Some technical contributions to the treatment of buried penis.

Buried penis is a rare condition in which the preputial skin and the fat in the hypogastric area cause the body of the organ to be involved in such a way as to convey the impression that the patient has a micro penis. We present a few technical contributions to the surgical treatment of buried penis, suggesting modifications that may be of help in the treatment of those patients.

Cardiac synchronism assessment by myocardial perfusion imaging in patients with cardiac resynchronization therapy

BACKGROUND: the treatment of heart failure has undergone major therapeutic advances in recent decades, among them, cardiac resynchronization therapy (CRT), a strategy capable of reducing symptoms, hospitalization and mortality. It is known that up to 30% of patients undergoing CRT do not have a satisfactory response, based on current selection criteria. Purpose: Myocardial perfusion scintigraphy by Gated-SPECT technique (Gated-SPECT) can provide important information such as mechanical timing, region of last mechanical activation and fibrosis which are very useful in the best selection of who would really benefit from this device. OBJECTIVE: to evaluate the presence of improvement in the mechanical synchronism of the left ventricle (LV) in patients with CRT, using the Synctool software used in the Gated-SPECT, as well as to correlate the data obtained with clinical improvement, defined by reduction of at least 1 New York Heart Association class and reduction of at least 5 points in the Minessota Living With Heart Failure Questionnaire (MLHFQ), and also correlate to other epidemiological, clinical, electrocardiographic and perfusional variables. METHODS: 31 patients (p) with CRT underwent Gated-SPECT at 2 different times: CRT on and off. A quality of life questionnaire was also applied and clinical data before and after implantation of the device were collected. RESULTS: improved synchronism with reduced histogram bandwidth (BWH) (215.6 ± 74.7 ° vs. 149.9 ± 67.9 °; p <0.001) and phase standard deviation (SD) (65, 3 ± 21.7 ° vs. 53.1 ± 22.7 °; p <0.001), after CRT is turned on. Patients who presented synchrony improvement had a higher frequency of clinical improvement (p = 0.026) and obtained lower values of LV end diastolic volume (204.4 ± 100.4 ml vs. 304.3 ± 77.2 ml; p = 0.028) and LV end-systolic volume (120.2 ± 88.8 ml vs. 197.5 ± 51.6 ml; p = 0.026). When clinical improvement was examined, 23 (74.1%) p were considered as responders and 8 (25.9%) as non-responders. Responders showed a significant increase in the LV ejection fraction (38.4 ± 14.1 vs. 47.9 ± 15.3; p <0.001). Non-responders had a higher mean of myocardial involvement by fibrosis (12.9 ± 5.5% vs. 5.7 ± 8.4%; p = 0.033) and higher frequency of fibrosis in the lateral and inferolateral walls (50% vs. 8.7%; p = 0.026), presented an even lower percentage of localization of the region of last mechanical activation (LMA) in the lateral and inferolateral walls (12.5% vs 56.5%; p = 0.045), thus assuming a discordant position between fibrosis and the CRT pacing electrode in the LV. CONCLUSION: Synctoll software are very useful to predict the evaluation of patients with CRT wich was able to improve the mechanical timing of the LV. Improvement in mechanical synchrony is associated with clinical improvement and marked reverse remodeling. Presence of fibrosis and region of last mechanical activation in the lateral and inferolateral walls are predictive factors of response to CRT.

Expounding structures of roller compacted concrete dam specimens by means of hard conventional X-ray inspection.

A simple solution to improve the contrast between the different concrete composites in X-ray imaging (radiography and tomography) of a highly compressed composite sample of real size roller compacted concrete (RCC) specimens is presented. This is made by applying a 9.5 mm thick Copper (Cu) filter at the output window of the X ray tube in a conventional X-ray inspection equipment. Our results show that with the employed filtration, at 140 kV and 200 kV, we were able to distinguish the gravel from the other concrete composites even in a highly compacted specimen. Cement and sand grains as well as porosity were not detected mainly due to the low spatial resolution of our detector system. This suggests a further improvement by using the now available high voltage microfocus X-ray tube (>= 200 kV), a bow-tie (or through) Cu filters and a high resolution flat panel detector for phase contrast imaging on real size compacted concrete specimens.

Efficacy and safety of midostaurin in patients with advanced systemic mastocytosis: 10-year median follow-up of a phase II trial.

