Long-term tafamidis efficacy in patients with transthyretin amyloid cardiomyopathy by baseline left ventricular ejection fraction.

AIMS: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) present with diverse left ventricular ejection fraction (LVEF). This study assessed tafamidis efficacy by baseline LVEF in the phase 3 Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and its long-term extension (LTE) study. METHODS AND RESULTS: Patients were randomized to 30 months of tafamidis or placebo treatment in ATTR-ACT. On completion, patients could join an LTE study to receive tafamidis. All-cause mortality (death, heart transplant, or cardiac mechanical assist device implantation) from baseline to the end of follow-up was assessed in patients continuously treated with tafamidis (80 mg meglumine or 61 mg free acid) or delayed tafamidis treatment (placebo in ATTR-ACT; tafamidis in the LTE study) according to baseline LVEF (<50% or ≥50%). Supportive outcomes were evaluated over a shorter follow-up. Patients with baseline LVEF <50% (n = 177: 88 tafamidis- and 89 placebo-treated) had signs of more severe heart failure, a higher proportion were Black, and had variant ATTR-CM than those with LVEF ≥50% (n = 171: 85 tafamidis- and 86 placebo-treated). At the end of follow-up (median 60-64 months), all-cause mortality was numerically higher in patients with baseline LVEF <50%; however, consistent with supportive findings, continuous tafamidis treatment was associated with a 47% reduction in mortality risk compared with delayed tafamidis treatment in patients with LVEF <50% and ≥50% (hazard ratio 0.53 [95% confidence interval 0.367-0.758]; p < 0.001, and 0.53 [0.344-0.818]; p < 0.01, respectively). CONCLUSIONS: Early initiation of tafamidis is associated with reduced mortality in patients with ATTR-CM, irrespective of initial LVEF value. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01994889, NCT02791230.

Long-term effectiveness of ARRY-371797 in people with dilated cardiomyopathy and a faulty LMNA gene: a plain language summary.

WHAT IS THIS PLAIN LANGUAGE SUMMARY ABOUT?: This summary explains the results of a long-term extension study on the effects of a specific medicine. A long-term extension study allows people who have already completed a research study to continue taking treatment. Researchers can then look at how a treatment works over a long period of time. This extension study looked at the effects of a medicine called ARRY-371797 (also known as PF-07265803) in people with dilated cardiomyopathy (DCM for short) caused by a faulty lamin A/C gene (also known as the LMNA gene). This condition is called LMNA-related DCM. In people with LMNA-related DCM, the heart muscle becomes thinner and weaker than normal. This can lead to heart failure, where the heart is unable to pump enough blood around the body. The extension study allowed people who had completed an earlier 48-week study to continue taking ARRY-371797 for another 96 weeks (around 22 months). WHAT WERE THE RESULTS OF THE EXTENSION STUDY?: 8 people joined the extension study and continued with the dose of ARRY-371797 that they had taken in the first study. This means that people could have taken ARRY-371797 continuously for up to 144 weeks (around 2 years and 9 months). Using the 6-minute walk test (6MWT for short), researchers regularly checked people taking ARRY-371797 to see how far they could walk. Throughout the extension study, people were able to walk further than they could before they started taking ARRY-371797. This suggests that people could maintain the improvements in their ability to do daily activities with long-term ARRY-371797 treatment. Researchers also looked at how severe people's heart failure was by using a test that measures levels of a biomarker called NT-proBNP. A biomarker is something found in the body that can be measured to indicate the extent of a disease. Throughout this study, the levels of NT-proBNP in people's blood was lower than before they started taking ARRY-371797. This suggests that they maintained stable heart function. Using the Kansas City Cardiomyopathy Questionnaire (KCCQ for short), researchers asked people about their quality of life, and if they experienced any side effects. A side effect is something that people feel while taking a treatment. Researchers evaluate if a side effect is related to the treatment or not. Some improvement in KCCQ response during the study was seen, although results were varied. There were no serious side effects that were considered related to treatment with ARRY-371797. WHAT DO THE RESULTS OF THE EXTENSION STUDY MEAN?: Researchers found that the improvements in functional capacity and heart function seen with ARRY-371797 treatment in the original study were maintained with long-term treatment. Larger studies are needed to determine if ARRY-371797 could be an effective treatment for people with LMNA-related DCM. One such study (called REALM-DCM) was started in 2018 but ended early, as it was unlikely to show a clear treatment benefit of ARRY-371797. Phase 2 long-term extension study (NCT02351856) Phase 2 study (NCT02057341) Phase 3 REALM-DCM study (NCT03439514).

