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1.
Acad Med ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38619446

RESUMO

PROBLEM: In the United States, physician bias is exhibited early in medical training and contributes to systemic inequities within the field of medicine. A lack of diversity, equity, inclusion, and antiracism (DEI-AR) content within medical curricula drives critical gaps in knowledge and deficiencies when preparing medical students to serve patients of diverse backgrounds. At the Mayo Clinic Alix School of Medicine (MCASOM), student-led curricular reviews between 2017 to 2018 and 2020 to 2021 revealed opportunities to improve DEI-AR content within preclinical courses. Course directors expressed concern of limited expertise and time to enact effective changes. APPROACH: The MCASOM DEI-AR teaching assistant (TA) program aims to curate a collaborative partnership between course directors and compensated student TAs to facilitate course enhancements responsive to the prior preclinical course review while centering standardized DEI-AR best practices. OUTCOMES: As of January 2024, the program has engaged 14 TAs and partnered with 24 preclinical courses. Postcourse student evaluation responses were collected from 8 courses for 2021 to 2022 (before enhancements) and 2022 to 2023 (after enhancements). Student satisfaction with DEI-AR content is tracked through postcourse evaluations, with preliminary data demonstrating improvement after DEI-AR curricular integration (improvement of mean preenhancement and postenhancement scores of 3.81 to 4.05; t12 = 1.79, P = .21). Qualitative student comments were sorted into general categories of positive, negative, or neutral, showing a 6.25% median increase in positive perception of DEI. NEXT STEPS: Plans for the MCASOM DEI-AR TA program include application of quality improvement strategies to improve program processes and outcomes. Development of a centralized dashboard that integrates course enhancement progress and ongoing feedback from evaluations is anticipated to facilitate this effort. The program additionally aims to develop partnerships with clinical clerkships, which would allow for a more comprehensive enhancement of the overall medical education experience related to DEI-AR.

2.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38484939

RESUMO

BACKGROUND AND AIM: Currently, we do not have a gold standard for pain management after total knee arthroplasty. We may use one of more drug delivery systems, none of which are ideal. An ideal depot delivery system would provide therapeutic, nontoxic, doses of drug at the surgical side, especially during 72h postoperatively. The bone cement used in arthroplasties has been used as a drug delivery system, especially antibiotics, since 1970. Based on this principle, we developed this study with the aim to characterize the elution profile of two local anaesthetics (lidocaine hydrochloride and bupivacaine hydrochloride) from PMMA (polymethilmethacrylate) bone cement. MATERIAL AND METHODS: Palacos® R+G bone cement and lidocaine hydrochloride or bupivacaine hydrochloride specimens were obtained depending on the study group. These specimens were immersed in PBS (phosphate buffered saline) and removed from the solution at different set times. Subsequently, the concentration of local anaesthetic in the liquid was analyzed by liquid chromatography. RESULTS: The percentage of lidocaine eluted from PMMA bone cement in this study was 9.74% of the total lidocaine content per specimen at 72h and 18.73% at 336h (14 days). In case of bupivacaine, the elution percentage was 2.71% of the total bupivacaine content per specimen at 72h and 2.70% at 336h (14 days). CONCLUSIONS: Local anaesthetics elute in vitro from PMMA bone cement, reaching doses at 72h close to the doses used in anaesthetic blocks.

3.
ANZ J Surg ; 94(4): 580-584, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38486439

RESUMO

BACKGROUND: The Ninth Perioperative Mortality Review Committee (POMRC) report found the likelihood of death was over three times higher in Maori youth compared to non-Maori (age: 15-18 years) in the 30-days following major trauma. The aim of our study is to investigate variations in care provided to Maori youth presenting to Te Whatu Ora Counties Manukau (TWO-CM) with major trauma, to inform policies and improve care. METHODS: This was a retrospective, observational study of 15-18-year-olds admitted to Middlemore Hospital from January 2018 to December 2021 following major trauma (Injury Severity Score (ISS) >12 or with (ISS) <12 who died). Data were obtained from the New Zealand Trauma Registry (NZTR). Six key performance indicators were studied against hospital guidelines/international consensus: Deaths, Cause-of-death, trauma call, RedBlanket activations, time-to-computed tomography (CT), and time-to-operating theatre (OT). RESULTS: Of 77 patients, five deaths occurred, four non-Maori, and one Maori (P = 0.645). Five trauma calls were not activated (P = 0.642). There was no statistically significant difference for both median time to CT (P = 0.917) and time to CT for patients with GCS >13 (P = 0.778) between Maori and non-Maori. Five patients did not meet guidelines for time-to-OT (three non-Maori and two Maori) (P = 0.377). CONCLUSION: No statistically significant variations in care were present for Maori youth presenting with major trauma, these findings did not match the national trend.


