Novel association of the obesity risk-allele near Fas Apoptotic Inhibitory Molecule 2 (FAIM2) gene with heart rate and study of its effects on myocardial infarction in diabetic participants of the PREDIMED trial.
The Fas apoptotic pathway has been implicated in type 2 diabetes and cardiovascular disease. Although a polymorphism (rs7138803; G > A) near the Fas apoptotic inhibitory molecule 2 (FAIM2) locus has been related to obesity, its association with other cardiovascular risk factors and disease remains uncertain. We analyzed the association between the FAIM2-rs7138803 polymorphism and obesity, blood pressure and heart rate in 7,161 participants (48.3% with type 2 diabetes) in the PREDIMED study at baseline. We also explored gene-diet interactions with adherence to the Mediterranean diet (MedDiet) and examined the effects of the polymorphism on cardiovascular disease incidence per diabetes status after a median 4.8-year dietary intervention (MedDiet versus control group) follow-up. We replicated the association between the FAIM2-rs7138803 polymorphism and greater obesity risk (OR: 1.08; 95% CI: 1.01-1.16; P = 0.011; per-A allele). Moreover, we detected novel associations of this polymorphism with higher diastolic blood pressure (DBP) and heart rate at baseline (B = 1.07; 95% CI: 0.97-1.28 bmp in AA vs G-carriers for the whole population), that remained statistically significant even after adjustment for body mass index (P = 0.012) and correction for multiple comparisons. This association was greater and statistically significant in type-2 diabetic subjects (B = 1.44: 95% CI: 0.23-2.56 bmp; P = 0.010 for AA versus G-carriers). Likewise, these findings were also observed longitudinally over 5-year follow-up. Nevertheless, we found no statistically significant gene-diet interactions with MedDiet for this trait. On analyzing myocardial infarction risk, we detected a nominally significant (P = 0.041) association in type-2 diabetic subjects (HR: 1.86; 95% CI:1.03-3.37 for AA versus G-carriers), although this association did not remain statistically significant following correction for multiple comparisons. We confirmed the FAIM2-rs7138803 relationship with obesity and identified novel and consistent associations with heart rate in particular in type 2 diabetic subjects. Furthermore, our results suggest a possible association of this polymorphism with higher myocardial infarction risk in type-2 diabetic subjects, although this result needs to be replicated as it could represent a false positive.


Current status of carotid endarterectomy for atheromatous disease.
The authors discuss the indications for both elective and emergency carotid endarterectomy. Reports on the surgical treatment of asymptomatic bruit and contralateral carotid stenosis are reviewed. The results of endarterectomy for symptomatic carotid disease, including transient ischemic attacks, acute neurological deficit, and complete carotid occlusion, are discussed. The complications and risks of carotid surgery are also presented.


[Necrotizing vasculitis with predominant kidney involvement].
We report five patients with necrotizing vasculitis with predominant renal involvement; the diagnostic and therapeutics was effected completely at regional hospital. We detach: a) the clinical presentation's forms with rapidly progressive renal failure with microscopic hematuria and minimal proteinuria; b) the biopsy of kidney with necrotizing vasculitis or necrotizing glomerulonephritis (microscopic polyarteritis). We review the necrotizing vasculitis with predominant renal involvement in its pathogenic, clinical and histological aspects, and we insist that the diagnostic and early treatment are fundamental for prognostic's improvement of these patients. We conclude that this diagnostic and treatment can be made in regional hospitals with sensible physicians by the theme.


Polynuclear cation-cation complexes of pentavalent uranyl: relating stability and magnetic properties to structure.
Reaction of {[UO2Pys][mu-KI2Py2]}n (1) with 2 equiv of potassium dibenzoylmethanate (Kdbm) in pyridine or acetonitrile affords, respectively, the corresponding tetranuclear complexes of pentavalent uranyl ([UO2(dbm),2]2[mu-K(Py)2]2[mu8-K(Py)]}2I2 x Py2 (2) (in 70% yield) and {[UO2(dbm)2]2[mu-K(MeCN)2][mu8-K]}2 (3) (in 40% yield) in which four UO2+ are mutually coordinated (T-shaped "cation-cation" interaction). The X-ray structures of 2 and 3 show also the presence of, respectively, six and four potassium cations involved in UO2+...K+ interactions. Reaction of 2 with an excess of 18-crown-6 (18C6) affords the dimeric complex [UO2(dbm)2K(18C6)]2 (4) presenting a diamond-shaped interaction between two UO2+ groups, in 45% yield. 1H and PFGSTE diffusion NMR spectroscopy of 2 and 3 in pyridine show unambiguously the presence of UO2+...UO2+ and UO2+...K+ interactions (tetrametallic species) in solution, which leads to a rapid (7 days) disproportionation of pentavalent uranyl to afford [U(dbm)4] and [UO2(dbm)2] species. The UO2+...K+ interaction plays an important synergistic role in the stabilization of the UO2+...UO2+ interactions. Accordingly, the lower affinity of (K(18C6))+ for the uranyl(V) oxygen in complex 4 results in a lower number of coordinated K+ and therefore in a weakened UP2+...UO2+ interaction. The UO24+...UO2+ interactions is completely disrupted in dmso or in the presence of Kdbm, preventing disproportionation of pentavalent uranyl. Solid-state variable-temperature magnetic susceptibility studies showed the unambiguous presence of antiferromagnetic coupling between the two oxo-bridged uranium centers of complex 4, with the appearance of a maximum in chi versus T at approximately 5 K. The different behavior of the tetrameric complex 3, which probably involves a magnetic coupling occurring at lower temperature, can be ascribed to the different geometric arrangement of the interacting uranyl(V) groups.


[Arthroscopic treatment of dorsal ganglion cyst at the wrist. About 54 cases].
Ganglion cyst of the wrist can, some time, need surgery. Different arthroscopic technical procedures have been described. We report our experience in all articular resection of dorsal ganglion cyst of the wrist. Evaluation of efficiency of resection of dorsal ganglion cyst of the wrist by of arthroscopic resection of the pedicle. Fifty-four cysts of 52 patients have been evaluated retrospectively. Operative data, pain, strength, recurrence and complications have been collected. Average follow up was 28 months (6 to 78). Return to work was 8,8 days, operative time 41 minutes (25 to 90). In 67% cases, the operation was judged easy. Three surgeries had to be performed open. Complications were one hematoma and one neurodystrophy. Pain decrease from 3,37 to 1,76 on analogical pain scale. Flexion was 89% of opposite side, extension 88%. Sixteen recurrences (29.7%) were found. Sixty percent of those recurrences occurred during the first year experience. But independently of experience, the operative performance was foun difficult in 1 time on 3. Endoarticular arthroscopic resection of the pedicle of ganglion cyst is not so reproducible. In experimented hands, it remains a difficult procedure after a long learning curve with a recurrence rate 3 times higher from what is reported in literature for open surgery. For our discharge, our long follow-up can contain some cases of de novo cyst explaining this high rate, the learning curve is certainly the main reason for our high recurrence.


Altered lower extremity movement variability in female soccer players during side-step cutting after anterior cruciate ligament reconstruction.
Anterior cruciate ligament (ACL) reconstruction (ACLR) is common after an ACL tear and is thought to restore functional stability to the knee. A recent investigation demonstrated that individuals who have undergone ACLR exhibited increased lower extremity coupling variability during gait, suggestive of altered dynamic stability. However, little is known about whether they exhibit alterations in lower extremity variability during dynamic sport-specific tasks. To determine if female soccer players who have had an ACLR demonstrate differences in lower extremity coupling variability as compared with athletes with no history of knee injury during a side-step cutting maneuver. Controlled laboratory study. Ten female soccer players who had undergone ACLR served as the experimental group, and 10 female soccer players with no history of knee ligament injury composed the control group (CON). Three-dimensional kinematics and ground-reaction forces were collected while each participant performed a side-step cutting maneuver. Based on known ACL loading patterns, 7 lower extremity intralimb couplings were created. With use of a vector-coding technique, the coordination variability was calculated for each coupling. Independent t tests were used to determine group differences in variability for each coupling (P ≤ .05). Individuals who had undergone ACLR exhibited increased lower extremity variability during side-step cutting as compared with control subjects in the following couplings: hip rotation/knee abduction-adduction (27.2° ± 11.5° [ACLR] vs 19.7° ± 6.8° [CON]; P = .04), hip flexion-extension/knee abduction-adduction (26.0° ± 13.3° [ACLR] vs 18.6° ± 5.3° [CON]; P = .05), knee abduction-adduction/knee flexion-extension (13.5° ± 5.7° [ACLR] vs 7.3° ± 2.7° [CON]; P < .01), and knee abduction-adduction/knee rotation (26.4° ± 10.8° [ACLR] vs 19.3° ± 4.5° [CON]; P = .03). In addition, there was a trend toward increased variability in the hip rotation/ankle inversion-eversion coupling (22.9° ± 9.3° [ACLR] vs 18.0° ± 6.7° [CON]; P = .09) and knee abduction-adduction/ankle inversion-eversion coupling (25.9° ± 10.0° [ACLR] vs 20.2° ± 9.7° [CON]; P = .10). Female soccer players who have undergone ACLR and returned to sports participation exhibit altered lower extremity coupling variability during side-step cutting. While individuals who have had an ACLR exhibit mechanical knee stability before returning to sports, the observed increased movement variability during side-step cutting is likely reflective of altered neuromuscular control and may contribute to the known increased risk for ACL reinjury and knee osteoarthritis after return to sports participation. Improving the understanding of altered lower extremity coupling variability after ACLR will aid in the development of more effective rehabilitation programs.


Genetic dissection of fruit maturity date in apricot (P. armeniaca L.) through a Single Primer Enrichment Technology (SPET) approach.
Single primer enrichment technology (SPET) is an emerging and increasingly popular solution for high-throughput targeted genotyping in plants. Although SPET requires a priori identification of polymorphisms for probe design, this technology has potentially higher reproducibility and transferability compared to other reduced representation sequencing (RRS) approaches, also enabling the discovery of closely linked polymorphisms surrounding the target one. The potential for SPET application in fruit trees was evaluated by developing a 25K target SNPs assay to genotype a panel of apricot accessions and progenies. A total of 32,492 polymorphic sites were genotyped in 128 accessions (including 8,188 accessory non-target SNPs) with extremely low levels of missing data and a significant correlation of allelic frequencies compared to whole-genome sequencing data used for array design. Assay performance was further validated by estimating genotyping errors in two biparental progenies, resulting in an overall 1.8% rate. SPET genotyping data were used to infer population structure and to dissect the architecture of fruit maturity date (MD), a quantitative reproductive phenological trait of great agronomical interest in apricot species. Depending on the year, GWAS revealed loci associated to MD on several chromosomes. The QTLs on chromosomes 1 and 4 (the latter explaining most of the phenotypic variability in the panel) were the most consistent over years and were further confirmed by linkage mapping in two segregating progenies. Besides the utility for marker assisted selection and for paving the way to in-depth studies to clarify the molecular bases of MD trait variation in apricot, the results provide an overview of the performance and reliability of SPET for fruit tree genetics.


