The human gene for beta glucuronidase is on chromosome 7.
Inconsistent assignments of the human gene for beta glucuronidase (GUS) to chromosomes 7 and 9 have previously been reported. In this study, we have correlated the expression of human GUS in 22 primary Chinese hamster/human hybrid lines with quantitative cytogenetic analysis. Eight hybrids were positive for human GUS as manifested by a five-band pattern on electrophoresis. All of them contained a human chromosome 7 in 34% or more of cells, and seven of them had not retained chromosome 9. One hybrid with only 6% of metaphases possessing a chromosome 7 had no detectable human GUS activity. Human GUS expression was absent in 10 hybrid clones containing chromosome 9 but not 7 and in control fibroblasts from a patient with GUS deficiency. These results support the assignment of presumably the structural gene for beta glucuronidase to chromosome 7.


Comparison of Lipoprotein Electrophoresis and Apolipoprotein E Genotyping in Investigating Dysbetalipoproteinemia.
Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity; however, lipoprotein electrophoresis may also be used to assist in the diagnosis. The aim of this study was to compare apolipoprotein E (apo E) genotyping and lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were collected over a three-year period from a lipid clinic in a tertiary referral centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Sixty-two patients had both apo E genotyping and lipoprotein electrophoresis. Of these, 16 patients showed broad beta band on electrophoresis. However, only 3 of them had apo E2E2 homozygosity on genotyping. Lipoprotein electrophoresis and apo E genotyping results showed poor concordance. This was primarily due to visual interpretation error of lipoprotein electrophoresis which may over diagnose dysbetalipoproteinemia.


Dissociating temporal inhibition of return and saccadic momentum across multiple eye-movement tasks.
Saccade latencies are longer prior to an eye movement to a recently fixated location than to control locations, a phenomenon known as oculomotor inhibition of return (O-IOR). There are theoretical reasons to expect that O-IOR would vary in magnitude across different eye movement tasks, but previous studies have produced contradictory evidence. However, this may have been because previous studies have not dissociated O-IOR and a related phenomenon, saccadic momentum, which is a bias to repeat saccade programs that also influences saccade latencies. The present study dissociated the influence of O-IOR and saccadic momentum across three complex visual tasks: scene search, scene memorization, and scene aesthetic preference. O-IOR was of similar magnitude across all three tasks, while saccadic momentum was weaker in scene search.


Azilsartan suppresses the antiapoptotic biomarker and pro-inflammatory cytokines in rat model of cisplatin-induced retinal and optic nerve toxicity.
The local renin-angiotensin system has been discovered in the eyes; thus, this study evaluates the Azilsartan effect in the retina and optic nerve toxicity induced by Cisplatin in vivo. Forty-eight male rats were randomly assigned into six groups of 8 animals. Group 1 was healthy control that received 0.5 mL/day of 0.5% carboxymethyl cellulose (CMC) orally (PO). Group 2 received a single dose of the 7.0 mg/kg CIS intraperitoneally with 0.5 mL/day of 0.5% CMC-PO. Groups 3 and 4 received 3.5 and 7.0 mg/kg/day of AZIL-PO, respectively. Groups 5 and 6 received 3.5 and 7.0 mg/kg/day of AZIL-PO, respectively together with a single dose of 7.0 mg/kg of CIS-IP. The ocular tissue and serum estimated the TNF-α, NF-kβ, and Casp-3. A complete blood count was also measured, and the eye was sent for histological examination. The administration of the 3.5 mg/kg AZIL significantly (p < 0.05) reduced the ocular tissue and serum TNF-α, NF-kB, and Casp-3 levels, when given to CIS treated group, while the 7.0 mg/kg AZIL does not. Additionally, azilsartan shows no negative impact on the CBC in rats. Finally, the eye histological examination showed a significant (p < 0.05) drop in the signs of inflammation and cellular degeneration, particularly after administration of the 3.5 mg/kg AZIL to the CIS-treated group. A low dose of AZIL exerts an anti-inflammation and an anti-apoptotic effect through significant suppression of the pro-inflammatory mediators and an apoptotic biomarker by blocking the local angiotensin II type.


Rabies Vaccine Disposition: Trends in Vaccination Among Israeli Travelers.
Travelers are a risk-group for rabies; however, few are protected. We describe changes in pre-travel vaccination rates and post-travel referrals after animal contact. We conducted a nationwide, retrospective study for 2014-2018. The ratio of rabies vaccine courses distributed to travelers and the number of Israeli-tourist-entries to endemic countries was calculated, as was the proportion of travelers referred to a post-travel clinic after animal contact. During the study period, the ratio of pre-travel vaccine courses distributed nationally to outgoing tourism to endemic countries was stable at ≈0.7%; 13% of 256,969 pre-travel consultations included recommendation for rabies vaccination. Backpackers were more likely to be immunized (40.2%) than business travelers (4.4%) or travelers planning organized/high-end travel (2.0%). However, rates of rabies vaccination among backpackers showed a decline during the study period. Post-travel referrals after animal contact were stable at 2% of all referrals; most were exposed in Asia (69.5%) and 51% were bitten by dogs. Only 38% received post-exposure prophylaxis abroad. We conclude that only a minority of Israeli travelers, including backpackers, receive rabies pre-exposure prophylaxis. The proportion of travelers with potentially rabid animal contact is not decreasing; however, many exposed travelers do not receive post-exposure prophylaxis during travel. Because rabies control programs have been compromised in endemic countries during the COVID-19 pandemic, the need to provide rabies protection to travelers has become more urgent. After the ACIP's adoption of the World Health Organization's (WHO) 2-dose regimen, a revision of current vaccine guidelines is required to provide a simplified, more inclusive rabies vaccine policy.


Improving the description of metabolic networks: the TCA cycle as example.
To collect the ever-increasing yet scattered knowledge on metabolism, multiple pathway databases like the Kyoto Encyclopedia of Genes and Genomes have been created. A complete and accurate description of the metabolic network for human and other organisms is essential to foster new biological discoveries. Previous research has shown, however, that the level of agreement among pathway databases is surprisingly low. We investigated whether the lack of consensus among databases can be explained by an inaccurate representation of the knowledge described in scientific literature. As an example, we focus on the well-known tricarboxylic acid (TCA) cycle and evaluated the description of this pathway as found in a comprehensive selection of 10 human metabolic pathway databases. Remarkably, none of the descriptions given by these databases is entirely correct. Moreover, consensus exists on only 3 reactions. Mistakes in pathway databases might lead to the propagation of incorrect knowledge, misinterpretation of high-throughput molecular data, and poorly designed follow-up experiments. We provide an improved description of the TCA cycle via the community-curated database WikiPathways. We review various initiatives that aim to improve the description of the human metabolic network and discuss the importance of the active involvement of biological experts in these.


Baby-friendly hospital practices are associated with duration of full breastfeeding in primiparous but not multiparous Iranian women.
There is evidence that the Baby-Friendly Hospital Initiative (BFHI) results in improved breastfeeding outcomes in Western countries, but little is known of its impact in Middle-Eastern countries. This study investigated the impact of BFHI practices on duration of full breastfeeding in a cohort of 700 Iranian mothers recruited between June 2014 and March 2015 from maternity hospitals in Shiraz and followed-up prospectively for 6 months. At baseline, mothers self-reported exposure to 7 of the BFHI Ten Steps to Successful Breastfeeding (Steps 3 to 9). Data on breastfeeding outcomes were collected at baseline, 1, 3, 4, and 6 months postpartum. Cox regression analysis was conducted to determine the impact of individual and cumulative BFHI Steps on the duration of full breastfeeding, defined as the number of weeks since discharge that an infant received only breast milk and no complementary formula or food. Mothers reported experiencing on average 3.9 (SD 1.13, range 1 to 7) Steps, and only 28% of infants were fully breastfed at 6 months. There was a protective inverse relationship for primiparous (p for trend = .022) but not multiparous mothers (p for trend = .069), between the number of Steps a woman was exposed to and the likelihood of her discontinuing full breastfeeding within 6 months postpartum. Greater exposure to BFHI practices potentially could increase primiparous mothers' chances of fully breastfeeding to 6 months. Continual monitoring of the BFHI Steps and repeated education of healthcare staff are required to ensure that Iranian mothers receive adequate breastfeeding support.


Dutch trends in the use of potentially harmful medication during pregnancy.
Recent population-based data on drug utilization around pregnancy are lacking. This study aims to examine the prevalence of drug exposure in the Netherlands during the preconception, pregnancy and postpartum periods, with special emphasis on trends of potentially harmful medication over the years. A population-based study was conducted using records from the PHARMO Perinatal Research Network. From 1999 to 2017, the proportion of pregnancies during which women used any medication or potentially harmful medication was assessed, overall and stratified by timing of exposure relative to pregnancy and by the year of delivery. Overall, 357 226 (73%) and 166 484 (34%) of 487 122 selected pregnancies were exposed to any and potentially harmful medication, respectively. Among these 487 122 pregnancies, preconception prevalence for use of potentially harmful medication was 43%, 24% during the first trimester, 19% during the second, 16% during the third, and 45% postpartum. A declining trend was observed for exposure to any medication, from 84% in 1999 to 68% in 2017. No clear changes were observed over time for the proportion of pregnancies exposed to potentially harmful medication. Our study shows that the use of potentially harmful medication was high over the last two decades. Although there was a declining trend over the years in overall medication use, during a steady one-third of pregnancies, women used potentially harmful medication. Our findings highlight the need for an increased sense of urgency among both healthcare providers and women of reproductive age regarding potential risks associated with pharmacological treatment during pregnancy.


The Role of Perseverative Cognition for Both Mental and Somatic Disorders in a Naturalistic Psychiatric Patient Sample.
Perseverative cognition (PC) is the repeated or long-term activation of the cognitive representation of psychological stressors and is associated with prolonged stress including somatic and mental consequences. Hence, PC might represent a cognitive process linking mental and somatic pathology, but current research on this link is limited by investigating healthy samples, markers of somatic disease, and single disorders. The present study explored the importance of PC for different mental and somatic disorders in psychiatric patients. Data from 260 naturalistic psychiatric outpatients were used. Psychiatric diagnoses were based on structured clinical interviews. Somatic diseases were assessed using a well-validated questionnaire and were clustered into (cardio)vascular and immune/endocrine diseases. PC was operationalized using the Perseverative Thinking Questionnaire (PTQ). Multiple regression complemented with relative importance analyses showed that the PTQ total and subscale scores were associated with the presence of mood disorders, addiction, and anxiety. Unexpectedly, no relatively important associations were found between the PTQ and autism spectrum disorder, attention-deficit/hyperactivity disorder, or somatic disease. Our data complement previous work linking PC to stress-related mental disorders but question its immediate role in neurodevelopmental and somatic disorders. Targeting PC in the treatment of mood disorders and perhaps also in addiction seems promising.


