Intestinal parasitic infections and micronutrient deficiency: a review.
Malnutrition including vitamin A and iron deficiency and parasitic diseases have a strikingly similar geographical distribution with the same people experiencing both insults together for much of their lives. Parasitic infections are thought to contribute to child malnutrition and micronutrient deficiency through subtle reduction in digestion and absorption, chronic inflammation and loss of nutrients. Parasites may affect the intake of food; it's subsequent digestion and absorption, metabolism and the maintenance of nutrient pools. The most important parasites related to nutritional status are intestinal parasites especially soil transmitted helminthes, Giardia duodenalis, Entamoeba histolytica, followed by other parasites such as the coccidia, Schistosoma sp. and malarial parasites.


Social stimuli interfere with cognitive control in autism.
Autism spectrum disorders are characterized by cognitive control deficits as well as impairments in social interactions. However, the brain mechanisms mediating the interactive effects of these deficits have not been addressed. We employed event-related functional magnetic resonance imaging (fMRI) to examine the effects of processing directional information from faces on activity within brain regions mediating cognitive control. High-functioning individuals with autism and age-, gender-, and IQ-matched neurotypical individuals attended to the direction of a centrally-presented arrow or gaze stimulus with similar flanker stimuli oriented in the same ("congruent") or opposite ("incongruent") direction. The incongruent arrow condition was examined to assess functioning of brain regions mediating cognitive control in a context without social-cognitive demands, whereas the incongruent gaze condition assessed functioning of the same brain regions in a social-cognitive context. Consistent with prior studies, the incongruent arrow condition recruited activity in bilateral midfrontal gyrus, right inferior frontal gyrus, bilateral intraparietal sulcus, and the anterior cingulate relative to the congruent arrow condition in neurotypical participants. Notably, there were not diagnostic group differences in patterns of regional fMRI activation in response to the arrow condition. However, while viewing the incongruent gaze stimuli, although neurotypical participants recruited the same brain regions, participants with autism showed marked hypoactivation in these areas. These findings suggest that processing social-cognitive stimuli interferes with functioning of brain regions recruited during cognitive control tasks in autism. Implications for research into cognitive control deficits in autism are discussed.


Mean platelet volume and neutrophil/lymphocyte ratio in adolescent idiopathic scoliosis: can they be predictive value in diagnosis?
In our study, we evaluated whether mean platelet volume (MPV) and neutrophil lymphocyte ratio (NLR) are predictive values in the diagnosis of Adolescent Idiopathic Scoliosis in patients diagnosed with scoliosis in our clinic. Approximately 15000 patients who applied to our spine outpatient clinic with the suspicion of scoliosis between 2011 and 2018 were reviewed retrospectively. 292 patients were included in the study. The patients were divided into 3 groups. Group 1; control group group 2; group with the possibility of developing scoliosis under follow-upand group 3; the patient group diagnosed with scoliosis. Spinal curvature degrees of the patients were measured using the Cobb method. The MPV and NLR values of the patients were compared with the degree of curvature measured by the cobb method. NLR was 2.17 ± 2.10 K/ul in Group 1, 2.42 ± 1.76 K/ul in Group 2, and 2.72 ± 3.91 K/ul in Group 3. Although the NLR of the 3rd group was higher than the other 2 groups, it was not statistically significant. (p > 0.05). MPV was 7.90 ± 1.07 fL in Group 1, 7.95 ±1.39 fL in Group 2, 8.33 ± 1.37 fL in Group 3.MPV was higher in Group 3 and was found to be statistically significant (p=0.024). After adjusting for the effects of gender and age variables on the groups, the difference in MPV between groups became more significant (p=0.017) . While there was no statistically significant difference between the groups in terms of NLR, it was observed that MPV was statistically significantly higher in patients with AIS.Could this relationship be a promising inflammatory marker for AIS? We think that this question should be answered by studies involving larger patient and control groups.


Grammatical treatment and specific language impairment: neighbourhood density & third person singular -s.
The purpose of this study was to test the effect of manipulating verb neighbourhood density in treatment targeting the third person singular lexical affix. Using a single-subject experimental design, six pre-schoolers with Specific Language Impairment (SLI) were randomly assigned to one of two conditions: (1) treatment with sparse verbs or (2) treatment with dense verbs in 12 sessions. The third person singular lexical affix was targeted for 12 sessions of treatment in both conditions. Treatment gain and generalization were measured as the dependent variables. Third person singular % correct change from pre-treatment to post-treatment was measured using sentence production tasks with comparisons across the two treatment conditions. Treatment gain and generalization were greater for children enrolled in the sparse condition. Preliminary clinical recommendations are made and theoretical implications are discussed relative to neighbourhood density effects on lexical activation and storage in children with SLI.


Internal models engaged by brain-computer interface control.
Internal models have been proposed to explain the brain's ability to compensate for sensory feedback delays by predicting the sensory consequences of movement commands. Single-neuron studies in the oculomotor and vestibulo-ocular systems have provided evidence of internal models, as have behavioral studies in the skeletomotor system. Here, we present evidence of internal models from simultaneously recorded population activity underlying closed-loop brain-computer interface (BCI) control. We studied cursor-based BCI control by a nonhuman primate implanted with a multi-electrode array in motor cortex. Using a novel BCI task, we measured the visual feedback processing delay to be about 130 milliseconds. By examining the task-based appropriateness of the population activity at different time lags, we found evidence that the subject compensates for the feedback delay by predicting upcoming cursor positions, suggesting the use of an internal forward model. Lastly, we examined the time course of internal model adaptation after altering the mapping between population activity and cursor movements. This study suggests that closed-loop BCI experiments combined with novel statistical analyses can provide insight into the neural substrates of feedback motor control and motor learning.


Sympathectomy reduces mechanical allodynia, tumor necrosis factor-alpha expression, and dorsal root ganglion apoptosis following nerve root crush injury.
An analysis of pain behavior and neuronal apoptosis in the dorsal root ganglion (DRG) following crush injury to the L5 nerve root, with or without surgical sympathectomy. To determine whether sympathectomy prevents pain behavior and to compare pain behavior with expression of tumor necrosis factor (TNF)-alpha and apoptosis in the DRG. Sympathetic block is used to relieve symptoms in radiculopathy patients. One effect of the block is improvement of blood flow to the nerve. However, this beneficial effect continues longer than the expected duration of local anesthesia, suggesting an unknown neuroprotective effect involving interference with sympathetic activity. Sprague-Dawley rats (n = 102) were used and divided into 4 experimental groups. In the crush group, animals received a crush injury to the L5 nerve root. In the sympathectomy group, animals received sympathectomy (Syx) on the left side. In the Syx + crush group, both sympathectomy and crush injury were performed. In the sham group, the surgical procedure was the same, but neither sympathectomy nor crush injury took place. Mechanical allodynia was determined in 4 groups. Expression of TNF-alpha was compared in rats with crush injury, with and without sympathectomy. Using immunostaining for caspase 3, NeuN, and GFAP, localization of apoptotic cells was observed. In addition, we compared the percentage of neurons undergoing apoptosis in the DRG. Sympathectomy prevented mechanical allodynia throughout the 14-day experimental period. TNF-alpha expression was increased in the DRG following crush-only injury, whereas it was decreased in animals undergoing sympathectomy after the crush injury. DRG apoptosis in the crush group was significantly higher than in the sympathectomy group at day 7 (P < 0.05). Surgical sympathectomy reduced mechanical allodynia for 14 days after nerve root crush injury, and that DRG apoptosis was decreased in injured animals that underwent sympathectomy. Sympathetic block may not only cause an increase in nerve blood flow, but may also prevent the development of significant TNF-alpha elevation, DRG apoptosis, and neuropathic pain.


Duodenal switch for intractable reflux gastroesophagitis after proximal gastrectomy.
Reflux gastroesophagitis is a common postgastrectomy complication after proximal gastrectomy, and conservative treatments including protease inhibitors and proton pump inhibitors are effective in most patients. Here we report a patient with severe reflux gastroesophagitis after proximal gastrectomy, in whom surgical treatment of duodenal switch was effective. An 80-year-old man complained of intractable heartburn, anorexia, and body weight loss after having undergone proximal gastrectomy, with reconstruction by esophagogastrostomy with valvuloplasty and pyloroplasty, for early gastric cancer 14 months before referral to our department. Oral administration of protease inhibitors and proton pump inhibitors was ineffective. Laboratory evaluation showed poor nutritional status. On endoscopic examination, we noted the redness, bleeding, and multiple erosions in the esophagus and the gastric remnant. He was diagnosed to have severe gastroesophagitis due to reflux of duodenal juice into the gastric remnant and esophagus. We performed duodenal switch to divert duodenal juice from the gastric remnant and esophagus; the duodenum was transected 2 cm distal to the pylorus, the duodenal distal end was closed, and a 50-cm Roux limb from the proximal jejunum was anastomosed to the proximal end of the duodenum. The heartburn disappeared postoperatively, and endoscopic examination revealed marked improvement of the reflux gastroesophagitis. One year postoperatively, the patient is free from symptoms including heartburn. His body weight increased, and laboratory data showed improvement in nutritional status. In conclusion, the duodenal switch may be surgical treatment of choice for intractable reflux gastroesophagitis after proximal gastrectomy.


