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ABSTRACT: Monkeypox (Mpox) is a zoonotic Orthopoxvirus of the Poxviridae family, endemic to Africa. In August 2022, the US government declared it an emergency because of the worldwide spread. Traditionally, Mpox infection spreads through contact with infected animals. However, the 2022 outbreak Centers for Disease Control and Prevention (CDC) data note that 94% of cases had recent male-to-male sexual or close intimate contact, suggesting a novel sexual transmission. In this article, we report a 39-year-old HIV-positive man presenting with a diffuse cutaneous rash, perianal pain, and bloody stool of 2-week duration. A medical history includes intravenous drug use and multiple sexual partners. Physical examination revealed umbilicated, tan-colored, crusted cutaneous papules scattered across the face, trunk, and genital regions. Perianal lesion biopsy showed an acanthotic epidermis with spongiosis, ballooning degeneration of keratinocytes, and the formation of multinucleated syncytial keratinocytes. A dermal superficial/lichenoid mixed inflammatory cell infiltrate with multinucleated giant cells was noted. Perianal lesion polymerase chain reaction (PCR) was positive for Mpox. Colonoscopy revealed a 3-cm circumferential rectal ulcer with gray exudate and necrosis. A rectal ulcer biopsy showed an ulcerated mucosa with acute proctitis and necrosis. There were scattered macrophages with intranuclear inclusion and glassy vacuolization, and Mpox infection was confirmed by immunostaining with a Mpox-specific anti-Vaccinia virus antibody.
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Mpox , Proctitis , Estados Unidos , Animales , Humanos , Masculino , Adulto , Úlcera , Proctitis/diagnóstico , Anticuerpos Antivirales , NecrosisRESUMEN
PCB 126 is a pervasive, dioxin-like chemical pollutant which can activate the aryl hydrocarbon receptor (AhR). Despite being banned from the market, PCB 126 can be detected in breast milk to this day. The extent to which interindividual variation impacts the adverse responses to this chemical in the breast tissue remains unclear. This study aimed to investigate the impact of 3 nM PCB 126 on gene expression in a panel of genetically diverse benign human breast epithelial cell (HBEC) cultures and patient derived breast tissues. Six patient derived HBEC cultures were treated with 3 nM PCB 126. RNAseq was used to interrogate the impact of exposure on differential gene expression. Gene expression changes from the top critical pathways were confirmed via qRT-PCR in a larger panel of benign patient derived HBEC cultures, as well as in patient-derived breast tissue explant cultures. RNAseq analysis of HBEC cultures revealed a signature of 144 genes significantly altered by 3 nM PCB 126 treatment. Confirmation of 8 targets using a panel of 12 HBEC cultures and commercially available breast cell lines demonstrated that while the induction of canonical downstream target gene, CYP1A1, was consistent across our primary HBECs, other genes including AREG, S100A8, IL1A, IL1B, MMP7, and CCL28 exhibited significant variability across individuals. The dependence on the activity of the aryl hydrocarbon receptor was confirmed using inhibitors. PCB 126 can induce significant and consistent changes in gene expression associated with xenobiotic metabolism in benign breast epithelial cells. Although the induction of most genes was reliant on the AhR, significant variability was noted between genes and individuals. These data suggest that there is a bifurcation of the pathway following AhR activation that contributes to the variation in interindividual responses.
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Bifenilos Policlorados , Receptores de Hidrocarburo de Aril , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Células Epiteliales/metabolismo , Femenino , Expresión Génica , Humanos , Bifenilos Policlorados/toxicidad , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismoRESUMEN
OBJECTIVES: Systemic sclerosis (SSc) is a complex disease of unknown aetiology in which inflammation and fibrosis lead to multiple organ damage. There is currently no effective therapy that can halt the progression of fibrosis or reverse it, thus studies that provide novel insights into disease pathogenesis and identify novel potential therapeutic targets are critically needed. METHODS: We used global gene expression and genome-wide DNA methylation analyses of dermal fibroblasts (dFBs) from a unique cohort of twins discordant for SSc to identify molecular features of this pathology. We validated the findings using in vitro, ex vivo and in vivo models. RESULTS: Our results revealed distinct differentially expressed and methylated genes, including several transcription factors involved in stem cell differentiation and developmental programmes (KLF4, TBX5, TFAP2A and homeobox genes) and the microRNAs miR-10a and miR-10b which target several of these deregulated genes. We show that KLF4 expression is reduced in SSc dFBs and its expression is repressed by TBX5 and TFAP2A. We also show that KLF4 is antifibrotic, and its conditional knockout in fibroblasts promotes a fibrotic phenotype. CONCLUSIONS: Our data support a role for epigenetic dysregulation in mediating SSc susceptibility in dFBs, illustrating the intricate interplay between CpG methylation, miRNAs and transcription factors in SSc pathogenesis, and highlighting the potential for future use of epigenetic modifiers as therapies.