Ghost artifact removal using a parallel imaging approach.
Parallel imaging techniques, which use several receive coils simultaneously, have been shown to enable a significant scan time reduction by subsampling k-space. Nevertheless, the data acquired with multiple coils in parallel exhibit some redundancy if the number of receive coils exceeds the subsampling factor. This redundancy leads to an overdetermination of the reconstruction problem, which is generally used to optimize the signal-to-noise ratio (SNR). However, it can yield further information about the quality of the reconstructed image, and can thus be used to identify and correct image artifacts. While some known approaches try to solve this problem in k-space, this study addresses it in the spatial domain and uses a modified SENSE reconstruction to reduce or completely remove ghost-type artifacts arising from processes such as motion or flow during data acquisition. Phantom and in vivo studies show significant improvements in image quality after correction, and serve as a basis for the discussion of the performance and limitations of this new approach.


A review of interventions addressing structural drivers of adolescents' sexual and reproductive health vulnerability in sub-Saharan Africa: implications for sexual health programming.
Young people particularly women are at increased risk of undesirable sexual and reproductive health (SRH) outcomes. Structural factors have been reported as driving some of these risks. Although several interventions have targeted some of the structural drivers for adolescent's SRH risk, little has been done to consolidate such work. This would provide a platform for coordinated efforts towards adolescent's SRH. We provide a narrative summary of interventions in sub-Saharan Africa (sSA) addressing the structural drivers of adolescents' SRH risk, explore pathways of influence, and highlight areas for further work. 33 abstracts and summary reports were retrieved and perused for suitability. Fifteen documents met the inclusion criteria and were read in full. Papers and reports were manually reviewed and 15 interventions that met the criteria for inclusion were summarised in a table format. Most of the interventions addressed multiple structural factors, such as social norms, gender inequality, and poverty. Some interventions focused on reducing economic drivers that increased sexual risk behaviours. Others focused on changing social norms and thus sexual risk behaviours through communication. Social norms addressed included gender inequality, gender violence, and child socialisation. The interventions included components on comprehensive sexuality and behaviour change and communication and parenting, using different designs and evaluation methods. Important lessons from the narrative summary included the need for a flexible intervention design when addressing adolescents, the need for coordinated effort among different stakeholders. There are encouraging efforts towards addressing structural drivers among adolescents in (sSA). There is, however, a need for interventions to have a clear focus, indicate the pathways of influence, and have a rigorous evaluation strategy assessing how they work to reduce vulnerability to HIV. There is also a need for coordinated effort among stakeholders working on adolescent vulnerability in sSA.


Impact of Recruitment Methods in Subjective Cognitive Decline.
Recruitment methods can determine sample characteristics in mild cognitive impairment and Alzheimer's disease dementia, but little is known about its influence in subjective cognitive decline (SCD). To determine the influence of two types of recruitment methods in the characteristics of individuals with SCD. We select and compare clinical and neuropsychological features, and frequency of APOE ɛ4 allele of 326 subjects with SCD from two cohorts: Open House Initiative (OHI) versus Memory Unit (MU). A logistic regression analysis (LRA), using gender and years of education as covariates, was used to examine the neuropsychological variables. The OHI sample were mostly women (75.9% versus 64.5%, p < 0.05), with higher educational level (12.15 [3.71] versus 10.70 [3.80] years, p = 0.001), and more family history of dementia (138 [62.7%] versus 44 [41.5%], p < 0.001) than the MU sample. Also, the OHI sample showed better overall neuropsychological performance than the MU sample, and after a LRA, this trend continued in automatic response inhibition capacity, abstract reasoning, and recognition memory. We did not find differences in age, depression history, and/or APOE ɛ4 allele frequency. SCD subjects showed different demographic and neuropsychological characteristics depending on the recruitment method, which should be taken into account in the design of research studies with this target population.


Structure and unexpected chiroptical properties of chiral 4-pyrrolidinyl substituted 2(5H)-furanones.
Planar 2(5H)-furanones substituted at C4 with a chiral pyrrolidinyl group show CD spectra which are apparently due to the distortion of the C4-N1 bond of sp2 character from the plane defined by the 2(5H)-furanone ring atoms and/or due to the presence of substituents in the pyrrolidine ring. This is a new, previously not encountered structural factor determining the chiroptical properties of 2(5H)-furanones and emerging from the analysis of X-ray diffraction data and quantum mechanical DFT computations. In the presence of a C5 pseudoaxial substituent in the furanone ring, the sign of the furanone n-pi* and pi-pi* transition Cotton effects is determined primarily by the previously postulated allylic helicity rule.


[Open-wedge high tibial osteotomy and unicomartmental knee arthroplasty in treating medial compartment osteoarthritis of the knee: a Meta analysis].
To systematic evaluate the outcome of open-wedge high tibial osteotomy(OWHTO) and unicomartmental knee arthroplasty (UKA) in treating medial compartment osteoarthritis of the knee. According to the retrieval strategy made by the Cochrane collaboration, a computer-base research of Medline, Pubmed, EMbase, Cochrane Library, CBM, CNKI, and Wanfang databases was performed and search deadline was March 2018. Related Chinese and English orthopedic journals and conference papers were manually searched. Controlled studies of OWHTO and UKA in the treatment of medial knee osteoarthritis were included. The quality of included researches was evaluated, and the data of postoperative knee function, complications, total knee arthroplasty(TKA) revision rates, and postoperative pain were extracted. Meta analysis was performed using the RevMan 5.0 software. A total of 8 articles that met the criteria were included containing a total of 675 patients. Meta-analysis showed that there was no significant difference in postoperative HSS score, knee score, functional score, and Lysholm score between the OWHTO and UKA groups(P=0.32, P=0.87, P=0.22, P=0.53). The range of joint motion in the OWHTO group was better than that in the UKA group, and the difference was statistically significant(P=0.009). There was no significant difference in postoperative complications and the rates of revision to TKA between the two groups(P=0.81, P=0.23). There was no difference in postoperative knee pain between the two groups. In the treatment of medial compartmental osteoarthritis of the knee that meets the surgical indications, OWHTO had better postoperative joint mobility. The results were similar in postoperative knee score, postoperative complications, and postoperative TKA revision rates between OWHTO and UKA groups.


The Link Between Bone Osteocalcin and Energy Metabolism in a Group of Postmenopausal Women.
There is a dual relationship between bone and tissues involved in energy metabolism (fat tissue and beta-pancreatic cells). Thus, bone remodeling is an energy consuming process, but osteocalcin, the main on-collagenic protein, synthesized by osteoblas during bone formation exerts a number of biological effects on beta-pancreatic and adipose cells. With this data, we wanted to see if the presence of a chronic metabolic disorder such as type 2 diabetes mellitus (T2DM) influence this complex dual relationship. For this, we conducted a cross-sectional study to evaluate the relation between osteocalcin and energetic metabolism in a group of 146 postmenopausal womens with and without T2DM at CI Parhon National Institute of Endocrinology, Bucharest. Clinical, metabolic and hormonal parameters were evaluated. For statistical analysis we used Student t-test and the Spearman correlation (statistical significance: p <0.05). Results: 63 patients with T2DM (63.88±8.56 years) and 83 women in the control group (60.21±8.77 years) were included. Diabetic women showed a lower level of serum total osteocalcin (p<0.05) HDL-cholesterol (p=0.02), and 25-hydroxyvitamin D (25(OH)D). The body mass index (BMI), glycemic metabolism parameters and triglyceride levels (p<0.05) were higher in this group. We found correlations between osteocalcin and metabolic elements: negative with BMI (r=-0.329, p<0.05), glycated hemoglobin (HbA1c) (r=-0.398, p<0.05), and serum triglycerides (r=-0.329, p<0.05) respectively positive with HDL-cholesterol (r=0.279, p=0.001) for the entire group of patients. Conclusions: Our study indicated the presence of significant correlations between serum osteocalcin and glycemic and lipid metabolism parameters, independent of the presence of diabetes.


The contribution of undergraduate palliative care education: does it influence the clinical patient's care?
The aim of this 2-year systematic review is to understand how learner assessment and curriculum evaluation of education in palliative care is being undertaken and to examine whether current undergraduate education influences the clinical patient's care. Almost half of the 30 studies reviewed used a qualitative approach to evaluate learning experiences. Only three of them were controlled studies and a further one was a cohort study.When students openly express themselves, they agree that there is 'something' deep as regards the core or the essence of medical practice or nursing. They feel that they become better professionals and better prepared for the patients, not only in terms of end of life care, but also as regards care, irrespective of the phase of the disease.The inclusion of palliative care in undergraduate education is a way of providing knowledge, skill, and competences about palliative care (especially communication) and also improving attitudes toward caring in advanced disease and at the end of life. Different methods of experiential learning, even brief experiences, which bring students into close contact with palliative care clinical cases or patients, are providing better results. From research studies, there is only indirect evidence that palliative care training at university leads to better clinical care of patients. In the future, long-term cohort or controlled studies might answer that question.


Poorhouses and the origins of the public old age home.
Public welfare in America--and its often ungainly structures--is as old and as varied as the history and social experiences of the last three hundred years. In the nineteenth century the poorhouse became the central arch of public welfare policy. Even in the twentieth century it did not disappear, but was gradually transformed into the public old age home.


Role of MicroRNA-103a Targeting ADAM10 in Abdominal Aortic Aneurysm.
MicroRNAs (miRNAs) are deregulated in various vascular ailments including abdominal aortic aneurysm (AAA). MiR-103 is involved in vascular, metabolic, and malignant diseases, but whether it participates in the pathogenesis of AAA remains elusive. ADAM10 plays a vital role in the formation of aneurysm, but whether miRs modulate its activity during AAA formation is totally unknown. In this study, we detected the significantly increased protein expression of ADAM10 in angiotensin II induced murine AAA specimens, while the mRNA expression of ADAM10 was similar between AAA and control, suggesting the posttranscriptional regulation. The ADAM10 specific inhibitor GI254023X dramatically reduced the macrophage infiltration of murine abdominal aorta. Bioinformatic predictions suggest that ADAM10 is the target of miR-103a/107 but the binding site is exclusive. At the cellular level, miR-103a-1 suppressed the protein expression of ADAM10, while antisense miR-103a-1 increased its expression. Particularly, with the progression of murine AAA, the mRNA expression of miR-103a/107 substantially decreased and the protein expression of ADAM10 greatly increased. Together, our data afford the new insight that miR-103a inhibited AAA growth via targeting ADAM10, which might be a promising therapeutic strategy to alleviate AAA.