Development of the HIV360 international core set of outcome measures for adults living with HIV: A consensus process.

OBJECTIVES: HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care. METHODS: An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice. RESULTS: From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years. CONCLUSIONS: Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.

Pectoral placement of tissue expanders affects inpatient opioid use.

Prepectoral breast reconstruction promises to minimize breast animation deformity and decrease pain associated with subpectoral dissection and tissue expansion. This latter benefit is particularly timely given the ongoing opioid epidemic; however, this theoretical benefit remains to be demonstrated clinically. As such, this study aimed to compare inpatient opioid use and prescription practices following prepectoral and subpectoral expander-based breast reconstruction. A retrospective review was performed of patients undergoing immediate tissue expander placement between January 2017 and April 2018. Medical records were reviewed for surgical details, 24-hour inpatient PRN opioid usage (oral morphine equivalents [OME]), and discharge prescriptions. Comparisons were made using chi-squared and student's t tests where appropriate. Two hundred and thirty-one patients were identified, (mean age 48.8 years), 222 of which met inclusion criteria. 89 underwent subpectoral and 133 prepectoral tissue expander placements. All but two subpectoral patients and two prepectoral patients were opioid-naïve. The rate of bilateral procedures did not differ between cohorts (P = .194). Overall, 94% of patients were discharged within 24 hours, and length of stay did not differ between cohorts (P = .0753). Two subpectoral and two prepectoral patients required prolonged admission due to postoperative pain. All patients were ordered standing acetaminophen, celecoxib, and gabapentin, and subpectoral patients cyclobenzaprine. Narcotic pain medication was offered on an "as needed" (PRN) basis. Opioid usage within the first 24-hours was halved in the prepectoral cohort (22.2 vs 44.5 OME, P = .0003), which was not associated with bi/unilaterality of procedure or the presence of any psychiatric conditions. The amount of opioids prescribed on discharge was not significantly different between cohorts (308.42 OME prepectoral vs 336.99 subpectoral, P = .3197). Prepectoral expander placement appears to be associated with decreased inpatient opioid use postoperatively. This may represent an opportunity to improve patient satisfaction and safety by decreasing outpatient opioid prescriptions.

Prepectoral 2-stage Breast Reconstruction with Carbon Dioxide Tissue Expansion.

Roughly 80% of patients undergoing mastectomy in the United States opt for reconstruction with implants. The introduction of acellular dermal matrices has allowed for placement of breast prostheses in the prepectoral plane, while a new carbon dioxide tissue expander (TE) (AeroForm) allows for needle-free, patient-controlled expansion. These 2 novel technologies have ushered in a new patient-centered era of breast reconstruction, with the possibility of reducing patient morbidity for the first time in decades. We hypothesize that AeroForm expanders placed in the prepectoral plane reduce time to second-stage reconstruction, reduce the number of clinic visits, and have lower complications than traditional saline TEs. METHODS: This is a retrospective review of all patients undergoing breast mastectomy and TE placement in the prepectoral plane over a 21-month period (169 patients, 267 breasts), comparing AeroForm expanders to TEs. RESULTS: The AeroForm group (n = 57) had a shorter period to second-stage reconstruction than the TE group (n = 210) (135.4 versus 181.7 days; P = 0.01) and required fewer clinic visits (5.1 versus 6.9; P < 0.01). Partial thickness (25.6% versus 12.3%, P = 0.03) and full thickness (8.7% versus 0.0%, P = 0.02) necrosis were more common in the saline cohort. The rates of infection, hematoma, and seroma requiring drainage were not statistically significant between the 2 groups. CONCLUSIONS: Two-staged breast reconstruction with the use of AeroForm expanders in the prepectoral space marks progress in improving care for breast cancer patients by demonstrating a reduction in some adverse events, the number of clinic visits, and the time to second-stage reconstruction.