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Fibroblastos/patología , Regulación de la Expresión Génica/fisiología , Factor 4 Similar a Kruppel/metabolismo , Esclerodermia Sistémica , Piel/patología , Células Cultivadas , Fibroblastos/metabolismo , Humanos , Factor 4 Similar a Kruppel/genética , MicroARNs/metabolismo , Esclerodermia Sistémica/genética , Esclerodermia Sistémica/metabolismo , Esclerodermia Sistémica/patología , Piel/metabolismo , Proteínas de Dominio T Box/metabolismo , Factor de Transcripción AP-2/metabolismo , TranscriptomaRESUMEN
Osteoarthritis is a condition in which joint cartilage and bone degenerate progressively over time. Total joint arthroplasty is a definitive treatment. Cortisol is a hormone that is associated with pain and inflammation. This study aims to investigate the cortisol levels in patients undergoing total joint arthroplasty. Plasma samples were collected from 71 total joint arthroplasty (TJA) patients at baseline (pre-surgery), 24 hours post-operation, and 5 days post-operation. Cortisol levels were measured in each sample using a commercially available ELISA kit. All results were compiled as group means ± SD. The plasma cortisol level at baseline were 218.5 ± 12 ng/mL. The 24-hour post-surgical samples showed a marked increase in cortisol levels 240.7 ± 15 ng/mL. The blood samples drawn at the 5th day after surgery showed a downward trend (74 ± 12 ng/mL). At 5 days post-operation, cortisol levels were significantly lower than at baseline or 24 hours post-operation. These results point to the fact that prior to surgery, the patient's emotional stress contributes to increased serum cortisol levels. The higher level of cortisol persists at 24 hours post-operation due to inflammation from the procedure. This data also suggests that at 5 days post-operation, the inflammatory response from the surgery and emotional stress subside, resulting in a near normalization of the cortisol levels. Cortisol is a hormone that plays a major role in the body's response to surgery. The relevance between cortisol and different points in the surgical timeline has the potential to prognosticate and improve recovery measures.
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Artroplastia de Reemplazo de Rodilla/métodos , Hidrocortisona/uso terapéutico , Osteoartritis/tratamiento farmacológico , Humanos , Hidrocortisona/farmacologíaRESUMEN
Our study aimed to investigate the levels and time-course of systemic inflammatory and hemostasis markers in the early postoperative period in patients undergoing total hip replacement (THR). The study included 70 patients of both sexes, average age 68.4 ± 10.9 years. Levels of inflammatory and hemostasis markers were measured before surgery (POD 0), a day after the surgery (POD 1) and 5 days after surgery (POD 5). In the postoperative period inflammatory markers increased. The operation provoked a significant increase of CRP on POD 1 in comparison to POD 0 (68.5 ± 5.4 vs 6.8 ± 2.2 µg/mL, p < 0.001) and the additional increase was registered on POD 5 (87.5 ± 8.1 vs 68.5 ± 5.4 µg/mL, p < 0.001). Interleukin-6 significantly increased on POD 1 (251.5 ± 21.6 vs 14.6 ± 7.1 µg/mL, p < 0.001) and after that (POD 5) decreased. After surgery leukocyte count, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were significantly higher compared to POD 0. Activation of coagulation in the postoperative period was shown by increased peak thrombin on POD 5 in comparison to POD 0 (185 ± 27 vs. 124 ± 31 nM, p < 0.001). D-dimer was increased on POD 1 and an additional rise was observed on POD 5. vWF also progressively increased in the observed period. Results of our study showed that after THR systemic inflammatory markers increased and coagulation function was enhanced. Determination of inflammatory and procoagulant markers could help identify patients at risk for cardiovascular thromboembolic events.