A candidate locus approach identifies a long QT syndrome gene mutation.
Long QT syndrome is an inherited disorder that results in lengthened cardiac repolarization. It can lead to sudden onset of torsades de pointes, ventricular fibrillation, and death. The authors obtained a family history, performed electrocardiograms, and drew blood for DNA extraction and genotyping from 15 family members representing 4 generations of an affected family. Seven individuals demonstrated prolonged QT intervals. The authors used polymorphic short tandem repeat markers at known LQTS loci, which indicated linkage to chromosome 11p15.5 where the potassium channel, KCNQ1, is encoded. Polymerase chain reaction was used to amplify the coding region of KCNQ1. During survey of the KCNQ1 coding region, a G-to-A transition (G502A) was identified. DNA from all clinically affected but from none of the clinically unaffected family members carried the G-to-A transition. The candidate locus approach allowed an efficient mechanism to uncover the potassium channel mutation causing LQTS in this family.


White matter microstructural integrity is associated with retinal vascular caliber in adolescents with bipolar disorder.
Reduced white matter integrity is observed in bipolar disorder (BD), and is associated with cardiovascular risk in adults. This topic is underexplored in youth, and in BD, where novel microvascular measures may help to inform understanding of the vascular-brain connection. We therefore examined the association of retinal vascular caliber with white matter integrity in a cross-sectional sample of adolescents with and without BD. Eighty-four adolescents (n = 42 BD, n = 42 controls) completed retinal imaging, yielding arteriolar and venular caliber. Diffusion tensor imaging measured white matter fractional anisotropy (FA). Multiple linear regression tested associations between retinal vascular caliber and FA in regions-of-interest; corpus callosum, anterior thalamic radiation, uncinate fasciculus, and superior longitudinal fasciculus. Complementary voxel-wise analyses were performed. Arteriolar caliber was elevated in adolescents with BD relative to controls (F(1,79) = 6.15, p = 0.02, η2p = 0.07). In the overall sample, higher venular caliber was significantly associated with lower corpus callosum FA (β = -0.24, puncorrected = 0.04). In voxel-wise analyses, higher arteriolar caliber was significantly associated with lower corpus callosum and forceps minor FA in the overall sample (β = -0.46, p = 0.03). A significant diagnosis-by-venular caliber interaction on FA was noted in 5 clusters including the right retrolenticular internal capsule (β = 0.72, p = 0.03), corticospinal tract (β = 0.72, p = 0.04), and anterior corona radiata (β = 0.63, p = 0.04). In each instance, venular caliber was more positively associated with FA in BD vs. controls. Retinal microvascular measures are associated with white matter integrity in BD, particularly in the corpus callosum. This study was proof-of-concept, designed to guide future studies focused on the vascular-brain interface in BD.


A National Evaluation of the Scholarly Activity Requirement in Residency Programs: A Survey of Emergency Medicine Program Directors.
The Review Committee for Emergency Medicine (RC-EM) requirement for scholarly activity, which programs may define as an original research project or some other form of scholarly activity, applies to all EM residents. The objectives of this study were to: 1) describe the percentage of residency programs that require an original research project to meet the RC-EM requirement for scholarly activity, 2) describe specific challenges and resources for residents completing the RC-EM scholarly activity requirement, and 3) identify associations between the interpretation of the requirement and early career outcomes. This was a cross-sectional online survey of program or research directors from all U.S. allopathic EM residency programs. Respondents were queried about key demographics and domains relating to research curriculum, resources, expectations, outcomes, challenges, and future opportunities. Data were analyzed using descriptive statistics. The overall response rate was 113 of 156 (72%) EM residency programs. Respondents were more likely to represent university-based programs, but otherwise did not differ from nonrespondents across key demographic criteria. An original research project was required by 39% of responding programs, with a minimum deliverable in 93% of these programs. Program directors listed data collection and study design as the principle challenges residents face while completing their scholarly activities. Faculty mentorship, biostatistical support, and travel support were common resources reportedly available to residents. Comparison of programs with an original research requirement to those without revealed many differences in outcomes. Programs with a research requirement were more likely to have residents with oral or poster presentations (46% vs. 25%, mean difference = 21%, 95% confidence interval [CI] = 16% to 28%), published manuscripts (25% vs. 18%, mean difference = 7%, 95% CI = 2% to 10%), entering fellowship training after residency (27% vs. 20%, mean difference = 7%, 95% CI = 4% to 10%), and using a biostatistician (64% vs. 28%, median difference = 26%, 95% CI = 24% to 28%). There were no statistically significant differences in other evaluations of resources or outcome measures, including resident choice of academic career after leaving residency. There is no consistent interpretation and implementation of the RC-EM requirement for scholarly activity among EM residency programs. Residency programs requiring an original research project were more likely to have residents with accepted oral or poster presentations, published manuscripts, and entering fellowships after residency training.


A new methodological tool for research on supernatural concepts.
We introduce the first set of stimuli designed to resolve methodological and theoretical issues that have muddled the interpretation of results on the memorability of supernatural concepts (e.g., ghosts, souls, spirits), an important line of research in the cognitive science of religion (Barrett, 2007). We focus here on Boyer's (1994), Boyer, 2001) pioneering minimally counterintuitive (MCI) hypothesis according to which supernatural concepts tap a special memory-enhancing mechanism linked to violations of default intuitive inferences. Empirical tests of the MCI account have given rise to a vexed picture that renders meaningful interpretation difficult. The lack of a common standard of comparison among different studies, coupled with the presence of uncontrolled variables independently known to affect memorability, lie at the heart of these problems. We show that our new stimuli offer the hope of resolving these issues, thereby establishing a more secure foundation for the study of the memorability of supernatural concepts.


An Yttrium Organic cyclo-P4 Complex and Its Selective Conversions.
The rare-earth-metal organic cyclo-P4 complex (LY·DMAP)2[1,2-R2- cyclo-P4] (2, L = N, N'-2,6-diisopropylphenyl-1,4-diazabutadiene, DMAP = 4- N, N'-dimethylpyridine, R = CH2C6H4NMe2-2) was synthesized by direct functionalization of P4 using the rare-earth-metal alkyl complex LYR(THF) (1) for the first time. Further investigations indicated that three selective conversions of the cyclo-P4 species have been realized by alkyl migration. Complex 2 was slowly transformed into a R2P-substituted cyclo-P3 cluster (LY·DMAP)2[ cyclo-P3PR2] (3) under heating conditions. The reaction of 2 with 1 equiv of KR gave the unsubstituted cyclo-P3 complex (LY·THF)2[ cyclo-P3]K (4) in quantitative yield, accompanied by the elimination of the organophosphorus compound PR3 (5). Treatment of 2 with HMPA afforded the structurally characterized Zintl-type P7 complex (LY·HMPA)3P7 (6). The formation of complexes 3, 4, and 6 revealed that unusual alkyl migrations in the polyphosphorus complexes occurred in these reactions, and the transformations from cyclo-P4 into cyclo-P3 also provided a new insight into the stepwise degradation of P4 using metal complexes.


Diagnostic performance of Japan NBI Expert Team classification for differentiation among noninvasive, superficially invasive, and deeply invasive colorectal neoplasia.
The Japan NBI Expert Team (JNET) classification is the first universal narrow-band imaging magnifying endoscopic classification of colorectal tumors. Considering each type in this classification, the diagnostic ability of Type 2B is the weakest. Generally, clinical behavior is believed to be different in each gross type of colorectal tumor. We evaluated the differences in the diagnostic performance of JNET classification for each gross type (polypoid and superficial) and examined whether the diagnostic performance of Type 2B could be improved by subtyping. We analyzed 2933 consecutive cases of colorectal lesions, including 136 hyperplastic polyps/sessile serrated polyps, 1926 low-grade dysplasias (LGDs), 571 high-grade dysplasias (HGDs), and 300 submucosal (SM) carcinomas. We classified lesions as polypoid and superficial type and compared the diagnostic performance of the classification system in each type. Additionally, we subtyped Type 2B into 2B-low and 2B-high based on the level of irregularity in surface and vessel patterns, and we evaluated the relationship between the subtypes and histology, as analyzed separately for polypoid and superficial types. We also estimated interobserver and intraobserver variability. The diagnostic performance of JNET classification did not differ significantly between polypoid and superficial lesions. Ninety-nine percent of Type 2B-low lesions were LGDs, HGDs, or superficial submucosal invasive (SM-s) carcinomas. In contrast, 60% of Type 2B-high lesions were deep submucosal invasive (SM-d) carcinomas. The results were not different between each gross type. Interobserver and intraobserver agreements for Type 2B subtyping were good, with kappa values of .743 and .786, respectively. Type 2B subtyping may be useful for identifying lesions that are appropriate for endoscopic resection. JNET classification and Type 2B sub classification are useful criteria, regardless of gross type.


Future remnant liver function as predictive factor for the hypertrophy response after portal vein embolization.
Preoperative portal vein embolization is widely used to increase the future remnant liver. Identification of nonresponders to portal vein embolization is essential because these patients may benefit from associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), which induces a more powerful hypertrophy response. 99mTc-mebrofenin hepatobiliary scintigraphy is a quantitative method for assessment of future remnant liver function with a calculated cutoff value for the prediction of postoperative liver failure. The aim of this study was to analyze future remnant liver function before portal vein embolization to predict sufficient functional hypertrophy response after portal vein embolization. Sixty-three patients who underwent preoperative portal vein embolization and computed tomography imaging were included. Hepatobiliary scintigraphy was performed to determine pre-portal vein embolization and post-portal vein embolization future remnant liver function. Receiver operator characteristic analysis of pre-portal vein embolization future remnant liver function was performed to identify patients who would meet the post-portal vein embolization cutoff value for sufficient function (ie, 2.7%/min/m2). Mean pre-portal vein embolization future remnant liver function was 1.80% ± 0.45%/min/m2 and increased to 2.89% ± 0.97%/min/m2 post-portal vein embolization. Receiver operator characteristic analysis in 33 patients who did not receive chemotherapy revealed that a pre-portal vein embolization future remnant liver function of ≥1.72%/min/m2 was able to identify patients who would meet the safe future remnant liver function cutoff value 3 weeks after portal vein embolization (area under the curve = 0.820). The predictive value was less pronounced in 30 patients treated with neoadjuvant chemotherapy (area under the curve = 0.618). A total of 45 of 63 patients underwent liver resection, of whom 5 of 45 developed postoperative liver failure; 4 of 5 patients had a post-portal vein embolization future remnant liver function below the cutoff value for safe resection. When selecting patients for portal vein embolization, future remnant liver function assessed with hepatobiliary scintigraphy can be used as a predictor of insufficient functional hypertrophy after portal vein embolization, especially in nonchemotherapy patients. These patients are potential candidates for ALPPS.