Effects of fillet weight on sensory descriptive flavor and texture profiles of broiler breast meat.
Four replications were conducted to compare sensory descriptive profiles of cooked boneless skinless chicken breast categorized by fillet (pectoralis major) weight or size. In each replication, 20 heavy fillets, 20 medium fillets, and 20 light fillets (deboned at 6-8 h postmortem) were obtained from a commercial processing plant. Fillets were trimmed and weighed before chosen for each of 3 size categories based on their weight as follows: light, average weight 112 g; medium, average weight 153 g; and heavy, average weight 204 g. Descriptive sensory texture and flavor attributes were measured after the frozen samples were thawed for 24 h at a refrigerated temperature (2°C) and cooked to an endpoint temperature of 78°C. Sensory evaluations were performed by trained descriptive panelists using 0 to 15 universal intensity scales for 8 texture and 10 flavor attributes. Our results show that there were differences (P < 0.05) in intensity scores of sensory descriptive texture and flavor attributes cohesiveness, hardness, juiciness, cardboardy, and sourness, among the 3 weight categories. The average cohesiveness, hardness, and sourness scores of the heavy and light fillets were higher than the medium fillets. The juiciness score of the heavy fillets was higher than that of the light fillets, and the cardboardy score of the light fillets was higher than those of the medium and heavy fillets. The juiciness score of the medium fillets did not differ from that of either the light or heavy fillets, and there was no difference for cardboardy scores between the medium and heavy fillets. These results indicate that fillet weight or size in the range (95-230 g) assessed in this study may influence sensory descriptive flavor and texture profiles of cooked broiler breast fillets deboned 6 to 8 h postmortem. Current genetic selection of broiler lines based on growth rate and feed efficiency may sacrifice breast meat quality. However, it remains to be determined if the differences in the sensory descriptive evaluation can be perceived by consumers.


Low-cost rapid prototyping of liquid crystal polymer based magnetic microactuators for glaucoma drainage devices.
Glaucoma is one of the leading causes of blindness in the world. Although there is no cure for glaucoma, pharmaceutical or surgical interventions are known to delay the progression of this debilitating disease. In recent years, implantation of glaucoma drainage devices (GDD) have increased due to their ability to manage IOP better than other therapeutic approaches. However, only 50% of the implanted devices remain functional after 5 years often due to biofouling. Here, we report our latest progress towards developing self-clearing GDDs using integrated magnetic microactuators. Our hypothesis is that these magnetic microdevices can provide local mechanical perturbations to prophylactically remove biological accumulation. To reduce the cost and increase the throughput of fabrication, we utilize a maskless photolithography setup and commercially available liquid crystal polymer foils to create prototype devices. The mechanical response of the devices is reported and compared with the theoretical values.


HbOThrace trait, HbOThrace hemoglobinopathy and HbOThrace/Hb beta zero hemoglobinopathy: a retrospective study of 118 cases.
HbOThrace is an abnormal hemoglobin which is constructed by defective beta chains (Glu121-->Lys121). It mostly characterises the Muslim minority of the Thrace region. During the last 6 years, our department detected HbOThrace in 118 cases. Four groups were formed, the first consisted of cases of HbOThrace trait with normal iron and ferritin levels, the second of cases of HbOThrace hemoglobinopathy, the third of cases of HbOThrace/Hb beta zero hemoglobinopathy and the fourth of cases of HbOThrace trait with low iron and ferritin levels. The second, third and fourth group were compared with the first one. The conclusion is that the presence of HbOThrace leads to a mild hypochromic anemia, with no clinical findings, but the coexistence of beta zero gene or iron deficiency produces more pronounced laboratory findings and even clinically evident anemia.


Associations of C-Reactive Protein, Free Triiodothyronine, Thyroid Stimulating Hormone and Creatinine Levels with Agitation in Patients with Schizophrenia: A Comparative Cross-Sectional Study.
Agitation is prevalent among inpatients with schizophrenia. The aim of this study was to investigate whether biochemical parameters are associated with agitation in schizophrenia. Agitation was evaluated by the Positive and Negative Syndrome Scale-Excited Component questionnaire (PANSS-EC). Fasting serum levels of C-reactive protein (CRP), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), uric acid (UA), creatinine, glucose and lipids were measured. The analysis included 154 inpatients with schizophrenia (71 with agitation, 83 without agitation) and 75 healthy control subjects. Patients with schizophrenia and agitation had higher serum levels of CRP, FT3, FT4 and UA as well as lower levels of serum TSH and creatinine than patients without agitation (all P < 0.05). Multivariate logistic regression analysis indicated that serum CRP (odds ratio [OR] = 1.470, P = 0.001), FT3 (OR = 13.026, P < 0.001), TSH (OR = 0.758, P = 0.033) and creatinine (OR = 0.965, P = 0.004) were significantly associated with agitation in schizophrenia. CRP, FT3, TSH and creatinine achieved an area under the ROC curve of 0.626, 0.728, 0.620 and 0.663 respectively in discriminating schizophrenia with or without agitation. Increased serum CRP and FT3 levels and decreased serum TSH and creatinine levels are independent risk factors for agitation in hospitalized patients with schizophrenia. Inflammation, thyroid hormones and renal function may be involved in the pathogenesis of agitation in schizophrenia.


Myelodysplastic syndrome with pseudoreticulocytosis.
A patient with myelodysplastic syndrome (MDS) with refractory anemia who had marked reticulocytosis in the absence of hemolytic anemia and/or blood loss is reported. Erythrocyte survival test showed that more than 50% of the patient's reticulocytes were still present on day seven. This should be due to the prolongation of reticulocyte maturation in MDS, and is known as pseudoreticulocytosis. This phenomenon which mimicks hemolytic anemia is an unusual presentation of myelodysplastic syndrome, with only 7 patients with pseudoreticulocytosis being reported previously.


Patterns of safer sex practices among allied health students at historically black colleges and universities.
With high human immunodeficiency virus (HIV) and STD transmission rates among African American young adults, there is a need to study the patterns of risk behaviors among this group for effective HIV prevention strategies. Many studies point to the problem of what is termed the knowledge-behavior gap, as a contributing factor for high transmission rates. In this phenomenon, the risks for HIV transmission are known, yet this knowledge does not translate into safer sex practices. It is unclear if this phenomenon applies to all young adults. This study examined sexual behaviors, risks for HIV infection, condom use, and HIV testing practices among allied health students. A sample of 614 respondents voluntarily completed questionnaires. The respondents were from seven historically black colleges and universities and four predominantly African American physician assistant programs. The significant findings reflect that this sample of mature and informed allied health students engaged in safer sex practices. There was a higher rate of condom use among African Americans compared with other racial and ethnic groups and significant differences for gender, race, and antibody testing. The outcomes of the study have implications for using allied health students as role models in designing effective prevention programs on college campuses and in African American communities to address knowledge-behavior gap issues.


A functional classification of ABCB4 variations causing progressive familial intrahepatic cholestasis type 3.
Progressive familial intrahepatic cholestasis type 3 is caused by biallelic variations of ABCB4, most often (≥70%) missense. In this study, we examined the effects of 12 missense variations identified in progressive familial intrahepatic cholestasis type 3 patients. We classified these variations on the basis of the defects thus identified and explored potential rescue of trafficking-defective mutants by pharmacological means. Variations were reproduced in the ABCB4 complementary DNA and the mutants, thus obtained, expressed in HepG2 and HEK293 cells. Three mutants were either fully (I541F and L556R) or largely (Q855L) retained in the endoplasmic reticulum, in an immature form. Rescue of the defect, i.e., increase in the mature form at the bile canaliculi, was obtained by cell treatments with cyclosporin A or C and, to a lesser extent, B, D, or H. Five mutations with little or no effect on ABCB4 expression at the bile canaliculi caused a decrease (F357L, T775M, and G954S) or almost absence (S346I and P726L) of phosphatidylcholine secretion. Two mutants (T424A and N510S) were normally processed and expressed at the bile canaliculi, but their stability was reduced. We found no defect of the T175A mutant or of R652G, previously described as a polymorphism. In patients, the most severe phenotypes appreciated by the duration of transplant-free survival were caused by ABCB4 variants that were markedly retained in the endoplasmic reticulum and expressed in a homozygous status. ABCB4 variations can be classified as follows: nonsense variations (I) and, on the basis of current findings, missense variations that primarily affect the maturation (II), activity (III), or stability (IV) of the protein or have no detectable effect (V); this classification provides a strong basis for the development of genotype-based therapies.


Cognition and Cognitive Fatigability: Association with Employment Status in Multiple Sclerosis.
Slowed processing speed impacts employment status in people with multiple sclerosis (PwMS). Studies on the Multiple Sclerosis Functional Composite (MSFC), which includes the Paced Auditory Serial Addition Test (PASAT), have demonstrated that the combined score predicts employment status. Whether PASAT performance alone is associated with employment status is less clear. In addition, no studies have yet evaluated whether cognitive fatigability (CF), as measured with the PASAT, is associated with employment status. The aim of the current study was to examine the association between PASAT performance, CF, and employment status in PwMS. Hundred and eighty-six PwMS completed the PASAT as part of a larger neuropsychological battery. ANOVAs and chi-squares analyzed group differences between employed and unemployed participants with respect to demographics, PASAT performance scores, and CF. Linear regression determined whether PASAT performance and/or CF scores were associated with employment status. After controlling for demographic influences, group differences were noted between employed vs. unemployed individuals on PASAT performance scores only. Employment status was associated with PASAT performance scores but not CF. The current study confirmed that PASAT performance is associated with employment status in MS. Given that CF was not associated, it seems difficulties with information processing speed (IPS) and working memory have more impact on a PwMS's ability to remain employed rather than within-task performance decline.


