Elk with a long incubation prion disease phenotype have a unique PrPd profile

The transmissible spongiform encephalopathies (TSEs) invariably result in fatal neurodegeneration and accumulation of PrP, an abnormal form of the host prion protein PrP, encoded by the PRNP gene. A naturally occurring polymorphism (methionine/valine) at PRNP codon 129 is associated with variation in relative disease susceptibility, incubation time, clinical presentation, neuropathology, and/or PrP biochemical characteristics in a range of human TSEs. A methionine/leucine polymorphism at the corresponding site in the Rocky Mountain elk PRNP gene is associated with variation in relative susceptibility and incubation time in the cervid TSE chronic wasting disease. We now report that elk lacking the predisposing 132-methionine allele develop chronic wasting disease after a long incubation period and display a novel PrP folding pattern.     

Consequences of endoscopic inguinal hernioplasty with mesh on subsequent open radical prostatectomy

AIM: To determine the effect of prior endoscopic hernia repair with prosthetic mesh on subsequent open radical prostatectomy. METHODS: A retrospective study from 1990 to 2004 identified nine patients with preperitoneal mesh placement followed by open radical prostatectomy. Case controls (n = 26) were matched for age, type of operation, year of surgery and pathologic stage of prostatic adenocarcinoma. Outcome variables of operating time, number of pelvic lymph nodes excised, duration of hospital stay, duration of urinary catheterization, recurrence rates, and incidence of complications were compared. Data analysis was performed using Wilcoxon's rank sums test. RESULTS: Intraoperatively, subjective difficulty in dissection was documented in all cases by the performing urologist. Duration of hospital stay was significantly increased by 1.3 days (p < 0.05), as compared to the control group. However, no statistically significant increase in mean operating time (173 vs. 172 min, p = 0.925), number of lymph nodes sampled (4.4 vs. 6.6, p = 0.147), duration of urinary catheterization (22 vs. 19 days, p = 0.925), oncologic recurrence (11 vs. 11% at 6.1 and 4.8 years follow-up), or complications was found. CONCLUSIONS: Prior TEP/TAPP did not increase the morbidity or mortality of subsequent prostate surgery. Despite some subjective operative difficulty, open prostatectomy was safe and feasible in all cases with a comparable oncologic outcome. Mesh-associated inflammation may preclude adequate nodal sampling. While endoscopic hernia repair remains an excellent option to fix unilateral, bilateral, and recurrent herniae, consideration of future prostate surgery is important. Inserting less "inflammatory" mesh or using an open, anterior approach may be prudent in some men at high risk for needing subsequent prostate surgery.     

Clinical applications of Silybum marianum in oncology

Milk thistle (Silybum marianum) is an herb that is increasingly used in oncology research and treatment settings. Historically, it has been used to treat liver and biliary disorders and has been used in detoxification and cleansing protocols. However, milk thistle is increasingly being investigated for its use in adult and pediatric populations for oncology indications. Possible indications during cancer treatment include cleansing and detoxification after chemotherapy, preventing hepatotoxicity during chemotherapy, treating hepatotoxicity after chemotherapy, and potentiating chemotherapy and radiation therapy as an adjunctive treatment. Milk thistle may also have applications in ameliorating long-term hepatic and cardiovascular effects of cancer treatment. Preliminary studies are investigating its use as a chemopreventive agent and possibly to treat cancer directly. Much of milk thistle's current clinical use grows out of historical uses but is informed by an increasing number of clinical trials and animal studies. This article provides an overview of the current clinical applications of milk thistle in the oncology setting, including guidelines on commonly used forms and doses.     

Culprit lesion plaque characterization and thrombus grading by high-definition intravascular ultrasound in patients with ST-segment elevation myocardial infarction

Background

Dedicated prospective studies investigating high-definition intravascular ultrasound (HD-IVUS)-guided primary percutaneous coronary intervention (PCI) are lacking. The aim of this study was to qualify and quantify culprit lesion plaque characteristics and thrombus using HD-IVUS in patients presenting with ST-segment elevation myocardial infarction (STEMI).

Methods

The SPECTRUM study is a prospective, single-center, observational cohort study investigating the impact of HD-IVUS-guided primary PCI in 200 STEMI patients (NCT05007535). The first 100 study patients with a de novo culprit lesion and a per-protocol mandated preintervention pullback directly after vessel wiring were subject to a predefined imaging analysis. Culprit lesion plaque characteristics and different thrombus types were assessed. An IVUS-derived thrombus score, including a 1-point adjudication for a long total thrombus length, long occlusive thrombus length, and large maximum thrombus angle, was developed to differentiate between low (0–1 points) and high (2–3 points) thrombus burden. Optimal cut-off values were obtained using receiver operating characteristic curves.