Downregulation of c-myc expression by antisense oligonucleotides inhibits proliferation of human smooth muscle cells.
Proliferation of smooth muscle cells (SMCs) plays an important role in vascular pathobiology, being involved in the development of coronary restenosis and atherosclerosis. The activation of nuclear proto-oncogenes appears to be a final common pathway onto which various mitogenic signals coverage. Accordingly, we attempted to determine whether the activation of the c-myc nuclear proto-oncogene is essential for human SMC proliferation and explored the possibility of inhibiting their growth using antisense oligonucleotides directed against c-myc messenger RNA (mRNA). Proliferation of human SMCs was associated with an increase in c-myc mRNA expression after growth stimulation. Using 15-mer phosphorothioate oligonucleotides (oligomers), we tested their growth-inhibitory effect in SMCs in vitro. Antisense oligomers directed against the translation initiation region of the human c-myc gene exhibited a significant antiproliferative effect, whereas sense and mismatched oligomers did not inhibit the growth. The growth-inhibitory effect of c-myc antisense oligomers was dose dependent and preventable by an excess of sense oligomers. Furthermore, growth inhibition of SMCs treated with c-myc antisense oligomers was associated with a marked decrease in the c-myc mRNA level. Phosphorothioate oligomers remained stable in medium containing 20% serum and were detectable in SMCs as early as 1 hour after cell exposure. Intact oligomers rapidly accumulated intracellularly and persisted within human SMCs for at least 16 hours. c-myc antisense oligomers reduced c-myc expression and produced a significant growth inhibition of human SMCs, indicating an important role of c-myc gene activation in the process of SMC proliferation. Furthermore, extracellular stability and rapid cellular uptake provide the basis for future studies assessing the therapeutic role of the c-myc antisense approach in reducing SMC proliferation in the process of vascular restenosis.


The bacteriology of recurrent otitis media and the effect of sulfisoxazole chemoprophylaxis.
Middle ear effusion specimens were obtained from 31 children with recurrent episodes of acute otitis media. Of 75 total specimens 28 were obtained from children during chemoprophylaxis with sulfisoxazole. A single organism was isolated in 65 of 70 instances. Beta-lactamase was produced from Gram-negative organisms in 11 instances, and penicillin resistance from Streptococcus pneumoniae occurred in one instance. Haemophilus influenzae predominated during prophylaxis; S. pneumoniae predominated without it. Serotyping and biotyping were performed on 28 isolates from 8 children with consecutive episodes. In 17 instances the infecting organism was the same species but seven of these strains differed in serotype or biotype. The average number of weeks between onset of recurrence in children with homologous strains was shorter (2.6 weeks) than in the children from whom heterologous strains were found (5.7 weeks). Three media were evaluated for efficacy in 32 episodes, and direct plating resulted in the highest rate of recovery.


Quantitative and Dynamic Imaging of ATM Kinase Activity.
Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase critical to the cellular DNA-damage response, including DNA double-strand breaks (DSBs). ATM activation results in the initiation of a complex cascade of events facilitating DNA damage repair, cell cycle checkpoint control, and survival. Traditionally, protein kinases have been analyzed in vitro using biochemical methods (kinase assays using purified proteins or immunological assays) requiring a large number of cells and cell lysis. Genetically encoded biosensors based on optical molecular imaging such as fluorescence or bioluminescence have been developed to enable interrogation of kinase activities in live cells with a high signal to background. We have genetically engineered a hybrid protein whose bioluminescent activity is dependent on the ATM-mediated phosphorylation of a substrate. The engineered protein consists of the split luciferase-based protein complementation pair with a CHK2 (a substrate for ATM kinase activity) target sequence and a phospho-serine/threonine-binding domain, FHA2, derived from yeast Rad53. Phosphorylation of the serine residue within the target sequence by ATM would lead to its interaction with the phospho-serine-binding domain, thereby preventing complementation of the split luciferase pair and loss of reporter activity. Bioluminescence imaging of reporter expressing cells in cultured plates or as mouse xenografts provides a quantitative surrogate for ATM kinase activity and therefore the cellular DNA damage response in a noninvasive, dynamic fashion.


Detection and Occurrence of Indicator Organisms and Pathogens.
This review summarizes the literature pertaining to the occurrence and detection of indicator organisms and pathogens published during 2014. It is organized into the following sections: i) detection and quantification of fecal indicators and waterborne pathogens, ii) microbial source tracking (MST) using genotypic and phenotypic methods, iii) antibiotic resistant bacteria (ARB), iv) live vs. dead cell differentiation methods, and v) next generation sequencing (NGS).


Anhydro-ara-5-fluorocytidine (AAFC) in gastrointestinal cancer. A phase II study.
Results of a phase II study of AAFC in 32 patients with advanced measurable gastrointestinal cancer are presented. Fourteen patients were treated with a weekly schedule, while 18 were treated with 5-day courses of the drug. There were 12 patients with pancreas cancer, eight with stomach cancer, seven with cancer of the esophagus, four with colorectal cancer, and one with cancer of the gallbladder. Response was observed in pancreas and stomach cancer. Two patients with pancreas cancer had partial remissions, three other patients (two pancreas and one stomach) had response of short duration, considered to be less than a partial remission. There appeared to be very little difference between the two different schedules of administration. AAFC shows limited activity in adenocarcinoma of pancreas and stomach; there does not appear to be a practical application for AAFC as a single agent.


Fast and accurate side-chain topology and energy refinement (FASTER) as a new method for protein structure optimization.
We have developed an original method for global optimization of protein side-chain conformations, called the Fast and Accurate Side-Chain Topology and Energy Refinement (FASTER) method. The method operates by systematically overcoming local minima of increasing order. Comparison of the FASTER results with those of the dead-end elimination (DEE) algorithm showed that both methods produce nearly identical results, but the FASTER algorithm is 100-1000 times faster than the DEE method and scales in a stable and favorable way as a function of protein size. We also show that low-order local minima may be almost as accurate as the global minimum when evaluated against experimentally determined structures. In addition, the new algorithm provides significant information about the conformational flexibility of individual side-chains. We observed that strictly rigid side-chains are concentrated mainly in the core of the protein, whereas highly flexible side-chains are found almost exclusively among solvent-oriented residues.


Enantiodetermining processes in the synthesis of alanine, serine, and isovaline.
In this study, quantum chemical calculations were used to explore the synthesis of three chiral α-amino acids, specifically alanine, serine, and isovaline, from reactants found in interstellar space. Our focus is on the crucial step in the synthesis pathway that determines the chirality of the amino acids. The results indicate that in the case of alanine, the determination of enantiomer is primarily influenced by the direction of the collision of molecules or functional groups, which leads to the formation of a chirality center in a crucial intermediate. However, contrary to chemical expectations, the enantiodetermining/enantioselection step for serine and isovaline synthesis occurs prior to the creation of a chirality center.


Management of concomitant maxillofacial, cervical spine and laryngeal trauma--case reports.
Three cases are presented to stress important points in the diagnosis and management of concomitant maxillofacial, cervical spine and laryngeal trauma. Emergency tracheostomy to control airway, immediate rigid fixation of maxillofacial fractures, early computed tomographic (CT) scans to evaluate the extent of laryngeal and cervical spine injury and the early repair of laryngeal injury will provide better aesthetic and functional results.


Calibration of a high spatial resolution laser two-color heterodyne interferometer for density profile measurements in the TJ-II stellarator.
A high spatial resolution two-color (CO(2), lambda=10.6 microm, He-Ne, lambda=633 nm) interferometer for density profile measurements in the TJ-II stellarator is under development and installation, based in the currently operational single channel two-color heterodyne interferometer. To achieve the objectives of 32 channels, with 4-5 mm lateral separation between plasma chords, careful design and calibration of the interferometric waveforms for both the measurement and vibration compensation wavelengths are undertaken. The first step has been to set up in our laboratories an expanded-beam heterodyne/homodyne interferometer to evaluate the quality of both interferometric wavefronts, a reported source of poor vibration compensation and thus low resolution in the density profile measurements. This novel interferometric setup has allowed us to calibrate the spatial resolution in the profile measurements resulting in approximately 2 mm lateral resolution in the reconstruction of the interferometric wavefront.


Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse model.
Loci linked to sensitivity to dietary obesity were identified by Quantitative Trait Locus (QTL) analysis of two mapping populations derived from a cross between AKR/J and SWR/J mice. AKR/J mice are sensitive to dietary obesity when fed a high fat diet while SWR/J mice are resistant. Intercrosses between these strains segregate the phenotype of sensitivity to dietary obesity. Using an F2 mapping population of 931 male mice we found significant linkage with a QTL on chromosome 9 (Likelihood of the Odds [LOD] ratio of 4.85) and another QTL on chromosome 15 (LOD = 3.93). The presence of a QTL on chromosome 15 was confirmed in a separate mapping population of 375 male F1 x SWR/J mice (LOD = 3.82). These two loci are designated dietary obese 2 (Do2) and dietary obese 3 (Do3) for the chromosome 9 and 15 loci, respectively. Both of these chromosomal regions contain candidate genes which may contribute to variation in the phenotype. These loci also exert a significant control over individual adipose depot weights.


