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1.
J Neurogastroenterol Motil ; 29(4): 501-512, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37612234

RESUMO

Background/Aims: The evidence suggests that a shorter esophageal length (EL) in gastroesophageal reflux disease (GERD) patients is associated with the presence of hiatal hernia (HH). However, there are no reports of this association in patients with achalasia. The aim is to (1) determine the prevalence of hiatal hernia in achalasia patients, (2) compare achalasia EL with GERD patients and healthy volunteers (HV), (3) measure achalasia manometric esophageal length to height (MELH) ratio, and (4) determine if there are differences in symptoms between patients with and without hiatal hernia. Methods: This retrospective and cross-sectional study consist of 87 pre-surgical achalasia patients, 22 GERD patients, and 30 HV. High-resolution manometry (HRM), barium swallow, and upper endoscopy were performed to diagnose HH. The EL and MELH ratio were measured by HRM. Symptoms were assessed with Eckardt, Eating Assessment Tool, and GERD-health-related quality of life questionnaires. Results: The HH in GERD's prevalence was 73% vs 3% in achalasia patients (P < 0.001). Achalasia patients had a longer esophagus and a higher MELH ratio than HV and GERD patients (P < 0.001). GERD patients had a lower MELH ratio than HV (P < 0.05). EAT-10 (P < 0.0001) and Eckardt (P < 0.05) scores were higher in achalasia without HH vs HH. Conclusions: The prevalence of HH in achalasia is significantly lower than in GERD. The longer EL and the higher MELH ratio in achalasia could explain the lower prevalence of HH. Despite the low prevalence of HH in achalasia patients, the surgeon should be encouraged not to rule out HH since the risk of postoperative reflux may increase if this condition is not identified and corrected.

2.
Front Med (Lausanne) ; 9: 941581, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36314004

RESUMO

Background: Episodic angina-like retrosternal pain is a prevalent symptom for achalasia patients pre- and post-treatment. The cause of postoperative chest pain remains poorly understood. Moreover, there are no reports on their predictive value for chest pain in the long-term post-treatment. The effect of laparoscopic Heller myotomy (LHM) and fundoplication techniques (Dor vs. Toupet) is unclear. Methods: We analyzed a cohort of 129 achalasia cases treated with LHM and randomly assigned fundoplication technique. All the patients were diagnosed with achalasia by high-resolution manometry (HRM). Patients were followed up at 1-, 6-, 12-, and 24-month post-treatment. We implemented unadjusted and adjusted logistic regression analyses to evaluate the predictive significance of pre- and post-operative clinical factors. Results: Preoperative chest pain with every meal was associated with an increased risk of occasional postoperative chest pain [unadjusted model: odds ratio (OR) = 12, 95% CI: 2.2-63.9, P = 0.006; adjusted model: OR = 26, 95% CI: 2.6-259.1, P = 0.005]. In type II achalasia, hypercontraction was also associated with an increased risk of chest pain (unadjusted model: OR = 2.6 e9 in all the patients). No significant differences were associated with age, type of achalasia, dysphagia, esophageal shape, and integrated relaxation pressure (IRP) with an increased risk of occasional postoperative chest pain. Also, there was no significant difference between fundoplication techniques or surgical approaches (e.g., length of myotomy). Conclusion: Preoperative chest pain with every meal was associated with a higher risk of occasionally postoperative chest pain.