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Artroplastia de Reemplazo de Cadera , Factores de Coagulación Sanguínea/metabolismo , Mediadores de Inflamación/sangre , Anciano , Artroplastia de Reemplazo de Cadera/efectos adversos , Biomarcadores/sangre , Coagulación Sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Tromboembolia/sangre , Tromboembolia/etiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To report the rate of new vessel (NV) regression after monthly injections of bevacizumab in laser-treated proliferative diabetic retinopathy (PDR) eyes with persistent neovascularization. DESIGN: Prospective cohort study. PARTICIPANTS: Eyes with PDR with incomplete response to prior complete panretinal photocoagulation (PRP). METHODS: Ninety eyes of 80 patients with persistent PDR (pPDR) despite adequate PRP were prospectively followed on a monthly basis with anti-vascular endothelial growth factor (VEGF) injections when needed and stereo fundus images looking at the regression of NVs. MAIN OUTCOME MEASURES: Regression of NVs. RESULTS: A total of 70 of 90 eyes (77.8%) had regression of the NV. Mean number of injections to reach quiescence was 9±3 for pPDR in the high-risk characteristics (HRC) group (80 eyes) and 3±1 for PDR in the group without HRC (10 eyes) (P < 0.001). All patients with PDR without HRC responded to the adjuvant therapy, whereas 75.0% of the eyes with PDR with HRC responded. Eyes with initial retinal neovascularization all responded to the adjuvant treatment. Eyes without a vitreous hemorrhage at study entry were more likely to respond (odds ratio, 5.43; 95% confidence interval, 1.37-21.44; P < 0.01). Therapy was judged unsuccessful because of the continuous growth of the NV despite treatment (3 eyes), the development of traction (5 eyes), and the development of a dense vitreous hemorrhage (6 eyes). CONCLUSIONS: Anti-VEGF rescue therapy has a potential role in select cases of laser-treated PDR with persistent NVs and no evidence of traction to achieve regression of neovessels.
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Bevacizumab/administración & dosificación , Retinopatía Diabética/terapia , Coagulación con Láser/métodos , Retina/patología , Neovascularización Retiniana/terapia , Agudeza Visual , Adulto , Inhibidores de la Angiogénesis/administración & dosificación , Retinopatía Diabética/complicaciones , Retinopatía Diabética/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Oftalmoscopía , Estudios Prospectivos , Neovascularización Retiniana/diagnóstico , Neovascularización Retiniana/etiología , Microscopía con Lámpara de Hendidura , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
BACKGROUND: Systemic sclerosis (SSc) is a rare autoimmune fibrosing disease with an incompletely understood genetic and non-genetic etiology. Defining its etiology is important to allow the development of effective predictive, preventative, and therapeutic strategies. We conducted this epigenomic study to investigate the contributions of DNA methylation to the etiology of SSc while minimizing confounding due to genetic heterogeneity. METHODS: Genomic methylation in whole blood from 27 twin pairs discordant for SSc was assayed over 450 K CpG sites. In silico integration with reported differentially methylated cytosines, differentially expressed genes, and regulatory annotation was conducted to validate and interpret the results. RESULTS: A total of 153 unique cytosines in limited cutaneous SSc (lcSSc) and 266 distinct sites in diffuse cutaneous SSc (dcSSc) showed suggestive differential methylation levels in affected twins. Integration with available data revealed 76 CpGs that were also differentially methylated in blood cells from lupus patients, suggesting their role as potential epigenetic blood biomarkers of autoimmunity. It also revealed 27 genes with concomitant differential expression in blood from SSc patients, including IFI44L and RSAD2. Regulatory annotation revealed that dcSSc-associated CpGs (but not lcSSc) are enriched at Encyclopedia of DNA Elements-, Roadmap-, and BLUEPRINT-derived regulatory regions, supporting their potential role in disease presentation. Notably, the predominant enrichment of regulatory regions in monocytes and macrophages is consistent with the role of these cells in fibrosis, suggesting that the observed cellular dysregulation might be, at least partly, due to altered epigenetic mechanisms of these cells in dcSSc. CONCLUSIONS: These data implicate epigenetic changes in the pathogenesis of SSc and suggest functional mechanisms in SSc etiology.