Feasibility of the Web-Based Intervention Designed to Educate and Improve Adherence Through Learning to Use Continuous Glucose Monitor (IDEAL CGM) Training and Follow-Up Support Intervention: Randomized Controlled Pilot Study.
Proper training and follow-up for patients new to continuous glucose monitor (CGM) use are required to maintain adherence and achieve diabetes-related outcomes. However, CGM training is hampered by the lack of evidence-based standards and poor reimbursement. We hypothesized that web-based CGM training and education would be effective and could be provided with minimal burden to the health care team. The aim of this study was to perform a pilot feasibility study testing a theory-driven, web-based intervention designed to provide extended training and follow-up support to adolescents and young adults newly implementing CGM and to describe CGM adherence, glycemic control, and CGM-specific psychosocial measures before and after the intervention. The "Intervention Designed to Educate and improve Adherence through Learning to use CGM (IDEAL CGM)" web-based training intervention was based on supporting literature and theoretical concepts adapted from the health belief model and social cognitive theory. Patients new to CGM, who were aged 15-24 years with type 1 diabetes for more than 6 months were recruited from within a public university's endocrinology clinic. Participants were randomized to enhanced standard care or enhanced standard care plus the IDEAL CGM intervention using a 1:3 randomization scheme. Hemoglobin A1c levels and psychosocial measures were assessed at baseline and 3 months after start of the intervention. Ten eligible subjects were approached for recruitment and 8 were randomized. Within the IDEAL CGM group, 4 of the 6 participants received exposure to the web-based training. Half of the participants completed at least 5 of the 7 modules; however, dosage of the intervention and level of engagement varied widely among the participants. This study provided proof of concept for use of a web-based intervention to deliver follow-up CGM training and support. However, revisions to the intervention are needed in order to improve engagement and determine feasibility. This pilot study underscores the importance of continued research efforts to optimize the use of web-based intervention tools for their potential to improve adherence and glycemic control and the psychosocial impact of the use of diabetes technologies without adding significant burden to the health care team. Enhancements should be made to the intervention to increase engagement, maximize responsiveness, and ensure attainment of the skills necessary to achieve consistent use and improvements in glycemic control prior to the design of a larger well-powered clinical trial to establish feasibility. ClinicalTrials.gov NCT03367351, https://clinicaltrials.gov/ct2/show/NCT03367351.


Hyperplasia and carcinoma of the endometrium.
Published criteria for classifying endometrial hyperplasias and their differential diagnosis from well-differentiated endometrioid-type adenocarcinoma are reviewed, and the author's own interpretations and recommendations are presented. Also discussed are the subjects of misdiagnosis of hyperplasia and carcinoma, premalignant significance of hyperplasia, and prognostic significance of hyperplasia in patients with carcinoma patients.


Assessment of microsatellite instability in head and neck cancer using consensus markers.
Head and neck cancer is the sixth most common cancer in the world and one of the most lethal cancers. Microsatellite instability is an important characteristic of tumor cells and is observed both in presence and absence of mismatch repair gene mutations. The importance of microsatellite instability in head and neck cancer is not well established due to the lack of a consensus panel and selection of different markers, criteria and methodological variances. The main objective of this study was to investigate the performance of a consensus panel of microsatellite repeats by automated fragment analysis. Matched tumor and normal tissue samples from 99 patients were analyzed using five mononucleotide markers. Following PCR the amplified fragments were analyzed by capillary electrophoresis on an ABI 310 genetic analyzer. Microsatellite instability was observed in 26 patients. In 17 patients instability was detected at multiple loci. NR21 and BAT25 were the most frequently altered targets. These two mononucleotide markers could detect all samples displaying high-instability. In this study we describe a standardized fluorescent multiplex PCR combined with computerized analysis, which allows rapid and accurate analysis of a high number of samples and obviates the need to compare tumors with matching normal tissue.


On designing an isotropic fiducial mark.
In this paper, the Cramér-Rao lower bound (CRLB) of image registration error using an isotropic fiducial mark is derived. The derived CRLB is a function of the intensity profile of the fiducial mark. Following the development of the CRLB, a new method for designing an isotropic fiducial mark, suitable for digital image registration, is presented. A parameterization method of the fiducial intensity profile is introduced which guarantees no aliasing effect when the fiducial mark is digitized with the proper sampling rate. A method for computing the fiducial intensity profile, based on minimization of the CRLB registration error, and subject to certain practical constraints, is developed. For imaging systems with a significant low-pass effect, it is proposed to pre-emphasize the high frequency components of the fiducial mark by converting the designed gray-scale fiducial marks into binary fiducial marks. Experimental results show that the designed fiducial mark can provide very accurate registration results and that the registration accuracy is independent of its location.


[Superacute lethal liver necrosis in monkeys infected with highly pathogenic variants of enteroviruses (ECHO 11 and ECHO 19 viruses)].
The authors studied the phenomenon of superhigh virulence for monkeys of viruses ECHO 11 (E11) and ECHO 19 (E19) isolated in 1981-1991 in Russia and Tadzhikistan from children with acute enterovirus uveitis or severe enterovirus infection. In 21 morphologically examined animals after coma, macrofocal or total necrosis of hepatocytes in weak inflammation was seen as early as experiment day 1-6. Hepatic lesion interpreted as hepatosis underlies acute hepatic failure with lethal outcome. The most intensive reproduction of viruses E11 and E19 occurred in the liver. Changes in the kidneys, lungs, spleen, adrenals, CNS detected in many animals aggravated the disease, but were not the primary cause of death. The disease in monkey was similar by the main criteria to superacute lethal diseases (acute hepatic failure against massive hepatic necrosis, hemorrhagic syndrome) registered in outbreaks of E11 and E19-virus infection in children in the USA, Great Britain, Israel, Russia and Ukraine. Monkeys can be used as man-adequate model for study of enterovirus superacute lethal necrosis of the liver.


Alcohol advertising at Boston subway stations: an assessment of exposure by race and socioeconomic status.
We investigated the frequency of alcohol ads at all 113 subway and streetcar stations in Boston and the patterns of community exposure stratified by race, socioeconomic status, and age. We assessed the extent of alcohol advertising at each station in May 2009. We measured gross impressions and gross rating points (GRPs) for the entire Greater Boston population and for Boston public school student commuters. We compared the frequency of alcohol advertising between neighborhoods with differing demographics. For the Greater Boston population, alcohol advertising at subway stations generated 109 GRPs on a typical day. For Boston public school students in grades 5 to 12, alcohol advertising at stations generated 134 GRPs. Advertising at stations in low-poverty neighborhoods generated 14.1 GRPs and at stations in high-poverty areas, 63.6 GRPs. Alcohol ads reach the equivalent of every adult in the Greater Boston region and the equivalent of every 5th- to 12th-grade public school student each day. More alcohol ads were displayed in stations in neighborhoods with high poverty rates than in stations in neighborhoods with low poverty rates.


Autonomic degeneration and altered blood pressure control in humans.
The study of patients with partial or total defects of their sympathetic nerves can help clarify the role of the sympathetic nervous system in blood pressure control. Denervation supersensitivity of both beta and alpha receptors develops in humans and is proportional to the degree of sympathetic withdrawal. Although alterations in beta-receptor sensitivity are familiar responses to beta agonists or antagonists, patients with decreased norepinephrine (NE) levels appear to develop alpha-receptor supersensitivity of greater hemodynamic importance. When beta supersensitivity is marked, there may be a pressor response to beta blockade even when circulating levels of NE and epinephrine are very low. Indomethacin blocks prostaglandin synthesis and causes an increase in blood pressure in patients with partial autonomic neuropathies. The drug increases blood pressure by enhancing alpha- and diminishing beta-receptor sensitivity to NE, so it is effective only in patients who have some residual NE release.


Involvement of BDNF receptor TrkB in spatial memory formation.
The N-methyl-D-aspartate (NMDA) receptors are involved in long-term potentiation (LTP), and are phosphorylated by several tyrosine kinases including a Src-family tyrosine kinase Fyn. Brain-derived neurotrophic factor (BDNF) is a neurotrophin, which also enhances hippocampal synaptic transmission and efficacy by increasing NMDA receptor activity. Here, we show that Fyn is a key molecule linking the BDNF receptor TrkB with NMDA receptors, which play an important role in spatial memory formation in a radial arm maze. Spatial learning induced phosphorylation of TrkB, Fyn, and NR2B, but not NR2A, in the hippocampus. Fyn was coimmunoprecipitated with TrkB and NR2B, and this association was increased in well-trained rats compared with control animals. Continuous intracerebroventricular infusion of PP2, a tyrosine kinase inhibitor, in rats delayed memory acquisition in the radial arm maze, but PP2-treated animals reached the same level of learning as the controls. The phosphorylation of Fyn and NR2B, but not TrkB, was diminished by PP2 treatment. Our findings suggest the importance of interaction between BDNF/TrkB signaling and NMDA receptors for spatial memory in the hippocampus.


Biomechanical comparison of extensile exposures in total knee arthroplasty.
The "banana peel" exposure is a novel technique for knee joint exposure that consists of partially peeling the patellar tendon off the tibia, leaving the extensor mechanism intact distally and laterally. Although good clinical results have been reported with this technique with no disruption of the extensor mechanism, concerns exist that it could cause extensor lag, quadriceps weakness, or patellar tendon rupture. We compared the banana peel exposure repair to tibial tubercle osteotomy repair, which we chose as our benchmark procedure because much is known about its associated healing and rehabilitation protocols. In our study of 16 paired, fresh-frozen human knee specimens, the 2 techniques were used alternately for the right and left knees. To measure acute strength, 10 pairs were tested. The patella was clamped and pulled superiorly at 25 mm/min until failure. For cyclical testing (6 pairs), the knee was extended from 90 degrees of flexion to 0 degrees for 2000 cycles at 0.25 Hz while we monitored the distance between the inferior pole of the patella and the tibial diaphysis using a passive optical kinematic measuring system. Mean failure strengths of the banana peel and osteotomy groups were 2642+/-1104 N and 2123+/-562 N, respectively, suggesting that the banana peel repair is not weaker than the osteotomy repair. Neither group had a significant increase (via paired Student t test, P>.05) in the distance between the inferior pole of the patella and the tibial diaphysis, suggesting that neither exposure would result in extensor lag.