3.
Clin Transl Sci ; 15(10): 2403-2436, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35892315

RESUMO

Taxane-based chemotherapy regimens are used as first-line treatment for breast cancer. Neurotoxicity, mainly taxane-induced peripheral neuropathy (TIPN), remains the most important dose-limiting adverse event. Multiple genes may be associated with TIPN; however, the strength and direction of the association remain unclear. For this reason, we systematically reviewed observational studies of TIPN pharmacogenetic markers in breast cancer treatment. We conducted a systematic search of terms alluding to breast cancer, genetic markers, taxanes, and neurotoxicity in Ovid, ProQuest, PubMed, Scopus, Virtual Health, and Web of Science. We assessed the quality of evidence and bias profile. We extracted relevant variables and effect measures. Whenever possible, we performed random-effects gene meta-analyses and examined interstudy heterogeneity with meta-regression models and subgroup analyses. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and STrengthening the REporting of Genetic Association Studies (STREGA) reporting guidance. A total of 42 studies with 19,431 participants were included. These evaluated 262 single-nucleotide polymorphisms (SNPs) across 121 genes. We conducted meta-analyses on 23 genes with 60 SNPs (19 studies and 6246 participants). Thirteen individual SNPs (ABCB1-rs2032582, ABCB1-rs3213619, BCL6/-rs1903216, /CAND1-rs17781082, CYP1B1-rs1056836, CYP2C8-rs10509681, CYP2C8-rs11572080, EPHA5-rs7349683, EPHA6-rs301927, FZD3-rs7001034, GSTP1-rs1138272, TUBB2A-rs9501929, and XKR4-rs4737264) and the overall SNPs' effect in four genes (CYP3A4, EphA5, GSTP1, and SLCO1B1) were statistically significantly associated with TIPN through meta-analysis. In conclusion, through systematic review and meta-analysis, we found that polymorphisms, and particularly 13 SNPs, are associated with TIPN, suggesting that genetics does play a role in interindividual predisposition. Further studies could potentially use these findings to develop individual risk profiles and guide decision making.


Assuntos
Neoplasias da Mama , Síndromes Neurotóxicas , Doenças do Sistema Nervoso Periférico , Taxoides , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Citocromo P-450 CYP2C8/genética , Citocromo P-450 CYP3A/genética , Marcadores Genéticos , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Síndromes Neurotóxicas/genética , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/complicações , Farmacogenética , Polimorfismo de Nucleotídeo Único , Taxoides/efeitos adversos
5.
Clin Transplant ; 35(12): e14466, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34545965

RESUMO

BACKGROUND: The demand for transplantable kidneys continues to outstrip supply, and the risk of donor-derived infection limits utilization. The effect of donor or recipient HBV status, defined by surface antigen (HBsAg) positivity, on long-term survival outcomes of kidney transplant (KT) is unknown. METHODS: We conducted a retrospective cohort study based on Organ Procurement and Transplantation Network (OPTN) data from 2000 to 2019. We identified three cohorts based on donor (D) or recipient (R) HBsAg status: D-R, D-R+, and D+R-. Pairwise comparisons of patient survival (PS) and all-cause graft survival (GS) after propensity score matching were performed to assess the effect of HBV infection in KT recipients. RESULTS: Our findings showed that there were no statistically significant differences in PS and GS among D-R, D-R+, and D+R-groups, nor was the patient or GS different between donor and recipient HBsAg+ status. Finally, in 2019 kidney discard rates were 15% higher for HBsAg+ deceased donors compared to HBsAg- donors. CONCLUSIONS: HBsAg+ status was not associated with worse PS or GS after KT. Prior to broadly advocating utilization of HbsAg+ kidneys, further studies assessing KT recipient morbidity and safety are necessary.


Assuntos
Hepatite B , Transplante de Rim , Sobrevivência de Enxerto , Vírus da Hepatite B , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Doadores de Tecidos
6.
Case Rep Ophthalmol ; 11(2): 356-363, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884550