TNF-α inhibition decreases MMP-2 activity, reactive oxygen species formation and improves hypertensive vascular hypertrophy independent of its effects on blood pressure.

Systemic arterial hypertension is a public health problem associated with an increased risk of cardiovascular disease. Matrix metalloproteinases (MMP) are endopeptidases that participate in hypertension-induced cardiovascular remodeling, which may be activated by oxidative stress. Angiotensin II (Ang II), a potent hypertrophic and vasoconstrictor peptide, increases oxidative stress, MMP-2 activity and tumor necrosis factor (TNF-α) expression. In vitro studies have shown that TNF-α is essential for Ang II-induced MMP-2 expression. Thus, this study evaluated whetherTNF-α inhibition decreases the development of hypertension-induced vascular remodeling via reduction of MMP-2 activity and reactive oxygen species (ROS) formation. Two distinct pharmacological approaches were used in the present study: Pentoxifylline (PTX), a non-selective inhibitor of phosphodiesterases that exerts anti- inflammatory effects via inhibition of TNF-α, and Etanercept (ETN), a selective TNF-α inhibitor. 2-kidney and 1-Clip (2K1C). 2-kidney and 1-Clip (2K1C) and Sham rats were treated with Vehicle, PTX (50 mg/Kg and 100 mg/kg daily) or ETN (0.3 mg/Kg and 1 mg/kg; three times per week). Systolic blood pressure (SBP) was measured weekly by tail cuff plethysmography. Plasma TNF-α and IL-1ß levels were evaluated by enzyme-linked immunosorbent assay (ELISA) technique. The vascular hypertrophy was examined in the aorta sections stained with hematoxylin/eosin. ROS in aortas was evaluated by dihydroethidium and chemiluminescence lucigenin assay. Aortic MMP-2 levels and activity were evaluated by gel zymography and in situ zymography, respectively. The 2K1C animals showed a progressive increase in SBP levels and was accompanied by significant vascular hypertrophy (p < 0.05 vs Sham). Treatment with PTX at higher doses decreased SBP and vascular remodeling in 2K1C animals (p < 0.05 vs 2K1C vehicle). Although the highest dose of ETN treatment did not reduce blood pressure, the vascular hypertrophy was significantly attenuated in 2K1C animals treated with ETN1 (p < 0.05). The increased cytokine levels and ROS formation were reversed by the highest doses of both PTX and ETN. The increase in MMP-2 levels and activity in 2K1C animals were reduced by PTX100 and ETN1 treatments (p < 0.05 vs vehicle 2K1C). Lower doses of PTX and ETN did not affect any of the evaluated parameters in this study, except for a small reduction in TNF-α levels. The findings of the present study suggest that PTX and ETN treatment exerts immunomodulatory effects, blunted excessive ROS formation, and decreased renovascular hypertension-induced MMP-2 up-regulation, leading to improvement ofvascular remodeling typically found in 2K1C hypertension. Therefore, strategies using anti-hypertensive drugs in combination with TNF alpha inhibitors could be an attractive therapeutic approach to tackle hypertension and its associated vascular remodeling.

Classification of breast tissue expander infections: Back to the basics.

BACKGROUND: Infections following tissue expander (TE) placement are frequent complications in breast reconstruction. While breast surgery is a clean case, implant-based breast reconstruction has rates of infection up to 31%, decidedly higher than the typical 1% to 2% rate of surgical site infections (SSI). Few authors use the Center for Disease Control's (CDC) SSI definition for TE infections. We highlight how adoption of a consistent definition of TE infection may change how infections are researched, categorized, and ultimately managed. METHODS: Two researchers with definitional discrepancies of infection performed an independent analysis of all postmastectomy patients receiving TEs (n = 175) in 2017. RESULTS: Researcher One, using a clinical definition, delineated an infection rate of 19.4%. Antibiotics alone successfully treated 50% of cases. Researcher Two found an infection rate of 13.7% using CDC criteria. These infections were further delineated by a SSI rate of 6.3% and a TE infection rate post port access of 7.4%. Only 45.5% SSI's and 15.4% of TE infections were salvaged with antibiotics alone. CONCLUSIONS: Rigorous adoption of CDC criteria for infection characterization in published research will help standardize the definition of infection and allow surgeons to create evidence-based infection prevention regimens.