Neocortical Layer 1: An Elegant Solution to Top-Down and Bottom-Up Integration.
Many of our daily activities, such as riding a bike to work or reading a book in a noisy cafe, and highly skilled activities, such as a professional playing a tennis match or a violin concerto, depend upon the ability of the brain to quickly make moment-to-moment adjustments to our behavior in response to the results of our actions. Particularly, they depend upon the ability of the neocortex to integrate the information provided by the sensory organs (bottom-up information) with internally generated signals such as expectations or attentional signals (top-down information). This integration occurs in pyramidal cells (PCs) and their long apical dendrite, which branches extensively into a dendritic tuft in layer 1 (L1). The outermost layer of the neocortex, L1 is highly conserved across cortical areas and species. Importantly, L1 is the predominant input layer for top-down information, relayed by a rich, dense mesh of long-range projections that provide signals to the tuft branches of the PCs. Here, we discuss recent progress in our understanding of the composition of L1 and review evidence that L1 processing contributes to functions such as sensory perception, cross-modal integration, controlling states of consciousness, attention, and learning.


Rat's Polycystic Ovary Due to Intraventromedial Hypothalamus Morphine Injection.
The most important alkaloid of opium family, morphine, may show unfavorable effect on the reproductive organs. This research investigated the effect of microinjection of morphine into the rat's ventromedial hypothalamus (VMH) on cystic genesis in the ovary and the health of neurons of VMH. Female rats (Wistar, weighing 200-250 g) kept under standard conditions were cannulated under anesthesia by Stoelting stereotaxic instrument at the coordinates anterior-posterior: -1.92, ventral: 9, lateral: 0.5. After being recovered, they were microinjected single morphine (0.1-0.4 µg/rat, once intra-VMH) and/or naloxone hydrochloride (0.1-0.4 µg/rat, once intra-VMH) using a 5-µL Hamilton syringe with the polyethylene tubing. The control group solely given physiological saline (1 µL/rat, intra-VMH). Three days after the experiment, both ovary and brain samples were collected from the control and the experimental groups, and they were studied histopathologically. The brain samples were checked out with the aid of the cresyl violet, and the ovaries were stained by the hematoxylin and eosin. The samples were also biometrically examined to compare the ovaries' cystic formations. Also, the number of healthy or injured neurons in the nuclei was compared. The ovaries of morphine-treated rats showed polycystic characteristics in comparison with the control samples. In addition, the brain slices of the morphine-treated rats illustrated a significant decrease in intact neurons. Both mal effects were resolved in the presence of naloxone. These results may show that the morphine induces anovulatory infertility probably by hypothalamus-pituitary-ovary axis dysfunction.


[Pancreatic blood flow and its regulation].
Regulatory mechanisms of the pancreatic circulation include general hemodynamics, autonomic nervous system, circulating vasoactive peptides, hormones and certain autoregulatory properties of the pancreatic vasculature. The pancreatic response to sympathetic stimulation is a decrease in pancreatic blood flow (PBF) due to co-release of norepinephrine and NPY. In contrast parasympathetic stimulation increase PBF and this could be attributed to the co-release of acetylcholine, VIP, PHI, GRP and other neuropeptides. Neurotransmitters of the NANC system such as: SP, NK, SK, CCK, VIP, cGRP are also potent neurogenic vasodilatators of the pancreatic vasculature. Control of the pancreatic circulation is related, in part to the exocrine function of the gland. Several factors have been implicated as mediators of functional hyperemia in the pancreas. Among these factors are such low PO2, ions, kinins, PGs, nucleotides and gastrointestinal hormones. Recently endothelium-derived NO has been shown to play an important role in the mediation of the pancreatic vasodilation in response to various endogenous factors.


Discovery of Small Molecule Therapeutics for Treatment of Chronic HBV Infection.
The chronic infection of hepatitis B virus (HBV) inflicts 250 million people worldwide representing a major public health threat. A significant subpopulation of patients eventually develop cirrhosis and hepatocellular carcinoma (HCC). Unfortunately, none of the current standard therapies for chronic hepatitis B (CHB) result in a satisfactory clinical cure rate. Driven by a highly unmet medical need, multiple pharmaceutical companies and research institutions have been engaged in drug discovery and development to improve the CHB functional cure rate, defined by sustainable viral suppression and HBsAg clearance after a finite treatment. This Review summarizes the recent advances in the discovery and development of novel anti-HBV small molecules. It is believed that an improved CHB functional cure rate may be accomplished via the combination of molecules with distinct MoAs. Thus, certain molecules may evolve into key components of a suitable combination therapy leading to superior outcome of clinical efficacy in the future.


Identification of radiation-sensitive expressed genes in the ICR and AKR/J mouse thymus.
We have investigated radiation-sensitive expressed genes (EGs), their signal pathways, and the effects of ionizing radiation in the thymus of ICR and AKR/J mice. Whole-body and relative thymus weights were taken and microarray analyses were done on the thymuses of high-dose-rate (HDR, (137) Cs, 0.8 Gy/min, a single dose of 4.5 Gy) and low-dose-rate (LDR, (137) Cs, 0.7 mGy/h, a cumulative dose of 1.7 Gy) irradiated ICR and AKR/J mice. Gene expression patterns were validated by quantitative polymerase chain reaction (qPCR). The effect of ionizing radiation on thymus cell apoptosis was measured terminal deoxynucleotidyl-transferase-mediated dUTP-end labeling (TUNEL). LDR-irradiation increased the mean whole-body weight, but decreased the relative thymus weight of AKR/J mice. Radiation-sensitive EGs were found by comparing HDR- and LDR-irradiated ICR and AKR/J mice. qPCR analysis showed that 12 EGs had dose and dose-rate dependent expression patterns. Gene-network analysis indicated that Ighg, Igh-VJ558, Defb6, Reg3g, and Saa2 may be involved in the immune response, leukocyte migration, and apoptosis. Our data suggest that expression of the HDR (Glut1, Glut4, and PKLR) and LDR radiation-response genes (Ighg and Igh-VJ558) can be dose or dose-rate dependent. There was an increased number of apoptotic cells in HDR-irradiated ICR mice and LDR-irradiated AKR/J mice. Thus, changes of the mean whole-body weight and relative thymus weight, EGs, signal pathways, and the effects of ionizing radiation on the thymus of ICR and AKR/J mice are described.


Multistage and tandem mass spectrometry of glycosylated triterpenoid saponins isolated from Bacopa monnieri: comparison of the information content provided by different techniques.
Whereas all state-of-the-art techniques in mass spectrometry (MS) have been extensively applied to oligosaccharides derived from glycoproteins, less effort has been devoted to the analysis of smaller glycoconjugates. In the present study, the application of a variety of MS techniques for the analysis of two dammarane-type triterpenoid saponins isolated from B. monnieri is reported. The structural information provided by ESI-ion trap (IT)-, AP-MALDI-IT-, and MALDI-IT/reflectron time-of-flight (RTOF)-MS, all utilizing low-energy collision-induced dissociation (CID), and MALDI-TOF/RTOF-MS, facilitating postsource decay and high-energy CID analysis, was compared. The applied desorption/ionization technique does not influence the fragmentation of identical precursor ions in low-energy CID. All three fragmentation techniques clearly yield the sequence and branching of the glycan moiety as well as the molecular mass of the intact aglycon. Cross-ring cleavage of the branching sugar, which gives some information about the sugar linkages, was mainly observed in low-energy CID. High-energy CID, on the other hand, yielded some additional diagnostic fragment ions from the aglycon moiety. Internal cleavage ions are formed by alternative mechanisms in high-energy CID and are assumed to be diagnostic for some linkages. However, none of the applied MS techniques facilitates the identification of those saponins that differ only by their aglycon moiety (i.e., jujubogenin or pseudojujubogenin).


Independent evaluation of the California Tobacco Control Program: relationships between program exposure and outcomes, 1996-1998.
This study sought to determine the effects of the California Tobacco Control Program on tobacco-related attitudes and behaviors. In 1996 and 1998, a telephone survey was conducted among adults in randomly selected households in 18 California counties. Tenth-grade youths in 84 randomly selected high schools completed a written survey. In analyses conducted at the county level, differences in outcomes were regressed on an index of program exposure. Among adults, program exposure was associated with decreased smoking prevalence rates, increased no-smoking policies in homes, and decreased violations of workplace no-smoking policies. Among youths, there was no effect of program exposure on outcomes. These results suggest that the California Tobacco Control Program may have reduced adult smoking prevalence rates and exposure to environmental tobacco smoke.


Tumor necrosis factor alpha and its soluble receptors in obese children with NAFLD.
To evaluate the serum levels of tumor necrosis factor (TNF) alpha and its soluble receptors in obese children with non-alcoholic fatty liver disease (NAFLD). Fasting serum levels of TNFalpha and its receptors were determined in 45 consecutive obese children with suspected liver disease and 20 lean controls. The degree of liver steatosis was graded in ultrasound according to Saverymuttu. 1H-MR spectroscopy was performed with 1.5T scanner with PRESS sequence. A fatty liver was confrmed in 32 children by ultrasonography (group I); 16 of them also had increased ALT activity (group Ia - NAFLD). Serum concentrations of TNFalpha and its receptors were significantly higher in obese children with NAFLD compared to controls. Significant correlation was found between ultrasonographic grade of liver steatosis and TNFalpha level but serum level of this adipokine was not significantly different in children with advanced liver steatosis (grade 2-3, n=13) compared to patients with mild steatosis (grade 1, n=19). The ability of TNFalpha and its receptors (R1, R2) to differentiate children with advanced liver steatosis from those with mild steatosis was insignificant. However, the ability of serum TNFalpha to differentiate obese children with liver steatosis from those without steatosis was significant (AUC=0.7448, p=0.0291). Although TNFalpha does not predict advanced liver steatosis, it may be suitable serum marker in predicting liver steatosis in obese children.


Quantifying cognitive dysfunction across the spectrum of end-stage kidney disease: A systematic review and meta-analysis.
Cognitive dysfunction is reportedly highly prevalent among chronic kidney disease (CKD) patients. A variety of screening tools and neuropsychiatric batteries are used to quantify the magnitude and nature of this dysfunction. Our objective is to summarize the neurocognitive testing used, and determine what degree cognitive dysfunction is reported in CKD patients. All study designs published in English that contained participants who were either pre-dialysis patients, haemodialysis (HD) or peritoneal dialysis (PD) patients or renal transplant recipients were considered. Reported comparative non-CKD control data was also collected. All study designs were included. The search period encompassed articles from 1980 to May 2018. This review is registered with PROSPERO (CRD42018096568). Of the 1711 articles screened, 148 articles were relevant and used in the meta-analysis. Commonly used assessments were The Mini-Mental State Examination (MMSE), The Modified Mini-Mental State Examination, the Trails Making Tests (TMT) forms A and B and components of the Wechsler Adult Intelligence Scale: Digit Span and Digit Symbol. Means for all assessments were adjusted using a random effects model to account for the differences in variance. Adjusted mean MMSE scores were significantly lower for both pre-dialysis (26.08, n = 17 073) and HD (26.31, n = 3314) patients when compared to non-CKD controls (28.21, n = 5226). PD (58.01 s, n = 859) and HD (56.04 s, n = 2344) patients also took significantly longer to complete the Trails Making Task A than non-CKD controls (37.62 s, n = 4809). Patients with CKD, especially pre-dialysis and those requiring dialysis, are likely to exhibit impairments in cognition that can be identified with specific screening neuropsychological assessments.