RESUMO

Sturge-Weber syndrome (SWS) is a rare, sporadic neurocutaneous disorder, primarily characterized by port-wine stain (PWS) over the ophthalmic division of the trigeminal nerve (V1) territory (hallmark feature) and glaucoma (in 30-60% of cases). Other ocular manifestations include episcleral involvement of the PWS, choroidal vascular malformations, and iris heterochromia. Two previous reports also associated ectopia lentis concomitantly among these cases. However, here we report spherophakia as a novel ophthalmological finding in SWS. A 56-year-old female previously diagnosed with SWS presented to the outpatient clinic complaining of right-sided decreased visual acuity and pain after a fall. Phenotypically, the patient had a PWS around V1 territory and involvement of both eyelids. Previous relevant ocular history included retinal detachment without macular involvement, ocular hypertension, and phacodonesis. The slit-lamp examination showed anterior lens luxation and elevated intraocular pressure (IOP) of 40 mm Hg by tonometry. Prior to the surgical approach, the patient received hypotensive treatment for elevated IOP. After intracapsular lens extraction, measurements were consistent with spherophakia. Postoperatively, the patient underwent optical coherence tomography (OCT). There was cystic macular edema (CME) by OCT and a detached posterior hyaloid membrane. The patient fully recovered with topical treatment of bromfenac for CME. To the best of our knowledge, this is the first report of concomitant anterior lens luxation and spherophakia (novel association) in a SWS patient. Our findings supplement the differential ocular diagnoses in SWS and should be considered in the routine ocular exam, specifically of the anterior segment. CME occurred similar to otherwise healthy eyes. However, in this case, topical anti-inflammatory medications had a good response and were well-tolerated.

7.
Ophthalmic Genet ; 41(6): 539-547, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32838591

RESUMO

BACKGROUND: CFH and HTRA1 are pivotal genes driving increased risk for age-related macular degeneration (AMD) among several populations. Here, we performed a hospital-based case-control study to evaluate the effects of three single nucleotide polymorphisms (SNPs) among Hispanics from Mexico. MATERIALS AND METHODS: 122 cases and 249 controls were genotyped using Taqman probes. Experienced ophthalmologists diagnosed AMD following the American Association of Ophthalmology guidelines. We studied CFH (rs1329428, rs203687) and HTRA1 (rs11200638) SNPs thoroughly by logistic regression models (assuming different modes of inheritance) and machine learning-based methods (ML). RESULTS: HTRA1 rs11200638 is the most significant polymorphism associated with AMD in our studied population. In a multivariate regression model adjusted for clinically and statistically meaningful covariates, the A/G and A/A genotypes increased the odds of disease by a factor of 2.32 and 7.81, respectively (P < .05) suggesting a multiplicative effect of the polymorphic A allele. Furthermore, this observation remains statistically meaningful in the allelic, dominant, and recessive models, and ML algorithms. When stratifying by phenotype, this polymorphism was significantly associated with increased odds for geographic atrophy (GA) in a recessive mode of inheritance (12.4, p < .05). CONCLUSIONS: In sum, this work supports a strong association between HTRA1 genetic variants and AMD in Hispanics from Mexico, especially with GA. Moreover, ML was able to replicate the results of conventional biostatistics methods unbiasedly.


Assuntos
Predisposição Genética para Doença , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Aprendizado de Máquina , Degeneração Macular/genética , Degeneração Macular/patologia , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Fator H do Complemento/genética , Etnicidade , Feminino , Humanos , Masculino , Fenótipo
8.
Adv Orthop ; 2020: 9398274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802520

RESUMO

OBJECTIVE: Polymerized-type I collagen (polymerized-collagen) is a downregulator of inflammation and a tissue regenerator. The aim was to evaluate the effect of intra-articular injections (IAIs) of polymerized-collagen among patients with symptomatic knee osteoarthritis (OA) in delaying or preventing joint replacement surgery. Patients and Methods. This was a cohort study of 309 patients with knee OA. Patients with mild-to-moderate disease were treated weekly with IAIs of 2 mL of polymerized-collagen for six weeks (n = 309). Follow-up was for 6-60 months. The primary endpoints included the following determinations: (1) therapeutic effect; (2) survival from total knee replacement surgery (TKR); (3) Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and pain (visual analogue scale, VAS). Clinical improvement was defined as a decrease in pain exceeding 20 mm on the VAS and the achievement of at least 20% improvement from baseline with respect to the WOMAC score. Radiographic analysis was performed at baseline and 60 months. The joint space width in the medial, lateral, and patellofemoral compartments was calculated. RESULTS: Patients who received IAIs of polymerized-collagen had a statistically significant improvement in the primary criteria (p < 0.05). Kaplan-Meier survival analysis of the therapeutic effect demonstrated 98.8% survival at 60 months with TKR as the endpoint. There was no significant reduction in joint space in any compartment based on the analyzed radiographs. No serious adverse events were recorded. CONCLUSION: Polymerized-collagen increased the time to TKR by at least 60 months, modifying the disease course, improving functional disability, and decreasing pain.