Assuntos
Escala de Gravidade do Ferimento , Povo Maori , Ferimentos e Lesões , Adolescente , Humanos , Hospitais , Nova Zelândia/epidemiologia , Estudos Retrospectivos , Ferimentos e Lesões/epidemiologia
4.
Invest Ophthalmol Vis Sci ; 65(3): 16, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38470329

RESUMO

Purpose: An early neurodegenerative component of diabetic retinal disease (DRD) that precedes the vascular findings of clinically diagnosed diabetic retinopathy (DR) is increasingly being recognized. However, the relevant molecular mechanisms and biomarkers for early DRD are poorly defined. The purpose of this study was to uncover novel potential mediators of early diabetic retinal neuronal dysfunction through analysis of the aqueous fluid proteome in preclinical DR. Methods: Aqueous fluid was collected from subjects with type 2 diabetes mellitus (DM) but no clinical DR and from nondiabetic controls undergoing routine cataract surgery. Preoperative spectral-domain optical coherence tomography of the macula was obtained. Tandem mass tag LC-MS/MS was performed to identify proteins differentially present in diabetic and control aqueous fluid, and proteins with >50% change and P < 0.05 were considered significant. Selected results were validated with western blot of human aqueous fluid samples. Results: We identified decreased levels of proteins implicated in neuronal synapse formation and increased levels of inflammatory proteins in the aqueous fluid from patients with type 2 DM but no DR compared with controls. Of the differentially present synaptic proteins that we identified and confirmed with western blot, the majority have not previously been linked with DRD. Conclusions: The proteomic profile of aqueous fluid from individuals with type 2 DM but no DR suggests that retinal neuronal dysfunction and inflammation represent very early events in the pathophysiology of DRD. These findings support the concept that diabetic retinal neurodegeneration precedes vascular pathology and reveal novel potential mediators and/or biomarkers warranting further investigation.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Doenças Retinianas , Humanos , Diabetes Mellitus Tipo 2/complicações , Humor Aquoso , Cromatografia Líquida , Espectrometria de Massa com Cromatografia Líquida , Proteômica , Espectrometria de Massas em Tandem , Biomarcadores
5.
PLoS One ; 19(3): e0298437, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38498459

RESUMO

Ionizing radiation (IR) and oncolytic viruses are both used to treat cancer, and the effectiveness of both agents depends upon stimulating an immune response against the tumor. In this study we tested whether combining image guided ionizing radiation (IG-IR) with an oncolytic vaccinia virus (VACV) could yield a better therapeutic response than either treatment alone. ΔF4LΔJ2R VACV grew well on irradiated human and mouse breast cancer cells, and the virus can be combined with 4 or 8 Gy of IR to kill cells in an additive or weakly synergistic manner. To test efficacy in vivo we used immune competent mice bearing orthotopic TUBO mammary tumors. IG-IR worked well with 10 Gy producing 80% complete responses, but this was halved when the tumors were treated with VACV starting 2 days after IG-IR. VACV monotherapy was ineffective in this model. The antagonism was time dependent as waiting for 21 days after IG-IR eliminated the inhibitory effect but without yielding any further benefits over IR alone. In irradiated tumors, VACV replication was also lower, suggesting that irradiation created an environment that did not support infection as well in vivo as in vitro. A study of how four different treatment regimens affected the immune composition of the tumor microenvironment showed that treating irradiated tumors with VACV altered the immunological profiles in tumors exposed to IR or VACV alone. We detected more PD-1 and PD-L1 expression in tumors exposed to IR+VACV but adding an αPD-1 antibody to the protocol did not change the way VACV interferes with IG-IR therapy. VACV encodes many immunosuppressive gene products that may interfere with the ability of radiotherapy to induce an effective anti-tumor immune response through the release of danger-associated molecular patterns. These data suggest that infecting irradiated tumors with VACV, too soon after exposure, may interfere in the innate and linked adaptive immune responses that are triggered by radiotherapy to achieve a beneficial impact.