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Metilación de ADN , Enfermedades en Gemelos/genética , Esclerodermia Sistémica/genética , Gemelos Monocigóticos/genética , Islas de CpG , Epigénesis Genética , Femenino , Redes Reguladoras de Genes , Marcadores Genéticos , Humanos , Masculino , Regiones Promotoras GenéticasRESUMEN
[This corrects the article DOI: 10.1155/2017/9805145.].
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OBJECTIVE: To compare nonmydriatic spectral domain optical coherence tomography (NMOCT) to comprehensive ophthalmologic evaluation (COE) in detecting adult macular abnormalities. METHODS: This is a single-reader observational pilot study of adults older than 50 years with no known ophthalmologic problems to assess the correlation between NMOCT and COE in detecting macular abnormalities classified as epiretinal, intraretinal, subretinal, or a combination thereof. Subjects underwent NMOCT of the macula followed by COE which included a dilated fundus examination and ancillary tests as needed. RESULTS: A total of 771 eyes of 406 patients were included. Cohen's kappa coefficient of agreement between NMOCT and COE for detecting any abnormality was high (0.90, p < 0.0001), with NMOCT having an overall sensitivity of 82.65% and specificity of 98.97%. Sensitivities and specificities of NMOCT in detecting each category of macular abnormalities were as follows: epiretinal (86.36%, 99.73%), intraretinal (80.00%, 99.58%), and subretinal (88.89%, 99.73%), respectively. CONCLUSION: NMOCT is a promising tool for detecting adult macular abnormalities.
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Mácula Lútea/patología , Oftalmoscopía/métodos , Enfermedades de la Retina/diagnóstico , Tomografía de Coherencia Óptica/métodos , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Midriáticos , Proyectos Piloto , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
The aim of this study was to verify body composition, cardiorespiratory fitness, and biochemical markers of prepubertal overweight and obese boys to a 16-week futsal training program. Methods: Sixteen boys (age: 7-10 y, body mass index>thanat 95th percentileaccording to Center for Disease Control and Prevention; 35.5±7.4 percent fat) participated to futsal training program. The assessment of body composition was estimated using skinfold thickness, and the following variables were evaluated: total body mass, body mass index, body fat percentage, and lean body mass. Aerobic fitness measurementwas performed by gas exchange analysis in treadmill. In addition, an evaluation of the biochemical profile was conducted: triglycerides, total cholesterol, low density lipoprotein cholesterol, high-density lipoprotein cholesterol, plasma concentrations of glucose, and insulin. The futsal intervention included 60-min sessions performed two times/week. The mean intensity during training was between 57 to 88% of maximal heart rate of the age-predicted. Individual portable heart rate monitor controlled training intensity. Results: Significant increases in total body mass (4%), height (3%), lean body mass (8%), and significant 6%-decrease in body fat percentage was observed. Body mass index remained unchanged. Maximal oxygen uptake was elevated (p<0.018) by 11%. Biochemical markers were not modified after intervention. No association was found between body composition and metabolic variables. The effect size of futsal training on most variables was small (<0.5). Conclusion: Controlled intensity and adherence to this 16-week futsal training program were determinant to enhance body composition, and cardiorespiratory fitness in this group of prepubertal boys.(AU)
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Humanos , Masculino , Niño , Consumo de Oxígeno/fisiología , Fútbol/fisiología , Composición Corporal , Índice de Masa Corporal , Sobrepeso , Obesidad Infantil , Ejercicio FísicoRESUMEN
OBJECTIVE: To estimate the 5-year incidence of progression rate and regression rate and risk factors for diabetic retinopathy (DR) in a cohort of Lebanese patients with type II diabetes. METHODS: We followed a cohort of 462 Lebanese patients with type II diabetes for over 5 years at the American University of Beirut Medical Center. Patients underwent yearly complete ophthalmic evaluation and fundus photographs and were assessed for the incidence, stage, and evolution of DR using modified Airlie House classification. RESULTS: Among the 462 patients, 281 had no DR at baseline. The 5-year cumulative incidence of any DR was 10% (95% CI: 6-13), and only baseline microalbuminuria correlated with the development of DR (OR = 10.53, 95% CI: 4.39-25.23, p < 0.0001). Among the 181 patients with baseline DR, the worsening and regression rates of DR were 31.5% (95% CI: 25-38) and 9% (95% CI: 5-13), respectively. Microalbuminuria also approached statistical significance as a risk factor for DR worsening (OR = 1.89, 95% CI: 0.97-3.70, p = 0.06). CONCLUSION: The 5-year incidence of DR in this hospital-based cohort is relatively low. Microalbuminuria was independently associated with the incidence and progression of the disease. We recommend to screen patients with type II diabetes for microalbuminuria as prognostic for the development and worsening of DR.