Rederivation of MHV and MEV antibody positive mice by cross-fostering and use of the microisolator caging system.
This study established the feasibility of rederiving numerous mouse hepatitis virus (MHV) and mouse encephalomyelitis virus (MEV) antibody positive strains of mice using cross fostering techniques and a new caging system, thus permitting introduction of virus antibody free mice into a barrier facility. Serologic status of dams within the nucleus breeding colony was determined, and all mice within the breeding colony were housed in individual Microisolator cages. Specific pathogen free (SPF) foster mothers purchased from a commercial source were determined to have no detectable serum antibody to 11 murine viruses including MEV and MHV. Pups delivered naturally from time pregnant dams were cross fostered onto the SPF foster dams. The procedure of cross fostering was conducted within a positive flow, HEPA-filtered, mass air displacement unit within 24 hours of parturition. The virus status of pups from 49 litters was monitored serologically at weaning and again at 6 weeks of age. All cross fostered litters were serologically negative for antibody to mouse hepatitis virus. Seven of 29 litters were negative for MEV antibody titer using this cross fostering technique. Those litters negative serologically to both MHV and MEV (at 3 and 6 weeks) were transferred to a barrier facility and held in isolation. All rederived mice transferred to the barrier facility remained negative for MHV and MEV when sampled at 12 weeks of age.


LTOT Patients' Experience of a Portable Oxygen Unit and Health-Related Quality of Life-A Cross-Sectional Study.
Background: The purpose of the present study was to elucidate the experiences of long-term oxygen therapy (LTOT) patients with a portable oxygen unit and to describe the patients' self-assessed health-related quality of life (HRQoL). Methods: The study employed a prospective cross-sectional design. Data collection entailed two questionnaires, namely the MedTech20 (patients' experience of the medical device in four areas) and EQ-5D (HRQoL). The informants consisted of patients (n = 148) treated with such a medical device and that were registered in Skåne University Hospital's database, Medusa. Results: In the domain Sense of security the informant felt the equipment reliable and safe to use and expressed a sense of control for the user. Regarding Social participation, the responses did not indicate the device to facilitate leisure activities, movement outside the homes, traveling or everyday tasks to a larger extent. The respondents did express a reduced sense of compromised integrity, with a minor effect on Intimacy. With regards to Convenience, the responses indicated the product to provide Adaptability to personal needs. Overall, a strongly affected HRQoL (Your current health condition, EQ-VAS Md = 50 (IQR 36-70)) with strong correlation with EQ-5D was seen. Conclusions: Informants experienced the portable oxygen unit as reliable and safe to use while giving a sense of control over the disease itself. A minor impact on social participation was reported, except for a reduced sense of compromised integrity. The patients also reported a strongly reduced HRQoL.


[Metamorphosis of endocrinology].
During the last half of century we witnessed not only changes in the definition of hormone, in the conception of endocrinology and in understanding of mechanisms of hormone action, but also an immense development of technical tools of endocrine diagnostic and therapy. Endocrinology has had a profound impact on other branches of medicine with the consequence that the frontiers of classical endocrinology are slowly vanishing. It is time to ask what will be the future demands of patients and whether there will be appropriate number of specialists in endocrinology in the near future. Besides the present type of care of the patients with endocrinopathies it is necessary to envision a new type of patient requesting "comfort therapy", as e.g. improvement of signs of aging, declining sexuality, or body height or weight.


Recruitment via the Internet and social networking sites: the 1989-1995 cohort of the Australian Longitudinal Study on Women's Health.
Faced with the challenge of recruiting young adults for health studies, researchers have increasingly turned to the Internet and social networking sites, such as Facebook, as part of their recruitment strategy. As yet, few large-scale studies are available that report on the characteristics and representativeness of the sample obtained from such recruitment methods. The intent of the study was to describe the sociodemographic and health characteristics of a national sample of young Australian women recruited mainly through the Internet and social networking sites and to discuss the representativeness of their sociodemographic, health, and lifestyle characteristics relative to the population. A cohort of 17,069 women (born between 1989 and 1995) was recruited in 2012-13 for the Australian Longitudinal Study on Women's Health. Sociodemographic characteristics (percentages, means, and 95% confidence intervals) from the online survey data were compared with women aged 18-23 years from the 2011 Australian Census. Sample data were compared by age and education level with data from the 2011-13 Australian Health Survey (AHS). Compared to the Australian Census data, study participants were broadly representative in terms of geographical distribution across Australia, marital status (95.62%, 16,321/17,069) were never married), and age distribution. A higher percentage had attained university (22.52%, 3844/17,069) and trade/certificate/diploma qualifications (25.94%, 4428/17,069) compared with this age group of women in the national population (9.4% and 21.7% respectively). Among study participants, 22.05% (3721/16,877) were not in paid employment with 35.18% (5931/16,857) studying 16 or more hours a week. A higher percentage of study participants rated their health in the online survey as fair or poor (rather than good, very good, or excellent) compared with those participating in face-to-face interviews in the AHS (18.77%, 3203/17,069 vs 10.1%). A higher percentage of study participants were current smokers (21.78%, 3718/17,069 vs 16.4%) and physically active (59.30%, 10,089/17,014 were classified as sufficiently active vs 48.3%) but alcohol consumption was lower (59.58%, 9865/16,558 reported drinking alcohol at least once per month vs 65.9% in the AHS). Using self-reported height and weight to determine body mass index (BMI, kg/m(2)), 34.80% (5901/16,956) of the cohort were classified as overweight or obese (BMI of 25 or more), compared with 33.6% respectively using measured height and weight in the AHS. Findings indicated that using the Internet and social networking sites for an online survey represent a feasible recruitment strategy for a national cohort of young women and result in a broadly representative sample of the Australian population.


Radiation-induced genetic instability in vivo depends on p53 status.
In response to ionizing radiation and other agents that damage DNA, the p53 tumor suppressor protein activates multiple cellular processes including cell cycle checkpoints and programmed cell death. Although loss of p53 function is associated with radiation-induced genetic instability in cell lines, it is not clear if this relationship exists in vivo. To study the role of p53 in maintenance of genetic stability in normal tissues following irradiation, we have measured mutant frequencies at the adenine phosphoribosyltransferase (Aprt) and hypothanine-guanine phosphoribosyltransferase (Hprt) loci and examined mechanisms of loss of heterozygosity (LOH) in normal T cells of p53-deficient, Aprt heterozygous mice that were subjected to whole-body irradiation with a single dose of 4Gy X-rays. The radiation-induced mutant frequency at both the Aprt and Hprt loci was elevated in cells from mice with different p53 genotypes. The radiation-induced elevation of p53-/- mice was significantly greater than that of p53+/- or p53+/+ mice and was caused by several different kinds of mutational events at the both chromosomal and intragenic levels. Most significantly, interstitial deletion, which occurs rarely in unirradiated mice, became the most common mechanism leading to LOH in irradiated p53 null mice. These observations support the idea that absence or reduction of p53 expression enhances radiation-induced tumorigenesis by increasing genetic instability at various loci, such as those for tumor suppressor genes.


Clinical response after sorafenib for hepatocellular carcinoma in elderly patients: a report of two cases.
Among primary liver cancers occurring worldwide, hepatocellular carcinoma (HCC) is the major histological type accounting for 70-85% of all cases. Phase III trials in patients with advanced HCC treated with sorafenib (SO), a multitargeted tyrosine kinase inhibitor, showed significant improvements in both overall and progression-free survival. We report the cases of two elderly patients with advanced HCC who had prolonged stable disease following treatment with SO (400 mg bid). Patient 1 was treated with SO for a period of 16 months until evidence of right sacral metastases was noted. Patient 2 received SO 400 mg bid from January 2009 to October 2009 until radiological evidence of disease progression was noted. Both patients experienced minimal toxicity, suggesting that SO can be safely administered to elderly patients.


A hypothetical model of crossing Bombyx mori nucleopolyhedrovirus through its host midgut physical barrier.
Bombyx mori nucleopolyhedrovirus (BmNPV) is a primary pathogen of silkworm (B. mori) that causes severe economic losses each year. However, the molecular mechanisms of silkworm-BmNPV interactions, especially the silkworm proteins that can interact with the virus, are still largely unknown. In this study, the total and membrane proteins of silkworm midguts were displayed using one- and two-dimensional electrophoresis. A virus overlay assay was used to detect B. mori proteins that specifically bind to BmNPV particles. Twelve proteins were located and identified using mass spectrometry, and the different expression of the corresponding genes in BmNPV susceptible and resistant silkworm strains also indicated their involvement in BmNPV infection. The 12 proteins are grouped based on their potential roles in viral infection, for example, endocytosis, intracellular transportation, and host responses. Based on these results, we hypothesize the following: I) vacuolar ATP synthase catalytic subunit A and subunit B may be implicated in the process of the membrane fusion of virus and the release of the nucleocapsid into cytoplasm; II) actin, enolase and phosphoglycerate kinase are cytoskeleton associated proteins and may play an important role in BmNPV intracellular transportation; III) mitochondrial prohibitin complex protein 2, ganglioside-induced differentiation-associated protein, calreticulin, regucalcin-like isoform X1 and 60 kDa heat shock protein are involved in cell apoptosis regulation during BmNPV infection in larvae midguts; IV) ribosomal P0 may be associated with BmNPV infection by regulating gene expression of BmNPV; V) arginine kinase has a role in the antiviral activities against BmNPV. Our work should prove informative by providing multiple protein targets and a novel direction to investigate the molecular mechanisms of the interactions between silkworms and BmNPV.


Quantitative toxoplasma gondii oocyst detection by a modified Kato Katz test using Kinyoun staining (KKK) in ME49 strain experimentally infected cats.
We detected Toxoplasma gondii oocysts in feces of experimentally infected cats, using a Kato Katz approach with subsequent Kinyoun staining. Animals serologically negative to T. gondii were infected orally with 5 x 10(2) mice brain cysts of ME49 strain. Feces were collected daily from the 3rd to the 30th day after challenge. Oocysts were detected by qualitative sugar flotation and the quantitative modified Kato Katz stained by Kinyoun (KKK). In the experimentally infected cats, oocysts were detected from the 7th to 15th day through sugar flotation technique, but oocysts were found in KKK from the 6th to 16th day, being sensitive for a larger period, with permanent documentation. The peak of oocysts excretion occurred between the 8th to 11th days after challenge, before any serological positive result. KKK could be used in the screening and quantification of oocysts excretion in feces of suspected animals, with reduced handling of infective material, decreasing the possibility of environmental and operator contamination.


Three-dimensional cone-beam computed tomographic sialography in the diagnosis and management of primary Sjögren syndrome: Report of 3 cases.
Sjögren syndrome is a chronic autoimmune inflammatory disease characterized by lymphocytic infiltration of exocrine glands, predominantly the parotid and lacrimal glands, thereby resulting in oral and ocular dryness. It has been reported to occur most frequently in women between 40 and 50 years of age. Sjögren syndrome has an insidious onset, is slowly progressive, and presents a wide range of clinical manifestations, leading to delays or challenges in the diagnosis. Early diagnosis of this condition is essential to prevent the associated complications that affect patients' quality of life. This report presents 3 cases of Sjögren syndrome in female patients aged between 40 and 75 years who presented with complaints of persistent dry mouth and burning sensation. The cases highlight the diagnostic value of 3-dimensional cone-beam computed tomographic sialography in the detection of salivary gland pathologies at an early stage.


