Endoscopic third ventriculostomy versus ventriculoperitoneal shunt in pediatric and adult population: a systematic review and meta-analysis

Neurosurgical Review - Treatment options for hydrocephalus include endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS). Some ambiguity remains regarding indications, safety,...     

Hemoglobin, erythropoietin and systemic inflammation in exacerbations of chronic obstructive pulmonary disease

Background

Systemic inflammation may represent a possible cause of anemia. Previous data support that anemic patients with COPD present high erythropoietin (EPO) levels, suggestive of EPO resistance, possibly mediated through inflammatory mechanisms.

Objectives

We aimed to determine whether systemic inflammation, which is usually up-regulated during exacerbations of COPD (ECOPD) is associated with low hemoglobin levels expressing erythropoietin resistance.

Methods

Hemoglobin (Hb), EPO and serum biomarkers of systemic inflammation [CRP, TNF-α, fibrinogen and IL-6] were assessed at three time points (admission, resolution and stable phases) in a selected cohort of 93 COPD patients.

Results

Hemoglobin levels were significantly lower on admission compared to resolution and stable phases (median 12.1 g/dl [interquartile ranges 11.2-12.7], vs 13.5 [12.4-14.3] vs 13.4 [12.7-14.08], respectively p = 0.002), whereas EPO was significantly higher on admission compared to resolution and stable phases. A negative association between Hb and IL-6 and a positive association between EPO and IL-6 were observed only during the acute phase of exacerbation. EPO and Hb were negatively associated during the acute phase, whereas they were positively associated during discharge and stable phase.

Conclusions

In this observational study we have shown that during admission for ECOPD Hb levels are decreased and EPO levels are increased. We have also identified a negative association between Hb and EPO. The above association is mainly related to increased IL-6 levels, indicating a possible EPO resistance through the mechanism of increased systemic inflammatory process.     

A geometric construction determines all permissible strand arrangements of sandwich proteins

For a large class of proteins called sandwich-like proteins (SPs), the secondary structures consist of two beta-sheets packed face-to-face, with each beta-sheet consisting typically of three to five beta-strands. An important step in the prediction of the three-dimensional structure of a SP is the prediction of its supersecondary structure, namely the prediction of the arrangement of the beta-strands in the two beta-sheets. Recently, significant progress in this direction was made, where it was shown that 91% of observed SPs form what we here call "canonical motifs." Here, we show that all canonical motifs can be constructed in a simple manner that is based on thermodynamic considerations and uses certain geometric structures. The number of these structures is much smaller than the number of possible strand arrangements. For instance, whereas for SPs consisting of six strands there exist a priori 900 possible strand arrangements, there exist only five geometric structures. Furthermore, the few motifs that are noncanonial can be constructed from canonical motifs by a simple procedure.     

Circulating sclerostin and Dickkopf-1 levels in patients with nonalcoholic fatty liver disease

There is increasing evidence for bone-liver interplay. The main aim of this study was to determine serum sclerostin and Dickkopf (DKK)-1 levels in patients with nonalcoholic fatty liver disease (NAFLD) and their association with the disease severity. Patients with biopsy-proven NAFLD, 13 with nonalcoholic simple steatosis (SS) and 14 with steatohepatitis (NASH), and 20 gender-, age-, body mass index- and waist circumference-matched controls were enrolled. Serum sclerostin, DKK-1, bone turnover markers, vitamin D, insulin and standard biochemical and hematologic parameters were measured; lumbar spinal dual-energy X-ray absorptiometry was performed. We observed that there was a progressive decline in serum sclerostin levels from the controls (76.1 ± 6.8) to SS (53.5 ± 6.4) and NASH (46.0 ± 8.1 pmol/l) patients (p = 0.009); in adjusted pairwise comparisons, sclerostin was significantly higher in the controls than in NASH patients (p = 0.012). Although serum DKK-1 did not differ between groups (p = 0.135), there was a trend toward U-shaped distribution (controls 35.8 ± 2.8; SS 27.3 ± 2.9; NASH 36.8 ± 4.4 pmol/l). Higher DKK-1 levels were independently associated with NASH. Regarding specific histological lesions, DKK-1 levels were marginally lower in NAFLD patients with lower (≤33 %) than higher (>33 %) steatosis grade (27.7 ± 3.1 and 38.8 ± 4.7 pmol/l, respectively; p = 0.049). No other significant difference was observed within histological lesions. In conclusion, serum sclerostin levels were lower in NASH patients than in controls. DKK-1 levels were independently associated with NASH in NAFLD patients. The potential importance of these findings indicates a possible bone-liver interaction and warrants further investigation.     