Patients with advanced systemic mastocytosis (SM) (e.g. aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN) and mast cell leukemia (MCL)) have limited treatment options and exhibit reduced survival. Midostaurin is an oral multikinase inhibitor that inhibits D816V-mutated KIT, a primary driver of SM pathogenesis. We conducted a phase II trial of midostaurin 100 mg twice daily, administered as 28-day cycles, in 26 patients (ASM, n=3; SM-AHN, n= 17; MCL, n=6) with at least one sign of organ damage. During the first 12 cycles, the overall response rate was 69% (major/partial response: 50/19%) with clinical benefit in all advanced SM variants. With ongoing therapy, 2 patients achieved a complete remission of their SM. Midostaurin produced a ⩾50% reduction in bone marrow mast cell burden and serum tryptase level in 68% and 46% of patients, respectively. Median overall survival for the entire cohort was 40 months, and 18.5 months for MCL patients. Low-grade gastrointestinal side effects were common and manageable with antiemetics. The most frequent grade 3/4 nonhematologic and hematologic toxicities were asymptomatic hyperlipasemia (15%) and anemia (12%). With median follow-up of 10 years, no unexpected toxicities emerged. These data establish the durable activity and tolerability of midostaurin in advanced SM.

A study of disseminated intravascular coagulation in acute leukemia reveals markedly elevated D-dimer levels are a sensitive indicator of acute promyelocytic leukemia.

INTRODUCTION: While the presence of disseminated intravascular coagulation (DIC) has been implicated in worse clinical outcome in acute leukemia, the relationship between different subtypes of acute leukemia and the clinicopathologic features of DIC has not been systematically well studied. METHODS: In this study, we retrospectively reviewed 149 cases of newly diagnosed acute leukemia and assessed the utility of evaluating red blood cell morphologic features, and coagulation parameters in determining the presence of DIC as well as differentiating subtypes of acute leukemia. RESULTS: Review of our cohort demonstrates a novel finding, that elevated D-dimer concentrations ≥19 000 ng/mL fibrinogen equivalent units (FEU) are a sensitive diagnostic indicator of acute promyelocytic leukemia (APL) with moderate specificity, sensitivity 96%, specificity 92% in acute leukemia subtyping. Similar to other studies, APL showed an increased incidence of DIC (P < 0.01) compared to other subtypes of acute leukemia. Surprisingly, the presence of schistocytes on the peripheral blood smear was not a statistically significant indicator of DIC, sensitivity of 36% and specificity of 89%. Finally, the presence of DIC was not a significant indicator of poorer prognosis amongst all patients with AML. CONCLUSION: Overall we identify elevated D-dimer concentrations ≥19 000 ng/mL FEU are a sensitive indicator of acute promyelocytic leukemia (APL), with a sensitivity of 96% and specificity of 92% in the subtyping of acute leukemias, and that the presence of schistocytes in peripheral blood smears is not a diagnostically sensitive screening test for DIC with a sensitivity of 36%.

Isocitrate dehydrogenase mutations in myeloid malignancies.

Alterations to genes involved in cellular metabolism and epigenetic regulation are implicated in the pathogenesis of myeloid malignancies. Recurring mutations in isocitrate dehydrogenase (IDH) genes are detected in approximately 20% of adult patients with acute myeloid leukemia (AML) and 5% of adults with myelodysplastic syndromes (MDS). IDH proteins are homodimeric enzymes involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation and DNA modification. The IDH2 protein is localized in the mitochondria and is a critical component of the tricarboxylic acid (also called the 'citric acid' or Krebs) cycle. Both IDH2 and IDH1 (localized in the cytoplasm) proteins catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). Mutant IDH enzymes have neomorphic activity and catalyze reduction of α-KG to the (R) enantiomer of 2-hydroxyglutarate, which is associated with DNA and histone hypermethylation, altered gene expression and blocked differentiation of hematopoietic progenitor cells. The prognostic significance of mutant IDH (mIDH) is controversial but appears to be influenced by co-mutational status and the specific location of the mutation (IDH1-R132, IDH2-R140, IDH2-R172). Treatments specifically or indirectly targeted to mIDH are currently under clinical investigation; these therapies have been generally well tolerated and, when used as single agents, have shown promise for inducing responses in some mIDH patients when used as first-line treatment or in relapsed or refractory AML or MDS. Use of mIDH inhibitors in combination with drugs with non-overlapping mechanisms of action is especially promising, as such regimens may address the clonal heterogeneity and the multifactorial pathogenic processes involved in mIDH myeloid malignancies. Advances in mutational analysis have made testing more rapid and convenient, and less expensive; such testing should become part of routine diagnostic workup and repeated at relapse to identify patients who may benefit from treatments that target mIDH.