Assuntos
Neoplasias Mamárias Animais , Terapia Viral Oncolítica , Vírus Oncolíticos , Radioterapia Guiada por Imagem , Vacínia , Humanos , Animais , Camundongos , Vaccinia virus/genética , Vírus Oncolíticos/genética , Neoplasias Mamárias Animais/radioterapia , Imunoterapia , Terapia Viral Oncolítica/métodos , Microambiente Tumoral
6.
J Egypt Public Health Assoc ; 99(1): 2, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38296917

RESUMO

BACKGROUND: The escalating emergence of the COVID-19 pandemic interrupted human life due to the ever-increasing morbidity, containment measures, and the associated emotional distress. This study examined the influence of COVID-19-related measures on the lifestyle behaviors of adults living in the Kingdom of Saudi Arabia (KSA). METHODS: The study recruited 638 participants through convenience sampling in Jeddah and Taif cities, Saudi Arabia. Demographic characteristics and COVID-19-related information were collected through an anonymous self-reported electronic questionnaire. Lifestyle behaviors were assessed before and during the quarantine using the Healthy Dietary Habits Index (HDHI)-A and the International Physical Activity Questionnaire (IPAQ-SF). RESULTS: The study revealed significant changes in the dietary pattern: a reduction in fish intake and increased consumption of French fries and candies. Vegetables and fruit intake increased significantly. Sedentary time > 6 h per day increased from 36.7% pre to 60.8% during the pandemic. Healthy dietary index score and physical activity MET-minutes/week values were respectively 3.5% and 37.9% significantly higher before compared to the full quarantine period. CONCLUSION: The pandemic detrimentally influenced eating habits and physical activity levels that led to weight gain, and hence higher vulnerability to COVID-19 infection and negative outcomes. This analysis provides public health agencies with data to tailor nutrition interventions that mitigate the observed adverse lifestyle behaviors.

7.
Can J Ophthalmol ; 59(2): 119-127, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36796442

RESUMO

OBJECTIVE: Investigate retinal characteristics of pathologic myopia (PM) among patients self-identifying as Black. DESIGN: Retrospective cohort single-institution retrospective medical record review. METHODS: Adult patients between January 2005 and December 2014 with International Classification of Diseases (ICD) codes consistent with PM and given 5-year follow-up were evaluated. The Study Group consisted of patients self-identifying as Black, and the Comparison Group consisted of those not self-identifying as Black. Ocular features at study baseline and 5-year follow-up visit were evaluated. RESULTS: Among 428 patients with PM, 60 (14%) self-identified as Black and 18 (30%) had baseline and 5-year follow-up visits. Of the remaining 368 patients, 63 were in the Comparison Group. For the study (n = 18) and Comparison Group (n = 29), median (25th percentile, 75th percentile) baseline visual acuity was 20/40 (20/25, 20/50) and 20/32 (20/25, 20/50) in the better-seeing eye and 20/70 (20/50, 20/1400) and 20/100 (20/50, 20/200), respectively, in the worse-seeing eye. In the eyes that did not have choroidal neovascularization (CNV) in the study and Comparison Group, median study baseline optical coherence tomography central subfield thickness was 196 µm (169, 306 µm) and 225 µm (191, 280 µm), respectively, in the better-seeing eye and 208 µm (181, 260 µm) and 194 µm (171, 248 µm), respectively, in the worse-seeing eye. Baseline prevalence of CNV was 1 Study Group eye (3%) and 20 Comparison Group eyes (34%). By the 5-year visit, zero (0%) and 4 (15%) additional eyes had CNV in the study and Comparison Group, respectively. CONCLUSION: These findings suggest that the prevalence and incidence of CNV may be lower in patients with PM self-identifying as Black when compared with individuals of other races.