The prevalence of sleep related disorders in Sivas, Turkey.
The prevalence of sleep-related disorders (SRD) in adults in Turkey is unknown. The main objective of our study was to assess the prevalence of SRD in Sivas, Turkey. Adults living in Sivas, a city of Turkey from the central region of Anatolia at 20-107 years of age, in both genders, of the 5339 persons, who attended the survey 2638 (49.4%) were male and 2701 (50.6%) were female. The prevalence of insomnia, habitual snoring, obstructive sleep apnea (OSA) and day time hyper somnolence was 40.3%, 37.0%, 6.4%, 24.0% respectively. The prevalence rates of narcolepsy and nocturnal myoclonus was 30.6%, 40.1% respectively. There was a statistical significance between the persons of above 60 years old and another age groups (p< 0.05). But we did not find any significant difference between smokers and non-smokers, also between males and females about SRD prevalence (p> 0.05). However, sleep apnea prevalence was about 9 times higher in the persons suffering from hypertension than without hypertension. Also sleep apnea prevalence was 12 times higher in the persons suffering from overweight. This study has shown that sleep-disordered breathing (SDB) prevalence in Turkey is as high as in other countries and may be more common.


Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection.
Polymorphisms in IL28B were shown to affect clearance of hepatitis C virus (HCV) infection in genome-wide association (GWA) studies. Only a fraction of patients with chronic HCV infection develop liver fibrosis, a process that might also be affected by genetic factors. We performed a 2-stage GWA study of liver fibrosis progression related to HCV infection. We studied well-characterized HCV-infected patients of European descent who underwent liver biopsies before treatment. We defined various liver fibrosis phenotypes on the basis of METAVIR scores, with and without taking the duration of HCV infection into account. Our GWA analyses were conducted on a filtered primary cohort of 1161 patients using 780,650 single nucleotide polymorphisms (SNPs). We genotyped 96 SNPs with P values <5 × 10(-5) from an independent replication cohort of 962 patients. We then assessed the most interesting replicated SNPs using DNA samples collected from 219 patients who participated in separate GWA studies of HCV clearance. In the combined cohort of 2342 HCV-infected patients, the SNPs rs16851720 (in the total sample) and rs4374383 (in patients who received blood transfusions) were associated with fibrosis progression (P(combined) = 8.9 × 10(-9) and 1.1 × 10(-9), respectively). The SNP rs16851720 is located within RNF7, which encodes an antioxidant that protects against apoptosis. The SNP rs4374383, together with another replicated SNP, rs9380516 (P(combined) = 5.4 × 10(-7)), were linked to the functionally related genes MERTK and TULP1, which encode factors involved in phagocytosis of apoptotic cells by macrophages. Our GWA study identified several susceptibility loci for HCV-induced liver fibrosis; these were linked to genes that regulate apoptosis. Apoptotic control might therefore be involved in liver fibrosis.


Evaluation of short-term antibiotic therapy in children with uncomplicated urinary tract infections.
This study was designed to determine whether serum C-reactive protein (CRP) concentrations could be used to identify children with uncomplicated lower urinary tract infection who would respond favorably to short-term antibiotic therapy. A one-day or ten-day regimen of cefadroxil (30 mg/kg/day in two divided doses) was assigned randomly to 80 children who had acute urinary tract infection and CRP concentrations less than 28 microgram/ml (CRP-negative group). Ten days of cefadroxil therapy was used to treat 44 children with urinary tract infection and CRP values greater than or equal to 28 microgram/ml (CRP-positive group). The clinical and laboratory characteristics of the children in the two CRP-negative therapy groups were similar to, but different from those of children with CRP-positive infections. Recurrent infections occurred significantly more often at four to five days after completion of therapy in CRP-negative children who received one day (44.4%) compared to ten days (20%) of cefadroxil therapy (P less than .05). When data from this study were combined with those from our previously published investigation of short-term antibiotic therapy in CRP-negative children, a significantly larger percentage of recurrences was documented immediately after one or four days of antibiotics (79%) compared to recurrences after the standard ten-day regimen (41%). Additionally, the total rate of recurrent infections for all children in both studies was significantly larger in those who received short-term therapy (48%) as opposed to conventional therapy (34%). These data indicate that short-term antibiotic therapy is less effective than the conventional ten-day regimen in children with CRP-negative urinary tract infection.


The heme oxygenase-1 genotype is a risk factor to renal impairment of IgA nephropathy at diagnosis, which is a strong predictor of mortality.
The induction of heme oxygenase-1 (HO-1) ameliorates oxidative stress and inflammatory process, which play important roles in IgA nephropathy. We hypothesized length polymorphism in the promoter region of the HO-1 gene, which is related to the level of gene transcription, is associated with disease severity of IgA nephropathy. The subjects comprised 916 patients with IgA nephropathy and gene data. Renal impairment was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) at diagnosis. The short (S: <23), medium (M: 23-28), and long (L: >28) (GT) repeats in the HO-1 gene was determined. The frequencies of S/S, S/M, M/M, S/L, L/M, and L/L genotypes were 7.2%, 6.9%, 3.1%, 30.8%, 22.7%, and 29.4%, respectively. The baseline characteristics were not different. In the S/S genotypic group, the renal impairment rate was 18.2%, which was lower than 32.2% in the group with M/M, L/M, or L/L genotype. The odds ratio of renal impairment in S/S genotype, compared to that in M/M, L/M, or L/L genotype, was 0.216 (95% confidence interval, 0.060-0.774, p=0.019). The HO-1 gene promoter length polymorphism was related to the renal impairment of IgA nephropathy at diagnosis, which is an important risk factor for mortality in IgA nephropathy patients.


Infliximab, adalimumab and vedolizumab concentrations across pregnancy and vedolizumab concentrations in infants following intrauterine exposure.
The impact of pregnancy on levels of biologic agents in patients with IBD is undefined and time to elimination in vedolizumab-exposed infants is unknown. To determine the effect of pregnancy on infliximab, adalimumab and vedolizumab levels and to study infant vedolizumab clearance METHODS: In a prospective observational study, maternal drug levels were measured pre-conception, in each trimester, at delivery and postpartum. The association between drug levels and gestation in weeks was assessed using generalised estimating equation modelling. Infant vedolizumab levels were performed at birth (cord blood), 6 weeks and 3 months or until undetectable. We included 50 IBD patients (23 on infliximab, 15 on adalimumab and 12 on vedolizumab) with at least two intrapartum observations, plus 5 patients on vedolizumab with only mother and baby samples at delivery. Modelling showed no change in adalimumab levels, an increase in infliximab levels of 0.16 (95% CI 0.08-0.24) µg/L/week (P < 0.001) and a decrease of 0.18 (95% CI: -0.33 to -0.02) µg/L/week (P = 0.03) for vedolizumab. In 17 mother-baby pairs, median infant vedolizumab levels at birth were lower than maternal levels (P < 0.05) with an infant:maternal ratio of 0.7 (IQR 0.5-0.9). Vedolizumab was undetectable between 15 and 16 weeks of age in all 12 infants completing follow-up testing. During pregnancy, adalimumab levels remain stable, while infliximab levels increase and vedolizumab levels decrease. However, the increments were small suggesting that intrapartum therapeutic drug monitoring and dose adjustment are not indicated. Unlike infliximab and adalimumab, infant vedolizumab levels are lower in cord blood than in mothers and appear to clear rapidly.


Differential biodistribution of intravenously administered endothelial progenitor and cytotoxic T-cells in rat bearing orthotopic human glioma.
A major challenge in the development of cell based therapies for glioma is to deliver optimal number of cells (therapeutic dose) to the tumor. Imaging tools such as magnetic resonance imaging (MRI), optical imaging, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has been used in cell tracking and/or biodistribution studies. In this study, we evaluate the dynamic biodistribution of systemic injected labeled cells [human cord blood derived endothelial progenitor cells (EPCs) and cytotoxic T-cells (CTLs)] in rat glioma model with in vivo SPECT imaging. Human cord blood EPCs, T-cells and CD14⁺ cells (monocytes/dendritic cells) were isolated using the MidiMACS system. CD14⁺ cells were converted to dendritic cells (DC) and also primed with U251 tumor cell line lysate. T-cells were co-cultured with irradiated primed DCs at 10:1 ratio to make CTLs. Both EPCs and CTLs were labeled with In-111-oxine at 37°C in serum free DMEM media. Glioma bearing animals were randomly assigned into three groups. In-111 labeled cells or In-111 oxine alone were injected through tail vein and SPECT imaging was performed on day 0, 1, and 3. In-111 oxine activity in various organs and tumor area was determined. Histochemical analysis was performed to further confirm the migration and homing of injected cells at the tumor site. EPCs and CTLs showed an In-111 labeling efficiency of 87.06 ± 7.75% and 70.8 ± 12.9% respectively. Initially cell migration was observed in lung following inravenous administration of In-111 labeled cells and decreased on day 1 and 3, which indicate re-distribution of labeled cells from lung to other organs. Relatively higher In-111 oxine activity was observed in tumor areas at 24 hours in animals received In-111 labeled cells (EPCs or CTLs). Histiological analysis revealed iron positive cells in and around the tumor area in animals that received labeled cells (CTLs and EPCs). We observed differential biodistribution of In-111-oxine labeled EPCs and CTLs in different organs and intracranial glioma. This study indicates In-111 oxine based SPECT imaging is an effective tool to study the biodistribution of therapeutically important cells.


Hypertrophic repair of articular cartilage in experimental osteoarthrosis.
Section of the anterior cruciate ligament has been performed in the knee of 11 mature dogs. The macroscopically normal cartilage from patella and femoral trochlea of animals killed from 2 to 32 weeks after operation was used for histological, histomorphometrical, and biochemical analysis. Previously undescribed degenerative lesions of the superficial matrix were observed, and there was evidence for secondary healing of these lesions. An early and progressive decrease in superficial cell density and a later progressive increase in cartilage thickness without any change in the cell density of the middle and deep cartilage layers was found. A slight increase in water content with no reduction in glycosaminoglycan content was observed. The results suggest that joint laxity results initially in superficial degenerative changes and later in hypertrophic regenerative changes due to cell proliferation and increased matrix synthesis. Hypertrophic remodeling of articular cartilage in response to abnormal mechanical stresses is postulated.