Depressão e ansiedade em mulheres com endometriose: uma revisão crítica da literatura / Depression and anxiety in women with endometriosis: an critical review

Essa revisão tem por objetivo apresentar os resultados dos estudos que avaliaram prevalência e/ou níveisde depressão e ansiedade nas mulheres com endometriose. Para isso, uma pesquisa bibliográfica foirealizada no PubMed, LILACS e Web of Science e foram selecionados para leitura 21 artigos. Destes,onze analisaram depressão e ansiedade simultaneamente, nove apenas depressão e um ansiedade. Foiobservado que as pacientes com endometriose exibem níveis elevados de depressão e ansiedade,provavelmente devido aos quadros frequentes de dor, a infertilidade, ao atraso no diagnóstico e arecorrência da doença. Conclui-se que um acompanhamento psicológico deve ser oferecido a mulherescom endometriose sendo, portanto um componente essencial para o tratamento dessa condiçãoginecológica(AU)

Utilização de embalagens tetra pak(r) como isolante térmico no revestimento de escamoteadores para leitões / Using tetra pak(r) packaging as insulation coating piglets' creeps

Foram conduzidos dois experimentos em laboratório e em condições de campo para avaliação da eficiência térmica da embalagem Tetra Pak(r)como isolante térmico em escamoteadores aquecidos. No experimento em laboratório, foi utilizado o delineamento inteiramente ao acaso, adotando-se dois tratamentos (com e sem revestimento de embalagens Tetra Pak(r)) com 15 repetições (dias). O experimento em condições de campo foi conduzido na sala de maternidade de suínos. O delineamento foi inteiramente ao acaso, adotando-se dois tratamentos com 12 repetições. Os tratamentos foram: escamoteadores aquecidos com e sem revestimento interno com embalagem Tetra Pak(r). Foram medidos os dados de temperatura ambiente, umidade relativa do ar, temperatura superficial do piso, temperatura superficial da pele, comportamento e ganho de peso dos leitões lactentes. O uso da embalagem Tetra Pak(r)como isolante térmico no revestimento de escamoteadores manteve a temperatura ambiente confortável (32°C), proporcionando conforto térmico aos leitões lactentes.

Two experiments were conducted in laboratory and field conditions to evaluate the thermal efficiency of the Tetra Pak packaging as insulation in heated creeps. In the laboratory experiment a completely randomized design was used, adopting two treatments (with and without packaging coating with Tetra Pak(r)) with 15 repetitions (days). The experiment under field conditions was conducted in a swine nursery. The design was completely randomized, adopting two treatments with 12 repetitions. The treatments consisted of heated creep with and without Tetra Pak(r) lining. The data measured were ambient temperature, relative humidity, surface temperature of the floor, surface temperature of skin, behavior and weight gain of suckling piglets. The use of Tetra Pak(r) packaging as insulation in creep coating maintained the ambient temperature comfortable (32 °C), providing thermal comfort to suckling piglets.

Pharmacological targeting of miR-155 via the NEDD8-activating enzyme inhibitor MLN4924 (Pevonedistat) in FLT3-ITD acute myeloid leukemia.

High levels of microRNA-155 (miR-155) are associated with poor outcome in acute myeloid leukemia (AML). In AML, miR-155 is regulated by NF-κB, the activity of which is, in part, controlled by the NEDD8-dependent ubiquitin ligases. We demonstrate that MLN4924, an inhibitor of NEDD8-activating enzyme presently being evaluated in clinical trials, decreases binding of NF-κB to the miR-155 promoter and downregulates miR-155 in AML cells. This results in the upregulation of the miR-155 targets SHIP1, an inhibitor of the PI3K/Akt pathway, and PU.1, a transcription factor important for myeloid differentiation, leading to monocytic differentiation and apoptosis. Consistent with these results, overexpression of miR-155 diminishes MLN4924-induced antileukemic effects. In vivo, MLN4924 reduces miR-155 expression and prolongs the survival of mice engrafted with leukemic cells. Our study demonstrates the potential of miR-155 as a novel therapeutic target in AML via pharmacologic interference with NF-κB-dependent regulatory mechanisms. We show the targeting of this oncogenic microRNA with MLN4924, a compound presently being evaluated in clinical trials in AML. As high miR-155 levels have been consistently associated with aggressive clinical phenotypes, our work opens new avenues for microRNA-targeting therapeutic approaches to leukemia and cancer patients.