Assuntos
Neovascularização de Coroide , Miopia , Adulto , Humanos , Estudos Retrospectivos , Retina/patologia , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/patologia , Tomografia de Coerência Óptica , Transtornos da Visão , Miopia/complicações , Angiofluoresceinografia
8.
Dig Dis ; 42(1): 12-24, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37757769

RESUMO

BACKGROUND: High-quality colonoscopic surveillance can lead to earlier and increased detection of colorectal neoplasia in patients with inflammatory bowel disease (IBD). In IBD clinical trials, endoscopy is used to assess mucosal disease activity before and after treatment but also provides an opportunity to surveil for colorectal neoplasia during follow-up. SUMMARY: Best practices for colorectal cancer identification in IBD clinical trials require engagement and collaboration between the clinical trial sponsor, site endoscopist and/or principal investigator, and central read team. Each team member has unique responsibilities for maximizing dysplasia detection in IBD trials. KEY MESSAGES: Sponsors should work in accordance with scientific guidelines to standardize imaging procedures, design the protocol to ensure the trial population is safeguarded, and oversee trial conduct. The site endoscopist should remain updated on best practices to tailor sponsor protocol-required procedures to patient needs, examine the mucosa for disease activity and potential dysplasia during all procedures, and provide optimal procedure videos for central read analysis. Central readers may detect dysplasia or colorectal cancer and a framework to report these findings to trial sponsors is essential. Synergistic relationships between all team members in IBD clinical trials provide an important opportunity for extended endoscopic evaluation and colorectal neoplasia identification.


Assuntos
Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Colonoscopia , Endoscopia Gastrointestinal/métodos
9.
Chest ; 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37977268

RESUMO

BACKGROUND: Although postinterview communication (PIC) guidelines exist, adherence is voluntary. There are no studies of PIC practices in critical care medicine (CCM) and pulmonary and critical care medicine (PCCM) fellowship recruitment. RESEARCH QUESTION: What is the frequency, format, goals, and content of PIC between CCM/PCCM applicants and program directors? What is the impact of PIC on applicant and program rank order lists (ROLs)? STUDY DESIGN AND METHODS: CCM/PCCM applicants and program directors were separately surveyed after the 2022-2023 National Resident Matching Program Specialty Match. Surveys included multiple-choice, Likert-scale, and two free text questions. Thematic content analysis of free text responses was performed. RESULTS: One-third of eligible participants responded (applicants: n = 373 [34%]; program directors: n = 86 [32%]). Applicant respondents applied to CCM (19%), PCCM (69%), or both (12%). Program directors represented CCM (17%), PCCM (57%), or both (26%) programs. Applicant (66%) and program director (49%) respondents reported initiating PIC. PIC did not impact ROL decision for most applicants (73%) or program directors (83%), though 21% of applicants and 17% of program directors moved programs or applicants up on their ROL in response to PIC. One-quarter (23%) of applicants strongly agreed or agreed that PIC was helpful in creating their ROL, 27% strongly disagreed or disagreed, and 29% were neutral. PIC challenges identified by both groups included time; lack of uniformity; peer pressure; misleading language; and uncertainty about motives, rules, and response protocols. INTERPRETATION: PIC is common among CCM/PCCM applicants and program directors. About 50% of applicants and 20% of program directors share ranking intentions via PIC. Although PIC did not impact ROL for most applicants and program directors, a minority of applicants and program directors moved programs up on their ROL after receiving PIC from the other party. Applicants have mixed perspectives on PIC value. Applicants and program directors alike desire clear guidance on PIC to minimize ambiguous and misleading communication.

10.
Rev. esp. cir. ortop. traumatol. (Ed. impr.) ; 67(5): T411-T417, Sept-Oct, 2023. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-224973

RESUMO

Antecedentes y objetivo:Actualmente, no disponemos de un gold standard para el manejo del dolor postoperatorio tras una artroplastia total de rodilla, dado que se pueden administrar analgésicos a través de diferentes vías y ninguna de estas está exenta de riesgos. El sistema ideal de administración de analgésicos debería proporcionar dosis terapéuticas, no tóxicas, en el sitio quirúrgico, especialmente durante las primeras 72h. El cemento óseo utilizado en las artroplastias se ha usado como un medio de liberación de fármacos, especialmente antibióticos, desde 1970. Basado en este principio, se desarrolló este estudio con el objetivo de conocer el perfil de elución de dos anestésicos locales (hidrocloruro de lidocaína e hidrocloruro de bupivacaína) desde el cemento óseo de polimetilmetacrilato (PMMA). Material y métodos: Se obtuvieron especímenes de cemento óseo Palacos® R+G e hidrocloruro de lidocaína o hidrocloruro de bupivacaína según el grupo de estudio. Estos especímenes se sumergieron en PBS (por sus siglas en inglés de phosphate buffered saline) y se retiraron de la solución en diferentes cortes temporales establecidos. Posteriormente, se analizó la concentración de anestésico local en el líquido mediante cromatografía líquida. Resultados: El porcentaje de lidocaína eludida del cemento óseo PMMA de este estudio ha sido del 9,74% del contenido total de lidocaína por espécimen a las 72h y del 18,73% a las 336h (14 días). En el caso de la bupivacaína, el porcentaje de elución ha sido del 2,71% del contenido total de bupivacaína por espécimen a las 72h y del 2,70% a las 336h (14 días). Conclusiones: Los anestésicos locales eluyen in vitro desde el cemento óseo, alcanzando a las 72h dosis cercanas a las dosis utilizadas en bloqueos anestésicos.(AU)