9.
Neurogastroenterol Motil ; 32(10): e13921, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32557989

RESUMO

BACKGROUND: It is unknown whether surgically treated achalasia cases regain or surpass their usual weight into obesity or overweight in the long-term post-operative period. Here, we aimed to assess the incidence of overweight/obesity (Ob/Ow) and the risk for reoccurrence up to 48 months post-laparoscopic Heller myotomy (LHM). METHODS: We performed a cohort of 114 achalasia cases undergoing LHM. All patients had a confirmed diagnosis of achalasia and had no added comorbidities. We followed up the body mass index (BMI) at the immediate post-operative period, and at one-, six-, 12-, 24-, and 48 months after LHM. We measured the incidence of Ob/Ow and its reoccurrence risk with Cox regression. KEY RESULTS AND CONCLUSIONS: In the immediate post-operative period, the incidence of Ob/Ow was significantly less than the usual BMI (before the onset of symptoms) (28.2% vs 66.3%). From the sixth to the 48th month, there was a progressive increase in the incidence of Ob/Ow and at this timepoint the percent of Ob/Ow was not statistically different from the usual BMI. The most significant hazard for Ob/Ow reoccurrence in the long term following LHM is a usual BMI with obesity grade I or III and males lacking pre-surgical weight loss. INFERENCES: Achalasia cases undergoing surgical treatment should be monitored closely in the post-operative period for weight regain, regardless of their pre-operative BMI. Notably, males who before the onset of symptoms were obese or overweight are at significantly increased risk of regaining or surpassing their weight, despite most having lost weight pre-surgically.


Assuntos
Trajetória do Peso do Corpo , Acalasia Esofágica/fisiopatologia , Acalasia Esofágica/cirurgia , Miotomia de Heller/tendências , Sobrepeso/fisiopatologia , Cuidados Pós-Operatórios/tendências , Adulto , Estudos de Coortes , Acalasia Esofágica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/fisiopatologia , Sobrepeso/diagnóstico , Fatores de Risco , Fatores de Tempo
10.
J Am Coll Surg ; 230(6): 853-861.e3, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32035979

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection has been deemed detrimental to kidney transplantation (KT) outcomes. Breakthrough HCV treatment with direct-acting antiviral (DAA) medications improved the probability of HCV+ kidney use for KT even in noninfected (HCV-) recipients. We hypothesized that recipient HCV infection influences deceased donor KT outcomes, and this effect could be modified by donor HCV status and use of DAAs. STUDY DESIGN: We conducted a retrospective cohort study based on data from the Organ Procurement and Transplantation Network as of September 2018. A mate kidneys analysis was performed with HCV+ and HCV- recipients of solitary adult KT from ABO-compatible deceased donor between January 1994 and June 2018. We selected donors where 1 KT recipient was HCV+ and the mate kidney recipient was HCV-. Both HCV- and HCV+ donors were identified and analyzed separately. Outcomes, including survival of patients, grafts, and death-censored grafts, were compared between the groups. RESULTS: Four-hundred and twenty-five HCV+ and 5,575 HCV- donor mate kidneys were transplanted in HCV-discrepant recipients. HCV+ recipients of HCV- donor had worse patient and graft survival (adjusted hazard ratio 1.28; 95% CI, 1.19 to 1.37 and adjusted hazard ratio 1.26; 95% CI 1.18 to 1.34, respectively) and death-censored grafts (adjusted hazard ratio 1.24; 95% CI, 1.15 to 1.34) compared with HCV- recipients. Comparable patient and graft survival and death-censored grafts were found in recipients of HCV+ donors, regardless of recipient HCV status. The risk associated with HCV positivity in donors or recipients in the pre-DAA era (before December 2013) was no longer statistically significant in the post-DAA era. CONCLUSIONS: Given comparable outcomes between HCV+ and HCV- recipients in post-DAA era or when receiving HCV+ donor kidneys, broader use of HCV+ kidneys regardless of the recipient's HCV status should be advocated, and allocation algorithm for HCV+ kidneys should be revised.