Curcumin modulates DNA methylation in colorectal cancer cells.
Recent evidence suggests that several dietary polyphenols may exert their chemopreventive effect through epigenetic modifications. Curcumin is one of the most widely studied dietary chemopreventive agents for colon cancer prevention, however, its effects on epigenetic alterations, particularly DNA methylation, remain unclear. Using systematic genome-wide approaches, we aimed to elucidate the effect of curcumin on DNA methylation alterations in colorectal cancer cells. To evaluate the effect of curcumin on DNA methylation, three CRC cell lines, HCT116, HT29 and RKO, were treated with curcumin. 5-aza-2'-deoxycytidine (5-aza-CdR) and trichostatin A treated cells were used as positive and negative controls for DNA methylation changes, respectively. Methylation status of LINE-1 repeat elements, DNA promoter methylation microarrays and gene expression arrays were used to assess global methylation and gene expression changes. Validation was performed using independent microarrays, quantitative bisulfite pyrosequencing, and qPCR. As expected, genome-wide methylation microarrays revealed significant DNA hypomethylation in 5-aza-CdR-treated cells (mean β-values of 0.12), however, non-significant changes in mean β-values were observed in curcumin-treated cells. In comparison to mock-treated cells, curcumin-induced DNA methylation alterations occurred in a time-dependent manner. In contrast to the generalized, non-specific global hypomethylation observed with 5-aza-CdR, curcumin treatment resulted in methylation changes at selected, partially-methylated loci, instead of fully-methylated CpG sites. DNA methylation alterations were supported by corresponding changes in gene expression at both up- and down-regulated genes in various CRC cell lines. Our data provide previously unrecognized evidence for curcumin-mediated DNA methylation alterations as a potential mechanism of colon cancer chemoprevention. In contrast to non-specific global hypomethylation induced by 5-aza-CdR, curcumin-induced methylation changes occurred only in a subset of partially-methylated genes, which provides additional mechanistic insights into the potent chemopreventive effect of this dietary nutraceutical.


MRI evidence of acute inflammation in leukocortical lesions of patients with early multiple sclerosis.
To identify gadolinium-enhancing lesions affecting the cortex of patients with early multiple sclerosis (MS) and to describe the frequency and evolution of these lesions. We performed a retrospective, observational, longitudinal analysis of MRI scans collected as part of the Betaseron vs Copaxone in Multiple Sclerosis with Triple-Dose Gadolinium and 3T MRI Endpoints (BECOME) study. Seventy-five patients with early-stage MS were scanned monthly, over a period of 12-24 months, using 3T MRI after administration of triple-dose gadolinium. A total of 1,188 scans were included in the analysis. A total of 139 were selected using an image pipeline algorithm that integrated the image information from cortical gray matter masks and gadolinium-enhancing lesion masks. These scans were evaluated to identify gadolinium-enhancing lesions affecting the cortex. The total number of gadolinium-enhancing lesions was 2,044. The number of gadolinium-enhancing lesions affecting the cortex was 120 (6%), 95% of which were leukocortical. The number of patients who showed gadolinium-enhancing lesions affecting the cortex was 27 (36%). The number of gadolinium-enhancing lesions affecting the cortex at baseline was 25 (21%) and the number of new lesions that developed in follow-up scans was 49 (41%). The number of persistent lesions was 46 (38%). The presence of enhancing lesions affecting the cortex and adjacent white matter, although transient and not frequent, suggests that at least some cortical lesions are related to blood-brain barrier disruption. Our data support the concept that there may be an acute inflammatory phase in the development of leukocortical MS lesions. NCT00176592.


[Short-term hospitalization and ambulatory care of patients with advanced hemorrhoidal disease].
The authors describe possible non-surgical treatment of extensive haemorrhoids grade 3 and 4, using Barron's rubber band ligation. To make comparison of therapeutic results possible Dennison's Sheffield classification is used. In the mentioned new approach indications for ambulatory treatment or short-term hospitalization in patients with an advanced grade of internal or external haemorrhoids are extended. From a group of 145 patients treated by this method 126 were free of subjective complains during a check-up 12 months after termination of treatment.


Stage susceptibility of Japanese medaka (Oryzias latipes) to selenomethionine and hypersaline developmental toxicity.
Anthropogenic disturbance of seleniferous soils can lead to selenium contamination of waterways. Although selenium is an essential micronutrient, bioaccumulation and maternal transfer of proteinaceous selenomethionine (SeMet) can result in embryo toxicity. Furthermore, as the climate changes, the salinity of spawning grounds in water-restrained estuaries is increasing. Although a small increase in salinity may not directly impact adult fish, it may alter the detoxification strategies of developing organisms. Previous research indicates that hypersalinity may potentiate SeMet embryo toxicity at an early developmental stage. However, embryonic development is a complex, spatiotemporal process with a constantly shifting cellular microenvironment. To generate thresholds and an adverse outcome pathway for the interactions between selenium and salinity, we sought to identify windows of susceptibility for lethality and deformities in the Japanese medaka (Oryzias latipes). Embryos were treated in freshwater or saltwater for 24 h with 0.5 µM, 5 µM, and 50 µM SeMet at 6 different developmental stages (9, 17, 25, 29, 34, and 38). Survival, hatch, deformities (total, type, and severity), and days to hatch were quantified. Selenium embryo tissue measurements were performed. Selenomethionine exposures of 5 µM and 50 µM significantly decreased survival and hatch at all stages. However, SeMet uptake was stage-dependent and increased with stage. Stage 17 (early neurulation) was identified as the most susceptible stage for lethality and deformities. Selenomethionine in saltwater caused significantly greater toxicity than freshwater at stage 25 (early organogenesis), suggesting a role for liver and osmoregulatory organogenesis in toxicity.


The optimum curing cycle for a light- and heat-cured composite inlay material.
The transverse bend test and surface microhardness test were used to determine the optimum curing cycle for a light- and heat-cured composite inlay material. Specimens were light-cured (control) and light- and heat-cured using the following temperatures: 50 degrees C for 5 min; 50 degrees C for 10 min; 100 degrees C for 1 min; 100 degrees C for 5 min; 100 degrees C for 10 min; and 100 degrees C for 15 min. Heat-curing in boiling water at 100 degrees C for at least 1 min significantly improved the transverse strength, modulus of elasticity and surface microhardness compared to light-curing only or at 50 degrees C. The curing cycle of 100 degrees C for 5 min is considered the most appropriate.


Bactericidal effect of HM-242, a novel disinfectant, against Pseudomonas aeruginosa.
The bactericidal effect of HM-242, a novel antimicrobial agent, against Pseudomonas aeruginosa was investigated by using Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values and the time-kill study. Furthermore, we also morphologically investigated its effect against P. aeruginosa by use of transmission electron microscopy (TEM) in comparison with that of chlorhexidine digluconate (CHG). The bactericidal activity of HM-242 after 1 min incubation evaluated by MBC was 25 microg/mL, while the MBC of CHG was 50 microg/mL. In the time-kill study, the killing activity of HM-242 with 25 microg/mL incubation was stronger than that of CHG with 50 microg/mL incubation. MIC values of HM-242 and CHG against P. aeruginosa were 25 microg/mL and 12.5 microg/mL, respectively. We also observed via TEM the morphological changes in the test bacteria after being treated with each drug at 1/2MBC, 1MBC, 2MBC and 4MBC after 1 min or 5 min incubation. Under treatment with the same concentration of the test drugs, the cell damage with HM-242 treatment was greater than that with CHG. The appearance of empty cells was recognized at the concentrations greater than 50 microg/mL (2MBC) of HM-242 and 200 microg/mL of CHG (4MBC) after 1 min exposure, although no cell damage was evident below these concentrations. The cell-damaging effect against the test strain was dependent on the drug concentration and incubation time. The release of cell components and bleb formation were also recognized. These results suggest that HM-242 has more potent bactericidal activity in low concentrations under shorter time treatments than CHG. Both HM-242 and CHG act on the cell membrane and cell wall of P. aeruginosa and can destroy the cell integrity. We finally emphasize that HM-242 as well as CHG might be a suitable disinfectant for use in the medical field.


Virtual estimator for piecewise linear systems based on observability analysis.
This article proposes a virtual sensor for piecewise linear systems based on observability analysis that is in function of a commutation law related with the system's outpu. This virtual sensor is also known as a state estimator. Besides, it presents a detector of active mode when the commutation sequences of each linear subsystem are arbitrary and unknown. For the previous, this article proposes a set of virtual estimators that discern the commutation paths of the system and allow estimating their output. In this work a methodology in order to test the observability for piecewise linear systems with discrete time is proposed. An academic example is presented to show the obtained results.


[Specific inhibitory action of a novel antidepressant paroxetine on 5-HT uptake].
Effect of a novel antidepressant, paroxetine, on the uptake of serotonin (5-HT), noradrenaline (NA) and dopamine (DA) as well as on various neuro-receptors were investigated in comparison with those of the tricyclic antidepressants amitriptyline, chlorimipramine and imipramine. Paroxetine showed a potent 5-HT uptake inhibitory action, giving the NA/5-HT ratio of 886 in comparison with the ratios of 1.7, 15 and 1.5 for amitriptyline, chlorimipramine and imipramine, respectively. On the other hand, paroxetine showed almost no inhibitory action on the binding of the [3H]-labeled ligands examined in this study [( 3H]quinuclidinyl benzilate, [3H]5-HT, [3H]ketanserine, [3H]pyrilamine, [3H]dihydroalprenolol, [3H]prazosin, [3H]clonidine and [3H]spiroperidol). In contrast, the tricyclic antidepressants showed inhibitory action on a number of bindings and also revealed comparatively high affinities especially for muscarine, histamine-1 and alpha 1-adrenaline receptors responsible for the side effects. From the above findings, it can be concluded that paroxetine has only a weak affinity for various neuro-receptors and inhibits specifically 5-HT uptake.


Isolation of the gene encoding lamp-1, a lysosomal membrane protein, by differential screening in an animal model of status epilepticus.
The present study employed differential library screening to identify genes associated with kainic acid (KA)-mediated selective neuronal death. One of the isolated clones was lamp-1, which encodes a major lysosomal membrane protein that is also present in the cell membrane. Following systemic KA treatment, lamp-1 was induced in vulnerable hippocampal and other limbic regions. This effect was blocked by cycloheximide (CHX) pre-treatment. Northern blot analysis also demonstrated the presence of lamp-1 transcripts in non-neural tissues. These findings suggest a novel role for lysosomal membrane proteins as markers of selective neuronal vulnerability.