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BACKGROUND AND OBJECTIVE: Nonmydriatic fundus photography (FP) has been a suboptimal tool for detecting age-related macular degeneration (AMD) changes. This study sought to enhance the detection of AMD changes by combining nonmydriatic FP with nonmydriatic spectral-domain optical coherence tomography (SD-OCT). PATIENTS AND METHODS: The study population included 249 patients aged 65 years and older who were assessed for AMD changes using standard mydriatic biomicroscopic fundus examination. Each eye then underwent nonmydriatic FP in one session followed 1 week later with nonmydriatic FP coupled with nonmydriatic SD-OCT. Images were interpreted for detection of AMD changes, and findings were compared to the original mydriatic biomicroscopic examination. RESULTS: Nonmydriatic FP had 64% sensitivity, 97% specificity, and a kappa value of 0.67 in detecting AMD changes compared with the traditional mydriatic biomicroscopic examination. Combined nonmydriatic FP and nonmydriatic SD-OCT increased sensitivity to 91.5%, specificity to 98.6%, and kappa to 0.91. CONCLUSION: The addition of nonmydriatic SD-OCT to nonmydriatic FP enhances the detection of AMD changes.
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Técnicas de Diagnóstico Oftalmológico , Atrofia Geográfica/diagnóstico , Fotograbar , Retina/patología , Tomografía de Coherencia Óptica , Degeneración Macular Húmeda/diagnóstico , Anciano , Anciano de 80 o más Años , Reacciones Falso Negativas , Femenino , Humanos , Masculino , Midriáticos/administración & dosificación , Valor Predictivo de las Pruebas , Pupila/efectos de los fármacos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Biological fluid identification is an important facet of evidence examination in forensic laboratories worldwide. While identifying bodily fluids may provide insight into which downstream DNA methods to employ, these screening techniques consume a vital portion of the available evidence, are usually qualitative, and rely on visual interpretation. In contrast, qPCR yields information regarding the amount and proportion of amplifiable genetic material. In this study, dilution series of either semen or male saliva were prepared in either buffer or female blood. The samples were subjected to both lateral flow immunochromatographic test strips and qPCR analysis. Analytical figures of merit-including sensitivity, minimum distinguishable signal (MDS) and limit of detection (LOD)-were calculated and compared between methods. By applying the theory of the propagation of random errors, LODs were determined to be 0.05 µL of saliva for the RSID™ Saliva cards, 0.03 µL of saliva for Quantifiler(®) Duo, and 0.001 µL of semen for Quantifiler(®) Duo. In conclusion, quantitative PCR was deemed a viable and effective screening method for subsequent DNA profiling due to its stability in different matrices, sensitivity, and low limits of detection.
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Cromatografía de Afinidad/instrumentación , Dermatoglifia del ADN/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis Químico de la Sangre , Femenino , Humanos , Límite de Detección , Masculino , Microscopía , Saliva/química , Semen/química , Semen/citología , Proteínas de Secreción de la Vesícula Seminal/análisis , Espermatozoides/citología , alfa-Amilasas/análisisRESUMEN
OBJECTIVES: The objective of this study was to evaluate the effect of discussing retinal findings following nonmydriatic retinal imaging during an endocrinology visit on subsequent HbA1c in poorly controlled diabetic patients with diabetic retinopathy (DR). MATERIALS AND METHODS: During a visit to an endocrinologist, patients with DR and documented HbA1c ≥ 8.0% within the preceding month were assigned to either addition of nonmydriatic imaging and discussion of retinal findings or standard endocrinology evaluation alone. Ophthalmology care was otherwise the same in both groups. Changes in HbA1c were evaluated 3 months later. RESULTS: One hundred thirteen (94%) of the original 120 subjects completed the study. The mean HbA1c change in the retinal imaging group was a decline of 1.35%, whereas the control group had a 0.26% increase. Controlling for gender, age, duration of diabetes, presence of hypertension, and use of insulin, the difference between groups was significant (p<0.0003). CONCLUSIONS: Nonmydriatic imaging and discussion of retinal findings during an endocrinologist visit may contribute, at least in the short term, to improved glycemic control in patients with DR and elevated HbA1c.