The role of adipocytokines in insulin resistance in normal pregnancy: visfatin concentrations in early pregnancy predict insulin sensitivity

BACKGROUND: Throughout pregnancy maternal adipose tissue is metabolically active, producing adipocytokines involved in the process of insulin resistance. We explored the role of serum adipocytokines, including the newly identified adipocytokine visfatin, in the process of insulin resistance in normal pregnancy. METHODS: We examined 80 pregnant nonobese, nondiabetic white women during the 3 trimesters of pregnancy. All study participants underwent anthropometric measurements, adipocytokine evaluation, and a 75-g oral glucose tolerance test. Homeostasis mathematical model assessment (HOMA-R), insulin sensitivity index (ISI), and indices of beta-cell secretion were calculated. RESULTS: Maternal weight, percentage total body fat, hip circumference, and indices of beta-cell secretion increased significantly during the 3 trimesters, and HOMA-R and ISI increased and decreased, respectively, in the 3rd trimester. During early pregnancy, insulin resistance, beta-cell secretion, and weight correlated positively with leptin. During the 1st trimester, visfatin correlated negatively with percentage body fat and was the best positive predictor of 2nd trimester ISI. In the 2nd trimester, serum visfatin was the best negative predictor of percentage body fat. CONCLUSIONS: During normal pregnancy of nonobese, nondiabetic women, adipose tissue increases, accompanied by a significant progressive increase of insulin resistance. Visfatin concentrations in the 1st trimester positively predict insulin sensitivity during the 2nd trimester. Body fat mass during 1st trimester of pregnancy is negatively associated with insulin sensitivity during the 2nd trimester and perhaps should be kept under control.     

Plaque distribution and vascular remodeling of ruptured and nonruptured coronary plaques in the same vessel: an intravascular ultrasound study in vivo

OBJECTIVES: This study was designed to identify potential differences between the intravascular ultrasound (IVUS) characteristics of spontaneously ruptured and nonruptured coronary plaques. BACKGROUND: The identification of vulnerable plaques in vivo may allow targeted prevention of acute coronary events and more effective evaluation of novel therapeutic approaches. METHODS: Intravascular ultrasound was used to identify 29 ruptured plaques in arteries containing another nonruptured plaque in an adjacent segment. Intravascular ultrasound characteristics of these plaques were compared with plaques of computer-matched controls without evidence of plaque rupture. Plaque distribution was assessed by measuring the eccentricity of lumen location (inside the total vessel). Lumen cross-sectional area narrowing was calculated as [1 - (target/reference lumen area)] x 100%. A remodeling index was calculated as lesion/reference arterial area (>1.05 = compensatory enlargement, <0.95 = shrinkage). RESULTS: Among the three groups of plaques, there was no significant difference in quantitative angiographic parameters, IVUS reference dimensions and IVUS lumen cross-sectional area narrowing. There was a difference in plaque distribution; lumen location by IVUS was significantly more eccentric in ruptured than in nonruptured (p = 0.002) and control plaques (p < 0.0001). The arc of disease-free vessel wall was larger in ruptured than in control plaques (p < 0.0001). The remodeling pattern of ruptured and nonruptured plaques differed significantly from that of the control plaques (p = 0.0001 and 0.003); compensatory enlargement was found in 66%, 48%, and 17%, whereas shrinkage was found in 7%, 10% and 48%, respectively. CONCLUSIONS: Intravascular ultrasound assessment of plaque distribution and vascular remodeling may help to classify plaques with the highest probability of spontaneous rupture.     

The healing potential of the periosteum molecular aspects

The presence of pluripotential mesenchymal cells in the under surface of the periosteum in combination with growth factors regularly produced or released after injury, provide this unique tissue with an important role in the healing of bone and cartilage. The periosteum contributes in the secondary callus formation with cells and growth factors and should always be preserved and protected when surgery is performed for the management of a fracture. The current evidence about the cellular interactions, the stimulants and the signalling pathways related to osteogenesis and chondrogenesis is described. An essential knowledge of the basics related to the contribution of the periosteum in the healing of fractures, osteotomies, during the process of distraction osteogenesis and in some degree in the repair of cartilagenous defects, provides the surgeons with a better insight to understand the upcoming "biological" interventions in the management of skeletal injuries.     

A PET study of dopamine D2 and serotonin 5-HT2 receptor occupancy in patients with schizophrenia treated with therapeutic doses of ziprasidone

OBJECTIVE: Ziprasidone is an atypical antipsychotic drug that shows a higher affinity for serotonin 5-HT(2) receptors compared with dopamine D(2) receptors in vitro. The affinity of ziprasidone for these receptors in vivo in patients was examined in a positron emission tomography (PET) study. METHOD: The authors conducted a PET study to evaluate D(2) occupancy (using [(11)C]raclopride) and 5-HT(2) occupancy (using [(18)F]setoperone) in brain regions of interest in 16 patients with schizophrenia or schizoaffective disorder randomly assigned to receive 40, 80, 120, or 160 mg/day of ziprasidone, which reflected the recommended dose range. PET scanning was done after 3 weeks of administration and at trough plasma levels, i.e., 12-16 hours after the last dose. RESULTS: The mean 5-HT(2) receptor occupancy was significantly higher than the mean D(2) receptor occupancy (mean=76%, SD=15%, and mean=56%, SD=18%, respectively). The estimated plasma ziprasidone concentration associated with 50% maximal 5-HT(2) receptor occupancy was almost four times lower than that for D(2) receptor occupancy. CONCLUSIONS: These data affirm that ziprasidone is similar to other novel antipsychotics in having greater 5-HT(2) than D(2) receptor occupancy at therapeutic doses and suggest that the optimal effective dose of ziprasidone is closer to 120 mg/day than to the lower doses suggested by previous PET studies. The relatively high D(2) receptor occupancy, even at trough plasma levels, suggests that ziprasidone is more similar to risperidone and olanzapine in receptor occupancy profile than to clozapine and quetiapine. Since ziprasidone plasma levels show significant (more than twofold) variation within a single dose cycle, studies that are aimed at peak plasma levels (6 hours after the last dose) and that examine extrastriatal regions are required to fully characterize the in vivo occupancy profile of ziprasidone.