[Neonatal diagnosis of primary ciliary dyskinesia. Recent advances].
Primary ciliary dyskinesia is a rare, autosomal recessive genetic disease resulting of an abnormal ultrastructural morphology of cilia. Such disease is rarely recognized in neonatal period. Recently, unexplained neonatal respiratory distress has been found to be a common clinical presentation of patients with primary ciliary dyskinesia, indicating that this is an important symptom in early life for this condition. The diagnosis requires a high index of suspicion, but this disease must be considered in any newborn at term who develops unexplained respiratory distress, particularly when situs viscerum inversus is present.


Applications of Quantum Dots in Cancer Detection and Diagnosis: A Review.
The mechanisms of carcinogenesis, cancer invasion and metastasis remain unclear because of the complexity of cancer cells and tumor microenvironment. Thus, the urgent development of a novel approach for cancer detection and real-time monitoring is crucial in order to decipher the intricate molecular information responsible for tumor biological behaviors. Quantum dots (QDs) are engineered fluorescent nanoparticles with unique optical and chemical properties, which have shown a great potential as promising platforms for biomedical applications. Here, we focus on the clinical applications of quantum dot-based nanotechnology in cancer detection and diagnosis, covering topics on individual cancer diagnosis and treatment by in-vitro and in-vivo molecular imaging technologies, sentinel lymph node (SLN) mapping, cancer associated proteins detection in blood, circulation tumor cells (CTCs) detection, and in-depth understanding of the biological behaviors from the perspective of tumor microenvironment. In addition, the major challenges in translating quantum dot-based detection methodologies into clinical applications and promising future directions are also discussed.


Efficacy of T2 Magnetic Resonance Assay in Monitoring Candidemia after Initiation of Antifungal Therapy: the Serial Therapeutic and Antifungal Monitoring Protocol (STAMP) Trial.
The performance of blood culture for monitoring candidemia clearance is hampered by its low sensitivity, especially during antifungal therapy. The T2 magnetic resonance (T2MR) assay combines magnetic resonance with nanotechnology to identify whole Candida species cells. A multicenter clinical trial studied the performance of T2MR in monitoring candidemia clearance compared to blood culture. Adults with a blood culture positive for yeast were enrolled and had blood cultures and T2MR testing performed on prespecified days. Thirty-one patients completed the trial. Thirteen of the 31 patients (41.9%) had at least one positive surveillance T2MR and/or blood culture result. All positive blood cultures (7/7 [100%]) had an accompanying positive T2MR result with concordance in the identified Candida sp., while only 7/23 (30.4%) T2MR results had an accompanying positive blood culture. There was one case of discordance in species identification between T2MR and the preenrollment blood culture with evidence to support deep-seated infection by the Candida spp. detected by the T2MR assay. Based on the log rank test, there was a statistically significant improvement in posttreatment surveillance using the T2MR assay compared to blood culture (P = 0.004). Limitations of the study include the small sample size and lack of outcome data. In conclusion, the T2MR assay significantly outperformed blood cultures for monitoring the clearance of candidemia in patients receiving antifungal therapy and may be useful in determining adequate source control, timing for deescalation, and optimal duration of treatment. However, further studies are needed to determine the viability of Candida species cells detected by the T2MR assay and correlate the results with patient outcomes. (This study is registered at ClinicalTrials.gov under registration number NCT02163889.).


Luminescence properties of KBaYSi2O7:Ce/Eu-Tb phosphors for multifunctional applications.
In this work, the multifunctional KBaYSi2O7:Ce/Eu-Tb (KBYS:Ce/Eu-Tb) phosphors were synthesized by using the conventional high-temperature solid-state reaction, and the luminescence properties were investigated for LED and optical thermometer applications. The single-phase samples were checked by x-ray diffractometer patterns. The energy transfer was found in both Eu2+-Tb3+ and Ce3+-Tb3+ codoped samples, which was verified by spectra and decay curves. Correspondingly, the tunable emission was realized by adjusting the dopant concentrations and white light was obtained in the KBYS:4%Eu2+,9%Tb3+ sample, owing to the energy transfers among Eu2+, Tb3+, and Eu3+. By studying the temperature dependence of the KBYS:2%Ce3+,7%Tb3+, it has been found that the fluorescence intensity ratio for Tb3+ and Ce3+ emissions changes with temperature, indicating the potential application in an optical thermometer. The high absolute sensitivity was determined to be 0.012 K-1. By evaluating the thermal quenching luminescence of the KBYS:4%Eu2+,9%Tb3+, the thermal quenching temperature T0.5 was determined to be 555 K, implying high thermally luminescent stability.


Clinical course of COVID-19 in a liver transplant recipient on hemodialysis and response to tocilizumab therapy: A case report.
The novel coronavirus disease 2019 (COVID-19) is a highly infectious and rapidly spreading disease. There are limited published data on the epidemiology and outcomes of COVID-19 infection among organ transplant recipients. After initial flulike symptoms, progression to an inflammatory phase may occur, characterized by cytokine release rapidly leading to respiratory and multiorgan failure. We report the clinical course and management of a liver transplant recipient on hemodialysis, who presented with COVID-19 pneumonia, and despite completing a 5-day course of hydroxychloroquine, later developed marked inflammatory manifestations with rapid improvement after administration of off-label, single-dose tocilizumab. We also highlight the role of lung ultrasonography in early diagnosis of the inflammatory phase of COVID-19. Future investigation of the effects of immunomodulators among transplant recipients with COVID-19 infection will be important.


Ultrastructure of Rat Rostral Nucleus of the Solitary Tract Terminals in the Parabrachial Nucleus and Medullary Reticular Formation.
Neurons in the rostral nucleus of the solitary tract (rNST) receive taste information from the tongue and relay it mainly to the parabrachial nucleus (PBN) and the medullary reticular formation (RF) through two functionally different neural circuits. To help understand how the information from the rNST neurons is transmitted within these brainstem relay nuclei in the taste pathway, we examined the terminals of the rNST neurons in the PBN and RF by use of anterograde horseradish peroxidase (HRP) labeling, postembedding immunogold staining for glutamate, serial section electron microscopy, and quantitative analysis. Most of the anterogradely labeled, glutamate-immunopositive axon terminals made a synaptic contact with only a single postsynaptic element in PBN and RF, suggesting that the sensory information from rNST neurons, at the individual terminal level, is not passed to multiple target cells. Labeled terminals were usually presynaptic to distal dendritic shafts in both target nuclei. However, the frequency of labeled terminals that contacted dendritic spines was significantly higher in the PBN than in the RF, and the frequency of labeled terminals that contacted somata or proximal dendrites was significantly higher in the RF than in the PBN. Labeled terminals receiving axoaxonic synapses, which are a morphological substrate for presynaptic modulation frequently found in primary sensory afferents, were not observed. These findings suggest that the sensory information from rNST neurons is processed in a relatively simple manner in both PBN and RF, but in a distinctly different manner in the PBN as opposed to the RF.


Using the Wild Bootstrap to Quantify Uncertainty in Mean Apparent Propagator MRI.
Purpose: Estimation of uncertainty of MAP-MRI metrics is an important topic, for several reasons. Bootstrap derived uncertainty, such as the standard deviation, provides valuable information, and can be incorporated in MAP-MRI studies to provide more extensive insight. Methods: In this paper, the uncertainty of different MAP-MRI metrics was quantified by estimating the empirical distributions using the wild bootstrap. We applied the wild bootstrap to both phantom data and human brain data, and obtain empirical distributions for the MAP-MRI metrics return-to-origin probability (RTOP), non-Gaussianity (NG), and propagator anisotropy (PA). Results: We demonstrated the impact of diffusion acquisition scheme (number of shells and number of measurements per shell) on the uncertainty of MAP-MRI metrics. We demonstrated how the uncertainty of these metrics can be used to improve group analyses, and to compare different preprocessing pipelines. We demonstrated that with uncertainty considered, the results for a group analysis can be different. Conclusion: Bootstrap derived uncertain measures provide additional information to the MAP-MRI derived metrics, and should be incorporated in ongoing and future MAP-MRI studies to provide more extensive insight.


Two-Armed Activation of Bone Mineral Deposition by the Flavones Baicalin and Baicalein, Encapsulated in Polyphosphate Microparticles.
In this study, we investigated the effect of the two flavonoids, baicalin (baicalein 7-O-[Formula: see text]- d-glucuronic acid) and its aglycone, baicalein (5,6,7-trihydroxyflavone), after encapsulation into amorphous calcium polyphosphate (Ca-polyP) microparticles on mineralization of primary human osteoblasts (phOSB). Both flavonoids, which come from root extracts of Scutellaria baicalensis Georgi, are used in Traditional Chinese Medicine, and are nontoxic in cells up to a concentration of 3[Formula: see text][Formula: see text]g/ml. The morphogenetically active, energy-rich Ca-polyP particles with a stoichiometric P:Ca ratio of 1:2 are degraded by cellular alkaline phosphatase (ALP) to ortho-phosphate used for bone hydroxyapatite formation. Here we show that the flavone-loaded Ca-polyP microparticles are readily taken up by phOSB, resulting in the accumulation of polyP around the nuclei and the formation of intracellular vesicles containing the ALP. In addition, we demonstrate that baicalin/baicalein causes a rise of the intracellular calcium [Ca[Formula: see text]]i a level which markedly is augmented after encapsulation into Ca-polyP, through activation of the phospholipase C. Moreover, both flavones, either alone or associated with Ca-polyP microparticles, upregulate the expression of the osteoblast calcium efflux channel, the plasma membrane Ca[Formula: see text]-ATPase (PMCA), while the expression of ALP, which promotes bone mineralization, is induced by Ca-polyP and by the flavones only if present in the Ca-polyP-microparticle-associated form. As a result, the extent of bone mineralization is markedly enhanced. Based on the two-armed activating function, new applications of baicalin/baicalein as a component of nutriceuticals for osteoporosis prevention or bone implants can be envisaged.


Two new tetrahydropterin intermediates in the adrenal medullary de novo biosynthesis of tetrahydrobiopterin.
Isolation of two kinetically competent tetrahydropterin intermediates on the de novo biosynthetic pathway to tetrahydrobiopterin is reported. The compounds were detected in HPLC chromatograms by electrochemical oxidation at 270 mv. The hydrodynamic voltamograms of the compounds are indistinguishable from those of tetrahydropterins . Both require Mg+ + for biosynthesis from dihydroneopterin triphosphate. One compound is produced in the absence of NADPH; the other requires NADPH for synthesis. Enzymatic conversion of the former into the latter intermediate requires NADPH. Conversion of either intermediate into tetrahydrobiopterin also requires NADPH. Mg+ +, which is required for the biosynthesis of the intermediates, is not needed for their conversion to tetrahydrobiopterin. Neither compound coelutes with 6-lactoyl tetrahydropterin, the tetrahydropterin analog of sepiapterin.


