Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: case report and review of the literature

Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence

Diabetes and lipid screening among patients in primary care: A cohort study

<p>Abstract</p> <p>Background</p> <p>Obesity is associated with increased cardiovascular diseases and diabetes mellitus. Guidelines call for intensified glucose and lipid screening among overweight and obese patients. Data on compliance with these guidelines are scarce. The purpose of this study was to assess rates of diabetes and lipid screening in primary care according to demographic variables and weight status.</p> <p>Methods</p> <p>Over a 3-year follow-up period, we assessed screening rates for blood glucose, triglycerides, and HDL- and LDL-cholesterol among 5025 patients in primary care. From proportional hazards models we estimated screening rates among low, moderate, high, and very-high risk patients and compared them with recommendations of the American Diabetes Association (ADA), National Cholesterol Education Program (ATP III) and U.S. Preventive Services Task Force (USPSTF).</p> <p>Results</p> <p>Mean (SD) age was 47.4 (15.6); 69% were female, 21% were non-white, and 30% of males and 25% of females were obese (BMI ≥ 30 kg/m²). For both diabetes and lipid screening, the adjusted hazard was 260–330% higher among ≥65 than <35 year-olds, 50–90% higher in persons with BMI ≥ 35 than <25 kg/m², 10–30% lower for females than males, and not lower among racial/ethnic minorities. Screening rates were at least 80% among very-high risk persons, which we defined as 55–64 years old, BMI ≥ 35 kg/m², non-white, with baseline hypertension. In contrast, high-risk persons who were younger (35–44 years old) and less obese (BMI 30–<35 kg/m²) were screened less often (43% for LDL-cholesterol among females to 83% for diabetes among males) even though ADA, ATP III and USPSTF recommend diabetes and lipid screening among them.</p> <p>Conclusion</p> <p>Patients with higher BMI or age were more likely to be screened for cardiometabolic risk factors. Women were screened at lower rates than men. Even in a highly structured medical group practice, some obese patients were under-screened for diabetes and dyslipidemia.</p

Mycobacterium paratuberculosis sheep type strain in Uruguay: evidence for a wider geographic distribution in South America

Johne's disease (JD) is an economically important disease of ruminants caused by Mycobacterium avium paratuberculosis (MAP), which also infects other species including humans. Two major MAP strain types are currently recognized: sheep (S) and cattle (C) types. Information on JD prevalence and MAP types infecting small ruminants in South America is limited, and all but one of the MAP types reported from this region are of the C type. This study describes clinicopathological, molecular and microbiological findings in 11 cases of JD caused by a type S MAP strain, and estimated true within-flock prevalence in a ~735-sheep operation in Uruguay. Postmortem examination and histology (hematoxylin-eosin and Ziehl-Neelsen stains) of samples from 41 selected sheep revealed lymphohistiocytic/granulomatous enteritis and mesenteric lymphadenitis in 11 animals, with moderate/severe multibacillary lesions in 6 clinical cases, and minimal/mild paucibacillary lesions in 5 sub-clinical cases. Immunohistochemistry using an antibody against Mycobacterium bovis that cross-reacts with MAP (2 cases), and transmission electron microscopy (1 case), revealed myriads of intrahistiocytic mycobacteria. MAP was isolated in one case and detected by PCR in 6 cases. The S type of MAP was identified using a multiplex PCR that distinguishes between S and C types, and PCR-REA. The estimated true within-flock prevalence was ≤ 2.3%. This represents the first communication on within-flock prevalence of JD associated with a type S MAP strain in South America and the second documentation of this strain in the subcontinent. Additional studies are required to better understand the molecular epidemiology of the different MAP types in the region.Centro de Diagnóstico e Investigaciones Veterinaria

Structure-based functional inference of hypothetical proteins from Mycoplasma hyopneumoniae

Enzootic pneumonia caused by Mycoplasma hyopneumoniae is a major constraint to efficient pork production throughout the world. This pathogen has a small genome with 716 coding sequences, of which 418 are homologous to proteins with known functions. However, almost 42% of the 716 coding sequences are annotated as hypothetical proteins. Alternative methodologies such as threading and comparative modeling can be used to predict structures and functions of such hypothetical proteins. Often, these alternative methods can answer questions about the properties of a model system faster than experiments. In this study, we predicted the structures of seven proteins annotated as hypothetical in M. hyopneumoniae, using the structure-based approaches mentioned above. Three proteins were predicted to be involved in metabolic processes, two proteins in transcription and two proteins where no function could be assigned. However, the modeled structures of the last two proteins suggested experimental designs to identify their functions. Our findings are important in diminishing the gap between the lack of annotation of important metabolic pathways and the great number of hypothetical proteins in the M. hyopneumoniae genome