Rendimentos de cortes, proporção tecidual da carcaça e composição centesimal da carne de caprinos jovens em função do grupo racial e do peso corporal de abate / Cut yields, carcass and tissue composition proportion in meat from young goats depending on the breed and slaughter body weight

O objetivo do presente trabalho foi avaliar as proporções de cortes comerciais, tecidos do lombo e composição da carne de cabritos de cinco grupos raciais: Alpino, ½ Boer + ½ Alpino (½ BA), ½ Anglo Nubiano + ½ Alpino (½ ANA), ¾ Boer + » Alpino (¾ BA), » Boer + » Alpino + ½ Anglo Nubiano (Tricross), submetidos a três pesos de abate (25, 30 e 35kg) em sistema de confinamento, com utilização de dieta completa. O cruzamento das raças Boer e Anglo Nubiana com fêmeas Alpinas apenas melhorou, nos cabritos, os rendimentos de cortes considerados de terceira categoria, como pescoço e costela. Pesos corporais de abate entre 30 e 35kg devem ser preferidos por aumentarem a proporção de lombo, reduzirem a proporção de pescoço nos Alpinos e aumentarem a de perna em Alpinos e ¾ Boer, além de proporcionarem quantidades adequadas de músculo e gordura intermuscular.

The purpose of this study was to evaluate the commercial cuts, loin tissues and composition proportions in meant from five racial groups: Alpine, ½ Boer + ½ Alpine (½ BA), ½ Anglo Nubian + ½ Alpine (½ ANA), ¾ Boer + » Alpine (¾ BA), » Boer + » Alpine + ½ Anglo Nubian (Tricross), submitted to three slaughter weights (25, 30 and 35kg) in feedlot, using a complete diet. The crossing of Boer and Anglo Nubian with Alpine females only improved, in kids, the yield of cuts considered third category such as neck and rib. Slaughter body weights between 30 and 35kg should be preferred due to increase in the proportion of the loin, reduction in the proportion of the neck in Alpine and increase in the leg in Alpine and ¾ Boer, beyond the appropriate amounts of intermuscular fat and muscle.

Assessment of extended-spectrum ß-lactamase, KPC carbapenemase and porin resistance mechanisms in clinical samples of Klebsiella pneumoniae and Enterobacter spp.

The emergence and spread of resistance mechanisms in Gram-negative bacilli has complicated the treatment of serious nosocomial infections. Current automated systems for detection of Klebsiella pneumoniae carbapenemase (KPC)-producing isolates are unreliable. One possible straightforward alternative method is evaluation of ertapenem resistance. However, the accuracy of this method is affected by other resistance mechanisms such as AmpC gene expression or extended-spectrum ß-lactamase production associated with porin loss. This study included 128 samples of K. pneumoniae and Enterobacter spp. that were non-susceptible to ertapenem. The disk diffusion and Etest method were applied to determine susceptibility to imipenem, meropenem and ertapenem. Isolates exhibiting intermediate or complete resistance to ertapenem were evaluated for resistance mechanisms. bla(TEM), bla(SHV), bla(CTX-M), bla(CTX-M-2) and bla(KPC) genes were tested for by PCR, and the presence of outer membrane protein was investigated by dot-blot assay. bla(TEM) was detected in 52.9% and 10.3%, bla(SHV) in 29.4% and 0.94%, bla(CTX-M) in 41.4% and 1.9% and bla(CTX-M-2) in 23.5% and 1.9% of K. pneumoniae and Enterobacter cloacae isolates, respectively. The bla(KPC) gene was present in 12.6% of Enterobacter spp. isolates. OmpC and OmpF were present in 6.6% of E. cloacae isolates. These results indicate that several resistance mechanisms contribute to potential therapeutic failure of carbapenem therapy and point to the need for better detection methods and surveillance strategies.

CD19-CD45 low/- CD38 high/CD138+ plasma cells enrich for human tumorigenic myeloma cells.