A method for studying expectorant action in the mouse by measurement of tracheobronchial phenol red secretion.
The paper reports a method for studying mucosecretolytic drugs in the mouse. After i.p. application of phenol red, part of the dye is secreted in the tracheobronchial tract and collected by lung washings with saline. The concentration of secreted phenol red is measured photometrically at 546 nm. All the most important expectorant drugs increase the tracheobronchial secretion of phenol red in the mouse. The ED50 values, calculated as mg/kg, show practically the same activity for N-acetylcysteine, Tiopronine, SF-1284 and S-carboxymethylcysteine, and a lower activity for Ambroxol and Sobrerol. The method was validated for reproducibility utilizing Tiopronine in many experiments performed over twelve months.


Peripapillary hyperreflective ovoid mass-like structures-a novel entity as frequent cause of pseudopapilloedema in children.
Optic nerve head drusen (ONHD) are considered the most common cause for pseudopapilloedema in children. We aimed to investigate and further characterize a new type of optic nerve head lesion on enhanced depth imaging optical coherence tomography (EDI-OCT) named peripapillary hyperreflective ovoid mass-like structures (PHOMS), and ONHD in asymptomatic children with pseudopapilloedema. Retrospective cohort study including 64 eyes from 32 patients with pseudopapilloedema due to PHOMS and/or ONHD. Mean age was 9.0 ± 3.1 years. PHOMS and ONHD were identified and classified on EDI-OCT and infrared images. Ultrasound images were classified for the presence of hyperechogenic structures of the optic nerve head. On EDI-OCT, PHOMS were detected in 63 out of 64 eyes (98.4%). In 60 eyes (93.8%), small hyperreflective foci inside the PHOMS were present. In all cases, we identified a new ring sign visible on infrared images, corresponding clearly to the edge of the PHOMS as seen on EDI-OCT. On ultrasound, we describe a new feature of PHOMS appearing as small hyperechogenic structures without posterior shadowing. In 13 eyes (20.3%), ONHD were present on EDI-OCT and ultrasound. This is the first study showing that PHOMS are the most common cause for pseudopapilloedema in children. PHOMS is a new entity of optic nerve head lesions. It might be a precursor of buried optic nerve head drusen, which can lead to visual field defects, haemorrhages and CNV. This study offers new tools to identify and follow-up these lesions early in childhood using EDI-OCT.


The Effect of Hemodynamic Parameters on Cerebral Oxygenization During Carotid Endarterectomy.
Near-infrared spectroscopy (NIRS) is a non-invasive technique to detect cerebral ischemia by monitoring changes in regional cerebral oxygenation (rSO2) in the frontal lobes. However, there are no studies showing the changes in NIRS values in response to hemodynamic variations during stages of carotid endarterectomy (CEA) procedure and clinical implications of these changes. The aim of this study was to determine if hemodynamic changes affect NIRS values during carotid endarterectomy and if our results may help to provide strategies for hemodynamic management in these patients. A total of 50 consecutive patients undergoing CEA were prospectively included in the study. NIRS was measured at first minute after clamping of carotid artery, and then systolic blood pressure was increased above 150 mmHg. NIRS values from both hemispheres were recorded simultaneously at certain time points and were analyzed to evaluate the changes at different stages of operation and to assess correlations with hemodynamic parameters. NIRS values on the right and left sides were correlated with systolic (right P<0.001, R2:0.24; left P=0.02, R2:0.10) diastolic (right P<0.001, R2:0.36; left P=0.001, R2:0.18) and mean (right P<0.001, R2:0.33; left P=0.003, R2:0.17) blood pressures when the patient was under general anaesthesia. NIRS values were significantly lower than pre-incision values just after clamping of carotid artery in both hemispheres (P=0.005 for the right and P<0.001 for the left side). NIRS values measured in our study show that there is a correlation between hemodynamic changes and cerebral oxygenation. This effect is especially pronounced while the patient is asleep and intubated, which implies the importance of close monitoring of patients with carotid disease during any surgery requiring general anaesthesia.


[Acute insular infarct increases risk of electrocardiogram changes and sudden cardiac death].
To investigate the influence of location and size of acute insular infarct on stroke-related electrocardiogram (ECG) changes and cardiovascular events. Ninety-nine cases admitted to hospital from October 2007 to June 2009, who were diagnosed as acute middle cerebral artery territory infarct within 48 h after onset and without the history of cardiac diseases, were included in the study. The patients were further divided into three groups: major insular infarct, minor insular infarct and control group, according to the infarct size on MRI diffusion-weighted image. The clinical data, ECG changes and cardiovascular events were compared between left and right insular infarct. Logistic regression was applied to determine the independent risk factors of ECG changes and cardiovascular events. Large artery atherosclerosis was the main cause of acute insular infarct (71.8 %), which was associated with higher NIHSS score compared to the control group (P < 0.01). Comparing the left and right insular infarct, the frequencies of sinus bradycardia and sudden cardiac death were significantly higher in left insular infarct (P < 0.01 and P < 0.05), while there was a trend that the frequency of atrial fibrillation was higher in right insular infarct (P = 0.079). With the larger size of insular infarct, the frequency of sinus bradycardia, new atrial fibrillation and sudden cardiac death (P<0.01, P<0.05 and P<0.05, respectively) became much higher. Logistic regression analysis showed that major insular infarct was related to the higher frequency of sinus bradycardia (OR = 4.660, 95% CI: 1.646 ~ 13.195; P = 0.004). Acute insular infarct is associated with the stroke-related ECG changes and sudden cardiac death. Left insular infarct is related to sinus bradycardia, possibly due to the enhanced parasympathetic tone. It deserves clinical attention that the incidence of cardiac autonomic disturbance becomes higher with the enlarged insular infarct size.


Hybrid Therapy versus Sequential Therapy for Eradication of Helicobacter pylori: A Randomized Controlled Trial.
To compare the sequential therapy (ST) with the hybrid therapy (HT) for the eradication of Helicobacter pylori. Patients with peptic ulcer disease and gastritis found to be H. pylori positive were randomized to HT group who received omeprazole (20 mg bid) and amoxicillin (1 g bid) for 7 days followed by omeprazole (20 mg bid), amoxicillin (1 g bid), clarithromycin (500 mg bid), and metronidazole (400 mg tid) for the next 7 days and ST group who received omeprazole and amoxicillin for 5 days followed by omeprazole, clarithromycin, and metronidazole for the next 5 days. Eradication rate, compliance, and complications were compared. A total of 120 patients were included, sixty in each group. H. pylori eradication rate was significantly higher in HT group on intention-to-treat analysis (88.3% [confidence interval (CI) 78.3%-94.8%] vs. 73.3% [CI 61.1%-83.3%]; P = 0.037). Per-protocol analysis showed higher eradication rate with HT (93% [CI 83.9%-93.7%] vs. 81.5% [CI 69.5%-90.2%]; P = 0.068); however, the difference was insignificant. Compliance and side effects were similar. A complete course of HT costs $10.77, while ST costs only $6.347. HT achieves significantly higher H. pylori eradication rate than ST with comparable patient compliance and side effects but at an higher price. However, it can be used in places where ST is ineffective.


A Summertime Stupor.
Most commonly seen with alcohol use disorder in the developed world, Wernicke's encephalopathy (WE), a disorder caused by thiamine deficiency can be readily missed in the setting of other predisposing conditions such as malnutrition, the most common cause worldwide. We present a case of a 21-year-old female with sudden progressive decline in her level of alertness and mentation along with severe hypothermia who had clinical features and imaging findings consistent with WE in the setting of pancreatitis and chronic gastritis. WE should be suspected in all patients who present with altered mental status (AMS) and who are at an increased risk of malnutrition despite a normal or high body mass index, so that treatment with thiamine may be initiated and further neurologic sequelae can be averted.


Dopamine agonist therapy in low-response children following traumatic brain injury.
The objective of this study was to determine whether a dopamine agonist could improve mental status among children in a low-response state following traumatic brain injury. In an 8-week, prospective, double-blind, randomized trial, 10 children and adolescents ages 8 to 21 years (X = 16.7 years) with traumatic brain injury sustained at least 1 month previously and remaining in a low-response state (Rancho Los Amigos Scale level pound 3) received pramipexole or amantadine. Medication dosage was increased over 4 weeks, weaned over 2 weeks, and then discontinued. At baseline and weekly during the study, subjects were evaluated with the Coma Near Coma Scale, Western NeuroSensory Stimulation Profile, and Disability Rating Scale. Scores improved significantly from baseline to the medication phase on the Coma Near Coma Scale, Western NeuroSensory Stimulation Profile, and Disability Rating Scale (P < .005). The weekly rate of change was significantly better for all three measures on medication than off medication (P < .05). Rancho Los Amigos Scale levels improved significantly on medication as well (P < .05). There was no difference in efficacy between amantadine and pramipexole. No unexpected or significant side effects were observed with either drug. This clinical trial supports the benefit of two dopamine agonists in the restoration of functional arousal, awareness, and communication. These drugs can be helpful in accelerating eligibility for acute rehabilitation among children and adolescents who have sustained significant brain injuries.


On-line preconcentration strategy for the simultaneous quantification of three local anesthetics in human urine using CZE.
The simultaneous determination of usually employed anesthetics (procaine, lidocaine, and bupivacaine) has been developed and validated using CE with ultraviolet detection at 212 nm. The separation of these three drugs has been achieved in less than 7 min, using a temperature of 25ºC and 25 kV, with a 150 mM citrate buffer (pH 2.5) as BGE. Field-amplified sample injection (FASI) has been used for on-line sample preconcentration. Ultrapure water and ACN 50/50 (v/v) mixture gave the greatest enhancement factor when it was employed as an injection solvent. Injection voltage and time were optimized, being 13 kV and 13 s, the optimum values, respectively. To avoid the possible irreproducibility associated with the electrokinetic injection, an internal standard such as tetracaine, was employed. The instrumental detection limits (LOD S/N = 3) for the compounds ranged between 2.6 and 7.0 μg L(-1) and the quantitation limits (LOQ S/N = 10) between 37.8 and 55.9 μg L(-1) . The detection limits obtained in real human urine samples ranged between 55.2 and 83.6 μg L(-1) and the quantitation limits between 196.0 and 276.0 μg L(-1) . The proposed method has demonstrated its applicability to the analysis of these local anesthetics in urine samples without any pretreatment, allowing the rapid determination of these target analytes.