Background and aim: Currently, we do not have a gold standard for pain management after total knee arthroplasty. We may use one of more drug delivery systems, none of which are ideal. An ideal depot delivery system would provide therapeutic, nontoxic, doses of drug at the surgical side, especially during 72h postoperatively. The bone cement used in arthroplasties has been used as a drug delivery system, especially antibiotics, since 1970. Based on this principle, we developed this study with the aim to characterize the elution profile of two local anesthetics (lidocaine hydrochloride and bupivacaine hydrochloride) from PMMA (polymethilmethacrylate) bone cement. Material and methods: Palacos® R+G bone cement and lidocaine hydrochloride or bupivacaine hydrochloride specimens were obtained depending on the study group. These specimens were immersed in PBS (phosphate buffered saline) and removed from the solution at different set times. Subsequently, the concentration of local anesthetic in the liquid was analyzed by liquid chromatography. Results: The percentage of lidocaine eluted from PMMA bone cement in this study was 9.74% of the total lidocaine content per specimen at 72h and 18.73% at 336h (14 days). In case of bupivacaine, the elution percentage was 2.71% of the total bupivacaine content per specimen at 72h and 2.70% at 336h (14 days). Conclusions: Local anesthetics elute in vitro from PMMA bone cement, reaching doses at 72h close to the doses used in anesthetic blocks.(AU)


Assuntos
Humanos , Cimentos Ósseos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Lidocaína/administração & dosagem , Bupivacaína/administração & dosagem , Articulação do Joelho/cirurgia , Técnicas In Vitro , Fraturas Ósseas/cirurgia , Traumatologia , Ortopedia , Procedimentos Ortopédicos , Analgesia , Traumatismos do Joelho
11.
Rev. esp. cir. ortop. traumatol. (Ed. impr.) ; 67(5): 411-417, Sept-Oct, 2023. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-224972

RESUMO

Antecedentes y objetivo:Actualmente, no disponemos de un gold standard para el manejo del dolor postoperatorio tras una artroplastia total de rodilla, dado que se pueden administrar analgésicos a través de diferentes vías y ninguna de estas está exenta de riesgos. El sistema ideal de administración de analgésicos debería proporcionar dosis terapéuticas, no tóxicas, en el sitio quirúrgico, especialmente durante las primeras 72h. El cemento óseo utilizado en las artroplastias se ha usado como un medio de liberación de fármacos, especialmente antibióticos, desde 1970. Basado en este principio, se desarrolló este estudio con el objetivo de conocer el perfil de elución de dos anestésicos locales (hidrocloruro de lidocaína e hidrocloruro de bupivacaína) desde el cemento óseo de polimetilmetacrilato (PMMA). Material y métodos: Se obtuvieron especímenes de cemento óseo Palacos® R+G e hidrocloruro de lidocaína o hidrocloruro de bupivacaína según el grupo de estudio. Estos especímenes se sumergieron en PBS (por sus siglas en inglés de phosphate buffered saline) y se retiraron de la solución en diferentes cortes temporales establecidos. Posteriormente, se analizó la concentración de anestésico local en el líquido mediante cromatografía líquida. Resultados: El porcentaje de lidocaína eludida del cemento óseo PMMA de este estudio ha sido del 9,74% del contenido total de lidocaína por espécimen a las 72h y del 18,73% a las 336h (14 días). En el caso de la bupivacaína, el porcentaje de elución ha sido del 2,71% del contenido total de bupivacaína por espécimen a las 72h y del 2,70% a las 336h (14 días). Conclusiones: Los anestésicos locales eluyen in vitro desde el cemento óseo, alcanzando a las 72h dosis cercanas a las dosis utilizadas en bloqueos anestésicos.(AU)