Epidemiology and Outcomes of Auricular Burn Injuries.

Auricular burns represent a unique type of injury. The acute management and clinical course of these injuries can be different from other facial burns. There is a paucity of literature pertaining to the epidemiology and acute management of auricular burns. Most studies focus on deformity reconstruction. The aim of this study was to characterize the epidemiology, treatment, and outcomes of auricular burns. Data from all patients presenting to a regional burn center in a 4-year period were reviewed and those with auricular burns were identified. Demographic data, burn mechanism, insurance status, method of treatment, need for skin grafting, percentage graft-take, time to reepithelialization and incidence of deformity were reviewed. During the study period, 593 facial burns were evaluated and 132 (22%) sustained burns to the auricle. The most common mechanisms of injury were flame (65.1%) and scalding (22.5%). Auricular burns were mostly second degree (88%), involved both ears in 44%, and involved only the ventral aspect of the ear in 57%. The majority of patients healed well with conservative management; none suffered from chondritis. Of the 89 patients followed to healing, 1 patient (1.1%) received full-thickness skin grafts to the auricle, resulting in excellent graft-take. All other patients were managed nonoperatively, and none suffered from ear deformities. Auricular burns occur with surprising frequency in patients presenting to burn centers. Careful acute management of these injuries can eliminate development of chondritis and minimize the rate of deformity and need for reconstruction. The majority of wounds heal with conservative management, but time to reepithelialization can be prolonged.

The Impact of Body Contouring Procedures on Urologic Outcomes in Massive Weight Loss Patients.

BACKGROUND: Post-massive weight loss body contouring is a growing area of plastic surgery. Studies have shown preexisting urinary incontinence amelioration in patients undergoing abdominal body-contouring procedures. These studies are small, focus on cosmetic abdominoplasties, and lack use of standardized surveys. The purpose of this study was to evaluate urinary incontinence endpoints in massive weight loss patients undergoing body-contouring procedures. METHODS: A retrospective review was conducted over a 6-year period. Patients excluded had previous body-contouring procedures or previously treated urinary incontinence. Participants completed validated surveys to catalogue preoperative and postoperative urinary habits. Patients were then subdivided based on presence of preoperative incontinence. Outcomes were compared within and between cohorts using the t test and chi-square test. RESULTS: A total of 102 patients completed the survey. Of those, 44 had preoperative urinary incontinence. Patients with incontinence were found to be significantly older than those who did not. Postoperatively, patients with preoperative incontinence had significant decreases in incidence and severity of symptoms (p < 0.01, respectively), and significantly improved their quality of life (p < 0.02). Over 20 percent noted symptom resolution, and 67 percent were mostly or completely satisfied with the outcome. CONCLUSIONS: This study is the first to document amelioration of urinary incontinence symptoms in massive weight loss patients undergoing body-contouring procedures. It adds to the literature suggesting that abdominoplasties in select patients may improve incontinence symptoms. Future work will focus on evaluating the mechanism of this outcome and documenting improvement in an objective, prospective manner. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Lippia origanoides essential oil: an efficient and safe alternative to preserve food, cosmetic and pharmaceutical products.

AIMS: The aim of this work was to evaluate the efficacy and safety of Lippia origanoides essential oil as a preservative in industrial products. METHODS AND RESULTS: The composition, antimicrobial activity, mutagenic and toxic potential of L. origanoides were determined. Then, the effect of essential oil as a preservative in food, cosmetics and pharmaceutical products was evaluated. The essential oil of L. origanoides consisted mainly of oxygenated monoterpenes (38·13%); 26·28% corresponded to the compound carvacrol. At concentrations ranging from 0·312 to 1·25 µl ml-1 and in association with polysorbate 80, the essential oil of L. origanoides inhibited the growth of all the tested micro-organisms. The medium lethal dose in mice was 3·5 g kg-1 , which categorizes it as nontoxic according to the European Union criteria, and negative results in the Ames test indicated that this oil was not mutagenic. In combination with polysorbate 80, the essential oil exerted preservative action on orange juice, cosmetic and pharmaceutical compositions, especially in the case of aqueous-based products. CONCLUSIONS: Lippia origanoides essential oil is an effective and safe preservative for orange juice, pharmaceutical and cosmetic products. SIGNIFICANCE AND IMPACT OF THE STUDY: This study allowed for the complete understanding of the antimicrobial action and toxicological potential of L. origanoides essential oil. These results facilitate the development of a preservative system based on L. origanoides essential oil.