Intraocular levels of cefuroxime in inflamed rabbit eyes.
The pharmacokinetics of cefuroxime was studied in the inflamed rabbit eye employing subconjunctival, intravitreal and combined intravitreal-intravenous routes of administration to study the intraocular levels and the duration of minimum inhibitory concentrations (MIC) of the antibiotic in the vitreous and in the aqueous. A standard inoculum of viable S. aureus was injected into the vitreous of 36 pigmented rabbits to establish experimental endophthalmitis. A biological method was used for the antibiotic assay. Penetration of systemically and subconjunctivally administered-cefuroxime into the inflamed vitreous was poor. Intraocular inflammation increased the clearance of the intravitreally injected cefuroxime. A dose of 75 mg subconjunctivally produced levels in the aqueous far exceeding MIC for over six hours. Penetration of intravitreally injected cefuroxime into the aqueous was poor, inconsistent and short lasting. Following a single intravitreal injection of 1000 micrograms cefuroxime, levels exceeding the MIC for common ocular pathogens persisted in the vitreous for at least 24 hours but supplementation with intravenous cefuroxime neither increased the intraocular levels nor delayed the clearance of the intravitreally injected antibiotic.


Influence of 8 Weeks of Tabata High-Intensity Interval Training and Nanocurcumin Supplementation on Inflammation and Cardiorespiratory Health among Overweight Elderly Women.
Nanocurcumin (NaC) and high-intensity interval training (HIIT) play crucial role in weight and inflammation control. The purpose of the current study was to evaluate the separate and combined effects of 8 weeks of Tabata-HIIT and NaC supplementation on the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, long non-coding RNA myocardial infarction associated transcript (lncRNA MIAT) expression, body composition, and cardiorespiratory health in elderly overweight women. A total of 48 healthy overweight elderly women were randomly divided into four groups: NaC, Tabata-HIIT+Pla, Tabata-HIIT+NaC, and placebo. Participants underwent a Tabata HIIT program (2 days per week, at 80∼0% of maximal HR) and NaC supplementation (daily 80 mg in two 40 mg capsules) for 8 weeks. Blood sampling, cardiorespiratory hemodynamic responses, and body composition evaluations were obtained before and after treadmill stress testing at the baseline timepoint and following 8 weeks of intervention. The mRNA of lncRNA-MIAT and NLRP3 were measured by real-time polymerase chain reaction. After 8 weeks, a significant improvement was observed in body composition and cardiorespiratory hemodynamics in the Tabata-HIIT groups compared to the NaC alone and placebo groups (P<0.05). Tabata training, both with and without the addition of nano curcumin supplementation, did not result significant effect on the resting levels of lncRNA-MIAT expression (P>0.05). Nevertheless, NaC supplementation along with Tabata training led to a significant reduction in NLRP3 inflammasome. In addition, NaC supplementation in overweight/preobese women improved systemic inflammation during treadmill stress testing. These findings indicating the suppressive effects of non-pharmacologic interventions on the sympathetic system and downregulation of the inflammasome.


Langevin equation approach to diffusion magnetic resonance imaging.
The normal phase diffusion problem in magnetic resonance imaging (MRI) is treated by means of the Langevin equation for the phase variable using only the properties of the characteristic function of Gaussian random variables. The calculation may be simply extended to anomalous diffusion using a fractional generalization of the Langevin equation proposed by Lutz [E. Lutz, Phys. Rev. E 64, 051106 (2001)] pertaining to the fractional Brownian motion of a free particle coupled to a fractal heat bath. The results compare favorably with diffusion-weighted experiments acquired in human neuronal tissue using a 3 T MRI scanner.


A Prospective Phase II Study of Cisplatin and Cremophor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors.
We conducted a prospective phase II study of cisplatin plus cremophor EL-free paclitaxel (Genexol-PM) in patients with unresectable thymic epithelial tumors to determine the efficacy and tolerability of the combination therapy. Patients were treated with cisplatin (70 mg/m) and Genexol-PM (230 mg/m) on day 1 of a 3-week cycle as first-line palliative chemotherapy. The primary end point of this study was objective response rate, and the secondary end points included toxicity, progression-free survival (PFS), overall survival, correlation between early 18F-fluorodeoxyglucose positron emission tomography/computed tomography response and PFS, and correlation between baseline flurododeoxyglucose uptake and histology. Forty-two patients with unresectable thymoma (n = 14) or thymic carcinoma (n = 28) were enrolled between May 2012 and October 2014. The median age was 59 years (range: 25-77) and 30 patients (71%) were male, and 39 patients (93%) had an ECOG PS of 1. The median number of treatment cycles was six (range: 1-6). For 40 assessable patients, the objective response rate was 62.5% (95% confidence interval [CI]: 47.6-77.4) with rates of 46% (95% CI: 23.3-76.9) for advanced thymoma (n = 13) and 70% (95% CI: 52.0-82.1) for thymic carcinoma (n = 27). With a median follow-up of 15.5 months, the median PFS for all 42 patients was 9.8 months (11.4 months for thymoma versus 8.1 months for thymic carcinoma). The 2-year overall survival was 77.9% for thymoma and 65.9% for thymic carcinoma. There were no treatment-related deaths. The most common grade 3 and 4 treatment-related adverse event was neutropenia in 11 patients (26%). Eight patients (19%) experienced grade 2 hypersensitivity reactions. There was no correlation between early positron emission tomography response and PFS, but tumor histology (thymoma versus thymic carcinoma) was correlated with SUVmax before chemotherapy. These data suggest that combination of cisplatin and Genexol-PM is highly effective and tolerable for the treatment of unresectable thymic epithelial tumors.


[Cytokines and malignant hemopathies: leukemias and bone marrow graft].
Cytokines are now part of the modern armentarium utilized against malignant blood diseases. The essentially lymphocytic haematopoietic growth factors (G-CSF, GM-CSF, IL-3) reduce the infectious morbidity associated with the deep and prolonged neuropoenia induced by the myelo-ablative conditioning for autologous or allogeneic bone marrow transplantations, and widening their indications is tempting. The reluctance expressed about their use in chemotherapy of acute myeloid leukaemia is abating now that controlled studies have shown that they preserve the complete response rate and shorten the duration of leucopoenia. Moreover, they modify the leukaemia biological response, which makes it possible to increase the cytotoxicity of certain drugs and constitutes a new approach to drug-resistant leukaemias. Immuno-modulating cytokines (interferon alpha, interferon gamma, interleukin-2) act through mechanisms that are still ill-defined: antitumoral activity, modification of biological responses, immunoactivation. Nevertheless, interferon alpha has revolutionized the treatment of hairy cell leukaemia and myeloid leukaemia, with a 70% remission rate. The scarcity of complete responses (10% of hairy cell leukaemias) or cytogenetic responses (20% of chronic myeloid leukaemias) justifies a combined treatment (chemotherapy+immunotherapy?) to improve these patients' cure rate. The anti-leukaemic activity of interleukin-2, observed in patients with refractory relapses, produces 33% of responses, including 10% of complete responses, and it is tempting to test the impact of this immunotherapy on the control of residual leukaemia as adjuvant of complete remission using randomized trials.


The power of behavioural approaches - we need a revival.
Behavioural approaches can be used very effectively to teach new skills and to change behaviours that are challenging and not socially adaptive. They have gone out of fashion but should be revived, as the studies discussed here indicate.


Latitudinal cogradient variation of development time and growth rate and a negative latitudinal body weight cline in a widely distributed cabbage beetle.
The evolutionary and phenotypic responses to environmental gradients are often assumed to be the same, a phenomenon known as "cogradient variation". However, only a few insect species display cogradient variation in physiological traits along a latitudinal gradient. We found evidence for such a response in the examination of the life history traits of the cabbage beetle Colaphellus bowringi from 6 different geographical populations at 16, 19, 22, 24, 26 and 28°C. Our results showed that larval and pupal development times significantly decreased as rearing temperature increased, and that growth rates were positively correlated with temperature. Body weight tended to decrease with increasing temperature, consistent with the general pattern in ectothermic animals. Larval development time was positively correlated with latitude, whereas the growth rate decreased as latitude increased, showing an example of latitudinal cogradient variation. Body weight significantly decreased with increasing latitude in a stepwise manner, showing a negative latitudinal body weight cline. Females were significantly larger than males, consistent with the female biased sex dimorphism in insects. Body weight tended to decrease with increasing rearing temperature, whereas the differences in sexual size dimorphism (SSD) tended to decrease with increasing body weight, which biased our results toward acceptance of Rensch's rule. We found that weight loss was an important regulator of SSD, and because male pupae lost significantly more weight at metamorphosis than female pupae, SSD was greater in adults than in pupae. Overall, our data provide a new example that a latitudinal cogradient variation in physiological traits is associated with a negative latitudinal body weight cline.


Anatomical Arthroscopic Graft Reconstruction of the Anterior Tibiofibular Ligament for Chronic Disruption of the Distal Syndesmosis.
Injuries of the distal tibiofibular syndesmosis are commonly overlooked or mismanaged, and chronic instability is a debilitating condition leading to premature joint degeneration. Several methods of treatment have been described, mainly screw fixation, arthrodesis, or ligament reconstruction. Most clinical evidence is limited to case series, mainly screw fixation, and there is a general paucity of evidence regarding ligament reconstruction, which is considered to be more anatomic and to restore joint biomechanics. Most papers describe open techniques. We describe an original technique for all-inside anatomic arthroscopic graft reconstruction of the anterior-inferior tibiofibular ligament, which is simpler than other previously described reconstruction procedures. In addition to being performed through standard ankle arthroscopy portals, we believe this technique avoids potential complications.


Ebola virus in West Africa: waiting for the owl of Minerva.
The evolving Ebola epidemic in West Africa is unprecedented in its size and scope, requiring the rapid mobilization of resources. It is too early to determine all of the ethical challenges associated with the outbreak, but these should be monitored closely. Two issues that can be discussed are (1) the decision to implement and evaluate unregistered agents to determine therapeutic or prophylactic safety and efficacy and (2) the justification behind this decision. In this paper, I argue that it is not compassionate use that justifies this decision and suggest three lines of reasoning to support the decision.