[Early changes in serum alpha-fetoprotein after chemotherapy in advanced testicular tumors].
The serum levels of alpha-fetoprotein (AFP) are known to undergo acute changes (paradoxical elevation) after effective chemotherapies for testicular germ cell tumors. In order to understand the clinical significance, the changes of the serum AFP levels after PVB therapy for testicular germ cell tumors were analyzed, and their relationship to the treatment effects was investigated in this retrospective study. Thirty-one patients with testicular germ cell tumors (11 with stage I, 7 with stage II, and 13 with stage III) which had been treated by PVB therapy were evaluated. The measurement of the serum AFP levels was performed by radioimmunoassay on Day 1 (the initiation day of the PVB therapy), thereafter on Day 8 and Day 22. The half-life (t1/2) or doubling time (t2) of the serum AFP were calculated. In patients with stage I disease, the serum AFP levels declined nearly according to its biological half-life between Day 1 and Day 22 after termination of chemotherapy (t1/2 = 6.2 days). In patients with stage II or III disease, the changes of the serum AFP levels were not consistent with the treatment results between Day 1 and Day 8. Namely, complete responders revealed a prolonged decline of the serum AFP levels (t1/2 = 63.0 days), partial responders a transient rise of the serum AFP levels (t2 = 49.5 days) and non-responders a sudden rise of the serum AFP levels (t2 = 9.9 days). On the contrary, the serum AFP levels changed in accordance with the treatment effects between Day 8 and Day 22. Early changes of the serum AFP levels were seen in patients with stage II or III disease between Day 1 and Day 8 after chemotherapy. It was indicated that the measurements of the serum AFP levels during this period were not useful for the evaluation of the treatment effects in these patients. Furthermore, it was suggested that the early changes of the serum AFP levels possibly correlate with the poor response. The mechanism of the early changes of the serum AFP was also discussed.


Evaluation of anti-arthritic potential of the methanolic extract of the aerial parts of Costus speciosus.
Costus speciosus Koen. (Keu, Crape ginger), an ornamental plant, widely distributed in India is traditionally used as astringent, aphrodisiac, purgative, anthelmintic, depurative, febrifuge and expectorant. The plant is also used in rheumatism, dropsy, urinary diseases and jaundice. The purpose of this study is to evaluate the anti-arthritic activity of the methanolic extract of the aerial parts of Costus speciosus (CS) in experimental animal models. The powdered drug was subjected to successive solvent extraction, with solvents in increasing order of polarity to obtain the methanolic extract of the aerial parts of the plant. CS was evaluated for anti-arthritic action by Freund's adjuvant induced arthritis test in adult Albino rats (150-200 gm). Rats were injected 0.1 ml of complete Freund's adjuvant into the planter region of the left hind paw. Statistical analysis was performed using One way analysis of variance (ANOVA) followed by Bonferonni test. P<0.05 was considered statistically significant. The methanolic extract of CS in doses of 400 and 800 mg/kg showed 75.50% and 68.33% protection against increase in paw edema, respectively. CS showed dose-dependent action in all the experimental models. The present study indicates that CS has significant anti-arthritic properties.


Identification of an optimized 2'-O-methylated trinucleotide RNA motif inhibiting Toll-like receptors 7 and 8.
Bacterial RNA serves an important function as activator of the innate immune system. In humans bacterial RNA is sensed by the endosomal receptors TLR7 and TLR8. Differences in the posttranscriptional modification profile of prokaryotic when compared with eukaryotic RNA allow innate immune cells to discriminate between "host" and "foreign" RNA. Ribose 2'-O-methylation is of particular importance and has been reported to antagonize TLR7/8 activation. Yet, the exact sequence context in which 2'-O-methylation has to occur to mediate its inhibitory activity remains largely undefined. On the basis of a naturally occurring 2'-O-methylated RNA sequence, we performed a systematic permutation of the methylated nucleotide as well as adjacent bases and hereby identify two minimal trinucleotide motifs within a 9-mer oligoribonucleotide that are necessary and sufficient to antagonize TLR7 and TLR8 activation, respectively. Given the growing interest in the development of inhibitors of nucleic acid-sensing TLRs for therapeutic purposes, these results will facilitate the rational design of such antagonists in the future.


Anomalous origin of left coronary artery from pulmonary artery - Duped by 2D; saved by color Doppler: Echocardiographic lesson from two cases.
Echocardiography is an important first-line investigation for detection of anomalous origin of a coronary artery from the pulmonary artery (ALCAPA). We report two cases of ALCAPA that illustrate the importance of systematic performance of the echocardiogram, mindful of technical artifacts that may mislead the echocardiographer color Doppler imaging in diagnosis of this condition.


Trends in the associations between family income, height and body mass index in US children and adolescents: 1971-1980 and 1999-2008.
This paper evaluates trends in the childhood and adolescent associations between family income, height and body mass index (BMI) between the periods 1971-1980 and 1999-2008. US-born children (aged 2-11) and adolescents (aged 12-19) in the NHANES I, NHANES II and 1999-2008 NHANES are evaluated for BMI and height using flexibly-estimated structured additive regression models. Three trends are identified: BMI gains have been greater in lower-income relative to higher-income children and adolescents; height has increased more in lower-income relative to higher-income children (but not in adolescents); and BMI has increased more in taller children than shorter children (but not in adolescents). Following from these trends is that contemporary children exhibit a negative height-income interaction effect on BMI such that the inverse association between income and BMI is larger in taller children. Similar results hold when categorical obesity is considered but with modest height-related changes and income-height interaction effect in adolescents. Race-sex differences are explored and descriptive evidence on the potential role of changes in caloric intake is presented. The relationship between the economic environment and growth in US youth has changed in recent decades. Contemporary taller and lower-income children exhibit greater body mass and obesity.


Multi-q Mesoscale Magnetism in CeAuSb_{2}.
We report the discovery of a field driven transition from a single-q to multi-q spin density wave (SDW) in the tetragonal heavy fermion compound CeAuSb_{2}. Polarized along c, the sinusoidal SDW amplitude is 1.8(2)μ_{B}/Ce for T≪T_{N}=6.25(10) K with a wave vector q_{1}=(η,η,1/2) [η=0.136(2)]. For H∥c, harmonics appearing at 2q_{1} evidence a striped magnetic texture below μ_{∘}H_{1}=2.78(1) T. Above H_{1}, these are replaced by coupled harmonics at q_{1}+q_{2}=(2η,0,0)+c^{*} until μ_{∘}H_{2}=5.42(5) T, where satellites vanish and magnetization nonlinearly approaches saturation at 1.64(2)μ_{B}/Ce for μ_{∘}H≈7 T.


Molecular Cloning and Characterization of Rice Pollen Profilin.
Profilin is a low molecular weight protein and is identified as an actin-binding protein in higher plants. Two pollen-specific cDNA clones of rice, RproA and RproB, were isolated from a cDNA library of rice mature pollen. The two cDNA clones was 821 bp and 805 bp long and contained an open reading frame of 131 amino acids, 5' and 3' untranslated regions and a long poly(A) tail. The comparison of deduced amino acid sequences from RproA and RproB cDNA and other plant profilin cDNA indicated that the two rice profilin are high homologous to each other, showed that 89% similarity to maize (ZmPRO3), 87% to C. dactylon, 83% to H.brasiliensis and 89% to P. pratense. Genomic southernblot analysis suggested the existence of two genes at least. Northern blot and reverse transcriptase polymerase chain reaction analysis demonstrated that the two rice profilin cDNA are anther or pollen specific.


Institutionalization and the elderly: international comparisons.
This paper is an exploratory attempt to examine international differences in the proportion of old people living in non-private households. The aim of the study was to provoke further discussion of the role which institutions play in the care of the elderly in various settings and to examine the effect of certain demographic and economic parameters on the proportion of elderly people in non-private households. Data were drawn from national censuses and indirect standardization was used to allow comparison of the probability of institutionalization in the countries considered. Considerable variation in standardized institutionalization ratios was found but this variation was not significantly associated with any of the demographic or economic variables considered.


Apheresis for babesiosis: Therapeutic parasite reduction or removal of harmful toxins or both?
Babesiosis is a potentially life-threatening illness caused by intraerythrocytic protozoan parasites of the genus Babesia that are transmitted most commonly by Ixodes ticks, and rarely from blood transfusion or congenitally. Clinical presentations of babesiosis include asymptomatic infection, mild to moderate disease, or severe disease. Antibiotics such as atovaquone plus azithromycin or clindamycin and quinine can be used effectively to treat this disease in most cases, however in high risk populations, the mortality rate can be as high as 20% despite therapy. Therapeutic exchange transfusion has been used in severe babesiosis and is of apparent therapeutic benefit. It is not entirely clear through what mechanism therapeutic exchange transfusion may help patients. Data suggests that in addition to parasite load reduction, it is possible that therapeutic exchange transfusion removes toxins generated by babesia infection. There are many remaining questions that need to be addressed regarding exchange transfusion for babesiosis. J. Clin. Apheresis 31:454-458, 2016. © 2015 Wiley Periodicals, Inc.