Multiple myeloma is a hematological neoplasm characterized by the accumulation of clonal plasma cells in the bone marrow. Its frequent relapse following achievement of clinical remissions implicates the existence of therapy-resistant myeloma-initiating cells. To date, results on the identity of myeloma-initiating cells have differed. Here, we prospectively identified a myeloma-initiating population by fractionating and transplanting patient bone marrow cells into human bone-bearing immunocompromised mice. Xenotransplantation of fractionated CD138(+)/CD38(high) cells from 40% of patients (8/20) led to a repopulation of CD19(+)CD38(low) or CD138(+)CD38(+) B-lineage cells in human bone grafts; and these grafts were clonally derived from patient myeloma cells. Meanwhile, CD19(+)CD38(low) xenografts were detected in human bone-bearing mice transplanted with CD19(+)CD38(low/-) B cells from 8 of 22 samples but were not clonally related to patient myeloma cells. Further fractionation and xenotransplantation of CD138(+)CD38(high) cells demonstrated that (CD45(low/-) or CD19(-)) CD38(high)/CD138(+) plasma cells, but not (CD45(high) or CD19(+)) CD38(high)/CD138(+) plasmablasts enrich for myeloma-initiating cells. Quantitative reverse transcription-PCR of two serially transplantable xenografts, which were CD19(-)CD138(+), revealed that they were Pax5 (a B-cell-specific transactivator)-negative. These results suggest that CD19(-)CD45(low/-) fully differentiated plasma cells enrich for long-lived and tumor-initiating cells whereas B cells or plasmablasts do not.

Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a disease of the elderly. Poor outcomes with standard therapies necessitate novel approaches. Outpatient regimens sufficiently potent and well tolerated to induce remissions and enable continuation therapy may be beneficial. In this phase-1 study, we determined the maximum tolerated dose (MTD) and the efficacy for sequential azacitidine and lenalidomide as remission induction and continuation therapy in elderly, previously untreated patients. We investigated the impact on global DNA methylation and bone marrow cytokines, and sought biological predictors of response. Eighteen patients were enrolled. The MTD was not reached. Median follow-up was 8.2 months (10.3 months for survivors). Common adverse events included fatigue, injection site reactions, constipation, nausea, pruritus and febrile neutropenia. Ten patients responded (56%), and the rate of complete remissions (CRs) or CRs with incomplete recovery of blood counts for evaluable patients was 44% (7/16). The median response duration was 6.2 months. DNA demethylation and changes in bone marrow cytokines were observed; responders had a unique cytokine profile and a trend towards lower methylation levels. Sequential azacitidine and lenalidomide was well tolerated with encouraging clinical and biological activity in previously untreated elderly AML patients. This trial is registered at ClinicalTrials.gov (NCT00890929).

Pre-clinical validation of a vaginal cream containing copaiba oil (reproductive toxicology study).

The aims of this study was to evaluate the effects of oil-resin of Copaiba (Copaifera duckei Dwyer), aired in vaginal cream on the reproductive performance of female rats (Rattus norvegicus). To determine the components of the C. duckei oleoresin, gas chromatography coupled with mass spectrometry (CG-MS) was used, and considering the trans-caryophyllene sesquiterpene as a phytochemical marker in the oleoresin. Due to the extensive use of copaiba oleoresin in the suppository form for gynecological infections, an evaluation was carried out on the effects of copaiba oleoresin (Copaifera duckei Dwyer), delivered in a vaginal cream, on the reproductive performance of female Wistar rats. For this purpose, three groups (n=5-6/group) of female rats were treated as follows: 1--vaginal cream of copaiba oleoresin (28.6 mg/kg), 2--base vaginal cream and 3--control (physiological saline 0.9%), administered intravaginally, for 30 days before pregnancy, and from day zero to day 20 during pregnancy. Laparotomy was performed on the 21st day of pregnancy, followed by the determination of reproductive variables: number of live and dead fetuses, mass of the fetuses and placentas, number of implantations and resorptions, number of corpora lutea, pre- and post-implantation loss, and analyses of the fetuses with regard to external and internal anomalies and/or malformations (skeletal and visceral). The trans-caryophyllene present in the sample is suggested as a phytochemical marker and the results of this study demonstrate an absence of maternal toxicity and foetotoxicity embryofoetotoxicity at the dose administered, corresponding to ten times the recommended dose for use in humans. Accordingly, no significant statistical difference was observed between the treated and control groups, for the variables analyzed. Thus, it is concluded that the vaginal cream containing 2.5% copaiba oleoresin is safe during gestation, in female rats (Rattus norvegicus) of the Wistar strain.