Background and aim: Currently, we do not have a gold standard for pain management after total knee arthroplasty. We may use one of more drug delivery systems, none of which are ideal. An ideal depot delivery system would provide therapeutic, nontoxic, doses of drug at the surgical side, especially during 72h postoperatively. The bone cement used in arthroplasties has been used as a drug delivery system, especially antibiotics, since 1970. Based on this principle, we developed this study with the aim to characterize the elution profile of two local anesthetics (lidocaine hydrochloride and bupivacaine hydrochloride) from PMMA (polymethilmethacrylate) bone cement. Material and methods: Palacos® R+G bone cement and lidocaine hydrochloride or bupivacaine hydrochloride specimens were obtained depending on the study group. These specimens were immersed in PBS (phosphate buffered saline) and removed from the solution at different set times. Subsequently, the concentration of local anesthetic in the liquid was analyzed by liquid chromatography. Results: The percentage of lidocaine eluted from PMMA bone cement in this study was 9.74% of the total lidocaine content per specimen at 72h and 18.73% at 336h (14 days). In case of bupivacaine, the elution percentage was 2.71% of the total bupivacaine content per specimen at 72h and 2.70% at 336h (14 days). Conclusions: Local anesthetics elute in vitro from PMMA bone cement, reaching doses at 72h close to the doses used in anesthetic blocks.(AU)


Assuntos
Humanos , Cimentos Ósseos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Lidocaína/administração & dosagem , Bupivacaína/administração & dosagem , Articulação do Joelho/cirurgia , Técnicas In Vitro , Fraturas Ósseas/cirurgia , Traumatologia , Ortopedia , Procedimentos Ortopédicos , Analgesia , Traumatismos do Joelho
12.
Eur J Immunol ; 53(12): e2350546, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37751619

RESUMO

Cryopreservation of mouse thymus depletes donor thymocytes but preserves thymus function when transplanted after thawing into athymic mice. No differences in immune reconstitution were observed between fresh and frozen/thawed transplants suggesting that donor thymocyte depletion does not affect outcome. Thus, cryopreservation of thymus may improve outcomes in thymus transplant patients.


Assuntos
Reconstituição Imune , Timócitos , Humanos , Animais , Camundongos , Timo , Criopreservação
13.
Transl Psychiatry ; 13(1): 245, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-37407569

RESUMO

The RASopathies are genetic syndromes associated with pathogenic variants causing dysregulation of the Ras/mitogen-activated protein kinase (Ras-MAPK) pathway, essential for brain development, and increased risk for neurodevelopmental disorders. Yet, the effects of most pathogenic variants on the human brain are unknown. We examined: (1) How Ras-MAPK activating variants of PTPN11/SOS1 protein-coding genes affect brain anatomy. (2) The relationship between PTPN11 gene expression levels and brain anatomy, and (3) The relevance of subcortical anatomy to attention and memory skills affected in the RASopathies. We collected structural brain MRI and cognitive-behavioral data from 40 pre-pubertal children with Noonan syndrome (NS), caused by PTPN11 (n = 30) or SOS1 (n = 10) variants (age 8.53 ± 2.15, 25 females), and compared them to 40 age- and sex-matched typically developing controls (9.24 ± 1.62, 27 females). We identified widespread effects of NS on cortical and subcortical volumes and on determinants of cortical gray matter volume, surface area (SA), and cortical thickness (CT). In NS, we observed smaller volumes of bilateral striatum, precentral gyri, and primary visual area (d's < -0.8), and extensive effects on SA (d's > |0.8|) and CT (d's > |0.5|) relative to controls. Further, SA effects were associated with increasing PTPN11 gene expression, most prominently in the temporal lobe. Lastly, PTPN11 variants disrupted normative relationships between the striatum and inhibition functioning. We provide evidence for the effects of Ras-MAPK pathogenic variants on striatal and cortical anatomy as well as links between PTPN11 gene expression and cortical SA increases, and striatal volume and inhibition skills. These findings provide essential translational information on the Ras-MAPK pathway's effect on human brain development and function.