Plate versus titanium elastic nail in treatment of displaced midshaft clavicle fractures: A comparative study.
With changing trends in treatment of displaced midshaft clavicle fractures (DMCF), plating remains the standard procedure for fixation. An attracting alternative method of fixation is the titanium elastic nailing (TEN). However, prospective randomized studies comparing the two methods of fixation are lacking. We assessed the effectiveness of minimally invasive antegrade TEN and plating technique for the treatment of DMCF. 80 unilateral displaced midclavicular fractures operated between October 2010 and May 2013 were included in study. This prospective comparative study was approved by the local ethical committee. Followups were at 2(nd) and 6(th) weeks and subsequently at 3, 6, 12, 18 and 24 months postoperatively. Primary outcome was measured by the Constant score, union rate and difference in clavicular length after fracture union. Secondary outcome was measured by operative time, intraoperative blood loss, wound size, cosmetic results and complications. During analysis, we had 37 patients in the plate group and 34 patients in the TEN group. There was no significant difference in Constant scores between the two groups. However, faster fracture union, lesser operative time, lesser blood loss, easier implant removal and fewer complications were noted in the TEN group. The use of minimally invasive antegrade TEN for fixation of displaced midshaft clavicle fractures is recommended in view of faster fracture union, lesser morbidity, better cosmetic results, easier implant removal and fewer complications; although for comminuted fractures plating remains the procedure of choice.


Characteristics of conventional blood pressure in studies on the predictive power of ambulatory blood pressure.
It is commonly believed that the associations of left ventricular mass and cardiovascular morbidity/mortality with blood pressure are stronger for 24-h ambulatory pressure than for conventional clinic or casual pressure. The investigation comprised a review of relevant studies, with particular emphasis on the characteristics of the conventional blood pressure measurement. A review of 21 studies on left ventricular mass, published between 1982 and 1993, showed that the relationship between mass and blood pressure was stronger for ambulatory blood pressure than for clinic blood pressure but that the methodology and conditions of the conventional blood pressure measurements were poorly described or standardized in several reports. Between 1983 and 2001, seven studies showed that ambulatory blood pressure was superior to conventional blood pressure with regard to the prediction of cardiovascular morbidity and/or mortality. From published data and requests for additional information, it appears that recommendations for the measurement of conventional blood pressure have been reasonably well observed, although the number of measurements has not always been adequate. Whereas the quality of the conventional blood pressure measurements left much to be desired in the studies on left ventricular mass, the quality appeared to be reasonably good in outcome studies, even though the published details were often incomplete.


Denileukin diftitox as novel targeted therapy for lymphoid malignancies.
Denileukin diftitox (DAB(389)IL-2; Ontak) is a cytotoxic fusion protein designed to target cells expressing the receptor for interleukin-2 (IL-2). It has been approved for treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL) whose malignant cells express the CD25 component of the IL-2 receptor, but more recent data indicate activity in the setting of not only T-cell but also B-cell malignancies. This review will update the experience to date of denileukin diftitox in T- and B-cell malignancies.


Effects of amine precursor administration on the morphological findings of transplanted argyrophil cell adenocarcinoma of the endometrium.
Argyrophil cell adenocarcinoma of the endometrium has been kept serially in nude mice. Histological appearances of the tumor were not much changed by transplantations. Argyrophil granules were located mainly in the apical portion of glandular tumor cells in the transplanted tumors as in the original one. However, the cells with argyrophil granules in the entire cytoplasm were made conspicuous after the administration of L-DOPA. These results may suggest the existence of latent APUD cells in the argyrophil cell adenocarcinoma of the endometrium which are activated by the treatment of amine-precursor.


Anion-binding properties of the tripyrrolemethane group: a combined experimental and theoretical study.
Tripyrrolemethane- and bistripyrrolemethane-containing systems were recently reported to be efficient and selective hosts for anions. Nevertheless, the basic intrinsic properties of tripyrrolemethane as a ligand for anions have not yet been explored. Here we report the study of the anion-binding properties of the tripyrrolemethane group. We applied a combined experimental and theoretical approach to determine the affinity of the tripyrrolemethane system for different anions in the gas phase, in solution and in the crystalline state. In the crystal, the tripyrrolemethane group forms a number of different complexes with the bromide ion, some involving the participation of more than one ligand species. Despite the very similar basicity of fluoride and dihydrogen phosphate, the tripyrrolemethane ligand exhibits a clear preference for the fluoride anion in solution, which indicates an anion-binding system and not merely deprotonation. Although the affinity of the tripyrrolemethane ligand for other ions was negligible in solution, gas-phase studies show that complexation with larger halide ions is favoured over complexation with fluoride.


[Case report presentation for treatment of pure red cell aplasia].
We presented a case of a 34 year old male patient with pure red cell aplasia. He was treated with antithymocyte globulin (Pasteur Merieux, France) at a dose of 175 mg in 350 ml 0.9% NaCl in intravenous drip infusion--10 drip/min for 5 consecutive days. The therapy resulted in normalization of morphological parameters. Patient was under clinical observation. After 9 years when hemoglobin level decreased monoclonal antibody OKT3 og IgG 2a type (Cilag Ag International, Switzerland) at a dose of 5 mg intravenous for 10 consecutive days was applied. During the first and second therapy course symptoms of serum sickness and "flu like" syndrome was observed. The results of the two treatment appeared positive. We received normalization of morphological parameters.


Differential expression of transcription factors NF-κB and STAT3 in periodontal ligament fibroblasts and gingiva of healthy and diseased individuals.
Pathogens and host mediators can activate transcription factors in periodontal cells to bring about gene level alterations, thereby accentuating the periodontal disease process. Nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription 3 (STAT3) are two pivotal transcription factors implicated in chronic inflammatory diseases. But their importance in periodontal pathogenesis has not been investigated in detail. The aim of the present study was to evaluate the expression of activated transcription factors and their target genes in healthy and diseased periodontium. Primary culture of periodontal ligament fibroblasts (PDLF) were established from healthy and diseased periodontium using explant culture methods. NF-κB and STAT3 activation in these cells by Porphyromonas gingivalis LPS (lipopolysaccharide) was demonstrated using confocal microscopy and mRNA expression of target genes were evaluated by quantitative real time PCR. NF-κB and STAT3 expression in diseased and healthy gingival tissues were analyzed using immunohistochemistry. A basal upregulation of transcription factors and their target genes were noted in diseased PDLF compared to healthy ones. LPS challenge induced differential expression of NF-κB and STAT3 and their target genes in diseased PDLF compared to healthy ones. Immunohistochemical analysis revealed significant activation of transcription factors in diseased gingival tissues. The findings of the present study reveal the role of transcription factors NF-κB and STAT3 in periodontal pathogenesis and disease susceptibility of fibroblast subpopulations in periodontal disease could be mediated through activation of NF-κB and STAT3. Since genetic factors are nonmodifyable, transcription factors are promising targets for future host modulation therapy.


Biodistribution, Clearance, and Long-Term Fate of Clinically Relevant Nanomaterials.
Realization of the immense potential of nanomaterials for biomedical applications will require a thorough understanding of how they interact with cells, tissues, and organs. There is evidence that, depending on their physicochemical properties and subsequent interactions, nanomaterials are indeed taken up by cells. However, the subsequent release and/or intracellular degradation of the materials, transfer to other cells, and/or translocation across tissue barriers are still poorly understood. The involvement of these cellular clearance mechanisms strongly influences the long-term fate of used nanomaterials, especially if one also considers repeated exposure. Several nanomaterials, such as liposomes and iron oxide, gold, or silica nanoparticles, are already approved by the American Food and Drug Administration for clinical trials; however, there is still a huge gap of knowledge concerning their fate in the body. Herein, clinically relevant nanomaterials, their possible modes of exposure, as well as the biological barriers they must overcome to be effective are reviewed. Furthermore, the biodistribution and kinetics of nanomaterials and their modes of clearance are discussed, knowledge of the long-term fates of a selection of nanomaterials is summarized, and the critical points that must be considered for future research are addressed.


Endoplasmic reticulum stress: a key player in human disease.
This Special Issue comprises eleven excellent reviews that illustrate the role of ER stress in different human diseases, including myopathies and lung diseases, as well as in modulating liver dysfunction and inflammatory responses. These reviews also highlight the function of the UPR in neurodegenerative disorders and cancer, while discussing the potential benefits of targeting the UPR as a therapeutic approach. We hope you find these reviews interesting and informative and we thank the authors for these excellent contributions.


Irradiated donor buffy coat following T cell-depleted bone marrow transplants.
Twenty patients aged 27-47 years (median, 35 years) with hematological malignancies, treated with T cell-depleted bone marrow transplantation received in a pilot study five donations of 15 Gy irradiated donor buffy coat cells at days +1, +3, +5, +7, +14 in order to prevent rejection and leukemic relapse. Patients were conditioned with etoposide, cyclophosphamide and 12 Gy fractionated total body irradiation and given cyclosporine postgrafting. Donor bone marrow was T cell-depleted (median 3% remaining T cells) by counterflow elutriation. All patients engrafted. Fourteen (70%) are alive. Two are living with relapse, 12 (60%) are alive and well without any signs of disease, 2-27 months (median, 9 months) post-transplant. Three patients died of interstitial pneumonitis and/or graft-versus-host-disease; three died of relapse. This pilot study supports previous animal data. Repeated infusions of 15 Gy irradiated donor buffy coat are feasible and do not appear to increase transplant related mortality. Whether this approach ultimately will reduce the rate of rejection and relapse following T cell depletion needs to be confirmed in a larger, prospective study.


Life adjustment postmyocardial infarction: determining predictive variables.
Sixty-eight patients with diagnosed myocardial infarctions were followed up for one year postinfarct onset to determine psychosocial adjustment. A previous pilot had differentiated between two groups of patients--depressive and deniers-who had poor vs good rehabilitation results, respectively. Results from this study substantiated previous findings in that 70% of those who were depressed postinfarct remained so throughout follow-up. These patients failed to remain at work and/or to function sexually and had a higher hospital readmission rate. The denial group, although still functioning with minimal psychosocial distress, was not distinguished from the remainder of the study population who generally also functioned well. Women postinfarct seemed to have the most difficult time, accounting for 80% of the deaths and 50% of the depressed group. Their noticeable type A behavior may account for this finding.


Necrotizing fasciitis after scrotum skin injury in an infant: A case report.
Necrotizing fasciitis (NF) is a life-threatening situation that is rare in children, especially infants, and early diagnosis is challenging. Timely identification and broad-spectrum antibiotic and supportive treatment before surgical debridement are very important for survival and may reduce scar formation. A previously healthy 4-month-old infant was admitted to our pediatric intensive care unit (PICU) with a history of fever and cough for 5 days and extreme swelling of the scrotum for one day. Necrotic-like tissue without margins appeared on his scrotum and perineum in 24 hours. NF was suspected, and the patient soon developed shock. The patient underwent surgical debridement after his condition stabilized. Pathological analysis confirmed the diagnosis of NF. Broad-spectrum antibiotic, immediate fluid resuscitation, assistant ventilation, and vasoactive drugs were administered. Surgical debridement and autologous split-thickness skin grafting were performed. The wound recovered well after 2 months. Ultrasound revealed normal testicles, and no anorectal injury was found. Close clinical monitoring and timely treatment of skin injuries in sick children are very important. Sufficient antibiotic administration and supportive treatment before surgical debridement are crucial for survival from NF.