Neurobiological correlates of antisociality across adolescence and young adulthood: a multi-sample, multi-method study.
Antisociality across adolescence and young adulthood puts individuals at high risk of developing a variety of problems. Prior research has linked antisociality to autonomic nervous system and endocrinological functioning. However, there is large heterogeneity in antisocial behaviors, and these neurobiological measures are rarely studied conjointly, limited to small specific studies with narrow age ranges, and yield mixed findings due to the type of behavior examined. We harmonized data from 1489 participants (9-27 years, 67% male), from six heterogeneous samples. In the resulting dataset, we tested relations between distinct dimensions of antisociality and heart rate, pre-ejection period (PEP), respiratory sinus arrhythmia, respiration rate, skin conductance levels, testosterone, basal cortisol, and the cortisol awakening response (CAR), and test the role of age throughout adolescence and young adulthood. Three dimensions of antisociality were uncovered: 'callous-unemotional (CU)/manipulative traits', 'intentional aggression/conduct', and 'reactivity/impulsivity/irritability'. Shorter PEPs and higher testosterone were related to CU/manipulative traits, and a higher CAR is related to both CU/manipulative traits and intentional aggression/conduct. These effects were stable across age. Across a heterogeneous sample and consistent across development, the CAR may be a valuable measure to link to CU/manipulative traits and intentional aggression, while sympathetic arousal and testosterone are additionally valuable to understand CU/manipulative traits. Together, these findings deepen our understanding of the fundamental mechanisms underlying different components of antisociality. Finally, we illustrate the potential of using current statistical techniques for combining multiple datasets to draw robust conclusions about biobehavioral associations.


Clinicopathologic correlations in the oligodendroglioma.
To determine the prognostic significance of histologic variables in oligodendroglial neoplasms, the presence and degree of 15 such variables were correlated with postoperative survival rates in 71 patients. By univariate analysis, prognostically significant factors, in order of decreasing importance, were mitoses (log), necrosis, nuclear cytologic atypia, vascular hypertrophy, and vascular proliferation. When studied by stepwise regression, necrosis and the number of mitoses contained all of the prognostically useful information. When each of the five variables significant by univariate analysis was tested in the Cox model by adding a variable to the model containing the other four, necrosis was found to be the only independently significant variable. There were significant positive pairwise correlations between each of the five significant histologic variables except for cytologic atypia with necrosis. The only histologic variable with a significant association with older age was the number of mitoses. These results suggest that necrosis and, to a lesser extent, the mitotic count are features that, in the appropriate setting, can be used to identify the "anaplastic" oligodendroglioma.


Improving retention in the early infant diagnosis of HIV program in rural Mozambique by better service integration.
Low mother/infant retention has impeded early infant diagnosis of HIV in rural Mozambique. We enhanced the referral process for postpartum HIV-infected women by offering direct accompaniment to the location of exposed infant testing before discharge. Retrospective record review for 395 women/infants (September 2009 to June 2010) found enhanced referral was associated with higher odds of follow-up (adjusted odds ratio = 3.18, 95% confidence interval: 1.76 to 5.73, P < 0.001); and among those followed-up, earlier infant testing (median follow-up: 33 days vs. 59 days, P = 0.01) compared with women receiving standard referral. This simple intervention demonstrates benefits gleaned from attention to system improvement through service integration without increasing staff.


Abdominal Contouring and Male Gender: Analysis of Complications Using the National Quality Improvement Program Database.
Males represent a significant portion of patients undergoing abdominal contouring. Despite this, there are few studies examining the implication of gender on complications. The aim of this study was to examine the association between gender and early postoperative outcomes in patients undergoing abdominal contouring procedures. The American College of Surgeons National Surgical Quality Improvement Program database (2006-2016) was queried to identify subjects undergoing panniculectomy or abdominoplasty. Minor and major complications were identified. Operative time and length of hospital stay were evaluated. A logistic regression model was used to examine associations between patient gender and adverse outcomes. Ten thousand four hundred seventy-three patients were identified. Of these, 4369 underwent abdominoplasties, and 6104 underwent panniculectomies. Males represented a higher percentage of the panniculectomy cohort (15.3% vs 9.2%). Males were older and generally had more comorbidities including diabetes, hypertension, chronic obstructive pulmonary disease, and elevated body mass index. Males also had a higher American Society of Anesthesiologists classification (P < 0.001). In the abdominoplasty cohort, male gender is an independent risk factor for any complication (odds ratio [OR], 1.3; confidence interval [CI], 1.16-1.45; P < 0.001) and major complications (OR, 1.52; CI, 1.01-2.29; P = 0.043). In the panniculectomy cohort, male gender is also an independent risk factor for any complication (OR, 1.47; CI, 1.24-1.75; P < 0.001) and major complications (OR, 1.43; CI, 1.12-1.83; P < 0.001). Males also had a significantly longer operative times in this cohort (171.3 vs 157.5 minutes; P < 0.001). Male gender is independently associated with minor and major complications in these patient populations. With this knowledge, plastic surgeons may be better able to identify higher-risk individuals and educate patients on their risk profile.


N-phosphoryl amino acids and biomolecular origins.
The possible role of phosphoryl amino acids for biomolecular origins is briefly reviewed. Peptide formation, ester formation, ester exchange on phosphorus and N to O migration occurred when the N-phosphoryl amino acid was incubated at room temperature. Short nucleotides and peptides were formed when nucleoside was reacted with N-phosphoryl amino acid at room temperature. Serine and threonine residues in their conjugate with different nucleosides (mediated with phosphorus) showed different self-cleavage activities. N-phosphoryl Histine and Ser-His dipeptide could cleave nucleic acids, proteins and esters in neutral medium. Based on a simple model, a pathway of 'co-evolution of protein and nucleic acid' was proposed.


Reimbursement of pharmaceuticals: reference pricing versus health technology assessment.
Reference pricing and health technology assessment are policies commonly applied in order to obtain more value for money from pharmaceuticals. This study focussed on decisions about the initial price and reimbursement status of innovative drugs and discussed the consequences for market access and cost. Four countries were studied: Germany, The Netherlands, Sweden and the United Kingdom. These countries have operated one, or both, of the two policies at certain points in time, sometimes in parallel. Drugs in four groups were considered: cholesterol-lowering agents, insulin analogues, biologic drugs for rheumatoid arthritis and "atypical" drugs for schizophrenia. Compared with HTA, reference pricing is a relatively blunt instrument for obtaining value for money from pharmaceuticals. Thus, its role in making reimbursement decisions should be limited to drugs which are therapeutically equivalent. HTA is a superior strategy for obtaining value for money because it addresses not only price but also the appropriate indications for the use of the drug and the relation between additional value and additional costs. However, given the relatively higher costs of conducting HTAs, the most efficient approach might be a combination of both policies.


[Delusions and society in Japan and China from a transcultural-psychiatric viewpoint].
The relationship between contents of schizophrenic delusions and sociocultural background in the modern society of Japan and China were studied from transcultural psychiatric aspects. The data of this study were derived from the public mental hospitals in Tokyo and Shanghai in a similar size; of 186 cases (88 cases of male, 98 cases of female) of the first admission in Tokyo Metropolitan Matsuzawa Hospital during 1981-1983, 112 cases with delusions (53 cases of male, 59 cases of female) were selected, and of 200 cases (112 cases of male, 88 cases of female) of the first admission in Shanghai Psychiatric Hospital in 1983, 129 cases with delusions (70 cases of male, 59 cases of female) were chosen. The incidence of delusions of physical persecution and grandeur was relatively high in patients of both hospitals in Tokyo and Shanghai, while the incidence of delusions with hypochondria and guilt was low in both hospitals. Only the incidence of delusion of poisoning was significantly higher in Shanghai than in Tokyo (mean 2 = 12.97, p less than 0.001). After the World War II, the patriarchally oriented family system was abolished in Japan which caused shifting the system from a large family to a nuclear family. In China where the property (land) and daily life were closely connected the close human relationship among generations had important values in relation to the labor power within the frame of a large family. It is believed that occurrence of the delusion of poisoning might be a reflection of the disturbed human relationship within the family member in dining which should be helpful for making further understanding and reliance. It's occurrence conflict and struggle in the community of the outside of the family. At present there is a marked difference between Chinese and Japanese in their structure of consciousness. The former places high value and meaningfulness on the participation to the group and seeks protection and safety of individuals. The latter reveals a less strong tie with the traditional conformity and dependency to the mass due to the conformation of the nuclear family. It can not be ignored the possible effect of the close horizontal interaction and cautious human relationships among neighbours with fear of rumor and watching in the Chinese community on the occurrence of the delusion of persecution. After the World War II, abolishment of the principle of vertical control system and introduction of multiple value system together with loss of authority had taken place in Japan.(ABSTRACT TRUNCATED AT 400 WORDS)


Tissue hemoglobin O2 saturation during resuscitation of traumatic shock monitored using near infrared spectrometry.
Near infrared (NIR) spectrometry offers a noninvasive monitor of tissue hemoglobin O2 saturation and has been developed to report a quantitative clinical variable, StO2 [= HbO2/(HbO2 + Hb)]. In this study, a prototype NIR oximeter was used to investigate the hypothesis that changes in systemic O2 delivery index (D(O2)I) would be reflected by changes in StO2 in skeletal muscle, subcutaneous tissue, or both, as reperfusion occurs during shock resuscitation. StO2 was also compared with other indices of severity of shock or adequacy of resuscitation, including arterial base deficit, lactate, gastric mucosal P(CO2) (PgCO2), and mixed venous hemoglobin O2 saturation (S(VO2)). Skeletal muscle and subcutaneous tissue StO2 were monitored simultaneously in eight severely injured trauma patients (88% blunt mechanism; age, 42 +/- 6 years; Injury Severity Score, 27 +/- 3) during standardized shock resuscitation in the intensive care unit with the primary goal of D(O2)I > or = 600 mL O2/min/m2 for 24 hours, and for an additional 12 hours during transition from resuscitation to standard intensive care unit care. Skeletal muscle StO2 increased significantly from 15 +/- 2% (mean +/- SEM) at the start of resuscitation to 49 +/- 14% at 24 hours, and to approximately 55% from 25 to 36 hours. Subcutaneous tissue StO2 approximately 82% and was significantly greater than skeletal muscle StO2 throughout. D(O2)I increased significantly from 372 +/- 54 to 718 +/- 47 mL O2/min/m2 during resuscitation. Over 36 hours, mean D(O2)I and skeletal muscle StO2 were highly correlated (r = 0.95). Neither D(O2)I-PgCO2 nor D(O2)I-S(VO2) were significantly correlated; neither S(VO2) nor subcutaneous tissue StO2 changed significantly. Hemoglobin O2 saturation was monitored noninvasively and simultaneously in skeletal muscle and subcutaneous tissues as StO2 (%) by using a prototype NIR oximeter. Skeletal muscle StO2 tracked systemic O2 delivery during and after resuscitation. As a rapidly deployable, noninvasive monitor of peripheral tissue oxygenation and O2 delivery, skeletal muscle StO2 obtained using NIR spectrometry would be useful to guide resuscitation in the intensive care unit, to monitor resuscitation status in the operating room, and, potentially, in combination with indicators such as base deficit and lactate, to detect shock during initial assessment of the severe trauma patient in the emergency department.