Genetic diversity analysis of Croton antisyphiliticus Mart. using AFLP molecular markers.

Croton antisyphiliticus Mart. is a medicinal plant native to Cerrado vegetation in Brazil, and it is popularly used to treat urogenital tract infections. The objective of the present study was to assess the genetic variability of natural C. antisyphiliticus populations using AFLP molecular markers. Accessions were collected in the states of Minas Gerais, São Paulo, and Goiás. The genotyping of individuals was performed using a LI-COR® DNA Analyzer 4300. The variability within populations was found to be greater than the variability between them. The F(ST) value was 0.3830, which indicated that the populations were highly structured. A higher percentage of polymorphic loci (92.16%) and greater genetic diversity were found in the population accessions from Pratinha-MG. Gene flow was considered restricted (N(m) = 1.18), and there was no correlation between genetic and geographic distances. The populations of C. antisyphiliticus exhibited an island-model structure, which demonstrates the vulnerability of the species.

Improving plant transformation using Agrobacterium tumefaciens.

Here, we report a quick and low-cost method to improve plant transformation using Agrobacterium tumefaciens. This method involves the use of physical wounding, ultrasound, and an increase in exposure time to the bacteria. We show how the transformation rate increased from 0 to 14% when an ultrasound pulse of 10 s was used in conjunction with 96 h of bacterial exposure in Eclipta alba explants.

Microvascularization of corpus luteum of bovine treated with equine chorionic gonadotropin.

This study aimed to evaluate the morphological changes in microvascular density and corpus luteum (CL) vascularization in cows treated with eCG during stimulatory and superovulatory protocols. Sixteen cows were synchronized and divided into three groups: control (n = 6), stimulated (n = 4) and superovulated (n =6), one was submitted to estrous synchronization (ES) and received no eCG (control), and those that were submitted to ES and received eCG before or after follicular deviation (superovulation and stimulation of the dominant follicle, respectively). Ovulation was synchronized using a progesterone device-based protocol. After six days of ovulation, the cows were slaughtered and the ovaries and CL were collected. The CLs were processed and photomicrographs were taken under light microscopy to assess the vascular volume density (Vv) by stereology, and scanning electron microscopy (SEM) was used to perform ultrastructural analysis of the microvasculature. The Vv in stimulated and superovulated cows significantly increased (P ≤ 0.0001) when compared to control, indicating that the eCG is able to induce angiogenic activity in bovine CL. However, no significant differences were observed between stimulated and superovulated cows. The SEM demonstrated ratings indicative of angiogenesis, marked by several button-shaped projections in the capillaries, and the presence of more dilated capillaries in CL treated with eCG. These morphological findings are evidence of an angiogenic effect of the eCG treatment in CL of cows.

Enraizamento in vitro de catuaba (Anemopaegma arvense (Vell. ) Stell. ex de Souza), uma planta medicinal do Cerrado / Study on the in vitro rooting of Anemopaegma arvense (Vell. ) Stell. ex de Souza, a medicinal plant of the Brazilian Cerrado