Assuntos
Seleção do Doador , Hepatite C/complicações , Nefropatias/cirurgia , Nefropatias/virologia , Transplante de Rim , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , Sobrevivência de Enxerto , Hepatite C/diagnóstico , Humanos , Nefropatias/mortalidade , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos
11.
Case Rep Ophthalmol ; 11(1): 1-7, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32009932

RESUMO

47, XYY syndrome affects males with variable phenotypic expression. Around 80-99% of affected individuals present low-set ears, malar flattening, motor delay, and tall stature. Yet, some cases lack signs or symptoms or are barely noticeable. There are four reports of ocular involvement among these individuals - one with unusual multiple retinal atrophic holes in the posterior pole, other with coloboma, an association with morning glory syndrome, and a case of congenital cataract. Here, we describe a plausible new ocular sign in a 4-year-old male with 47, XYY syndrome who was brought to the outpatient clinic for vision loss. After a complete assessment, we diagnosed a right-sided phacomorphic glaucoma and microspherophakia treated with phacoemulsification and aspiration with posterior capsulotomy and anterior vitrectomy, followed by an Ahmed valve implant for intraocular pressure control. Even though there is a low prevalence of ocular involvement in 47, XYY syndrome cases, this might reflect the rarity of the full expression of the disease leading to an underdiagnosis, added to the scarcity of cases. Microspherophakia and phacomorphic glaucoma among four others previously reported ocular findings could be looked for in 47, XYY syndrome patients.

12.
Int J Mol Sci ; 20(21)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31689918

RESUMO

Age-related macular degeneration (AMD) is the leading cause of central vision loss and severe blindness among the elderly population. Recently, we reported on the association of the SGCD gene (encoding for δ-sarcoglycan) polymorphisms with AMD. However, the functional consequence of Sgcd alterations in retinal degeneration is not known. Herein, we characterized changes in the retina of the Sgcd knocked-out mouse (KO, Sgcd-/-). At baseline, we analyzed the retina structure of three-month-old wild-type (WT, Sgcd+/+) and Sgcd-/- mice by hematoxylin and eosin (H&E) staining, assessed the Sgcd-protein complex (α-, ß-, γ-, and ε-sarcoglycan, and sarcospan) by immunofluorescence (IF) and Western blot (WB), and performed electroretinography. Compared to the WT, Sgcd-/- mice are five times more likely to have retinal ruptures. Additionally, all the retinal layers are significantly thinner, more so in the inner plexiform layer (IPL). In addition, the number of nuclei in the KO versus the WT is ever so slightly increased. WT mice express Sgcd-protein partners in specific retinal layers, and as expected, KO mice have decreased or no protein expression, with a significant increase in the α subunit. At three months of age, there were no significant differences in the scotopic electroretinographic responses, regarding both a- and b-waves. According to our data, Sgcd-/- has a phenotype that is compatible with retinal degeneration.


Assuntos
Degeneração Retiniana/genética , Sarcoglicanas/genética , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Retina/metabolismo , Retina/patologia , Sarcoglicanas/metabolismo
13.
PLoS One ; 13(12): e0209488, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30589882