Dissection of Tbx1 and Fgf interactions in mouse models of 22q11DS suggests functional redundancy.
The 22q11 deletion syndrome (22q11DS) is characterized by abnormal development of the pharyngeal apparatus. Mouse genetic studies have identified Tbx1 as a key gene in the etiology of the syndrome, in part, via interaction with the fibroblast growth factor (Fgf) genes. Three murine Fgfs, Fgf3, Fgf8 and Fgf10 are coexpressed in different combinations with Tbx1. They are all strongly downregulated in Tbx1-/- embryos, implicating epistatic interactions. Supporting this, Tbx1 and Fgf8 have been shown to genetically interact in the development of the fourth pharyngeal arch artery (PAA) and Fgf10 was identified to be a direct downstream target of Tbx1. To dissect the epistatic relationships of these genes during embryonic development and the molecular pathogenesis of the Tbx1 mutant phenotype, we generated Fgf10+/-;Tbx1+/- and Fgf3-/-;Tbx1+/- mice. Despite strong hypotheses that Fgf10 is the key gene downstream of Tbx1 in the development of the anterior heart field, we do not find evidence for genetic interaction between Tbx1 and Fgf10. Also, the Fgf3-/-;Tbx1+/- mutant mice do not show an additive phenotype. Furthermore, more severe defects do not occur in Fgf8+/-;Tbx1+/- mutants by crossing in the Fgf3 null allele. There is a possible additive effect only in PAA remodeling in the Fgf10+/-;Tbx1+/-;Fgf8+/- embryos. Our findings underscore the importance of potential functional redundancy with additional Fgfs in the development of the pharyngeal apparatus and cardiovascular system via Tbx1. This redundancy should be considered when looking at individual FGF genes as modifiers of 22q11DS.


[Research progress in signal molecules and transcription factors related to the development of temporomandibular joint in embryonic stage].
Temporomandibular joint (TMJ) is a unique synovial joint in mammals. There have been many reports on the structure and function of TMJ during embryonic development.Although studies on TMJ related signal molecules and transcription factors during embryonic development have been carried out since the last century, there are few reports on the molecular genetic regulation of TMJ compared with the abundant molecular regulation information of synovial joint. The studies on signal molecules and transcription factors of TMJ embryonic development were mainly conducted in rodents.There were few studies on the regulatory molecules and their regulatory mechanisms related to the development of TMJ conducted in large mammals and human embryos. This article reviews the research progress of key signal molecules and transcription factors of TMJ in embryonic development on the basis of modern molecular biology technology in order to find more core regulatory molecules and understand their regulation mechanism on TMJ development.


Disc leak in the pathogenesis of posterior retinal degenerations.
Pathogenesis of the posterior retinal degenerations and the role of argon laser para-disc coagulation in its treatment. The posterior retinopathies sometimes follow the degeneration of the retinal pigment epithelium with a release of the hypothetical vasoproliferative factor. There is clinical evidence to show that a slow degeneration of the retinal pigment epithelium also produces a vasoproliferation from the circulation which comes from the choroidal vessels supplying the disc. Treatment by argon laser at the disc margin inhibits the rate of degeneration, and extension of the vasoproliferation.


Thyroxine transfer from cerebrospinal fluid into choroid plexus and brain is affected by brefeldin A, low sodium, BCH, and phloretin, in ventriculo-cisternal perfused rabbits.
Thyroxine (T4) hormone is synthesized by the thyroid gland and then released into the systemic circulation where it binds to a number of proteins. Dysfunction in T4 transport mechanisms has been demonstrated in multiple central nervous system (CNS) diseases including Alzheimer's disease. In the presence of different compounds that inhibit potential T4 transport mechanisms, this study investigated the transfer of T4 from cerebrospinal fluid (CSF) into Choroid Plexus (CP) and other brain tissues. The compounds used were brefeldin A, low sodium artificial CSF (aCSF), BCH, phloretin, and taurocholate (TA). Radiolabeled T4 ((125)I-T4) was perfused continuously into the CSF and was assessed in several brain compartments with reference molecule (14)C-mannitol and blue dextran, using the in vivo ventriculo-cisternal perfusion (V-C) technique in the rabbit. The aCSF containing the drug of interest was infused after 1 h of perfusion. Drugs were applied independently to the aCSF after 1 h of control perfusion. Of interest, in presence of low sodium or BCH, the percentage recovery of (125)I-T4, was increased compared to controls, with concomitant increase in T4 clearance. Conversely, brefeldin A, phloretin, and TA did not exert any significant effect on the recovery and clearance of (125)I-T4 assessed in aCSF. On the other hand, the uptake of (125)I-T4 into CP was raised by 18 fold compared to controls in the presence of brefeldin A. In addition, low sodium, BCH, or phloretin alone, enhanced the uptake of (125)I-T4 by almost 3-fold, whereas TA did not show any significant effect. Finally, the uptake and distribution of (125)I-T4 into other brain regions including ependymal region (ER) and caudate putamen (CAP) were significantly higher than in controls. Our study suggests the involvement of different mechanisms for the transfer of (125)I-T4 from CSF into CP and other brain regions. This transfer may implicate sodium-dependent mechanisms, amino acid "L" system, or organic anion transporting polypeptide (OATP).


[A giant inflammatory fibroid polyp of the esophagus].
Inflammatory fibroid polyp (IFP) is an uncommon benign tumor of the gastrointestinal tract. IFP in the esophagus is very rare, in particular in giant size. A case of a 63 year old woman with a 13 × 7 × 4.5 cm polyp originated of the lower third of the oesophagus is presented. Her esophageal polyp extended proximally from the level of the tracheal bifurcation, prolapsing through the cardia as well as the herniated stomach, and entered distally into the abdominal part of the stomach. Resection of the polyp was performed via a right oesophago-gastrotomy. Histology verified inflammatory fibroid polyp of the esophagus. An overview of clinical features of the inflammatory fibroid polyp is presented in connection of our case report.


Changes in the brain monoamine metabolism in acute liver failure produced by ischemia-reperfusion injury in rats.
To investigate the relationship between behavioral alterations and changes in monoaminergic systems provoked by ischemia-reperfusion liver injury in rats. Prospective, randomized, controlled animal study. University animal laboratory. Male Wistar rats. Acute liver failure was induced by occlusion of the left portal vein and the hepatic artery for 90 mins. Twenty animals were subjected to the behavioral examination. The brain water content was measured in 12 animals. Forty-two animals were used for the evaluation of brain monoamine turnover. Half of animals in each experiment were subjected to the ischemic operation. A step-through passive avoidance test was used for the behavioral evaluation 48 hrs after the ischemic operation. Then, plasma concentrations of amino acids were determined. The brain water content was measured with the dry weight method. The brain monoamine turnover was evaluated by the depletion of norepinephrine and dopamine induced by alpha-methyl-p-tyrosine, or the accumulation of 5-hydroxyindoleacetic acid induced by probenecid. In the plasma analysis performed 48 hrs after the operation, marked damage was found in animals subjected to liver ischemia. Injured rats demonstrated impairment in the passive avoidance test. The plasma concentrations of branch-chain amino acids were decreased, and the plasma concentrations of aromatic amino acids were increased. However, the brain water content was not changed by liver ischemia. The turnover of both norepinephrine in the cerebral cortex and dopamine in the striatum was decreased. The turnover of 5-hydroxytryptamine in the cerebral cortex was increased markedly. In liver injury caused by liver ischemia, the excitatory neurotransmission by norepinephrine and dopamine is depressed and the inhibitory neurotransmission mediated by 5-hydroxytryptamine is facilitated, especially in the telencephalon.


Cross-talk between phosphatidylinositol 3-kinase/AKT and c-jun NH2-terminal kinase mediates survival of isolated human islets.
Therapeutic strategies aimed at the inhibition of specific cell death mechanisms may increase islet yield and improve cell viability and function after routine isolation. The aim of the current study was to explore the possibility of AKT-JNK cross-talk in islets after isolation and the relevance of c-jun NH2-terminal kinases (JNK) suppression on islet survival. After routine isolation, increased AKT activity correlated with suppression of JNK activation, suggesting that they may be related events. Indeed, the increase in AKT activation after isolation correlated with suppression of apoptosis signal-regulating kinase 1 (ASK1), a kinase acting upstream of JNK, by phosphorylation at Ser83. We therefore examined whether modulators of phosphatidylinositol 3-kinase (PI3K)/AKT signaling affected JNK activation. PI3K inhibition led to increased JNK phosphorylation and islet cell death, which could be reversed by the specific JNK inhibitor SP600125. In addition, IGF-I suppressed cytokine-mediated JNK activation in a PI3K-dependent manner. We also demonstrate that inhibition of PI3K rendered islets more susceptible to cytokine-mediated cell death. SP600125 transiently protected islets from cytokine-mediated cell death, suggesting that JNK may not be necessary for cytokine-induced cell death. When administered immediately after isolation, SP600125 improved islet survival and function, even 48 h after removal of SP600125, suggesting that JNK inhibition by SP600125 may be a viable strategy for improving isolated islet survival. Taken together, these results demonstrate that PI3K/AKT suppresses the JNK pathway in islets, and this cross-talk represents an important antiapoptotic consequence of PI3K/AKT activation.


Randomized Controlled Trial of Mineralocorticoid Receptor Blockade in Children with Chronic Kidney Allograft Nephropathy.
We showed that mineralocorticoid receptor blockade (MRB) prevented acute and chronic cyclosporine nephropathy (CsA-Nx) in the rat. The aim of this translational study was to investigate the effect of long-term eplerenone administration on renal allograft function in children with biopsy-proven chronic allograft nephropathy (CAN). Renal transplant children <18 years, biopsy-proven CAN, and a GFR>40 ml/min per 1.73 m2 were included. Patients with BK virus active nephritis, recurrence of renal disease, GFR decline in previous 3 months, or treated with calcium antagonists or antifungal drugs were excluded. They were randomized to receive placebo (n=10) or eplerenone 25 mg/d for 24 months (n=13). Visits were scheduled at baseline, 6, 12, and 24 months. At each period, a complete clinical examination was performed and blood and urine samples were taken. Urine creatinine, 8-hydroxylated-guanosine, heat shock protein 72 (HSP72), and kidney injury molecule (KIM-1) levels were also assessed. In kidney biopsy samples, the tubulo-interstitial area affected by fibrosis (TIF) and glomerulosclerosis were measured at baseline and after 24 months. The baseline eGFR was 80±6 in the placebo and 86±6 ml/min per 1.73 m2 in the eplerenone group; at 24 months it was 66±8 and 81±7 ml/min per 1.73 m2, respectively (P=0.33; 95% confidence intervals, -18 to 33 at baseline, and -11 to 40 after 24 months). The albumin-to-creatinine ratio was 110±74 in the placebo, and 265±140 mg/g in the eplerenone group; and after 24 months it was 276±140 and 228±88 mg/g, respectively (P=0.15; 95% confidence intervals, -283 to 593, and -485 to 391, respectively). In addition, the placebo exhibited a greater TIF, glomerulosclerosis, and urinary HSP72 compared with the eplerenone group. Although this study was underpowered to provide definitive evidence that long-term eplerenone administration attenuates the progression of CAN in pediatric transplant patients, it encourages testing the potential benefit of MRB in this pediatric population.