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Retinopatía Diabética/diagnóstico , Endocrinología/métodos , Hemoglobina Glucada/análisis , Fotograbar/métodos , Retina/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Líbano , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVE: Nonmydriatic digital color imaging is rapidly gaining an important role in screening for diabetic retinopathy. However, it has yet to equal a dilated fundus examination or seven Early Treatment Diabetic Retinopathy Study field 35-mm photography. The authors therefore attempted to enhance efficacy and validity by adding two low-cost steps to the nonmydriatic digital image evaluation. PATIENTS AND METHODS: The fundi of 145 consecutive patients with diabetes mellitus were evaluated for diabetic retinopathy using two different nonmydriatic reading techniques: creating a red-free view (using digital filters) and looking at a stereo pair of each field taken. These methods were each compared to a mydriatic fundus examination. RESULTS: Although the first technique yielded views with sensitivities and specificities similar to what exists in the literature using this same technique, enhancing these photographs (second technique) yielded a statistically significant increase in sensitivity and specificity (P < .005). CONCLUSION: The authors recommend using both low-cost steps when screening for diabetic retinopathy through nonmydriatic digital color imaging.
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Retinopatía Diabética/diagnóstico , Técnicas de Diagnóstico Oftalmológico , Fotograbar/métodos , Retina/patología , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Midriáticos/administración & dosificación , Valor Predictivo de las Pruebas , Pupila/efectos de los fármacos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND AND PURPOSE: The loss of an extraocular muscle is an infrequent but serious complication of strabismus surgery. The purpose is to show that a tailored tongue of Tenon's capsule, 7.0 mm to 9.0 mm wide and 12.0 mm to 14.0 mm long, fashioned in the direction of a lost medial rectus muscle and attached at the site of its original insertion can restore full ocular movement in the direction of action of the muscle. CASE REPORT: Thisis a report of a patient who underwent re-shaping and attachment of Tenon's capsule to the original insertion of the medial rectus muscle that ruptured during attempted medial rectus recession for longstanding esotropia with medial rectus restriction. The procedure was done immediately following the loss and failure to retrieve the lost muscle. RESULTS: Residual large angle esotropia and good adduction were obtained postoperatively despite a severed and consecutively lost medial rectus muscle. CONCLUSION: A tongue of Tenon's capsule, attached at the original site of a lost extraocular rectus muscle in a young adult, works as a pseudo-tendon successfully restoring function in the direction of action of that muscle.
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Complicaciones Intraoperatorias , Trastornos de la Motilidad Ocular/cirugía , Músculos Oculomotores/cirugía , Tendones/cirugía , Cápsula de Tenon/cirugía , Adulto , Esotropía/cirugía , Movimientos Oculares/fisiología , Femenino , Humanos , Trastornos de la Motilidad Ocular/etiología , Músculos Oculomotores/patología , Rotura EspontáneaRESUMEN
OBJECTIVE: Our aim was to determine the prevalence and the risk factors for diabetic retinopathy (DR) in a cohort of type II diabetic patients in Lebanon. DESIGN: Prospective observational cohort study. PARTICIPANTS: Five hundred consecutive patients with type II diabetes mellitus followed at the American University of Beirut Medical Center diabetes clinic were enrolled in the study. METHODS: All patients 18 years or older with diabetes mellitus who did not have gestational diabetes and who were able to complete the laboratory data and the retinal examination were invited to participate in the study; they were followed up for a period of 3 years. RESULTS: DR was present in 175 patients (35%), 130 (26%), and 45 (9%) having nonproliferative and proliferative DR, respectively. Clinically significant macular edema was present in 42 patients (8%). Microvascular and macrovascular diabetic complications, duration of disease, glycemic control, presence of hypertension (p < 0.003), systolic blood pressure (p = 0.04), and insulin use (p < 0.001) were individually significantly associated with a higher prevalence of DR on bivariate analysis. However, on multivariate regression analysis, only glycosylated hemoglobin >7% (odds ratio [OR] 2.81, 95% CI 1.06-7.43, p = 0.038), duration of diabetes (per 10 years, OR 9.0, 95% CI 4.0-20.0, p < 0.001), macroalbuminuria (OR 2.6, 95% CI 1.14-5.96 p = 0.023), and systolic blood pressure (per 10 mm Hg, OR 1.27, 95% CI 1.0-1.56, p = 0.037) were independent risk factors for DR. CONCLUSIONS: The elevated prevalence of DR in type II diabetic patients with high risk profiles calls for early medical intervention and education about DR and its identified controllable risk factors.