Results

The mean age was 63.5 (±12.1) years and 69 (69.0%) patients were male. The median culprit lesion length was 33.5 (22.8–38.9) mm. Plaque rupture and convex calcium were appreciated in 48 (48.0%) and 10 (10.0%) patients, respectively. Thrombus was observed in 91 (91.0%) patients (acute thrombus 3.3%; subacute thrombus 100.0%; organized thrombus 22.0%). High IVUS-derived thrombus burden was present in 37/91 (40.7%) patients and was associated with higher rates of impaired final thrombolysis in myocardial infarction flow (grade 0–2) (27.0% vs. 1.9%, p < 0.001).

Conclusions

HD-IVUS in patients presenting with STEMI allows detailed culprit lesion plaque characterization and thrombus grading that may guide tailored PCI.     

Position-specific and position-invariant face aftereffects reflect the adaptation of different cortical areas

Adaptation to faces leads to face aftereffects and currently this topic attracts a lot of attention because it clearly shows that adaptation occurs even at the higher stages of visual cortical processing. Recently it has been found that long-term exposure to a face stimulus results in adaptation of a position-specific population of face sensitive neurons in addition to a position-invariant neural population, the later being also adapted in the case of short-term adaptation. Here we used the fMRI adaptation technique to investigate the neural locus of position-specific and position-invariant face adaptation. We show that in the right fusiform face area adaptation effects are position invariant and can be evoked by short (500 ms) as well as long (4500 ms) adaptation durations. On the other hand adaptation effects in the right occipital face area are position-specific and require long-term adaptation to develop. These findings imply that the behaviourally observed face aftereffects reflect time-dependent adaptation processes of both position-specific and invariant face sensitive neurons at different stages of visual processing.     

fMRI evidence for sensorimotor transformations in human cortex during smooth pursuit eye movements

Smooth pursuit eye movements (SP) are driven by moving objects. The pursuit system processes the visual input signals and transforms this information into an oculomotor output signal. Despite the object's movement on the retina and the eyes' movement in the head, we are able to locate the object in space implying coordinate transformations from retinal to head and space coordinates. To test for the visual and oculomotor components of SP and the possible transformation sites, we investigated three experimental conditions: (I) fixation of a stationary target with a second target moving across the retina (visual), (II) pursuit of the moving target with the second target moving in phase (oculomotor), (III) pursuit of the moving target with the second target remaining stationary (visuo-oculomotor). Precise eye movement data were simultaneously measured with the fMRI data. Visual components of activation during SP were located in the motion-sensitive, temporo-parieto-occipital region MT+ and the right posterior parietal cortex (PPC). Motor components comprised more widespread activation in these regions and additional activations in the frontal and supplementary eye fields (FEF, SEF), the cingulate gyrus and precuneus. The combined visuo-oculomotor stimulus revealed additional activation in the putamen. Possible transformation sites were found in MT+ and PPC. The MT+ activation evoked by the motion of a single visual dot was very localized, while the activation of the same single dot motion driving the eye was rather extended across MT+. The eye movement information appeared to be dispersed across the visual map of MT+. This could be interpreted as a transfer of the one-dimensional eye movement information into the two-dimensional visual map. Potentially, the dispersed information could be used to remap MT+ to space coordinates rather than retinal coordinates and to provide the basis for a motor output control. A similar interpretation holds for our results in the PPC region.     

Vascular compression of the oculomotor nerve disclosed by thin-slice magnetic resonance imaging

Purpose: To describe the thin-slice magnetic resonance imaging features of vascular compressive oculomotor nerve paresis.Methods: We performed thin-slice (2 mm thick) magnetic resonance imaging of the brainstem in a 74-year-old woman with right partial oculomotor nerve paresis using spoiled gradient recalled acquisition in the steady state.Results: Thin-slice magnetic resonance images disclosed that the right oculomotor nerve was compressed and dislocated superiorly and laterally by the tortuous basilar artery. No other abnormalities were observed.Conclusion: This is the first case report of vascular compressive oculomotor nerve paresis disclosed by thin-slice magnetic resonance imaging.     

Characterization of the p67phox gene: genomic organization and restriction fragment length polymorphism analysis for prenatal diagnosis in chronic granulomatous disease

The genetic defect in the p67phox-deficient form of chronic granulomatous disease (CGD) follows an autosomal recessive pattern of inheritance. When genomic DNA from normal individuals is digested with HindIII and probed with p67phox cDNA an allelic restriction fragment length polymorphism (RFLP) of 4.0 kb or 2.3 kb is detected. We cloned and characterized the p67phox gene using the cDNA and sequenced the exon/intron boundaries, mapping 16 exons on the 40-kb gene. The polymorphic region was then sequenced to identify the inheritance pattern of amniocentesis-derived fetal cells by genomic amplification. The proband, a 9-year-old female patient with p67phox-deficient CGD, and her phenotypically normal mother are homozygous for the RFLP marker, whereas the father and two brothers are heterozygous. The fetus was shown to be heterozygous as well, showing it had inherited at least one normal p67phox gene from the father and that it was predicted to have a normal phenotype. Cord blood samples at birth showed normal oxidative function. Amplification allows rapid detection of the inheritance pattern for fetal diagnosis in informative families. We report the genomic structure of p67phox and an amplification-based method for detection of the marker on chromosome 1q25, used here for prenatal diagnosis of CGD.