Este trabalho foi realizado com o objetivo de otimizar o protocolo para enraizamento in vitro de Anemopaegma arvense, planta medicinal do Cerrado em risco de extinção e conhecida popularmente como catuaba, a qual é amplamente utilizada na medicina popular. Brotações cultivadas in vitro foram inoculadas em meio de cultura MS/2 liquido e MS sólido suplementado com diferentes concentrações de auxinas, poliaminas ou dithiothreitol (DTT). As avaliações foram realizadas quanto à porcentagem de enraizamento, número e comprimento das raízes. A presença de NAA (Ácido naftaleno acético) no meio de cultura foi essencial para promover a indução de raízes adventícias nas brotações. A maior porcentagem de enraizamento, 50%, foi obtida no tratamento 2 mg L-1 de NAA com tempo de permanência de 15 dias nesta auxina. No experimento com poliaminas o melhor tratamento foi MS/2 + 5 mg L-1 de putrescina, com 27% de brotações enraizadas. Na presença de DTT (Dithiothreitol), 23% das brotações enraizaram em 0,10 mg L-1 de DTT. A presença da auxina NAA e a alternância no tempo de permanência foi a melhor condição para promover o enraizamento in vitro da de A. arvense. .

This work was carried out in order to optimize an efficient protocol for the in vitro rooting of Anemopaegma arvense, a medicinal plant of the Brazilian Cerrado in danger of extinction, popularly known as Catuaba in Portuguese and widely used in folk medicine. Shoots cultivated in vitro were inoculated in liquid MS/2 and solid MS culture medium supplemented with different concentrations of auxins, polyamines or dithiothreitol (DTT). Evaluations were performed for the rooting percentage and for the number and length of roots. The presence of NAA (naphthaleneacetic acid) in the culture medium was essential to promote the induction of adventitious roots. Higher rooting percentage (50%) was obtained in the treatment with 2 mg L-1 NAA and duration of stay of 15 days in this auxin. In the experiment with polyamines, the best treatment was MS/2 + 5 mg L-1 putrescine with 27% of shoots rooted. In the presence of DTT (dithiothreitol), 23% of shoots rooted at 0.10 mg L-1 DTT. The presence of the auxin NAA and the alternation in length of stay was the best condition to promote in vitro rooting of A. arvense. .

Eliminating Health Care Disparities With Mandatory Clinical Decision Support: The Venous Thromboembolism (VTE) Example.

BACKGROUND: All hospitalized patients should be assessed for venous thromboembolism (VTE) risk factors and prescribed appropriate prophylaxis. To improve best-practice VTE prophylaxis prescription for all hospitalized patients, we implemented a mandatory computerized clinical decision support (CCDS) tool. The tool requires completion of checklists to evaluate VTE risk factors and contraindications to pharmacological prophylaxis, and then recommends the risk-appropriate VTE prophylaxis regimen. OBJECTIVES: The objective of the study was to examine the effect of a quality improvement intervention on race-based and sex-based health care disparities across 2 distinct clinical services. RESEARCH DESIGN: This was a retrospective cohort study of a quality improvement intervention. SUBJECTS: The study included 1942 hospitalized medical patients and 1599 hospitalized adult trauma patients. MEASURES: In this study, the proportion of patients prescribed risk-appropriate, best-practice VTE prophylaxis was evaluated. RESULTS: Racial disparities existed in prescription of best-practice VTE prophylaxis in the preimplementation period between black and white patients on both the trauma (70.1% vs. 56.6%, P=0.025) and medicine (69.5% vs. 61.7%, P=0.015) services. After implementation of the CCDS tool, compliance improved for all patients, and disparities in best-practice prophylaxis prescription between black and white patients were eliminated on both services: trauma (84.5% vs. 85.5%, P=0.99) and medicine (91.8% vs. 88.0%, P=0.082). Similar findings were noted for sex disparities in the trauma cohort. CONCLUSIONS: Despite the fact that risk-appropriate prophylaxis should be prescribed equally to all hospitalized patients regardless of race and sex, practice varied widely before our quality improvement intervention. Our CCDS tool eliminated racial disparities in VTE prophylaxis prescription across 2 distinct clinical services. Health information technology approaches to care standardization are effective to eliminate health care disparities.

Mechanisms of type 2 diabetes resolution after Roux-en-Y gastric bypass.