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Diabetes Mellitus Tipo 2/epidemiología , Retinopatía Diabética/epidemiología , Hemoglobina Glucada/metabolismo , Medición de Riesgo/métodos , Intervalos de Confianza , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/sangre , Retinopatía Diabética/etiología , Femenino , Estudios de Seguimiento , Humanos , Líbano/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Estudios Prospectivos , Factores de RiesgoRESUMEN
BenM and CatM control transcription of a complex regulon for aromatic compound degradation. These Acinetobacter baylyi paralogues belong to the largest family of prokaryotic transcriptional regulators, the LysR-type proteins. Whereas BenM activates transcription synergistically in response to two effectors, benzoate and cis,cis-muconate, CatM responds only to cis,cis-muconate. Here, site-directed mutagenesis was used to determine the physiological significance of an unexpected benzoate-binding pocket in BenM discovered during structural studies. Residues in BenM were changed to match those of CatM in this hydrophobic pocket. Two BenM residues, R160 and Y293, were found to mediate the response to benzoate. Additionally, alteration of these residues caused benzoate to inhibit activation by cis,cis-muconate, positioned in a separate primary effector-binding site of BenM. The location of the primary site, in an interdomain cleft, is conserved in diverse LysR-type regulators. To improve understanding of this important family, additional regulatory mutants were analysed. The atomic-level structures were characterized of the effector-binding domains of variants that do not require inducers for activation, CatM(R156H) and BenM(R156H,T157S). These structures clearly resemble those of the wild-type proteins in their activated muconate-bound complexes. Amino acid replacements that enable activation without effectors reside at protein interfaces that may impact transcription through effects on oligomerization.
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Acinetobacter/genética , Proteínas Bacterianas/metabolismo , Factores de Transcripción/metabolismo , Activación Transcripcional , Acinetobacter/metabolismo , Sustitución de Aminoácidos , Proteínas Bacterianas/genética , Benzoatos/metabolismo , Sitios de Unión , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación Bacteriana de la Expresión Génica , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Estructura Terciaria de Proteína , Factores de Transcripción/genéticaRESUMEN
Impalement injuries to the head and neck are quite rare, commonly lethal, and vision threatening when involving the orbit. Here, a case of impalement injury involving a steel bar to the neck and left orbit with full visual recovery is presented. The bar was removed, leaving non-displaced fractures of the floor of the left orbit and ethmoid bone. The disinserted left medial rectus was resutured. The perforated upper eyelid was sutured. The patient ended with mild ptosis.
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LysR-type transcriptional regulators comprise the largest family of homologous regulatory DNA-binding proteins in bacteria. A problematic challenge in the crystallization of LysR-type regulators stems from the insolubility and precipitation difficulties encountered with high concentrations of the full-length versions of these proteins. A general oligomerization scheme is proposed for this protein family based on the structures of the effector-binding domain of BenM in two different space groups, P4(3)22 and C222(1). These structures used the same oligomerization scheme of dimer-dimer interactions as another LysR-type regulator, CbnR, the full-length structure of which is available [Muraoka et al. (2003), J. Mol. Biol. 328, 555-566]. Evaluation of packing relationships and surface features suggests that BenM can form infinite oligomeric arrays in crystals through these dimer-dimer interactions. By extrapolation to the liquid phase, such dimer-dimer interactions may contribute to the significant difficulty in crystallizing full-length members of this family. The oligomerization of dimeric units to form biologically important tetramers appears to leave unsatisfied oligomerization sites. Under conditions that favor association, such as neutral pH and concentrations appropriate for crystallization, higher order oligomerization could cause solubility problems with purified proteins. A detailed model by which BenM and other LysR-type transcriptional regulators may form these arrays is proposed.