Experimental study of the effects of DNAPL distribution on mass rebound.
The release of stored dissolved contaminants from low permeability zones contributes to plume persistence beyond the time when dense nonaqueous phase liquid (DNAPL) has completely dissolved. This is fundamental to successfully meeting acceptable low concentrations in groundwater that are driven by site-specific cleanup goals. The study goals were to assess the role of DNAPL entrapment morphology on mass storage and plume longevity. As controlled field studies are not feasible, two-dimensional (2D) test tanks were used to quantify the significance of mass loading processes from source dissolution and stored mass rebound. A simple two-layer soil domain representing a high permeable formation sand overlying a zone of lower permeability sand was used in the tests. DNAPL mass depletion through dissolution was monitored via X-ray photon attenuation, and effluent samples were used to monitor the plume. These data enabled analysis of the DNAPL distribution, the dissolved plume, and the dissolved phase distribution within the low permeability layer. Tests in an intermediate tank showed that mass storage contributes substantially to plume longevity. Detectable effluent concentrations persisted long after DNAPL depletion. The small tank results indicated that the DNAPL morphology influenced the flow field and caused distinctive transport mechanisms contributing to mass storage. Zones of high DNAPL saturation at the interface between the low and high permeability layers exhibited flow bypassing and diffusion dominated transport into the low permeability layer. In the absence of a highly saturated DNAPL zone near the soil interface the contaminant penetrated deeper into the low permeability layer caused by a combination of advection and diffusion.


Can favourable psychosocial working conditions in midlife moderate the risk of work exit for chronically ill workers? A 20-year follow-up of the Whitehall II study.
To investigate if favourable psychosocial working conditions can reduce the risk of work exit and specifically for workers with chronic disease. Men and women (32%) aged 35-55, working and having no chronic disease at baseline of the Whitehall II study of London-based civil servants were selected (n=9040). We observed participants' exit from work through retirement, health-related exit and unemployment, new diagnosis of chronic disease (ie, coronary heart disease, diabetes, stroke and cancer) and their psychosocial working conditions in midlife. Using cause-specific Cox models, we examined the association of chronic disease and favourable psychosocial working conditions and their interaction, with the three types of work exit. We adjusted for gender, occupational grade, educational level, remaining in civil service, spouse's employment status and mental health. Chronic disease significantly increased the risk of any type of work exit (HR 1.27) and specifically the risk of health-related exit (HR 2.42). High skill discretion in midlife reduced the risk of any type of work exit (HR 0.90), retirement (HR 0.91) and health-related exit (HR 0.68). High work social support in midlife decreased the risk of health-related exit (HR 0.79) and unemployment (HR 0.71). Favourable psychosocial working conditions in midlife did not attenuate the association between chronic disease and work exit significantly. The chronically ill have increased risks of work exit, especially through health-related exit routes. Chronic disease is an obstacle to extended working lives. Favourable working conditions directly relate to reduced risks of work exit.


Spray drying TB vaccines for pulmonary administration.
New developments in materials science provide innovative technologies that allow mucosal immunization against tuberculosis. Recent studies report that spray-drying Mycobacterium bovis Bacillus Calmette-Guérin (BCG) allows efficient aerosol delivery of TB vaccines to the lung. To consider powder formulation of BCG for inhalation by spray-drying and its potential application to other vaccines given the unique challenges in the process, formulation and delivery. Description of current advances in spray-drying and aerosol delivery, and its application to preparation of BCG TB vaccine for inhalation. Special consideration is given to physical properties, viability, stability and delivery aspects. Spray-drying generates powders with excellent dispersion qualities suitable for targeted delivery to the deep lung. TB vaccine for inhalation prepared by spray-drying is feasible, low-cost and pharmaceutically scaleable.


Attachment Style and Internet Addiction: An Online Survey.
One of the clinically relevant problems of Internet use is the phenomenon of Internet addiction. Considering the fact that there is ample evidence for the relationship between attachment style and substance abuse, it stands to reason that attachment theory can also make an important contribution to the understanding of the pathogenesis of Internet addiction. The aim of this study was to examine people's tendency toward pathological Internet usage in relation to their attachment style. An online survey was conducted. Sociodemographic data, attachment style (Bielefeld questionnaire partnership expectations), symptoms of Internet addiction (scale for online addiction for adults), used Web-based services, and online relationship motives (Cyber Relationship Motive Scale, CRMS-D) were assessed. In order to confirm the findings, a study using the Rorschach test was also conducted. In total, 245 subjects were recruited. Participants with insecure attachment style showed a higher tendency to pathological Internet usage compared with securely attached participants. An ambivalent attachment style was particularly associated with pathological Internet usage. Escapist and social-compensatory motives played an important role for insecurely attached subjects. However, there were no significant effects with respect to Web-based services and apps used. Results of the analysis of the Rorschach protocol with 16 subjects corroborated these results. Users with pathological Internet use frequently showed signs of infantile relationship structures in the context of social groups. This refers to the results of the Web-based survey, in which interpersonal relationships were the result of an insecure attachment style. Pathological Internet use was a function of insecure attachment and limited interpersonal relationships.


Optimal electron and combined electron and photon therapy in the phase space of complication-free cure.
The possibility of using intensity-modulated high-energy electrons beams alone or in combination with photon beams to treat tumours located at depths from 5 cm to 25 cm has been investigated. A radiobiologically based optimization algorithm using the probability of complication-free tumour control has been used to calculate the optimal dose distributions. Two different target volumes have been used; one advanced cervical cancer with locally involved lymph nodes and one astrocytoma in the upper brain hemisphere. Treatments with only electron beams and also combinations between electron and photon beams have been investigated. The dependence of the expected treatment outcome on the beam energy and directions was investigated, and to some extent on the number of beam portals. It is shown that the beam direction intervals resulting in a high expected treatment outcome increase with increasing electron energy and also with some electron-photon combinations. For an eccentrically placed, not too deeply situated tumour surrounded by sensitive normal tissue it is shown that the expected treatment outcome can be improved by using electron beams in combination with photon beams compared with using two photon beams, and using two electron beams results in almost as high an expected treatment outcome. The possibility of improving the dose conformity from electron beams by adding photon fields parallel or orthogonal to the electron beams is demonstrated.


Altered pathogenesis of a mutant of the murine coronavirus MHV-A59 is associated with a Q159L amino acid substitution in the spike protein.
C12, an attenuated, fusion delayed, very weakly hepatotropic mutant of mouse hepatitis virus strain A59 (MHV-A59( has been further characterized. We have previously shown that C12 has two amino acid substitutions relative to wild type virus in the spike protein, Q159L (within a region of S1 shown to bind to viral receptor in an in vitro assay) and H716D (in the proteolytic cleavage recognition site). We have sequenced the rest of the 31-kb genome of C-12 and compared it to wild type virus. Only three additional amino acids substitutions were found, all encoded within the replicase gene. Analysis of C12 in vivo in C57Bl/6 mice has shown that despite the fact that this virus replicates in the brain to titers at least as high as wild type and causes acute encephalitis similar to wild-type, this virus causes a minimal level of demyelination and only at very high levels of virus inoculation. Thus acute encephalitis is not sufficient for the induction of demyelination by MHV-A59. Analysis of mutants isolated at earlier times from the same persistently infected glial cell culture as C12, as well as mutants isolated from a second independent culture of persistently infected glial cells, suggests that both the weakly demyelinating and the weakly hepatotropic phenotypes of C12 are associated with the Q159L amino acid substitution.


Dual roles of the nuclear cap-binding complex and SERRATE in pre-mRNA splicing and microRNA processing in Arabidopsis thaliana.
The processing of Arabidopsis thaliana microRNAs (miRNAs) from longer primary transcripts (pri-miRNAs) requires the activity of several proteins, including DICER-LIKE1 (DCL1), the double-stranded RNA-binding protein HYPONASTIC LEAVES1 (HYL1), and the zinc finger protein SERRATE (SE). It has been noted before that the morphological appearance of weak se mutants is reminiscent of plants with mutations in ABH1/CBP80 and CBP20, which encode the two subunits of the nuclear cap-binding complex. We report that, like SE, the cap-binding complex is necessary for proper processing of pri-miRNAs. Inactivation of either ABH1/CBP80 or CBP20 results in decreased levels of mature miRNAs accompanied by apparent stabilization of pri-miRNAs. Whole-genome tiling array analyses reveal that se, abh1/cbp80, and cbp20 mutants also share similar splicing defects, leading to the accumulation of many partially spliced transcripts. This is unlikely to be an indirect consequence of improper miRNA processing or other mRNA turnover pathways, because introns retained in se, abh1/cbp80, and cbp20 mutants are not affected by mutations in other genes required for miRNA processing or for nonsense-mediated mRNA decay. Taken together, our results uncover dual roles in splicing and miRNA processing that distinguish SE and the cap-binding complex from specialized miRNA processing factors such as DCL1 and HYL1.