RESUMO

INTRODUCTION: In this study we developed the Disability Beliefs Scale to assess Veterans' beliefs that engaging in treatment, as well as other behaviors, would affect the likelihood of a Veteran's being awarded disability-related benefits. We posited that Veterans with stronger beliefs that attending mental health treatment would facilitate a service-connection award would be more likely to attend PTSD treatment before their compensation and pension examinations for PTSD. METHODS: Electronic health records for 307 post-9/11-era Veterans applying for compensation and pension for service-connected PTSD and engaging in a clinical trial of a treatment-referral intervention were analyzed for PTSD-specific and more general mental health treatment use around the time of their compensation examinations. All participants completed the Disability Beliefs Scale and other baseline assessments. Multilevel models assessed change in treatment use as a function of time relative to the C&P exam, compensation examination status (before or after), and the interaction between examination status and beliefs about treatment benefits. RESULTS: No main effects of time or examination status were observed. As hypothesized, beliefs about treatment benefits moderated the effect of examination status on PTSD treatment use. Veterans believing more strongly that mental health treatment would help a claim differentially attended PTSD treatment before the examination than after. The effect was not observed for general mental health treatment use. CONCLUSION: The association between Veterans' use of PTSD treatment and their service-connection examination status was moderated by beliefs that receiving treatment affects the service-connection decision. This suggests that factors reported to motivate seeking service-connection-finances, validation of Veterans' experiences, and the involvement of significant others-might also help motivate Veterans' use of effective PTSD treatments. However, the results reflect correlations that could be explained in other ways, and service-connection was one of many factors impacting PTSD treatment engagement.


Assuntos
Compensação e Reparação , Pensões/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/terapia , Ajuda a Veteranos de Guerra com Deficiência , Veteranos/psicologia , Adulto , Cultura , Avaliação da Deficiência , Pessoas com Deficiência/psicologia , Pessoas com Deficiência/estatística & dados numéricos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Masculino , Saúde Mental/economia , Saúde Mental/estatística & dados numéricos , Psicometria , Transtornos de Estresse Pós-Traumáticos/economia , Transtornos de Estresse Pós-Traumáticos/psicologia , Fatores de Tempo , Estados Unidos , United States Department of Veterans Affairs/economia , United States Department of Veterans Affairs/estatística & dados numéricos
14.
Genes (Basel) ; 9(10)2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30257524

RESUMO

CFH and HTRA1 genes are traditional markers of increased risk of age-related macular degeneration (AMD) across populations. Recent findings suggest that additional genes-for instance, in the dystrophin-associated protein complex-might be promising markers for AMD. Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of an under-studied population from Hispanics in Mexico City, with 134 cases with 134 unpaired controls. Cases were 60 years or older (Clinical Age-Related Maculopathy Staging (CARMS) grade 4⁻5, as assessed by experienced ophthalmologists following the American Association of Ophthalmology (AAO) guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or retinal pigment epithelium (RPE) changes on a fundus exam and a negative family history of AMD. We examined SNPs in the SGCD gene (rs931798, rs140617, rs140616, and rs970476) by sequencing and real-time PCR. Genotyping quality checks and univariate analyses were performed with PLINK v1.90b3.42. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% of cases (1.81; 95% CI 1.06⁻3.14; p = 0.031), especially the geographic atrophy phenotype (1.82; 95% CI 1.03⁻3.21; p = 0.038) compared to the G/G homozygous genotype. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (adjusted odds ratio (OR) 0.13; 95% CI 0.02⁻0.91; p = 0.041). SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted, especially among other Hispanic ethnicities.

15.
Neurosci Lett ; 658: 142-149, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-28855126

RESUMO

INTRODUCTION: Multiple components of the dystrophin-associated protein complex (DAPC) are expressed in numerous tissues including the brain. Members of the DAPC and dysbindin are abnormally expressed in the brain of Duchenne Muscular Dystrophy (DMD) patients, which has been associated with cognitive impairments. However, little is known about the expression pattern of individual members of the DAPC in animal models of DMD and their relationship with dysbindin. METHODS: Ten mdx mice were randomly allocated into a control and intervention group [(-)-epicatechin (Epi) 1mg/kg/day for four weeks] and results compared to a wild-type mice. After sacrifice, brain pre-frontal cortices were collected for Western blotting and immunoprecipitation assays, and sagittal sections processed for immunohistochemistry. RESULTS: Epi promotes a partial recovery of DAPC members [α1-Syntrophin, sarcoglycans (SG), dystrophin 71 (Dp71)], dysbindin, and utrophin protein levels. Epi also appears to restore the association of DAPC between dysbindin, and utrophin with Dp71 and ε-SG. Co-immunostaining evidence increased protein levels of dysbindin, dystrophin, and ε-SG and their colocalization. CONCLUSIONS: Altogether, results suggest that Epi is capable of restoring pre-frontal cortex DAPC and dysbindin levels of mdx mice towards that of healthy brains. The functional implications of such studies warrant further investigation.


