Estimating the net contribution of interleukin-28B variation to spontaneous hepatitis C virus clearance

The identification of associations between interleukin-28B (IL-28B) variants and the spontaneous clearance of hepatitis C virus (HCV) raises the issues of causality and the net contribution of host genetics to the trait. To estimate more precisely the net effect of IL-28B genetic variation on HCV clearance, we optimized genotyping and compared the host contributions in multiple- and single-source cohorts to control for viral and demographic effects. The analysis included individuals with chronic or spontaneously cleared HCV infections from a multiple-source cohort (n = 389) and a single-source cohort (n = 71). We performed detailed genotyping in the coding region of IL-28B and searched for copy number variations to identify the genetic variant or haplotype carrying the strongest association with viral clearance. This analysis was used to compare the effects of IL-28B variation in the two cohorts. Haplotypes characterized by carriage of the major alleles at IL-28B single-nucleotide polymorphisms (SNPs) were highly overrepresented in individuals with spontaneous clearance versus those with chronic HCV infections (66.1% versus 38.6%, P = 6 × 10(-9) ). The odds ratios for clearance were 2.1 [95% confidence interval (CI) = 1.6-3.0] and 3.9 (95% CI = 1.5-10.2) in the multiple- and single-source cohorts, respectively. Protective haplotypes were in perfect linkage (r(2) = 1.0) with a nonsynonymous coding variant (rs8103142). Copy number variants were not detected. CONCLUSION: We identified IL-28B haplotypes highly predictive of spontaneous HCV clearance. The high linkage disequilibrium between IL-28B SNPs indicates that association studies need to be complemented by functional experiments to identify single causal variants. The point estimate for the genetic effect was higher in the single-source cohort, which was used to effectively control for viral diversity, sex, and coinfections and, therefore, offered a precise estimate of the net host genetic contribution.

Differences and similarities between spontaneous dissections of the internal carotid artery and the vertebral artery

Background and Purpose—To compare potential risk factors, clinical symptoms, diagnostic delay, and 3-month outcome between spontaneous internal carotid artery dissection (sICAD) and spontaneous vertebral artery dissection (sVAD). Methods—We compared patients with sICAD (n=668) and sVAD (n=302) treated in 3 university hospitals. Results—Patients with sICAD were older (46.3±9.6 versus 42.0±10.2 years; P<0.001), more often men (62.7% versus 53.0%; P=0.004), and presented more frequently with tinnitus (10.9% versus 3.4%; P<0.001) and more severe ischemic strokes (median National Institutes of Health Stroke Scale, 10±7.1 versus 5±5.9; P<0.001). Patients with sVAD had more often bilateral dissections (15.2% versus 7.6%; P<0.001) and were more often smokers (36.0% versus 28.7%; P=0.007). Thunderclap headache (9.2% versus 3.6%; P=0.001) and neck pain were more common (65.8% versus 33.5%; P<0.001) in sVAD. Subarachnoid hemorrhage (6.0% versus 0.6%; P<0.001) and ischemic stroke (69.5% versus 52.2%; P<0.001) were more frequent in sVAD. After multivariate analysis, sex difference lost its significance (P=0.21), and all other variables remained significant. Time to diagnosis was similar in sICAD and sVAD and improved between 2001 and 2012 compared with the previous 10-year period (8.0±10.5 days versus 10.7±13.2 days; P=0.004). In sVAD, favorable outcome 3 months after ischemic stroke (modified Rankin Scale, 0–2: 88.8% versus 58.4%; P<0.001), recurrent transient ischemic attack (4.8% versus 1.1%; P=0.001), and recurrent ischemic stroke (2.8% versus 0.7%; P=0.02) within 3 months were more frequent. Conclusions—sICAD and sVAD patients differ in many aspects. Future studies should perform separate analyses of these 2 entities.

[Spontaneous bacterial peritonitis]

Spontaneous bacterial peritonitis (SBP) is the most frequent infection in patients with cirrhosis during hospitalization and is associated with high acute and long-term mortality. Diagnosis is made by paracentesis with determination of neutrophil count in ascitic fluid. Empirical antibiotic therapy must be initiated immediately. The choice of drug is dependent on prior therapies. Liver transplantation has to be considered in the absence of contra-indications. Prophylaxis of SBP is indicated in patients with ascites and gastrointestinal hemorrhage, and in patients after SBP. Primary prophylaxis should be considered in high-risk patients with cirrhosis and ascites. The development of resistance to antibiotic drugs is a relevant side-effect.

Stress and pain response of neonates after spontaneous birth and vacuum-assisted and cesarean delivery

The objective of the study was to compare the stress response and pain expression of newborns (NBs) in the early postpartum period.

Correlation properties of spontaneous motor activity in healthy infants: a new computer-assisted method to evaluate neurological maturation

Qualitative assessment of spontaneous motor activity in early infancy is widely used in clinical practice. It enables the description of maturational changes of motor behavior in both healthy infants and infants who are at risk for later neurological impairment. These assessments are, however, time-consuming and are dependent upon professional experience. Therefore, a simple physiological method that describes the complex behavior of spontaneous movements (SMs) in infants would be helpful. In this methodological study, we aimed to determine whether time series of motor acceleration measurements at 40-44 weeks and 50-55 weeks gestational age in healthy infants exhibit fractal-like properties and if this self-affinity of the acceleration signal is sensitive to maturation. Healthy motor state was ensured by General Movement assessment. We assessed statistical persistence in the acceleration time series by calculating the scaling exponent α via detrended fluctuation analysis of the time series. In hand trajectories of SMs in infants we found a mean α value of 1.198 (95 % CI 1.167-1.230) at 40-44 weeks. Alpha changed significantly (p = 0.001) at 50-55 weeks to a mean of 1.102 (1.055-1.149). Complementary multilevel regression analysis confirmed a decreasing trend of α with increasing age. Statistical persistence of fluctuation in hand trajectories of SMs is sensitive to neurological maturation and can be characterized by a simple parameter α in an automated and observer-independent fashion. Future studies including children at risk for neurological impairment should evaluate whether this method could be used as an early clinical screening tool for later neurological compromise.