Assuntos
Proteínas Quinases Ativadas por Mitógeno , Síndrome de Noonan , Criança , Feminino , Humanos , Síndrome de Noonan/genética , Encéfalo/diagnóstico por imagem , Substância Cinzenta , Expressão Gênica , Mutação
15.
Rev Esp Cir Ortop Traumatol ; 67(5): T411-T417, 2023.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37311482

RESUMO

BACKGROUND AND AIM: Currently, we do not have a gold standard for pain management after total knee arthroplasty. We may use one of more drug delivery systems, none of which are ideal. An ideal depot delivery system would provide therapeutic, nontoxic, doses of drug at the surgical side, especially during 72h postoperatively. The bone cement used in arthroplasties has been used as a drug delivery system, especially antibiotics, since 1970. Based on this principle, we developed this study with the aim to characterise the elution profile of two local anaesthetics (lidocaine hydrochloride and bupivacaine hydrochloride) from PMMA (polymethilmethacrylate) bone cement. MATERIAL AND METHODS: Palacos® R+G bone cement and lidocaine hydrochloride or bupivacaine hydrochloride specimens were obtained depending on the study group. These specimens were immersed in PBS (phosphate buffered saline) and removed from the solution at different set times. Subsequently, the concentration of local anaesthetic in the liquid was analysed by liquid chromatography. RESULTS: The percentage of lidocaine eluted from PMMA bone cement in this study was 9.74% of the total lidocaine content per specimen at 72h and 18.73% at 336h (14 days). In case of bupivacaine, the elution percentage was 2.71% of the total bupivacaine content per specimen at 72h and 2.70% at 336h (14 days). CONCLUSIONS: Local anaesthetics elute in vitro from PMMA bone cement, reaching doses at 72h close to the doses used in anaesthetic blocks.

16.
BMC Nurs ; 22(1): 175, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37211603

RESUMO

BACKGROUND: Black fungus (mycoses) is an opportunistic invasive infection that predominantly occurred among immunosuppressed persons. It has been recently detected in COVID-19 patients. The pregnant diabetic woman is susceptible to such infections and needs recognition for protection. This study aimed to evaluate the effect of the nurse-led intervention on the knowledge and preventive practice of diabetic pregnant women regarding fungal mycosis during the COVID-19 pandemic. METHOD: This quasi-experimental study was conducted at maternal health care centers in Shebin El-Kom, Menoufia Governorate, Egypt. The study recruited 73 diabetic pregnant women through a systematic random sampling of pregnant women attending the maternity clinic during the period of the study. A structured interview questionnaire was used to measure their knowledge regarding Mucormycosis and COVID-19 manifestations. The preventive practices were assessed through an observational checklist of hygienic practice, insulin administration, and blood glucose monitoring for the prevention of Mucormycosis infection. RESULTS: The study revealed a statistically significant increment in the participants' knowledge, preventive practice, personal hygiene, and diabetes self-care scores (9.56 ± 1.75 ,3.6 ± 1.18, 3.18 ± 1.29 post-intervention) comparable to (6.19 ± 1.66, 1.97 ± 1.35, 0.89 ± 1.38 pre-intervention) respectively. There was a significant improvement in the overall COVID-19 protective score against Mucormycosis (from 2.66 ± 1.74 to 4.53 ± 1.43). CONCLUSION: Nursing educational sessions had a positive effect on pregnant women's awareness and preventive behavior. Hence, it is recommended to integrate nurse-led intervention targeting the preventive practice against COVID-19-associated Mucormycosis infection (CAM) as routine services for diabetic pregnant women during antenatal care.

17.
Rev Esp Cir Ortop Traumatol ; 67(5): 411-417, 2023.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37023978

RESUMO

BACKGROUND AND AIM: Currently, we do not have a gold standard for pain management after total knee arthroplasty. We may use one of more drug delivery systems, none of which are ideal. An ideal depot delivery system would provide therapeutic, nontoxic, doses of drug at the surgical side, especially during 72h postoperatively. The bone cement used in arthroplasties has been used as a drug delivery system, especially antibiotics, since 1970. Based on this principle, we developed this study with the aim to characterize the elution profile of two local anesthetics (lidocaine hydrochloride and bupivacaine hydrochloride) from PMMA (polymethilmethacrylate) bone cement. MATERIAL AND METHODS: Palacos® R+G bone cement and lidocaine hydrochloride or bupivacaine hydrochloride specimens were obtained depending on the study group. These specimens were immersed in PBS (phosphate buffered saline) and removed from the solution at different set times. Subsequently, the concentration of local anesthetic in the liquid was analyzed by liquid chromatography. RESULTS: The percentage of lidocaine eluted from PMMA bone cement in this study was 9.74% of the total lidocaine content per specimen at 72h and 18.73% at 336h (14 days). In case of bupivacaine, the elution percentage was 2.71% of the total bupivacaine content per specimen at 72h and 2.70% at 336h (14 days). CONCLUSIONS: Local anesthetics elute in vitro from PMMA bone cement, reaching doses at 72h close to the doses used in anesthetic blocks.