The association between visual impairment and the risk of mortality: a meta-analysis of prospective studies.
The findings from prospective studies on visual impairment (VI) and the risk of mortality are not consistent. A meta-analysis of prospective studies was conducted to quantitatively summarise the evidence about the association between VI and the risk of mortality. Pertinent studies were identified by a search of PubMed, Web of Science and the Chinese National Knowledge Infrastructure and Wanfang databases up to December 2015. The random-effect model was used to combine study-specific relative risks (RRs) and 95% CIs. Meta-regression and subgroup analysis were conducted to explore potential sources of heterogeneity. Publication bias was estimated by Egger's test and the funnel plot. Dose-response relationship was assessed by restricted cubic spline functions. This meta-analysis contained 29 prospective studies including 269 839 participants and 67 061 deaths. Compared to the no VI, the highest VI level was significantly associated with an increased risk of mortality (RR: 1.36, 95% CI 1.25 to 1.46). The association remained significant in participants older than 65 years (RR: 1.28, 95% CI 1.18 to 1.39), and a significant association was also observed in men (RR: 1.29, 95% CI 1.07 to 1.54) and women (RR: 1.39, 95% CI 1.14 to 1.70), respectively. For dose-response analysis, a linear relation was found between visual acuity (VA) and the risk of mortality. For every 0.1 Logarithm of the Minimum Angle of Resolution (LogMAR) increment, the risk of mortality increased by 4% (RR: 1.04, 95% CI 1.01 to 1.06). VI was significantly associated with an increased risk of mortality.


Poor patient comprehension of abnormal mammography results.
Screening mammography for women 50 to 69 years of age may lead to 50% having an abnormal study. We set out to determine the proportion of women who understand their abnormal mammogram results and the factors that predict understanding. We surveyed 970 women age 40 to 80 years identified with abnormal mammograms from 4 clinical sites. We collected information on demographic factors, language of interview, consultation with a primary care physician, receipt of follow-up tests, and method of notification of index mammogram result. This study examines the following outcomes: the participant's report of understanding of her physician's explanation of results of the index mammogram, and a comparison of the radiology report to the participant's report of her index mammogram result. Multivariate models controlled for age, education, income, insurance status, and clinical site. The majority (70%) reported a "full understanding" of their physician's explanation of their abnormal mammogram, but a significant minority (30%) reported less than a full understanding (somewhat, not at all, did not explain). Among women of Asian ethnicity, only 63% reported full understanding. Asian ethnicity was a negative predictor (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.3 to 0.7), and consultation with a primary care physician was a positive predictor (OR, 2.3; 95% CI, 1.7 to 3.3) of reported full understanding. Of the 304 women with a suspicious abnormality, only 51% understood their result to be abnormal. Women notified in person or by telephone were more likely than women notified in writing to understand their result to be abnormal (OR, 2.3; 95% CI, 1.2 to 4.8). Almost half of women with the most suspicious mammograms did not understand that their result was abnormal. Our data suggest that direct communication with a clinician in person or by phone improves comprehension.


A Rare Case of Primary Plasma Cell Leukaemia with Monosomy X.
Primary Plasma Cell Leukaemia (pPCL) is a very rare and aggressive subtype of plasma cell dyscrasias with a very poor outcome and characterized by presence of >2x109/l circulating plasma cells. Overall incidence being 1%-2% of all malignant plasma cell diseases and 0.9% of all acute leukaemias. Patients with primary and secondary PCL have similar clinical features but differences do exist. Here we report a rare and interesting case diagnosed as primary PCL in a 44-year-old female with unusual clinical presentation and complex karyotyping. Her serum electrophoresis showed a monoclonal IgG component and immunohistochemistry of bone marrow plasma cells showed CD 38 positive and CD 20 negative. The patient initially responded partially for combination chemotherapy, but succumbed after 20 days of diagnosis. We are presenting this case to highlight the importance of early diagnosis of such haematological malignancies in settings where treatment options like stem cell transplantation are limited.


Proton percolation on hydrated lysozyme powders.
The framework of percolation theory is used to analyze the hydration dependence of the capacitance measured for protein samples of pH 3-10, at frequencies from 10 kHz to 4 MHz. For all samples there is a critical value of the hydration at which the capacitance sharply increases with increase in hydration level. The threshold h(c) = 0.15 g of water per g of protein is independent of pH below pH 9 and shows no solvent deuterium isotope effect. The fractional coverage of the surface at h(c) is in close agreement with the prediction of theory for surface percolation. We view the protonic conduction process described here for low hydration and previously for high hydration as percolative proton transfer along threads of hydrogen-bonded water molecules. A principal element of the percolation picture, which explains the invariance of h(c) to change in pH and solvent, is the sudden appearance of long-range connectivity and infinite clusters at the threshold h(c). The relationship of the protonic conduction threshold to other features of protein hydration is described. The importance of percolative processes for enzyme catalysis and membrane transport is discussed.


Plasma cell densities and glomerular filtration rates predict renal allograft outcomes following acute rejection.
The contribution of T cells and graft-reactive antibodies to acute allograft rejection is widely accepted, but the role of graft-infiltrating B and plasma cells is controversial. We examined 56 consecutive human renal transplant biopsies classified by Banff schema into T-cell-mediated (N = 21), antibody-mediated (N = 18), and mixed (N = 17) acute rejection, using standard immunohistochemistry for CD3, CD20, CD138, and CD45. In a predominantly African-American population (75%), neither Banff classification nor C4d deposition predicted the return to dialysis. Immunohistochemical analysis revealed CD3(+) T cells as the dominant cell type, followed by CD20(+) B cells and CD138(+) plasma cells in all acute rejection types. Using univariate Cox Proportional Hazard analysis, plasma cell density significantly predicted graft failure while B-cell density trended toward significance. Surprisingly T-cell density did not predict graft failure. The estimated glomerular filtration rate (eGFR) at diagnosis of acute rejection also predicted graft failure, while baseline eGFR ≥6 months prior to biopsy did not. Using multivariate analysis, a model including eGFR at biopsy and plasma cell density was most predictive of graft loss. These observations suggest that plasma cells may be a critical mediator and/or an independently sensitive marker of steroid-resistant acute rejection.


Carrier-mediated uptake and phloem systemy of a 350-Dalton chlorinated xenobiotic with an alpha-amino acid function.
In a previous paper we have shown that epsilon-(phenoxyalkanecarboxylyl)-L-Lys conjugates are potent inhibitors of amino acid transport systems and that it is possible to modulate the uptake inhibition by hydrophobic or hydrophilic additions in the 4-position of the aromatic ring (J.F. Chollet, C. Delétage, M. Faucher, L. Miginiac, J.L. Bonnemain [1997] Biochem Biophys Acta 1336: 331-341). In this report we demonstrate that epsilon-(2,4-dichlorophenoxyacetyl)-L-Lys (2,4D-Lys), one of the largest molecules of the series and one of the most potent inhibitors, is a highly permeant conjugate. Uptake of 2,4D-Lys by broad bean (Vicia faba) leaf discs is mediated by an active carrier system (Km1 = 0.2 mM; Vmax1 = 2.4 nmol x cm(-2) x h(-1) at pH 5.0) complemented by an important diffusive component. Among the compounds tested (neutral, basic, and acidic amino acids, auxin, glutathione, and sugars), only the aromatic amino acids clearly compete with 2,4D-Lys. The conjugate accumulates in the vein network, is exported toward the growing organs, and exhibits a distribution pattern different from that of the herbicide moiety. However, over time 2,4D-Lys progressively splits into 2,4D and lysine. Analyses by high-performance liquid chromatography and liquid scintillation spectrometry of the phloem sap collected from the castor bean system, used as a systemy test, indicate decreasing capacities of 2,4D, 2,4D-Lys, and glyphosate, respectively, to move from the epidermis cell wall to the sieve element. Our results show that it is possible to design synthesis of large-size xenobiotics (approximately 350 D) with a lipophilic pole, exhibiting high mobility within the vascular system.


[Dependence N200 and P300 ERPs in P300-based brain-computer interface on the variations of voluntary attention].
Hypothesis about dependence P300 and N200 potentials evoked by flashes of rows and columns of the stimulation matrix on type of the task and voluntary attention was evaluated. We tested three types of the task: 1) just look at target symbol; 2) look at the target symbol, count its flashes and report the amount of flashes after finishing the task; 3) type target symbol in P300-based brain-computer interface (BCI). In 17 subjects research we showed that maximum amplitudes of P300 and N200 ERPs was occurred in the second type of the task ("look at and count flashes"). Also in this type of task we observed most of all cases statistically reliable difference between target and nontarget P300 and N200 ERPs. Lowest amplitudes of ERPs and number of cases of statistically reliable differences between target and nontarget were showed in the first type of the task ("just look at the symbol"). So we assume that succesful working in P300-based BCI doesn't need the maximum amplitudes of the relevent ERPs but most depend on spatiotemporal complex of these potentials.


Arabidopsis eIF3e (INT-6) associates with both eIF3c and the COP9 signalosome subunit CSN7.
The Arabidopsis COP9 signalosome is a multisubunit repressor of photomorphogenesis that is conserved among eukaryotes. This complex may have a general role in development. As a step in dissecting the biochemical mode of action of the COP9 signalosome, we determined the sequence of proteins that copurify with this complex. Here we describe the association between components of the COP9 signalosome (CSN1, CSN7, and CSN8) and two subunits of eukaryotic translation initiation factor 3 (eIF3), eIF3e (p48, known also as INT-6) and eIF3c (p105). To obtain a biochemical marker for Arabidopsis eIF3, we cloned the Arabidopsis ortholog of the eIF3 subunit eIF3b (PRT1). eIF3e coimmunoprecipitated with CSN7, and eIF3c coimmunoprecipitated with eIF3e, eIF3b, CSN8, and CSN1. eIF3e directly interacted with CSN7 and eIF3c. However, eIF3e and eIF3b cofractionated by gel filtration chromatography in a complex that was larger than the COP9 signalosome. Whereas eIF3, as detected through eIF3b, localized solely to the cytoplasm, eIF3e, like CSN7, was also found in the nucleus. This suggests that eIF3e and eIF3c are probably components of multiple complexes and that eIF3e and eIF3c associate with subunits of the COP9 signalosome, even though they are not components of the COP9 signalosome core complex. This interaction may allow for translational control by the COP9 signalosome.


