superior , Dor Abdominal/etiologia , Adolescente , Criança , Serviço Hospitalar de Emergência , Feminino , Humanos , Síndrome da Artéria Mesentérica Superior/diagnóstico por imagem , Ultrassonografia , Vômito
14.
Cureus ; 12(9): e10331, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-33052292

RESUMO

Background and objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the cause of a worldwide outbreak of respiratory illness, which has been declared as coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO). The outbreak has posed a huge challenge to countries around the world and has resulted in a global lockdown. The pandemic has especially overburdened the healthcare sector, resulting in a shortage of personnel and equipment. Along with many other manifestations, it has resulted in stress and anxiety for the physicians as well. Furthermore, many healthcare workers have been reluctant in treating COVID-19 patients. This study aimed to explore the concerns of physicians in the context of the COVID-19 pandemic and to evaluate the reasons for their reluctance to treat the patients. Methodology This descriptive cross-sectional study included 235 physicians from seven hospitals of Pakistan who were actively working amid the COVID-19 pandemic. Data were collected from March 1, 2020, to May 30, 2020, using a structured online questionnaire. Participants were approached via non-probability convenient sampling. Two hundred and eight respondents were included in the data analysis. SPSS Statistics version 23.0 (IBM Corp., Armonk, NY) was used for data entry and analysis. Results A striking 83.7% (n=174) of the respondents expressed their reluctance to treat patients with COVID-19. Concerns they raised included one or more of the following four reasons; lack of proper personal protective equipment (PPE), fear of self-infection, excessive workload, and fear of transmitting the infection to their family members. Of note, 92% (n=161) of the respondents reported a lack of PPE while 74.1% (n=129) reported fear of transmitting the infection to their family members as reasons for their reluctance. The vast majority of the participants reported the need for psychological training to treat the patients' anxiety (95.2%, n=198). Many participants were afraid that their own anxiety might be affecting the quality of care patients were receiving (67.3%, n=140). Hence, most of the participants reported that psychological counseling should be provided (93.3%, n=194). Participants with family members older than 60 years were found to be reluctant to treat patients due to the risk of transmitting the infection to them (69.7%, n=145, p=0.001). Therefore, a major proportion of the participants (96.2%, n=200) felt that the hospitals should provide a place for them to rest and temporarily isolate themselves to avoid coming into contact with their family members. Conclusions We conclude that a major proportion of physicians is reluctant to treat their patients due to multiple factors. The grave situation of the pandemic has taken a toll on their mental health, which could be affecting the quality of care that the patients receive. Their concerns should be addressed to not only provide them with support and improve their working environment but also to ensure that they are fully equipped to provide state-of-the-art care to the patients in these grave times.

15.
Pharmacol Res Perspect ; 8(6): e00673, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33124765

RESUMO

While allosteric modulation of GPCR signaling has gained prominence to address the need for receptor specificity, efforts have mainly focused on allosteric sites adjacent to the orthosteric ligand-binding pocket and lipophilic molecules that target transmembrane helices. In this study, we examined the allosteric influence of native peptides derived from the C-terminus of the Gα subunit (G-peptides) on signaling from two Gi-coupled receptors, adenosine A1 receptor (A1 R) and cannabinoid receptor 1 (CB1 ). We expressed A1 R and CB1 fusions with G-peptides derived from Gαs, Gαi, and Gαq in HEK 293 cells using systematic protein affinity strength modulation (SPASM) and monitored the impact on downstream signaling in the cell compared to a construct lacking G-peptides. We used agonists N6 -Cyclopentyladenosine (CPA) and 5'-N-Ethylcarboxamidoadenosine (NECA) for A1 R and 2-Arachidonoylglycerol (2-AG) and WIN 55,212-2 mesylate (WN) for CB1 . G-peptides derived from Gαi and Gαq enhance agonist-dependent cAMP inhibition, demonstrating their effect as positive allosteric modulators of Gi-coupled signaling. In contrast, both G-peptides suppress agonist-dependent IP1 levels suggesting that they differentially function as negative allosteric modulators of Gq-coupled signaling. Taken together with our previous studies on Gs-coupled receptors, this study provides an extended model for the allosteric effects of G-peptides on GPCR signaling, and highlights their potential as probe molecules to enhance receptor specificity.


Assuntos
Cromograninas/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fragmentos de Peptídeos/metabolismo , Receptor A1 de Adenosina/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Regulação Alostérica/efeitos dos fármacos , Regulação Alostérica/fisiologia , Cromograninas/farmacologia , Relação Dose-Resposta a Droga , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/farmacologia , Subunidades alfa Gs de Proteínas de Ligação ao GTP/farmacologia , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Fragmentos de Peptídeos/farmacologia
16.
J Asthma ; 57(12): 1316-1322, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31340703

RESUMO

Objectives: The aim of this exploratory study was to assess the impact of caregiver health literacy (HL) on health care outcomes for their child with asthma.Methods: Caregiver dyads across two different healthcare delivery systems completed a battery of validated asthma outcome instruments, including the Newest Vital Sign™ as a measure of HL for the caregivers of children ages 7-18 y. Utilization history was obtained through the electronic medical record. Descriptive analysis with bivariate associations was conducted.Results: There was no direct relationship between HL and asthma outcomes in the 34 Hispanic and African American caregiver-child dyads. However, caregiver health literacy was significantly related to language (p = 0.02). African American English-speaking caregivers, seen in an urban emergency department, demonstrated adequate health literacy. Hispanic Spanish-speaking caregivers, seeking care in a mobile asthma van, showed limited health literacy. There was no significant association between caregivers' HL and routine asthma care visits when language and child age were controlled.Conclusions: Assessing patient factors can identify persons at risk who need additional support to negotiate the healthcare system when providing care for a child with asthma.