18.
Front Oncol ; 13: 1090582, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36761944

RESUMO

Objective: Magnetic resonance imaging (MRI) is a standard imaging modality in intracranial stereotactic radiosurgery (SRS) for defining target volumes. However, wide disparities in MRI resolution exist, which could directly impact accuracy of target delineation. Here, sequences with various MRI resolution were acquired on phantoms to evaluate the effect on volume definition and dosimetric consequence for cranial SRS. Materials/Methods: Four T1-weighted MR sequences with increasing 3D resolution were compared, including two Spin Echo (SE) 2D acquisitions with 5mm and 3mm slice thickness (SE5mm, SE3mm) and two gradient echo 3D acquisitions (TFE, BRAVO). The voxel sizes were 0.4×0.4×5.0, 0.5×0.5×3.0, 0.9×0.9×1.25, and 0.4×0.4×0.5 mm3, respectively. Four phantoms with simulated lesions of different shape and volume (range, 0.53-25.0 cm3) were imaged, resulting in 16 total sets of MRIs. Four radiation oncologists provided contours on individual MR image set. All observer contours were compared with ground truth, defined on CT image according to the absolute dimensions of the target structure, using Dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance-to-agreement (MDA), and the ratio between reconstructed and true volume (Ratiovol ). For dosimetric consequence, SRS plans targeting observer volumes were created. The true Paddick conformity index ( C I p a d d i c k t r u e ), calculated with true target volume, was correlated with quality of observer volume. Results: All measures of observer contours improved as increasingly higher MRI resolution was provided from SE5mm to BRAVO. The improvement in DSC, HD and MDA was statistically significant (p<0.01). Dosimetrically, C I p a d d i c k t r u e   strongly correlated with DSC of the planning observer volume (Pearson's r=0.94, p<0.00001). Conclusions: Significant improvement in target definition and reduced inter-observer variation was observed as the MRI resolution improved, which also improved the quality of SRS plans. Results imply that high resolution 3D MR sequences should be used to minimize potential errors in target definition, and multi-slice 2D sequences should be avoided.

19.
Retin Cases Brief Rep ; 17(1): 9-12, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33323897

RESUMO

PURPOSE: To report a case of syphilitic outer retinopathy revealed after progression to panuveitis after a course of oral steroids for suspected poison ivy. METHODS: Retrospective case report. RESULTS: A 44-year-old diabetic man presented with progressive symptoms of nyctalopia and color vision changes associated with outer retinal disruption on macular imaging but minimal evidence of intraocular inflammation on examination. A short course of oral steroids for an unrelated skin condition induced rapid progression to frank panuveitis with retinal vascular sheathing and retinal whitening. Systemic workup identified syphilis as the etiology. The patient's visual symptoms and disruption of the photoreceptor and retinal pigment epithelial layers on OCT improved after treatment with IV penicillin. CONCLUSION: Syphilitic outer retinopathy represents an unusual manifestation of ocular syphilis that can present with minimal examination findings. We present here a case of oral steroid use resulting in the progression of syphilitic outer retinopathy to a more fulminant form of syphilitic uveitis that ultimately revealed the correct diagnosis and prompted the correct intervention. This case highlights the importance of maintaining a high level of suspicion for this treatable condition.


Assuntos
Pan-Uveíte , Doenças Retinianas , Sífilis , Uveíte , Masculino , Humanos , Adulto , Sífilis/complicações , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Pan-Uveíte/induzido quimicamente , Pan-Uveíte/diagnóstico , Doenças Retinianas/complicações , Uveíte/diagnóstico , Esteroides
20.
J Mol Med (Berl) ; 100(11): 1617-1627, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36121467

RESUMO

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.


Assuntos
Síndrome do Intestino Irritável , Humanos , Feminino , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/metabolismo , Serotonina , Receptores de Serotonina/genética , Genótipo , Fatores de Risco , Estudos Multicêntricos como Assunto
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