Interfacial localization and voltage-tunable arrays of charged nanoparticles.
Experiments and computer simulations provide a new perspective that strong correlations of counterions with charged nanoparticles can influence the localization of nanoparticles at liquid-liquid interfaces and support the formation of voltage-tunable nanoparticle arrays. We show that ion condensation onto charged nanoparticles facilitates their transport from the aqueous-side of an interface between two immiscible electrolyte solutions to the organic-side, but contiguous to the interface. Counterion condensation onto the highly charged nanoparticles overcomes the electrostatic barrier presented by the low permittivity organic material, thus providing a mechanism to transport charged nanoparticles into organic phases with implications for the distribution of nanoparticles throughout the environment and within living organisms. After transport, the nanoparticles assemble into a two-dimensional (2D) nearly close-packed array on the organic side of the interface. Voltage-tunable counterion-mediated interactions between the nanoparticles are used to control the lattice spacing of the 2D array. Tunable nanoparticle arrays self-assembled at liquid interfaces are applicable to the development of electro-variable optical devices and active elements that control the physical and chemical properties of liquid interfaces on the nanoscale.


A close look at fenfluramine and dexfenfluramine.
In an effort to combat obesity, several medications have been developed. The nonamphetamine anorectics, such as phentermine, fenfluramine, and dexfenfluramine, have been recommended as first-line drug therapy for the treatment of obesity once diet and exercise alone have failed. Numerous studies have shown that these agents can promote weight loss when combined with diet restriction and exercise. Although fenfluramine and dexfenfluramine lack the abuse potential of amphetamine and its congeners, these agents are associated with drug interactions and adverse effects. Concomitant administration of fenfluramine or dexfenfluramine with medications that enhance serotonin levels (e.g., antidepressants, monoamine oxidase inhibitors, and migraine medications) can precipitate serotonin syndrome. Sudden discontinuation of fenfluramine or dexfenfluramine after prolonged administration can precipitate withdrawal depressive symptoms. Primary pulmonary hypertension, a potentially fatal disorder, has been reported to occur approximately 30 times more frequently in patients receiving anorectic agents for more than 3 months compared to the general population. More recently, the association of these popular anorectics with valvular heart disease has caused increased concerns about their use. The risks of primary pulmonary hypertension, valvular heart disease, and the occurrence of convulsions, coma, and death in overdose appear to be equally likely with dexfenfluramine and fenfluramine. In addition, many patients who lose weight while taking these anorectics rapidly regain it after the medication has been discontinued.


Arthro-osteo-renal dysplasia. Report of a case.
A rare case of bone dysplasia with moderate modelling anomalies of the long bones, joint dislocation, osteolysis, a congenital calvarial defect, a patent ductus arteriosus, a mild degree of hypospadias and hypertensive renal cystic dysplasia is presented. In spite of many similarities with the Hajdu - Cheney Syndrome (HCS), important dissimilarities indicate that this case may be either an extreme variant of HCS, or a closely related, separate entity for which the term Arthro-Osteo-Renal Dysplasia is proposed.


Quantum interference in coherent molecular conductance.
Coherent electronic transport through individual molecules is crucially sensitive to quantum interference. We investigate the zero-bias and zero-temperature conductance through pi-conjugated annulene molecules weakly coupled to two leads for different source-drain configurations, finding an important reduction for certain transmission channels and for particular geometries as a consequence of destructive quantum interference between states with definite momenta. When translational symmetry is broken by an external perturbation we find an abrupt increase of the conductance through those channels. Previous studies concentrated on the effect at the Fermi energy, where this effect is very small. By analyzing the effect of symmetry breaking on the main transmission channels we find a much larger response thus leading to the possibility of a larger switching of the conductance through single molecules.


Acute sulfasalazine overdose.
Sulfasalazine (salicylazosulfapyridine, Azulfidine) has been widely used over the last half century for inflammatory bowel diseases, but overdose has not been reported. A 23 year-old male ingested 25 g of sulfasalazine in a suicide attempt. He underwent prompt treatment and survived with no ill-effects.


Molecular Mechanism and Evolution of Nuclear Pre-mRNA and Group II Intron Splicing: Insights from Cryo-Electron Microscopy Structures.
Nuclear pre-mRNA splicing and group II intron self-splicing both proceed by two-step transesterification reactions via a lariat intron intermediate. Recently determined cryo-electron microscopy (cryo-EM) structures of catalytically active spliceosomes revealed the RNA-based catalytic core and showed how pre-mRNA substrates and reaction products are positioned in the active site. These findings highlight a strong structural similarity to the group II intron active site, strengthening the notion that group II introns and spliceosomes evolved from a common ancestor. Prp8, the largest and most conserved protein in the spliceosome, cradles the active site RNA. Prp8 and group II intron maturase have a similar domain architecture, suggesting that they also share a common evolutionary origin. The interactions between maturase and key group II intron RNA elements, such as the exon-binding loop and domains V and VI, are recapitulated in the interactions between Prp8 and key elements in the spliceosome's catalytic RNA core. Structural comparisons suggest that the extensive RNA scaffold of the group II intron was gradually replaced by proteins as the spliceosome evolved. A plausible model of spliceosome evolution is discussed.


Bleb Revision With Temporalis Fascia Autograft.
We report the first description of temporalis fascia autograft to repair a late leakage bleb with scleral defect that occurred long time after trabeculectomy with mitomycin C. A 65-year-old woman was referred to our hospital with chronic late bleb leakage on her right eye. She had previously undergone a trabeculectomy with mitomycin C 3 years ago for a pigmentary glaucoma. Bleb leakage occurred 1½ year after the initial surgery. She underwent 2 surgical revisions consisting of a conjunctival advancement then an autologous conjunctival with partial scleral grafts without success. The initial best-corrected visual acuity of the right eye was 20/50 (Snellen scale). Slit-lamp examination revealed an avascular filtering bleb with leakage (massive positive Seidel test) and a scleral defect. The anterior chamber was deep and intraocular pressure (IOP) was 9 mm Hg.Faced with the risk of blebitis, endophthalmitis, and with the failure of the previous surgeries announced earlier, a surgical revision with autologous superficial temporalis fascia graft was decided to repair the leaking bleb. After local anesthesia, a sample of superficial temporalis fascia was harvested. The necrotic avascular conjunctiva around the bleb was dissected to separate and excise it from the sclera. The autologous fascia graft was sutured on the scleral defect with 10-0 nylon. Subsequently healthy conjunctiva was sutured above the graft. No bleb leakage occurred postoperatively, best-corrected visual acuity improved to 20/25, and IOP remained within normal levels 6 months after surgery without IOP-lowering medication. Superficial temporalis fascia autograft seems to be an effective, safe, and easy technique for ophthalmologists. It is a new procedure in the management of late-onset bleb leakage.


Andreev probe of persistent current states in superconducting quantum circuits.
Using the extraordinary sensitivity of Andreev interferometers to the superconducting phase difference associated with currents, we measure the persistent current quantum states in superconducting loops interrupted by Josephson junctions. Straightforward electrical resistance measurements of the interferometers give a continuous readout of the states, allowing us to construct the energy spectrum of the quantum circuit. The probe is estimated to be more precise and faster than previous methods, and can measure the local phase difference in a wide range of superconducting circuits.


A Convenient and Effective Method to Deposit Low-Defect-Density nc-Si:H Thin Film by PECVD.
Hydrogenated nanocrystalline silicon (nc-Si:H) thin film has received a great deal of attention as a promising material for flat panel display transistors, solar cells, etc. However, the multiphase structure of nc-Si:H leads to many defects. One of the major challenges is how to reduce the defects conveniently. In this work, we developed a simple and effective method to deposit low-defect-density nc-Si:H thin film. This method is simply by tuning the deposition pressure in a high-pressure range in plasma-enhanced chemical vapor deposition (PECVD) process. Microstructures of the nc-Si:H were characterized by Raman, AFM, and SEM. Furthermore, we focused on the defect density which was the key characteristic for photovoltaic materials and achieved the defect density of 3.766 × 1016 cm-3. This defect density is lower than that of previous studies on the fabrication of low-defect-density nc-Si:H by other complex methods in PECVD process. The minority carrier lifetime of nc-Si:H is thus greatly improved. Moreover, we demonstrated the mechanism about the effect of deposition pressure on the ion bombardment and proved that the defect density is the key characteristic for nc-Si:H photovoltaic material.


Descriptive results of a prospective cohort study of avian influenza in the Mekong River Delta of Viet Nam.
A prospective cohort study of avian influenza infection in poultry flocks was carried out in the Mekong River Delta of Viet Nam between December 2008 and April 2010. Our objectives were to (i) estimate the prevalence and incidence of avian influenza virus infection and (ii) assess the efficacy of H5N1 vaccination programmes as indicated by the presence of H5 antibody in vaccinated and unvaccinated poultry. Real-time PCR and H5 multiplex assays were used to detect the antigen of avian influenza viruses from swab samples. The haemagglutination inhibition test was used to detect H5 antibody. A total of 17 968 swab and 14 878 blood samples were collected from 5476 birds over the study period. The overall incidence rate of influenza type A virus infection was 5 (95% CI 4-7) positive birds per 100 bird-months at risk. The overall incidence rate of H5 virus infection was 0.2 (95% CI 0.1-0.5) positive birds per 100 bird-months at risk. Fifty (95% CI 48-52) birds per 100 tested birds were H5 HI positive in the unvaccinated group compared with 71 (95% CI 69-73) birds per 100 in the vaccinated group. Influenza type A and H5 viruses were circulating in village poultry throughout the study period with no recorded signs of clinical disease. This implies that interventions need to be carried out continuously throughout the year rather than only focusing on the established high-risk periods. Broiler ducks had an incidence rate of influenza H5 virus infection approximately four times greater than that of layer ducks and in-contact species. We conclude that broiler ducks are likely to be the main entry route for H5 virus into poultry flocks in the MRD. Control efforts would benefit from understanding why there is a difference between villages in H5 incidence and developing strategies to provide greater protection to broiler ducks.