BACKGROUND: Bariatric surgery is the most effective treatment for the reduction of weight and resolution of type 2 diabetes mellitus (T2 DM). The objective of this study was to longitudinally assess hormonal and tissue responses after RYGB. METHODS: Eight patients (5 with T2 DM) were studied before and after RYGB. A standardized test meal (STM) was administered before and at 1, 3, 6, 9, 12, and 15 months. Separately, a 2-hour hyperinsulinemic-euglycemic clamp (E-clamp) and a 2-hour hyperglycemic clamp (H-clamp) were performed before and at 1, 3, 6, and 12 months. Glucagon-like peptide-1 (GLP-1) was infused during the last hour of the H-clamp. Body composition was assessed with DXA methodology. RESULTS: Enrollment body mass index was 49±3 kg/m(2) (X±SE). STM glucose and insulin responses were normalized by 3 and 6 months. GLP-1 level increased dramatically at 1, 3, and 6 months, normalizing by 12 and 15 months. Insulin sensitivity (M of E-clamp) increased progressively at 3-12 months as fat mass decreased. The insulin response to glucose alone fell progressively over 12 months but the glucose clearance/metabolism (M of H-clamp) did not change significantly until 12 months. In response to GLP-1 infusion, insulin levels fell progressively throughout the 12 months. CONCLUSION: The early hypersecretion of GLP-1 leads to hyperinsulinemia and early normalization of glucose levels. The GLP-1 response normalizes within 1 year after surgery. Enhanced peripheral tissue sensitivity to insulin starts at 3 months and is associated with fat mass loss. ß-cell sensitivity improves at 12 months and after the loss of ≈33% of excess weight. There is a tightly controlled feedback loop between peripheral tissue sensitivity and ß-cell and L-cell (GLP-1) responses.

Indirect ELISA for diagnosis of Brucella ovis infection in rams / ELISA indireto para diagnóstico da infecção por Brucella ovis em carneiros

Brucella ovis is a major cause of epididymitis in sexually mature rams, resulting in subfertility, infertility, and economic losses for the sheep industry worldwide. The aim of this study was to develop an indirect ELISA (iELISA) using recombinant proteins, namely rBoP59 and rBP26, as antigens for serological diagnosis of B. ovis infection. The BoP59 and BP26 recombinant proteins were expressed in E. coli and purified by affinity chromatography. Antigenicity was tested by Western blot and iELISA. Standardization of iELISA was performed with 500ng and 1µg BoP59 and rBP26 per well, testing serum from uninfected and experimentally infected rams. rBP26 was effective in distinguishing positive from negative rams. The rBP26 iELISA developed in this study is the first to use a completely purified rBP26 as antigen resulting in high sensitivity (100%) and specificity (90.2%), and an overall accuracy equal to 1.0...

Brucella ovis é uma das principais causas de epididimite em carneiros sexualmente maduros, resultando em subfertilidade e infertilidade e consequentes perdas econômicas para a ovinocultura em todo o mundo. O objetivo deste estudo foi desenvolver ELISA indireto (ELISAi), utilizando como antígeno proteínas recombinantes BoP59r e BP26r para diagnóstico da infecção por B. ovis. BoP59r e BP26r foram expressas em E. coli e purificadas por cromatografia de afinidade e a antigenicidade testada por Western blot e ELISAi. A padronização do ELISAi foi realizada testando 500 ng e 1 µg de BoP59r e BP26r por poço e soros de carneiros infectados e não infectados. A BP26r foi eficiente em diferenciar ovinos negativos de positivos. O ELISAi com BP26 desenvolvido neste estudo foi o primeiro a utilizar BP26 completamente purificada como antígeno, resultando em elevada sensibilidade (100%) e sensibilidade (90,2%), com acurácia igual a 1,0...

Multiple congenital defects in a newborn foal / Defeitos congênitos múltiplos em um potro recém-nascido

A case of multiple congenital defects in a newborn foal is reported. The animal showed hypoplasia of the left pelvic limb bones, uterus unicornis, congenital diaphragmatic hernia, and unilateral renal and ureteral agenesis. This report includes the macroscopic and microscopic lesions observed in the case...

Relata-se um caso de defeitos congênitos múltiplos em um potro recém-nascido. O animal apresentou hipoplasia dos ossos do membro pélvico esquerdo, útero unicorno, hérnia diafragmática congênita e agenesia renal e ureteral unilateral. Este relato inclui as lesões macroscópicas e microscópicas observadas no caso...