Assuntos
Catequina/genética , Disbindina/metabolismo , Complexo de Proteínas Associadas Distrofina/metabolismo , Lobo Frontal/metabolismo , Distrofia Muscular de Duchenne/metabolismo , Animais , Distrofina/metabolismo , Camundongos Endogâmicos mdx , Utrofina/metabolismo
16.
Oncotarget ; 8(63): 106454-106467, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29290962

RESUMO

Locally advanced breast cancer (LABC) cases have a varying five-year survival rate, mainly influenced by the tumor response to chemotherapy. Paclitaxel activity (response rate) varies across populations from 21.5% to 84%. There are some reports on genetic traits and paclitaxel; however, there is still considerable residual unexplained variability. In this study, we aimed to test the association between eleven novel markers and tumor response to paclitaxel and to explore if any of them influenced tumor protein expression. We studied a cohort of 140 women with LABC. At baseline, we collected a blood sample (for genotyping), fine needle aspirates (for Western blot), and tumor measurements by imaging. After follow-up, we ascertained the response to paclitaxel monotherapy by comparing the percent change in the pre-, post- tumor measurements after treatment. To allocate exposure, we genotyped eleven SNPs with TaqMan probes on RT-PCR and regressed them to tumor response using linear modeling. In addition, we compared protein expression, between breast tumors and healthy controls, of those genes whose genetic markers were significantly associated with tumor response. After adjusting for multiple clinical covariates, SNPs on the LPHN2, ROBO1, SNTG1, and GRIK1 genes were significant independent predictors of poor tumor response (tumor growth) despite paclitaxel treatment. Moreover, proteins encoded by those genes are significantly downregulated in breast tumor samples.

17.
Cir Cir ; 80(5): 462-5, 2012.
Artigo em Espanhol | MEDLINE | ID: mdl-23351453

RESUMO

BACKGROUND: Mucormycosis are opportunistic infections with high morbidity and mortality caused by fungi of the class Zygomycetes, they mainly affect diabetic and immunocompromised patients. In up to 20% of all cases the main infection is localized in the skin, with a great number of them presenting in healthy patients that have suffered from severe trauma or burns. Zygomycetes tend to invade arteries, which leads to thrombosis and generates wide necrotic areas; this favors the progress of the infection and invasion of deep tissues. Up to 24% of primary cutaneous mucormycosis can be complicated with necrotizing fasciitis. CLINICAL CASE: We present the case of a 52 year-old male that received the clinical diagnosis of necrotizing fasciitis. The patient received wide spectrum antibiotics and was submitted to extensive debridement of the wound bed; transoperative biopsy revealed the presence of zygomycetes in the tissues and the diagnosis of primary cutaneous zygomycosis was made. Antifungal treatment with amphotericin B was initiated and two weeks later autologous skin grafts were applied over the wounds. CONCLUSION: A high index of suspicion is needed to diagnose cutaneous zygomycosis, therefore it should always be considered amongst the differentials of necrotic wounds that do not respond to standard treatment. The rapid evolution of the disease remarks the importance of biopsying the wound bed early and treating aggressively.


Assuntos
Fasciite Necrosante/etiologia , Mucormicose/complicações , Acidentes de Trânsito , Anfotericina B/uso terapêutico , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Biópsia , Terapia Combinada , Desbridamento , Diabetes Mellitus Tipo 2/complicações , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/tratamento farmacológico , Fasciite Necrosante/cirurgia , Humanos , Hipertensão/complicações , Traumatismos da Perna/complicações , Úlcera da Perna/etiologia , Úlcera da Perna/microbiologia , Masculino , Pessoa de Meia-Idade , Mucormicose/microbiologia , Fatores de Risco , Transplante de Pele , Fumar , Infecção dos Ferimentos/etiologia , Infecção dos Ferimentos/microbiologia
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