A 9 keV electron-impact liquid-gallium-jet x-ray source.
We demonstrate a high-brightness compact 9 keV electron-impact microfocus x-ray source based on a liquid-gallium-jet anode. A approximately 30 W, 50 kV electron gun is focused onto the approximately 20 ms, 30 mum diameter liquid-gallium-jet anode to produce an approximately 10 microm full width at half maximum x-ray spot. The peak spectral brightness is >2 x 10(10) photons(s mm(2) mrad(2)x0.1% BW). Calculation and experiments show potential for increasing this brightness by approximately three orders of magnitude, making the source suitable for laboratory-scale x-ray crystallography and hard x-ray microscopy.


Global Text Mining and Development of Pharmacogenomic Knowledge Resource for Precision Medicine.
Understanding patients' genomic variations and their effect in protecting or predisposing them to drug response phenotypes is important for providing personalized healthcare. Several studies have manually curated such genotype-phenotype relationships into organized databases from clinical trial data or published literature. However, there are no text mining tools available to extract high-accuracy information from such existing knowledge. In this work, we used a semiautomated text mining approach to retrieve a complete pharmacogenomic (PGx) resource integrating disease-drug-gene-polymorphism relationships to derive a global perspective for ease in therapeutic approaches. We used an R package, pubmed.mineR, to automatically retrieve PGx-related literature. We identified 1,753 disease types, and 666 drugs, associated with 4,132 genes and 33,942 polymorphisms collated from 180,088 publications. With further manual curation, we obtained a total of 2,304 PGx relationships. We evaluated our approach by performance (precision = 0.806) with benchmark datasets like Pharmacogenomic Knowledgebase (PharmGKB) (0.904), Online Mendelian Inheritance in Man (OMIM) (0.600), and The Comparative Toxicogenomics Database (CTD) (0.729). We validated our study by comparing our results with 362 commercially used the US- Food and drug administration (FDA)-approved drug labeling biomarkers. Of the 2,304 PGx relationships identified, 127 belonged to the FDA list of 362 approved pharmacogenomic markers, indicating that our semiautomated text mining approach may reveal significant PGx information with markers for drug response prediction. In addition, it is a scalable and state-of-art approach in curation for PGx clinical utility.


Barriers and facilitators to antiretroviral medication adherence among HIV-infected paediatric patients in Ethiopia: A qualitative study.
Medication adherence is a complex behaviour with multiple determinants. Understanding the barriers and facilitators of adherence is invaluable for programme improvement, which assists the foundation of adherence intervention strategies. A qualitative study was conducted in six selected hospitals of Addis Ababa in 2008, to explore barriers and facilitators to antiretroviral medication adherence among HIV-infected paediatric patients. Twelve caregivers of adherent and non-adherent children and 14 key informants in five hospitals were included in the study. The findings revealed that over-dosage (heavy pill burden), fear of stigma and discrimination, cost and access to transportation, lack of understanding of the benefit of taking the medication, economic problems in the household, and lack of nutritional support were the barriers to adherence to HAART. The presence of mobile/wall alarm, the presence of follow-up counselling, improved health of the child, ART clinic setups, and disclosure of HIV serostatus were among the facilitators. This study indicated that paediatric adherence to antiretroviral therapy faces a huge challenge. It suggests the provision of income-generating schemes to caregivers for assisting HIV-infected children. Health care providers should address proper usage of medication reminders.


Investigating the value dairy farmers place on a reduction of lameness in their herds using a willingness to pay approach.
A survey was conducted to elicit dairy farmers' willingness to pay (WTP) to reduce the prevalence of lameness in their herds. A choice experiment questionnaire was administered using face-to-face interviews of 163 farmers in England and Wales. Whole herd lameness assessments by trained researchers recorded a mean lameness prevalence of nearly 24% which was substantially higher than that estimated by farmers. Farmers' responses to a series of attitudinal questions showed that they strongly agreed that cows can suffer a lot of pain from lameness and believed that they could reduce lameness in their herds. Farmers' mean WTP to avoid lameness amounted to UK£411 per lame cow but with considerable variation across the sample. Median WTP of UK£249 per lame cow was considered a better measure of central tendency for the sample. In addition, the survey found that farmers had a substantial WTP to avoid the inconvenience associated with lameness control (a median value of UK£97 per lame cow) but that they were generally prepared to incur greater inconvenience if it reduced lameness. The study findings suggest that farmers need a better understanding of the scale and costs of lameness in their herds and the benefits of control. To encourage action, farmers need to be convinced that lameness control measures perceived as inconvenient will be cost effective.


Versican V1 Overexpression Induces a Myofibroblast-Like Phenotype in Cultured Fibroblasts.
Versican, a chondroitin sulphate proteoglycan, is one of the key components of the provisional extracellular matrix expressed after injury. The current study evaluated the hypothesis that a versican-rich matrix alters the phenotype of cultured fibroblasts. The full-length cDNA for the V1 isoform of human versican was cloned and the recombinant proteoglycan was expressed in murine fibroblasts. Versican expression induced a marked change in fibroblast phenotype. Functionally, the versican-expressing fibroblasts proliferated faster and displayed enhanced cell adhesion, but migrated slower than control cells. These changes in cell function were associated with greater N-cadherin and integrin β1 expression, along with increased FAK phosphorylation. The versican-expressing fibroblasts also displayed expression of smooth muscle α-actin, a marker of myofibroblast differentiation. Consistent with this observation, the versican fibroblasts displayed increased synthetic activity, as measured by collagen III mRNA expression, as well as a greater capacity to contract a collagen lattice. These changes appear to be mediated, at least in part, by an increase in active TGF-β signaling in the versican expressing fibroblasts, and this was measured by phosphorylation and nuclear accumulation of SMAD2. Collectively, these data indicate versican expression induces a myofibroblast-like phenotype in cultured fibroblasts.


[Consumption and cost of antipsychotic drugs].
In recent years, new atypical antipsychotic drugs have been marketed. This study aims to analyze the evolution of the consumption pattern and pharmaceutical cost of the antipsychotic drugs during the last years and the impact that the new atypical antipsychotic drugs have had. Based on the ECOM database of the Ministry of Health and Consumer Affairs of Spain, the sales data of the antipsychotic drugs in Catalonia during the 1990-2001 period have been chosen. The drugs have been classified into typical or classical and atypical. Consumption data have been expressed in daily defined dose (DDD) per 1,000 inhabitants and per day of treatment (DID), and cost data in constant euros. Antipsychotic consumption increased from 3.31 DID in 1990 to 6.04 DID in 2001. Typical drugs consumption decreased (from 100 % consumption in 1990 to 46 % in 2001) and that of the atypical ones increased (from 1% consumption in the year 1993 to 54% in the year 2001). A change in the use pattern of different drugs is verified. In the year 1990, the most consumed drugs were flupenthixol (0.86 DID) and haloperidol (0.67 DID), and in the year 2001 olanzapine (1.69 DID) and risperidone (1.30 DID). The drugs with a greater increase in consumption were olanzapine, which multiplied its consumption five fold from 1997 to 2001 and risperidone, which multiplied it by 20 from 1994 to 2001. During the study period, the cost increased 13 times, above all due to increase in cost of atypical antipsychotics (from less than 1 % of the total cost in 1993 to 92 % of the total cost in 2001). The DDD cost of antipsychotics increased (6.48 euros in 1990 and 20.31 euros in 2001). However, that of the typical antipsychotics decreased (6.48 euros in 1990 and 4.62 euros in 2001) and that of the atypical ones increased (2.06 euros in 1993 and 15.69 euros in 2001). The marketing of the new atypical antipsychotic drugs has had an extraordinary impact on antipsychotic drug consumption and cost. The cost/effectiveness ratio of the new atypical antipsychotic drugs in the clinical practice should be evaluated to determine the economic resources aimed at costs of the different antipsychotic drugs.


Fairness in Assessment: Identifying a Complex Adaptive System.
Assessment design in health professions education is continuously evolving. There is an increasing desire to better embrace human judgement in assessment. Thus, it is essential to understand what makes this judgement fair. This study builds upon existing literature by studying how assessment leaders conceptualise the characteristics of fair judgement. Sixteen assessment leaders from 15 medical schools in Australia and New Zealand participated in online focus groups. Data collection and analysis occurred concurrently and iteratively. We used the constant comparison method to identify themes and build on an existing conceptual model of fair judgement in assessment. Fairness is a multi-dimensional construct with components at environment, system and individual levels. Components influencing fairness include articulated and agreed learning outcomes relating to the needs of society, a culture which allows for learner support, stakeholder agency and learning (environmental level), collection, interpretation and combination of evidence, procedural strategies (system level) and appropriate individual assessments and assessor expertise and agility (individual level). We observed that within the data at fractal, that is an infinite pattern repeating at different scales, could be seen suggesting fair judgement should be considered a complex adaptive system. Within complex adaptive systems, it is primarily the interaction between the entities which influences the outcome it produces, not simply the components themselves. Viewing fairness in assessment through a lens of complexity rather than as a linear, causal model has significant implications for how we design assessment programs and seek to utilise human judgement in assessment.