An in vitro study on spontaneous myometrial contractility in the mare during estrus and diestrus

Uterine smooth muscle specimens were collected from euthanatized mares in estrus and diestrus. Longitudinal and circular specimens were mounted in organ baths and the signals transcribed to a Grass polygraph. After equilibration time and 2 g preload, their physiologic isometric contractility was recorded for a continuous 2.0 h. Area under the curve, frequency and time occupied by contractions were studied. Differences between cycle phases, between muscle layers, and over the recorded time periods were statistically evaluated using linear mixed-effect models. In the mare, physiologic contractility of the uterus decreased significantly over time for all variables evaluated (time as covariate on a continuous scale). For area under the curve, there was a significant effect of muscle layer (longitudinal > circular). For frequency, higher values were recorded in estrus for circular smooth muscle layer, whereas higher values were seen in longitudinal smooth muscle layers during diestrus. In longitudinal layer and in diestrus, more time was occupied by contractions than in circular layer, and in estrus. This study is describing physiologic myometrial motility in the organ bath depending on cycle phase.

Serum leptin and C-reactive protein levels in the physiological spontaneous menstrual cycle in reproductive age women

OBJECTIVE: Only a few studies have investigated variations of different markers for inflammatory processes during the physiological menstrual cycle. The results are conflicting, particularly concerning the correlation between the marker leptin and steroid hormones. The aim of the study was to investigate the inflammatory markers C-reactive protein (CRP) and leptin in the serum of healthy, normally ovulating women and to correlate these with each other and with the hormones of the gonadal axis. A cycle-dependence of the markers studied would imply an exact timing of the blood sampling for clinical needs. DESIGN: Observational study investigating the two inflammatory markers CRP and leptin in relation to the hormonal pattern of the gonadal axis during the normal cycle. METHODS: Ovulatory cycles of 36 healthy, young, normo-androgenic women, having a normal body mass index were evaluated. Serum concentrations of leptin and CRP, as well as of follicle-stimulating hormone, luteinising hormone, 17beta-oestradiol, progesterone, prolactin (PRL) and free testosterone were measured every 1-2 days during one full cycle. RESULTS: Serum levels of leptin and CRP behaved differently during ovulatory cycles, with higher concentrations for leptin only during certain phases. Significant correlations were found in the follicular phase between leptin and PRL and leptin and free testosterone. CONCLUSIONS: Leptin levels change during the menstrual cycle. Leptin levels are more stable on cycle days 1-5 than later in the cycle. For precise cycle-independent measurements, these fluctuations have to be taken into account. There is no similar cyclic pattern for CRP.

[Spontaneous and post-therapeutic cartilage repair: evaluation criteria.]

Articular cartilage has poor reparative capacities, and once damaged cartilage lesions remain chronic and can lead to osteoarthritis. Over the last decade, several innovative therapies have been introduced to promote the regeneration of articular cartilage while sustaining sufficient mechanical stress and permitting a pain free motion. An important measure of outcome is the morphological characterization of the repair tissue in order to allow for cross-study evaluation. The International Cartilage Repair Society has developed a analogue visual scale to quantify repair tissue, which is described in this paper.

Gender differences in spontaneous cervical artery dissection

We analyzed sex differences in 696 patients with spontaneous cervical artery dissection. There were more men (n = 399; p < 0.0001), and men showed a higher frequency of hypertension (31% vs 15%; p < 0.0001). Women were younger (42.5 +/- 9.9 vs 47.5 +/- 9.3 years; p < 0.0001), had more often multiple dissections (18 vs 10%; p = 0.001), migraine (47 vs 20%; p < 0.0001), and tinnitus (16 vs 8%; p = 0.001). Outcome and mortality were similar in both sexes.

Seasonal variability in spontaneous cervical artery dissection

We examined the seasonal variability of spontaneous cervical artery dissection (sCAD) by analysing prospectively collected data from 352 patients with 380 sCAD (361 symptomatic sCAD; 305 carotid and 75 vertebral artery dissections) admitted to two university hospitals with a catchment area of 2,200,000 inhabitants between 1985 and 2004. Presenting symptoms and signs of the 380 sCAD were ischaemic stroke in 241 (63%), transient ischaemic attack in 40 (11%), retinal ischemia in seven (2%), and non-ischaemic in 73 (19%) cases; 19 (5%) were asymptomatic sCAD. A seasonal pattern, with higher frequency of sCAD in winter (31.3%; 95% confidence interval (CI): 26.5 to 36.4; p=0.021) compared to spring (25.5%; 95% CI: 21.1 to 30.3), summer (23.5%; 95% CI: 19.3 to 28.3), and autumn (19.7%; 95% CI: 15.7 to 24.1) was observed. Although the cause of seasonality in sCAD is unclear, the winter peaks of infection, hypertension, and aortic dissection suggest common underlying mechanisms.