Assuntos
Asma/tratamento farmacológico , Cuidadores/estatística & dados numéricos , Letramento em Saúde/estatística & dados numéricos , Grupos Minoritários/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Cuidadores/educação , Criança , Estudos Transversais , Escolaridade , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Masculino , Pobreza/estatística & dados numéricos , Medição de Risco/métodos , Resultado do Tratamento
17.
Nat Commun ; 10(1): 4836, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645561

RESUMO

Despite the crowded nature of the cellular milieu, ligand-GPCR-G protein interactions are traditionally viewed as spatially and temporally isolated events. In contrast, recent reports suggest the spatial and temporal coupling of receptor-effector interactions, with the potential to diversify downstream responses. In this study, we combine protein engineering of GPCR-G protein interactions with affinity sequestration and photo-manipulation of the crucial Gα C terminus, to demonstrate the temporal coupling of cognate and non-cognate G protein interactions through priming of the GPCR conformation. We find that interactions of the Gαs and Gαq C termini with the ß2-adrenergic receptor (ß2-AR), targeted at the G-protein-binding site, enhance Gs activation and cyclic AMP levels. ß2-AR-Gα C termini interactions alter receptor conformation, which persists for ~90 s following Gα C terminus dissociation. Non-cognate G-protein expression levels impact cognate signaling in cells. Our study demonstrates temporal allostery in GPCRs, with implications for the modulation of downstream responses through the canonical G-protein-binding interface.


Assuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Agonistas Adrenérgicos beta , Regulação Alostérica , Animais , Sítios de Ligação , AMP Cíclico/metabolismo , Epinefrina/metabolismo , Fenoterol/metabolismo , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , Isoproterenol/metabolismo , Cinética , Ligantes , Camundongos , Modelos Moleculares , Ligação Proteica , Engenharia de Proteínas , Estrutura Terciária de Proteína , Ratos , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Vasopressinas/metabolismo , Transdução de Sinais
18.
Neurology ; 90(23): e2034-e2041, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29728528

RESUMO

OBJECTIVE: We studied the performance of a 15-item, health-related quality-of-life polyneuropathy scale in the clinic setting in patients with diabetic distal sensorimotor polyneuropathy (DSPN). METHODS: Patients with DSPN from 11 academic sites completed a total of 231 Chronic Acquired Polyneuropathy Patient-Reported Index (CAPPRI) scales during their clinic visits. Conventional and modern psychometric analyses were performed on the completed forms. RESULTS: Conventional and modern analyses generally indicated excellent psychometric properties of the CAPPRI in patients with DSPN. For example, the CAPPRI demonstrated unidimensionality and performed like an interval-level scale. CONCLUSION: Attributes of the CAPPRI for DSPN include ease of use and interpretation; unidimensionality, allowing scores to be summed; adequate coverage of disease severity; and the scale's ability to address relevant life domains. Furthermore, the CAPPRI is free and in the public domain. The CAPPRI may assist the clinician and patient with DSPN in estimating disease-specific quality of life, especially in terms of pain, sleep, psychological well-being, and everyday function. The CAPPRI may be most useful in the everyday clinical setting but merits further study in this setting, as well as the clinical trial setting.


Assuntos
Neuropatias Diabéticas/psicologia , Psicometria , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Adulto , Canadá/epidemiologia , Neuropatias Diabéticas/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estados Unidos/epidemiologia
20.
J Pak Med Assoc ; 67(10): 1470-1475, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28955058

RESUMO

OBJECTIVE: To evaluate the strength of anti-mullerian hormone in reflecting the stages of ovarian toxicity-induced by cyclophosphamide. METHODS: This study was conducted in December 2014 and comprised female mice that were divided into four groups: group A served as control, group B received three weekly injections of cyclophosphamide, group C was co administered alpha-tocopherol along with cyclophosphamide, while group D solely received alpha-tocopherol. The ovaries were evaluated for follicular dynamics, and anti-mullerian hormone was assessed using mouse enzyme-linked immunosorbent assay kit. The data was analysed using SPSS 19. RESULTS: There were 40 mice in the study. Histological analysis revealed severely reduced ovarian reserve in group B(p<0.01).In group C alpha-tocopherol conserved the ovarian reserve to near normal, thus follicle count was significantly higher than group B (p<0.05). However, this moderate reduction was still lower than the controls (p<0.01). Furthermore, the number of corpus lutea and atretic follicles were significantly higher in groups B and C (p<0.01). Regarding hormonal analyses in comparison to controls, anti-mullerian hormone levels were low in group B (p<0.01), while group C reported an insignificant fall in serum anti-mullerian hormone levels (p=0.101). CONCLUSIONS: There was substantial evidence that anti-mullerian hormone monitoring during chemotherapy administration may fulfil the criteria of earliest diagnostic indicator of secondary infertility.


Assuntos
Hormônio Antimülleriano/sangue , Ciclofosfamida/efeitos adversos , Reserva Ovariana/efeitos dos fármacos , Ovário , alfa-Tocoferol/farmacologia , Animais , Feminino , Camundongos , Ovário/química , Ovário/efeitos dos fármacos
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