Withdrawal of antiepileptic drugs: guidelines of the Italian League Against Epilepsy.
The Italian League Against Epilepsy has issued evidence-based guidelines to help practicing physicians in their decision to stop or withhold antiepileptic drugs (AEDs) in patients achieving a prolonged period of seizure freedom. Six adult and two child neurologists, divided into four pairs, critically appraised 128 published reports and provided graded recommendations answering 15 key questions: length of the seizure-free period after treatment initiation, difference in seizure-free periods in children and adults, electroencephalography (EEG) pattern at the time of discontinuation, etiology of epilepsy, seizure type(s), patient's age and sex, family history of epilepsy, history of febrile seizures, epilepsy syndrome, seizure frequency before entering remission, duration of active epilepsy, tapering period, number and type of AEDs taken at time of discontinuation, combination of risk factors for recurrence, and length of patient monitoring after treatment discontinuation. Based on the available data, the following recommendations can be outlined: (1) antiepileptic treatment might be discontinued after a minimum period of 2 years of seizure freedom; shorter seizure-free periods are associated to a higher risk of relapse; (2) in children, AED discontinuation could be considered after less than two seizure-free years because of a marginally higher risk of relapse for early withdrawal; (3) factors, such as abnormal EEG (including epileptiform abnormalities) at the time of treatment discontinuation, a documented etiology of seizures (including mental retardation, perinatal insults, and abnormal neurologic examination), partial seizures, or an older age at disease onset, enhance the risk of relapse; however, patients should not be encouraged to withhold treatment unless a combination of two or more of these factors is present; (4) female sex, family history of epilepsy, history of febrile seizures, disease length/severity, and number and type of drugs taken should not influence the decision to stop treatment; (5) epilepsy syndrome should be always included in the decision process; (6) slow (at least 6 months) AED discontinuation should be encouraged; in any case the duration of the tapering period should be tailored to the patient's needs and preference; and (7) patient discontinuing treatment should be followed for no <2 years. As a general habit, the decision to stop treatment should be discussed and shared with each patient, taking into account social and personal complications of a seizure relapse and the medical complications of chronic AED treatment.


Induction therapy in renal transplant recipients: a review.
Transplant science has improved significantly over the last decade. Influenced by novel advancements, rejection rates and short-term graft losses diminished substantially. Induction therapy was shown to reduce rejection rates and improve short-term graft survival. In this article, we discuss the most commonly used induction agents and the choice of induction therapy in different renal transplant recipient subgroups. The medical literature as well as our own experience was used to prepare this review. At this time, induction therapy is commonly used in upwards of 80%, of renal transplant recipients. Depleting agents are the most frequently used agents and they account for more than 75% of all induction therapies in the United States. Currently, there is no consensus regarding the choice of induction therapy. The type of induction therapy is generally selected based on a comprehensive evaluation of the recipient and the donor's immunological risks, the risk of developing opportunistic infection and malignancy, recipient comorbidities, financial burden and the choice of maintenance immunosuppressive regimen.


Neural-specific deletion of the focal adhesion adaptor protein paxillin slows migration speed and delays cortical layer formation.
Paxillin and Hic-5 are homologous focal adhesion adaptor proteins that coordinate cytoskeletal rearrangements in response to integrin signaling, but their role(s) in cortical development are unknown. Here, we find that Hic-5-deficient mice are postnatal viable with normal cortical layering. Mice with a neural-specific deletion of paxillin are also postnatal viable, but show evidence of a cortical neuron migration delay that is evident pre- and perinatally, but is not detected at postnatal day 35 (P35). This phenotype is not modified by Hic-5 deficiency (double knockout). Specific deletion of paxillin in postmitotic neurons using Nex-Cre-mediated recombination as well as in utero electroporation of a Cre-expression construct identified a cell-autonomous requirement for paxillin in migrating neurons. Paxillin-deficient neurons have shorter leading processes that exhibited multiple swellings in comparison with control. Multiphoton imaging revealed that paxillin-deficient neurons migrate ∼30% slower than control neurons. This phenotype is similar to that produced by deletion of focal adhesion kinase (FAK), a signaling partner of paxillin, and suggests that paxillin and FAK function cell-autonomously to control migrating neuron morphology and speed during cortical development.


An evaluation of the telepsychiatry programme in Victoria, Australia.
We evaluated the use of telepsychiatry in Victoria, a state of Australia with some five million people. There were 39 sites at the time of the survey, 12 metropolitan and 27 rural. Interviews and postal questionnaires were used. A total of 99 staff were surveyed, 69 by post and 30 during visits. There were 37 participants from metropolitan sites and 62 from rural sites. Rural sites conducted an estimated 137 sessions per month (i.e. an average of 5.1 per month per site). The majority (70%) of the usage in Victoria was for clinical purposes, both primary and secondary consultations.


Ampelisca eschrichtii Krøyer, 1842 (Ampeliscidae) of the Sakhalin Shelf in the Okhotsk Sea starve in summer and feast in winter.
Ampelisca eschrichtii Krøyer, 1842 of the Sakhalin Shelf of the Okhotsk Sea, Far Eastern Russia, comprise the highest known biomass concentration of any amphipod population in the world and are a critically important prey source for western gray whales. Growth and reproduction in this population has not been apparent in summer. However, they are not accessible for sampling in winter to test a previous default conclusion that they grow and reproduce in winter. We tested the default winter growth and reproduction hypothesis by detailed comparisons of the brood and gonad development among 40 females and 14 males and brood sizes among females observed since 2002. Our test included six predictions of reproductive synchrony that would be apparent from gonad and brood morphology if active reproduction occurs in summer. We found high prevalences of undersized and damaged oocytes, undersized broods, a lack of females brooding fully formed juveniles, atrophied ovaries, and males with mature sperm but lacking fully developed secondary sex morphologies required for pelagic mating. All of these conditions are consistent with trophic stress and starvation. These A. eschrichtii populations therefore appear to starve in summer and to grow and reproduce in winter. The Offshore A. eschrichtii populations occur in summer below water strata bearing high phytoplankton biomasses. These populations are more likely to feed successfully in winter when storms mix phytoplankton to their depths.


Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients.
Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake. Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed. Results: 18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions. Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification.


A study of water relations in neem (Azadirachta indica) seed that is characterized by complex storage behaviour.
Neem (Azadirachta indica) seed is reputed to have limited tolerance to desiccation, to be sensitive to chilling and imbibitional stress, and to display intermediate storage behaviour. To understand this behaviour the properties of water in seed tissues were studied. Water sorption isotherms showed that at similar relative humidity (RH), the water content was consistently higher in axes than in cotyledons, mainly due to the elevated lipid content (51%) in the cotyledons. Using differential scanning calorimetry, melting transitions of water were observed at water contents higher than 0.14 g H2O g-1 DW in the cotyledons and 0.23 g H2O g-1 DW in the axes. Beside melting transitions of lipid, as verified by infrared spectroscopy, changes in heat capacity were observed which shifted with water content, indicative of glass-to-liquid transitions. State diagrams are given on the basis of the water content of seed tissues, and also on the basis of the RH at 20 degrees C. Longevity was considerably improved, and the sensitivity to chilling/subzero temperatures was reduced when axis and cotyledons were dehydrated to moisture contents < or = of approximately 0.05 g H2O g-1 DW. However, longevity during storage at very low water contents was limited. A possible mechanism for the loss of sensitivity to chilling/subzero temperatures at low water contents is discussed. The results suggest that dry neem seeds in the glassy state have great potential for extended storability, also at subzero temperatures.


Stent deployment resolves a petrous carotid artery angioplasty dissection.
A patient with a symptomatic petrous carotid artery stenosis underwent balloon angioplasty, which was complicated by a flow-limiting dissection. The problem was resolved by deploying a balloon-expandable coronary stent. The patient suffered no neurologic deficit, was discharged within 12 hours, and was asymptomatic at last follow-up, 5 months after the procedure, without warfarin therapy. This therapeutic option may prove useful as a means to correct endovascular procedural complications.


[Apoptosis of the hypothalamus neurosecretory cells in stress and ageing: the role of immune modulators].
There is assumption about active role of immune modulators in cell death process. The involvement of interferon-alpha and cycloferon in apoptosis regulation of hypothalamic neurons of mice during stress and aging was studied. We determined the expression of apoptosis markers (Bcl-2, Mcl-1, Bax) in comparison with apoptosis level. We have found that immune modulators suppress activity of nonapeptidergic neurons. Thus, interferon-alpha treatment reduces synthesis of Bcl-2; cycloferon treatment inhibits expression of Bax and Bcl-2. So the role of immune modulators in neuron apoptosis depends on the stage of ontogenesis and type of immune modulator. Cycloferon is able to reduce the level of age-dependent apoptosis of neurons in aging, but under stress condition both interferon-alpha and cycloferon act as protectors of cell death.


Cooperative function of deltaC and her7 in anterior segment formation.
Segmentation of paraxial mesoderm in vertebrates is regulated by a genetic oscillator that manifests as a series of wavelike or cyclic gene expression domains in the embryo. In zebrafish, this oscillator involves members of the Delta/Notch intercellular signaling pathway, and its down-stream targets, the Her family of transcriptional repressors. Loss of function of any one of the genes of this system, such as her7, gives rise to segmentation defects in the posterior trunk and tail, concomitant with a disruption of cyclic expression domains, indicating that the oscillator is required for posterior segmentation. Control of segmentation in the anterior trunk, and its relationship to that of the posterior is, however, not yet well understood. A combined loss of the cyclic Her genes her1 and her7 disrupts segmentation of both anterior and posterior paraxial mesoderm, indicating that her genes function redundantly in anterior segmentation. To test whether this anterior redundancy is specific to the her gene family, or alternatively is a more global feature of the segmentation oscillator, we looked at anterior segmentation after morpholino knock down of the cyclic cell-surface Notch ligand deltaC (dlc), either alone or in combination with her7, or other Delta/Notch pathway genes. We find that dlc is required for coherence of wavelike expression domains of cyclic genes her1 and her7 and maintenance of their expression levels, as well as for cyclic transcription of dlc itself, confirming that dlc is a component of the segmentation oscillator. Dose dependent, posteriorly-restricted segmentation defects were seen in the dlc knock down, and in combination with the deltaD or notch1a mutants. However, combined reduction of function of dlc and her7 results in defective segmentation of both anterior and posterior paraxial mesoderm, and a failure of cyclic expression domains to initiate, similar to loss of both her genes. Thus, anterior segmentation requires the functions of both her and delta family members in a parallel manner, suggesting that the segmentation oscillator operates in paraxial mesoderm along the entire vertebrate axis.